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pmc-6142765-1 | An 81-year-old Caucasian woman was referred to our department for several weeks of symptoms such as chills, fever, malaise, fatigue, and recurrent tumble despite antibiotic therapy. She was treated prior to admission for approximately two weeks with antibiotics in another hospital. The patient had an important abdominal surgery due to gastric carcinoma three months prior to admission. Gastrectomy, lymphadenectomy, and esophageal stent because of esophageal anastomosis insufficiency were performed during this surgery. The patient had initially presented with chills and recurrent tumble at the family doctor and was at this time admitted in another hospital. With increasing inflammation parameters despite antibiotic therapy and recurrent fever, the medication was changed from amoxicillin to piperacillin/tazobactam on admission. Three independent sets of peripheral blood cultures were obtained before the start of changed antibiotic. All three sets depicted Lactobacillus species. The patient denied ingesting any probiotics. We suspected endocarditis because of bacteremia with Lactobacillus, recurrent symptoms with worsening of condition, and persistent infection despite antibiotic. On admission, she was febrile to 38.3°C, somnolent, complaining of generalized fatigue and malaise. Her heart rate was 85 bpm, and her blood pressure was 110/75 mmHg. Clinical examination revealed a grade 2/6 systolic murmur loudest at the apex such as no painful haemorrhagic spots (Janeway lesion) on all fingertips of the left hand. Lung auscultation and chest X-ray showed no anomaly. Laboratory studies showed a normocytic anaemia (haemoglobin: 9.0 g/dl; MCV: 85.0 fl), a regular white blood cell count (8.960/µl), reduced platelet count (123.000/µl), elevated C-reactive protein (12.6 mg/dl), and an elevated lactate dehydrogenase (310 U/l). We performed a transesophageal echocardiogram for further diagnosis. It showed degenerative changes of the mitral valve with moderate regurgitation as well as small endocarditis vegetation (Figures and Pronounced vegetation of the mitral valve could not be seen. The susceptibility testing showed that the isolate was resistant to vancomycin. After application of the Duke criteria (one major criterion and three minor criteria were found) [] in combination with the clinical condition, the diagnosis of endocarditis was more likely. The major criterion was the vegetation and degenerative changes of the mitral valve, and the minor criteria were the three positive blood cultures with Lactobacillus species, fever over 38.0°C, and the Janeway lesion found on the left hand. We started an intravenous antibiotic therapy with ampicillin (2 g with six administrations per day) combined with gentamicin (with maximum 80 mg per day) for six weeks. The CT scan on admission revealed subcapsular fluid formation of the spleen (). During antibiotic therapy, we performed a PET/CT scan to localize potential inflammatory foci due to embolic complication. Florid inflammatory processes were found in several locations within the spleen (Figures and ). This result was interpreted as peripheral embolization due to endocarditis. We discussed the result of the PET/CT scan with our abdominal/visceral surgeons. They decided upon an operational treatment of the splenic abscesses. The patient underwent an abdominal surgery with splenectomy. Other blood cultures were drawn under the antibiotic therapy. They were all negative without exception. The patient required no mitral valve replacement for cure. |
pmc-6143088-1 | A 37-year-old gravida 2 para 1 (one previous c-section for breech position with a daughter of 3300 g) presented at 19 weeks due to an increased alfafetoprotein on an integrated biochemical screening test (AFP: 3.5 MoM).
Ultrasound revealed normal fetal growth, no structural anomalies, normal dopplers. Placental lakes (>50 % of the placenta) were present. A non- invasive prenatal test (NIPT) on parental request was normal.
Follow-up scan for growth at 26 weeks revealed normal fetal growth, normal dopplers and 2 subchorionic placental cysts located near the umbilical cord insertion, measuring 5 x 3 and 5x 4 cm ().
Gestational diabetes, diagnosed following abnormal glucose challenge test and OGTT, was treated with dietary advise.
At 30 weeks fetal growth had declined (percentile 11), amniotic fluid and fetal dopplers were normal, but the amniotic fluid (AF) was stained and fetal movements were decreased. The placental cysts were equal in size and two intraplacental echogenic cystic lesions were reported.
The glucose profile showed postprandial sub- optimal low glycemic values and patient received dietary advise with improvement of glycemia and of fetal movements.
At 32 weeks ultrasound revealed 6 large subchorionic placental cysts, all measuring > 5 cm, with intracystic heterogenous material compatible with clotting (). Fetal growth was on the 9 th centile with stained amniotic fluid and normal fetal dopplers.
Due to the sudden change of the placental aspect the patient was admitted for fetal monitoring and a repeat c-section was at 34 weeks for suboptimal fetal monitoring. A girl of 1850 g with Apgar scores 6 and 8 at 1 and 5 minutes and arterial cord PH of 7.21 was born, with an uncomplicated neonatal course.
The placenta weighed 513 g, measured 16x 15 x 6 cm and had a 50 cm 3-vessel cord. Multiple large subchorionic cysts (measuring each 6 cm), all with intracystic hemorraghe and massive perivillous fibrin deposits were described (). |
pmc-6143159-1 | A 62-year-old man presented to our ambulatory clinic with an elevated prostate-specific antigen (PSA) of 7.7 ng/mL. The digital rectal examination revealed no changes. Transrectal biopsies were performed, revealing prostate cancer Gleason 6 (3 + 3) on the right side (apex). He was subjected to a transperitoneal laparoscopic radical prostatectomy at our institution (Federal University of Espírito Santo—HUCAM/UFES) in February/2017. The specimen was removed with a glove entrapment bag, and the port-site fascia was closed at the end of the surgery. Histopathological analysis confirmed prostate cancer pT2aNxMx, Gleason 6 (3 + 3) (). Urethral Surgical margin was positive and vesical margin was negative. The PSA, on postoperative week 6 was 0.04 ng/mL. Three months after the surgery, he comes back to the emergency department complaining of an abdominal pain especially on the right flank. Our examination of the abdomen revealed a small palpable mass at the right upper port-site scar. Computed tomography of the abdomen and pelvis, with contrast, revealed a hypodense nodular lesion with barely defined contours located on the abdominal wall near the upper port site and adjacent to the pancreatic tail measuring 1.7 and 4.1 cm, respectively (). The patient was subjected to diagnostic laparoscopy with pancreatic nodule biopsy followed by an excisional biopsy of the subcutaneous lesion, which showed pancreatic adenocarcinoma and presence of metastatic adenocarcinoma, respectively (). The material was sent to immunohistochemistry and a metastasis from pancreatic lesion was confirmed. An MRI of the pelvis and a bone scan did not reveal any changes. Currently, the patient is in a quarterly follow-up and did not present biochemical recurrence at this time. |
pmc-6143322-1 | A 9-year-old female presented with progressive, PG-like lesions involving her left arm following a minor abrasive trauma in a playground accident (Fig. A). She had been previously diagnosed with LAD-1 at 18 months of age. Her CD18 expression level was 5–10%, or mild/moderate phenotype. She had never experienced life-threatening wounds. Her most recent clinical course involved 3.5 weeks of IV antibiotics and multiple wound debridement procedures at a peripheral site. Her lesions significantly expanded after debridement, consistent with PG-like wounds. She was then transferred to our tertiary center.
The patient was cared for by pediatrics (general medical care, care coordination), immunology (direction of immunosuppressive therapies) infectious disease (direction of empiric and culture-directed antibiotic and antifungal therapies) and plastic surgery (direction of wound care, debridement, and acquisition of biopsies). A punch biopsy was obtained from the central wound, histology demonstrated necrosis, focal superficial ulceration of the epidermis with mixed inflammatory infiltrate including histioctyes, multinucleated giant cells, lymphocytes, and focal neutrophils. There was a lack of dermal neutrophilia, consistent with PG-like disease. Systemic therapy consisting of prednisone (1 mg/kg/d), cyclosporine (goal trough level 100–200 ng/mL) and intravenous immunoglobulin (1 g/kg every 2 weeks) was initiated. Initially the wounds were treated empirically with broad spectrum antibiotics involving meropenem (500 mg IV q8h) and vancomycin (500 mg IV q12h). On day 104, a tissue culture obtained during debridement demonstrated deep infection with Fusarium, an invasive fungal infection typically occurring in immunocompromised patients. This corresponded to clinical worsening and elevation in C-reactive protein. She was treated initially with dual liposomal amphotericin (10 mg/kg/d IV) and voriconazole (9 mg/kg/dose IV q12), which was then stepped down to liposomal amphotericin alone (see table, Supplemental Digital Content 1, which displays Laboratory findings and medications during treatment course, ). This treatment continued until the wounds were closed. The wounds were initially dressed with SilvaSorb Site Dressing (Medline Industries Inc., Salt Lake City, Utah.) and changed every 3 days.
Despite this management, her wounds continued to worsen. Methylprednisolone (30 mg/kg IV weekly) was added to the treatment regimen after 3 weeks. During dressing changes, the wounds were meticulously handled and only frankly necrotic or loose hypergranulation tissue was debrided to mitigate the risk of secondary infection. Sargramostim (Sanofi US, Bridgewater, N.J.), a recombinant granulocyte-macrophage colony-stimulating factor, was applied topically at each dressing change.
The dressing was substituted with Aquacel Ag (ConvaTec, Bridgewater, N.J.), an antimicrobial hydrofiber dressing, and this dressing was changed twice per week to limit the amount of wound manipulation. Shortly thereafter, IV infliximab infusions (10 mg/kg every 2 weeks), a tumor necrosis factor blocker and topical tacrolimus, a macrolide calcineurin inhibitor, were added to the regimen. Within days, the wounds had stabilized, and granulation tissue became apparent. Epithelialization was observed at all edges of the wound bed. As wound healing progressed, hypergranulation tissue was noted (Fig. B). Cautious debridement of the hypergranulation tissue with removal of necrotic tissue along with frequent infection monitoring was required to allow for complete epithelialization of the wound.
The dressing change frequency was changed from twice weekly to weekly, as healing progressed. Complete epithelialization of the wound was accomplished in 8 months (Fig. C). Aggressive physiotherapy was employed throughout the healing process to avoid the development of contractures. Full range of motion was maintained. The wound was observed and stable for 2 years postoperatively. |
pmc-6143370-1 | A 32-year-old woman (59 kg, 1.68 m) with a five-year history of generalized tonic-clonic seizures presented to Inova Loudoun Hospital's emergency room on June 6, 2016. Upon presentation, the patient suffered a generalized tonic-clonic seizure that lasted for more than one minute. She recently immigrated from Honduras, had no US medical insurance, and reported a history of nonadherence to her antiepilepsy medications. Currently, the patients were not on any routine home medications as an outpatient and denied any known treatment for NCC. The patient admitted that she had a seizure episode in Honduras three years ago, which was treated with intravenous (IV) fosphenytoin at the time. She had been seizure-free since.
In the emergency department, a computed tomography (CT) scan of the brain was performed without remarkable findings. The patient was loaded with a single dose of IV levetiracetam 1000 mg and then started on oral levetiracetam 500 mg twice a day after admission to the hospital. Given her prior seizure history, a magnetic resonance imaging (MRI) scan of the brain was requested to rule out any space-occupying vascular or ischemic insult. An electroencephalogram (EEG) was also requested. The patient was afebrile with mild leucocytosis (WBC 11.02) and elevated creatinine kinase (CK) of 1.6. The liver panel was normal. The physical exam and review of systems were noncontributory.
On hospital day 2, the MRI scan of the brain revealed a 5 mm ring-enhancing lesion in the posterior right frontal lobe of the cerebral cortex, with surrounding vasogenic edema, suggestive of an infective neurocysticercosis lesion. CT scan and EEG were normal. A positive serological antibody test utilizing a western blot assay for cysticercosis immunoglobulin G (IgG) antibody established the diagnosis of parenchymal neurocysticercosis. The patient was commenced on oral ABZ 400 mg twice daily plus oral PZQ 1,200 mg three times daily, dexamethasone 6 mg IV daily, and oral levetiracetam 500 mg twice daily.
On hospital day 3, no recurrent seizure episodes were observed. Leucocytosis and elevated CK resolved. On hospital day 4, the patient was discharged and given further instructions to continue taking oral ABZ 400 mg twice daily in combination with oral PZQ 1,200 mg three times daily for a total of 14 days, oral dexamethasone 6 mg daily for a total of 14 days, and oral levetiracetam 500 mg twice daily for one year. Follow-up appointments at the neurology clinic were scheduled on a monthly basis to evaluate the resolution of neurocysticercosis cysts, the presence of any seizure episodes, and other associated symptoms. The first follow-up visit in three weeks revealed no recurrent seizure episodes. The patient had finished and tolerated well the 14-day course of combination ABZ plus PZQ. Physical exam and labs were normal. A repeat MRI scan of the brain confirmed the complete resolution of cysticerci. The patient continues to be seizure free and is being monitored for one year. |
pmc-6143371-1 | Case 1: A 49-year-old woman presented to the dermatologist for routine skin screening. Her past medical history was significant for fibromyalgia, hyperlipidemia, hypertension, and obstructive sleep apnea. She had also a history of actinic keratosis, basal cell carcinoma, and melanoma. Cutaneous examination showed dark pigmented lesions on her right scapula, right axilla, and left chest. Biopsy revealed benign nevi. Her skin examination also revealed ragged cuticles with erosions. In addition, the lunula were markedly enlarged on both thumbs (macrolunula). The lunula on some of her other fingers were also prominent (Figure ). Additional history revealed that she habitually used the nails of one hand to pick at the cuticles (eponychium) of the other hand. Her macrolunula-associated characteristics are summarized in Table . |
pmc-6143371-2 | Case 2: A 58-year-old woman came in for evaluation of a lesion on her right thigh that had enlarged. She had a past medical history of arthritis. A cutaneous exam showed an ulcerated nodule on her right thigh. Biopsy showed benign prurigo nodularis. Examination of her nails showed a split in the lateral portion of her left thumbnail that extended from the proximal nail fold to the tip of the nail. The lunula of the left thumb was significantly enlarged (Figure ). Additional history revealed that the finger had been caught in a car door when she was age 17, and the nail plate had subsequently split. Her macrolunula-associated characteristics are summarized in Table . |
pmc-6143371-3 | Case 3: A 64-year-old man came in for evaluation of a lesion on his left upper lip. His past medical history included gastroesophageal reflux disease, hyperlipidemia, and obstructive sleep apnea. Skin history included a prior basal cell carcinoma. Cutaneous examination revealed a plaque on his upper lip; a biopsy of the lesion diagnosed squamous cell carcinoma in situ. Cutaneous examination of the fingers also showed erosions and altered nail folds. Moreover, the lunula of his right thumb was markedly enlarged (Figure ). Further history indicated that the patient often bites off the distal ends of his fingernails. He also habitually rubs the proximal nail fold of his right thumb. His macrolunula-associated characteristics are summarized in Table . |
pmc-6143664-1 | MT is a 43-year-old right-handed woman who used to work as a lawyer. At the age of 42 years, she had suffered a rupture of the cerebellar arteriovenous malformation (AVM), which was treated with embolization (July 2014). Ten months after the lesion (May 2015), she was admitted to the Ataxia Laboratory of IRCCS Fondazione Santa Lucia. A neurological examination revealed severe ataxia with a total motor score of 46/100 on the International Cooperative Ataxia Rating Scale (ICARS) ().
During the anamnestic interview, no cognitive problems were apparent prior to the cerebellar lesion. However, episodes of inappropriate behaviours were described in childhood, although they had been underestimated by MT's parents. The patient's major complaint was the worsening of some symptoms (i.e., impulsiveness) and the onset of other behavioural abnormalities, also confirmed by the husband, and included referred hallucinations, together with a euphoric state similar to a manic mood phase. These symptoms arose after the cerebellar accident; they were already present in September 2014 (5 months after the acute event) and worsened over time.
Therefore, an assessment of her personality and mood changes was performed by an expert psychotherapist using the Structured Clinical Interview for DSM IV Axis I Disorders (SCID I) () and the Structured Clinical Interview for DSM IV Axis II Disorders (SCID-II) (). It should be noted that, at the time of the patient's evaluation, the Italian version of SCID I and SCID II scale related to the new DSM- 5 criteria () was not yet available. It was determined that MT suffered from borderline personality organization and bipolar I disorder, mixed episode, as already described by Lupo et al. ().
Moreover, an adjustment disorder with a disturbance in conduct, from which she had been suffering since childhood, was also diagnosed. In Lupo et al. (), the authors linked these behavioural alterations to an abnormal cerebellar influence during cerebral development due to the congenital nature of the AVM ().
The patient was never pharmacologically treated for psychiatric symptomatology.
The patient's major psychiatric symptoms, as detected by the psychological assessment, and experienced during the manic mood phase, are listed below:
- Euphoria
- Disinhibited and inadequate behaviour (e.g., laughter during funerals)
- Impairment in social interaction
- Impulsiveness (e.g., spending money irresponsibly)
- Aggressiveness
- Transient stress-related psychotic-like symptoms (e.g., hallucinations and dissociative symptoms)
- Emotional lability and mood swings (e.g., from a mild depression to a euphoric mood state)
- Alexithymia
At the time of psychological assessment (May 2015), a whole brain investigation was performed by means of an advanced MRI examination. MT's lesion affected the left hemispheric regions of the cerebellum, specifically lobules VI, VIIa (crus I), and IX, and the posterior area of the vermis, with a sparing of dentate nucleus (total lesion extent: 3934 mm3). No other cortical or subcortical lesions were detected (see Figure ).
The selective cerebellar lesion was also confirmed by examination of tomography images (PET).
Furthermore, in January 2016, an MRI follow-up did not show any modification in comparison with the scan from 8 months before (see Figure ). |
pmc-6144491-1 | A male infant, who was term appropriate for gestational age, was born via repeat caesarean section to a healthy 26-year-old woman. No family history of bleeding disorders was reported by the mother. Pregnancy was unremarkable, and Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. On initial physical examination, a localized hematoma to the left parietotemporal region was identified. A routine complete blood count (CBC) displayed normal counts. It was decided to repeat the CBC in 12 hours and, in the interim, to observe for dissemination of the blood collection. Prior to the next blood test, the physician was called to the bedside because the infant now had a change in his clinical examination: pale and tachycardic. His examination now revealed a large palpable fluid wave that extended behind the neck and left ear. Given the infant’s change in clinical status and concern for a subgaleal hematoma, the infant was transferred to the neonatal intensive care unit (NICU). The repeat CBC showed a hemoglobin level of 7.6 g/dL, with a hematocrit of 22% and platelets of 169 × 109/L. In the NICU, the patient received a transfusion of 20 cc/kg of O Rh-negative packed red cells. His coagulation profile disclosed a normal prothrombin time but an activated partial thromboplastin time (PTT) of 101 seconds (normal = 25-30 seconds).
Subsequently, a FVIII level was ordered, which was very low at <0.01 U/mL. He was diagnosed with severe HA and was initially treated with 50 U/kg of recombinant FVIII. His repeat doses were adjusted to bring his FVIII level to 100%. A computed tomography (CT) scan of the head revealed a large subgaleal hematoma, beginning in the left parietal area, extending to the occiput and down the nape of the neck. The infant was discharged at 1 week of age following a repeat head imaging confirming complete resolution of the extracranial hemorrhage (ECH) without any evidence of intracranial bleeding. |
pmc-6144491-2 | A term male infant weighing 3885 g (>95th percentile) was born vaginally to a 22-year-old woman. No family history of bleeding disorders was reported by the mother. The pregnancy was uneventful and resuscitation was uncomplicated. The initial physical examination in the newborn nursery was unremarkable; however, at 6 hours of age, the infant acutely developed a bluish discoloration to the skin diffusely throughout his body, became hypotensive, and had marked abdominal distention. His hemoglobin was 5.5 g/dL, and his PTT was greater than 100 seconds. A blood transfusion of 20 cc/kg of O Rh-negative packed cells was provided. An abdominal radiograph showed a normal bowel gas pattern, but the intestines were clustered in the center of the abdomen, indicative of free fluid in the peritoneal cavity ().
A bedside abdominal ultrasound demonstrated a ruptured splenic hematoma with a large amount of free fluid in the peritoneal cavity. FVIII was <0.01 U/mL, and he responded quickly to repeated intermittent infusions of blood clotting FVIII concentrate. The infant had a rapid recovery and therefore did not require a surgical intervention. He went home on the 10th day of life after abdominal ultrasound confirmed resolution of the splenic laceration and hemoperitoneum. A head ultrasound excluded cranial bleeds. |
pmc-6144491-3 | A large-for-gestational-age, term male infant was born via spontaneous vaginal delivery to a 34-year-old woman. Pregnancy was complicated by little to no prenatal care. Maternal serologies were unknown. The labor was prolonged with rupture of membranes 29 hours before delivery. The infant required oxygen and brief bag mask ventilation with Apgar scores of 4 and 9 at 1 and 5 minutes, respectively. In the first hours of life, a hematoma was noted over the forehead and left parietal area. The CBC done at birth demonstrated a normal hematocrit concentration of 37.6%. The following morning, during his examination, the physician noted the frontal-occipital circumference had increased by 2 cm. The infant also showed signs of increased work of breathing. A repeat blood test revealed a precipitous drop in hemoglobin level from 12.5 g/dL to 8.6 g/dL, and his new hematocrit was 25.7%. FVIII levels were measured at <0.01 U/mL.
While awaiting the coagulation profile, he was given 10 mL/kg of fresh frozen plasma and 10 mL/kg of packed red blood cells. The PTT was very elevated, consistent again with severe HA. Hematology was consulted and recommended a continuous infusion of FVIII concentrate until FVIII levels were well over 100%. Meanwhile, a CT of the head showed a subdural hematoma on the right side and a subgaleal hematoma involving the left and right frontoparietal region ().
At 36 hours of life, he began having tonic-clonic seizures and was given a loading dose of phenobarbital (20 mg/kg). The electroencephalogram confirmed epileptiform activity. The patient had continuous infusion of the blood clotting factor for 1 week and went home with a central line for daily treatment. The patient was discharged after 3 weeks in the NICU with a magnetic resonance imaging of the head yielding complete resolution of the intracranial and extracranial hemorrhages. The anti-seizure medication was discontinued after 1 week of therapy with a concomitantly normal electroencephalogram. Several days after the infant was born, the mother revealed she knew of a male family member with a bleeding disorder. |
pmc-6145046-1 | A 59-year-old male was diagnosed with AATD in 1997 by AAT immunoassay (level) and began augmentation therapy in 2014. In 2015, Pi phenotyping yielded Pi MZ results and AAT level of 72mg/dL (13.8 uM). He was identified as a MZ heterozygote and informed his family members of MZ-associated familial risk. Two siblings had genotyping (MM, MZ) and two did not test. The participant received a double lung transplant during the study. The ZZ diagnosis explained his severe, progressive lung disease disproportionate to the MZ genotype. Augmentation therapy was appropriate for severely low pretreatment AAT level and clinical emphysema. The ZZ diagnosis is risk-raising for liver disease where evaluation and monitoring are recommended. The untested siblings have a risk for ZZ-AATD and should be tested. |
pmc-6145046-2 | An 18-year-old male was referred to pulmonology with documented MZ status and AAT level of 64 mg/dL (12.3 uM). The participant's father died of ZZ-AATD disease. He had targeted familial genotyping, which identified a single Z allele as expected, and received consultation about MZ health and reproductive risks. The SZ result by NGS conferred higher health and reproductive risks that require follow-up. Should symptoms worsen in the future, augmentation therapy may be considered (whereas is not recommended for MZ heterozygotes). His results revealed that his mother carries an S allele, and the maternal half-siblings are at previously unknown increased risk. |
pmc-6145046-3 | A 58-year-old female tested through the ACT study in 2014 due to pulmonary symptoms. Prior to 2015 the ACT study performed targeted genotyping for the S and Z mutations only and estimated AAT level. She received a MZ result with AAT level 78 mg/dL (15 uM). The F allele is a dysfunctional allele where the functional capacity to inhibit neutrophil elastase, rather than the quantity of AAT, is altered []. The FZ result by NGS diagnosed a rare form of AATD. In the presence of emphysema and fixed obstruction on spirometry, augmentation therapy may be indicated (whereas is not indicated for MZ heterozygotes with the same symptomology). Full siblings have a risk for FZ-AATD and should be tested. Familial testing should cover the F allele to ensure accurate results. Retesting may be recommended for relatives who tested before the F allele was commonly detected. Since 2015, the ACT study genotypes for the Z, S, F, and I mutations. |
pmc-6145046-4 | A 57-year-old male tested through the ACT study in 2016 after his brother was diagnosed with AATD-emphysema. He did not know his brother's genotype. ACT results reported the MZ genotype and level of 70.1 mg/dL (13.6 uM). NGS identified the Smunich variant (c.1061C>T, p.Ser330Phe) which was classified by Biocerna LLC as likely pathogenic [, ]. The ZSmunich genotype should be interpreted in the context of AAT level and clinical presentation. This result may alter surveillance and treatment for AATD disease. Genetic risks to relatives are altered by this result although the clinical implications are not well known. |
pmc-6145046-5 | A 34-year-old male tested through the ACT study in 2011 and received results with the MZ genotype and level of 80.6 mg/dL (15.5 uM). NGS identified the M2obernburg variant (c.710T>C, p.Gly148Trp) which was classified by Biocerna LLC as a variant of uncertain pathogenicity and uncertain clinical significance [, ]. Interpretation of this result in the context of AAT level and clinical symptoms is recommended. Relatives have an increased risk for this variant, although this variant's contribution to AATD risk is unknown. |
pmc-6145046-6 | A 65-year-old female tested through the ACT study in 2013 and received results with the MZ genotype and level of 77.0 mg/dL (14.8 uM). NGS identified the c.922G>T (p.Ala308Ser) which was classified by Biocerna LLC as a variant of unknown clinical significance []. Interpretation of this result in the context of AAT level and clinical symptoms is recommended. Relatives have an increased risk for this variant, although this variant's contribution to AATD risk is unknown. |
pmc-6145057-1 | A 93-year-old Caucasian female was brought to emergency room for gradual decline in mental status over a course of one week. Her past medical history was significant for coronary artery disease, hypertension, diabetes mellitus, hyperlipidemia, and mild cognitive dysfunction. Her medications included aspirin 81 mg daily, metoprolol 25 mg daily, amlodipine 10 mg daily, and atorvastatin 20 mg daily. Four days prior to the onset of symptoms, she was started on escitalopram 10 mg daily by her primary care physician for newly diagnosed depression. She had a routine blood work immediately prior to the outpatient visit and on retrospective review was found to have a serum sodium level of 136 mEq/L. Patient developed drowsiness and inability to maintain conversation after four days of starting escitalopram. Her mental status continued to gradually decline over the course of next few days and on the day of presentation, which was seven days from the onset of symptoms, she was noted to have intermittent severe agitation. She did not have fever, chills, neck rigidity, myalgia, recent trauma, or fall. There was no reported seizure activity or loss of consciousness. At the time of admission, patient was afebrile, blood pressure was 134/57 mm Hg, pulse rate was 75 beats/min, and respiratory rate of 18 and saturating was 99% on room air. Her BMI was 27.1. She was noted to be lethargic and was only responsive to painful stimuli. Mucous membranes were moist, and the skin turgor was intact. Her GCS score was 7 (E2V1M4). Neurological examination was negative for any gross focal neurological deficits. The rest of the physical examination was unremarkable. While, in the emergency room, patient was noted to have generalized tonic-clonic seizure which was controlled with a single dose of intravenous lorazepam 1 mg. Initial laboratory investigation results are presented in , along with reference range values. Notably, patient's serum osmolality was 234mosm/kg (normal range: 275–295 mosm/kg), urine osmolality was 468 mosm/kg, serum sodium was 105 mEq/L (normal range: 135–145 mEq/L), and urinary sodium was 68 mEq/L (normal range 25-150 mEq/L). Her thyroid-stimulating hormone (TSH) and early morning free cortisol were 0.8μIU/mL (normal range 0.5-5.0 μIU/mL) and 49.2 μg/dL (normal range 1-75 μg/dL), respectively. Chest X-ray as well as CT Head without contrast were unremarkable. |
pmc-6145100-1 | MECM, a 49-years-old previously healthy woman, married and childless, was admitted at a private hospital in Natal City, Rio Grande do Norte State, Brazil, in June, 2014 for a microsurgery of neuroma. She used to live in a flat with a parrot who had an unknown disease that caused loss of feathers. The microsurgery was performed via the cranial middle fossa to remove a left sided acoustic neuroma. After 40 days of the procedure, she presented a predominantly and intensive occipital holocranial headache, followed by vomiting. She was managed with analgesia and prednisone 20 mg/day for 5 days. The patient also had hyporexia that was accentuated with the worsening of headache, 12 kg of weight loss, asthenia, irritability, difficulty to concentrate and rotator vertigo. She did not have a fever. On physical examination, the patient presented classic signs of irritability of meningeal inflammation.
On the 50th postoperative day, she was diagnosed with a cerebrospinal fistula in the occipital region and submitted to a surgical correction. The CSF analysis revealed 126 cells/mm3, composed by 63% of lymphomonocytes, 13 mg/dl of glucose levels (89 mg/dl of glycemia) and 189 mg/dL of proteins. Direct examination and CSF microbiological culturing (including common bacterial, mycobacterial and fungal procedures) did not detect any pathogen. Hemogram and biochemical examination of blood were normal. Vancomycin and ceftriaxone were prescribed for 14 days, dexamethasone, 16 mg/day, for 10 days, followed by 15 days of prednisone weaning. She was discharged with partial improvement of headache, without vomiting and presenting normal CSF. After 3 weeks, the headache intensified and vomiting returned. Prednisone 80 mg/day, for 7 days, followed by 30 days of weaning was prescribed, resulting in mild improvement of headache, but with persistent vomiting and return of rotational vertigo. Therefore, cinnarizine, esomeprazole, bromopride and paracetamol/codeine were prescribed. As no relief was obtained after 30 days, the patient was re-hospitalized and CSF analysis revealed: 245 cells/mm3, 88% of lymphomonocytes, 23 mg/dL of glucose levels and proteins of 324 mg/dL. Microbiological cultures for bacteria and fungi were negative. Hemogram and biochemical examination of blood were still normal. She was diagnosed again with occipital liquoric fistula and submitted to clinical treatment. She was under the same antimicrobial and corticoid regimen of the last hospitalization and was discharged with mild headache. Dexamethasone 16 mg/day, for 10 days, followed by 30 days of weaning with prednisone was prescribed. At that moment, the CSF still had 68 cells/mm3, with 100% of lymphomonocytes, 56 mg/dL of glucose levels and 78 mg/dL of proteins. Prednisone was prescribed for 30 days.
When the corticoid was discontinued, headache worsened and vomiting returned. After 5 months of the onset of the disease, a new computed tomography (CT) scan of the skull showed a CSF fistula on the same topography. She was hospitalized and submitted to a surgery to correct the fistula. She had leukocytosis on admission (16,000 leukocytes/mm3, with 88% segmented cells) and CSF analysis showed 280 cells/mm3, being 88% of lymphomonocytes cells, 12 mg/dL of glucose levels and 312 mg/dL of proteins. Bacterial and fungal cultures were negative. Empirical treatment with vancomycin and cefepime was introduced for 21 days and dexamethasone 16 mg/day for 10 days, followed by 20 days of weaning with prednisone. As the headache worsened, she was again hospitalized and submitted to surgical correction of the fistula. New CSF showed 184 cells, 63% of lymphomonocytes, 41 mg/dL of glucose levels and 285 mg/dL of proteins. Vancomycin, meropenem and dexamethasone, 10 mg/day were initiated. On the 5th day of treatment, headache remained intense and frequent vomiting. A new CT suggested hydrocephalus and the patient was submitted to a ventriculoperitoneal (VP) shunt. After 3 days of VP, the patient continued to present with vomiting and leukocytosis and the CSF pressure was above 300 mmH2O. She was admitted to the intensive care unit. A magnetic resonance imaging (MRI) of the skull suggested meningeal thickening, spinal cord compression at the level of C5-C6 and the alteration of the CSF signal was compatible with viral or fungal disease (Fig. ). The initial suspicion was cryptococcosis. Liposomal amphotericin B (300 mg/day) and acyclovir therapy were empirically initiated. After several invasive procedures, broad spectrum antibiotics and corticosteroids, CSF culture showed growth of Trichosporon spp. After 2 weeks, another Trichosporon CSF positive culture was obtained. As there was progressive worsening of the clinical condition, voriconazole (200 mg/every 12 h) was added to the previous prescription. On the 20th day of hospitalization, the patient died (Table ).
The CSF was centrifuged at 2500 rpm for 10 min and the sediment was used for direct examination and culture. Direct examination was performed with India ink which revealed no encapsulated blastoconidia. The sediment of 2 CSF samples collected at different days (14th and 28th of April, 2015) were plated on Sabouraud Dextrose Agar at room temperature (28 + 2 °C) and yielded positive yeast cultures after 72 h of incubation. The two cultures were send to the Medical and Molecular Mycology Laboratory, Clinical and Toxicological Analyses Department, Federal University of Rio Grande do Norte State for further molecular identification. Of note, both colonies had a mucoid aspect. Besides, because Cryptococcus spp. are the main etiological fungal agents obtained from meningitis, that was the first suspicion. Yeast isolates from original cultures were plated onto CHROMagar Candida (CHROMagar Microbiology, Paris, France) and corn meal-Tween 80 (to induce sporulation). Surprisingly, both isolates had a macroscopic wrinkled appearance, were able to produce arthroconidia, as revealed by their micromorphology, and to hydrolyze urea (Fig. to ). Therefore, they were considered to belong to the genus Trichosporon and named HGT198 and HGT914, respectively. Both strains were further identified by molecular techniques.
A single colony of each strain was used for DNA extraction with PrepMan Ultra sample preparation reagent (Applied Biosystems, Foster City, CA) according to the manufacturer’s instructions. Genomic DNA concentration and purity were checked with a NanoDrop instrument (Thermo Scientific; Amersham Pharmacia Biotech, Wilmington, DE, USA). Both strains were further identified by a molecular method as detailed elsewhere []. DNA amplification was obtained by using the primer pair TRF (5′-AGAGGCCTACCATGGTATCA-3′) and TRR (5′-TAAGACCCAATAGAGCCCTA-3′) []. Nucleotide sequences were submitted for BLAST analysis at the NCBI site () for species identification. Only sequences deposited in GenBank showing high similarities with our query sequences and an E-value of lower than 10− 5 were used in this study. BLAST searches showed the best match with T. inkin (FJ153608.1), 100% identity (619 of 619 bp without gap sites) for both strains (HGT198 and HGT914). IGS1 rDNA sequences of these strains have been deposited in GenBank under accession numbers KY807052 and KY807053, respectively. Of note, both strains were considered of 100% identity, after blastn analysis (all the 641 bp compared among them), with an E-value of 0 and no gaps found between the two IGS1 rDNA sequences.
Strains HGT198 and HGT914 were evaluated according to their ability to adhere to human buccal epithelial cells, biofilm formation, hemolysins and phospholipase production by using the methods described by Zuza-Alves []. DNAse production was determined according to Montoya []. Both strains did not produce phospholipase or DNAse. However, they showed high biofilm formation capability as compared to C. albicans ATCC90028 and T. asahii CBS2630 and similar levels of hemolysin production of the two reference strains. In addition, they were able to adhere to epithelial cells to the same extension of T. asahii reference strain (Table ).
Both strains were tested against fluconazole, itraconazole and amphotericin Bby using the CLSI protocol [–]. As illustrated on Table , they exhibited very low MIC values against all antifungal drugs tested. |
pmc-6145115-1 | A 56 year old Sri Lankan female presented with fever, chills and rigors for 2 weeks. She was diabetic and her glycaemic control was fairly good with oral hypoglycaemic drugs: fasting blood sugar was 112 mg/dl and HbA1C was 5.7%. At presentation, fever was associated with constitutional symptoms like malaise and loss of appetite, but she didn’t have any other symptoms on systemic review. She is a housewife, not engaged in gardening or farming.
On admission, upon examination, she was febrile (temperature was 101.4 0 F), did not have lymphadenopathy, oral ulcers, uveitis, peripheral signs of infective endocarditis, rashes or hepatosplenomegaly. Rest of her clinical examination was unremarkable.
On the third day of admission, blood culture reported positive with the growth of Burkholderia cepacia. She was started on IV ceftazidime 2 g every 6 h, with the suspicion of Burkholderia pseudomallei and melioidosis serology was ordered. Colony morphology consisted of grey-white small, smooth colonies. Gram stain showed gram negative slender rods with bipolar staining, antibiotic susceptibility pattern gave clues to the microbiological diagnosis of Burkholderia pseudomallei, sensitive for ceftazidime and meropenem and resistant to gentamycin (Figs. and ). The melioidosis antibody titer Ig M was 1:640, measured by enzyme linked immunosorbent assay (ELISA). The isolate was confirmed as Burkholderia pseudomallei by PCR the following day.
She was continued on IV ceftazidime 2 g every six hours. During her 2nd week of hospital stay (24th day of fever), she developed right hip joint pain, right sided low backache, right buttock pain, difficulty walking and restricted right hip joint movements. She did not have any other joint involvement or history of arthritis. She did not have past history of tuberculosis or significant contact history of tuberculosis. She did not have change of bowel habits, red eyes to suggest inflammatory bowel disease. She didn’t have any skin rashes to suggest psoriasis or vasculitis or recurrent oral ulcerations to suggest behcet’s disease. She did not have a history of raw milk ingestion to suggest brucellosis. She didn’t have family history of arthritis or autoimmune diseases. By that time, her right hip joint movements were restricted due to pain, she had severe tenderness over right sacroiliac joint and sacroiliac stretch maneuvers were positive for a clinical diagnosis of right sacroiliitis. She had a neutrophilic leukocytosis, with high inflammatory markers. Ultrasound Scan of the hip joint detected a large fluid collection measuring 5 cm × 18 cm involving the right iliopsoas, without extension into hip joint. A Contrast Enhanced CT scan (CE CT) of Chest, abdomen and pelvis showed multiple intramuscular abscesses over right psoas, iliacus, gluteus and obturator internus (the largest abscess measured 18 cm × 4 cm over right psoas and iliacus (Fig. )). There were no visceral abscesses in the liver or spleen. Initially US guided aspiration and drainage was carried out to drain the iliopsoas abscesses (by the 28th day of fever), followed by a pig tail catheter drainage over 5 days, since it was a large collection. The aspirated fluid culture was also positive for Burkholderia pseudomallei.
One week post aspiration, she had an MRI scan of spine and sacroiliac joints: which showed resolving infection in right iliacus muscle, with a thin collection of fluid and muscle oedema. It also showed right sacroiliitis with surrounding marrow oedema and mild reactive bone changes (Fig. ). We didn’t aspirate fluid from sacroiliac joint, since an alternative cause for sacroiliitis was unlikely, melioidosis was the likely cause for her right sacroiliitis.
Fever, multiple abscesses with sacroiliitis, pointed towards the musculoskeletal involvement of melioidosis. Her sacroiliitis was infectious in nature, so inflammatory causes like psoriatic arthritis, ankylosing spondylitis and inflammatory bowel disease were unlikely. Anyway we wanted to exclude co-infection of melioidosis with tuberculosis/ brucellosis/ fungal infections and immunosuppressed states like AIDS (Acquired Immuno Deficiency Syndrome).
Her Mantoux test was negative, chest X ray was normal, sputum for acid fast bacilli were negative and pus drained from abscesses didn’t yield any growth on bacterial cultures, AFB cultures or fungal cultures. Brucella and HIV antibodies were also negative.
Despite treatment with IV ceftazidime, her fever spikes continued attributable to the complications with intramuscular abscesses and sacroiliitis. Her Melioidosis antibody titers obtained 2 weeks apart increased from 1/640 to 1/10240. Thus IV ceftazidime (given for 12 days) was changed over to IV meropenem 2 g every 8 h with oral co-trimoxazole 3 tablets (each tablet = 400 mg of sulfamethoxale and 80 mg of trimethoprim) every 12 h was added on the 28th day of fever.
Results of some of the relevant investigations are shown below, given in a Table .
According to the recent international guidelines, in deep seated abscesses, duration of intensive phase of melioidosis is extended and retimed from the date of most recent drainage of Burkholderia pseudomallei. [–]. Therefore our patient’s IV therapy was extended additional 14 days of abscess drainage. She developed pancytopenia, during the second week of treatment with co-trimoxazole. Her haemoglobin was 7.9 g/dL, white cell count was 2.8 × 109/L and platelet count was 113× 109 /L. This was changed into oral doxycycline 100 m grams every 12 h to avoid bone marrow suppression. Her intensive phase was continued with IV meropenem 2 g every 8 h another 6 weeks together with oral doxycycline. During the 6th week of intensive phase treatment, she also developed Syndrome of Inappropriate Secretion of ADH (SIADH), with persistent hyponatraemia (120-135 mmol/L), urinary sodium of 92 mmol/L, and serum osmolality 264mosm/kg and urine osmolality of 389mosm/l. She responded within 1 week with fluid restriction therapy alone, without change of medical management.
She was restarted on oral co-trimoxazole 4 tablets every 12 h, at the end of intensive phase treatment, (each tablet = 400 mg of sulfamethoxazole and 80 mg of trimethoprim) and discharged her on eradication phase (since cotrimoxazole is the best drug in eradication phase, it was restarted and she didn’t develop pancytopaenia this time). She was followed up monthly for 6 months and she made an uneventful recovery at the end of eradication phase. Follow up MRI Scan of sacroiliac joints done after 2 months showed marked reduction of infection, oedema and sacroiliitis and by that time, she was completely asymptomatic (Fig. ). |
pmc-6145116-1 | A 12-year-old Saudi boy of Arab ethnicity, with no past relevant medical, surgical, family, or psychosocial history, presented to the King Saud Medical City emergency department with bleeding per rectum and mild abdominal pain 3 days after blunt abdominal trauma while playing football. On examination, his abdomen was slightly tender and bowel sounds were present. Initially, focused assessment with sonography for trauma (FAST) showed mild intraperitoneal fluid in his pelvis. A subsequent computed tomography (CT) scan of his abdomen revealed mild pelvic hemoperitoneum, but there was no definite solid or hollow visceral injury. So, he was admitted to the general ward for serial abdominal observation. On admission to the surgical ward, he was stable with a heart rate (HR) of 86 beats per minute (bpm) and blood pressure (BP) of 100/70 mmHg. His hemoglobin (Hb) was 9.6 gm/dl. We kept him nil per mouth and a nasogastric tube was inserted. The intake and output chart was regularly calculated. Serial Hb monitoring showed a continuous fall in his Hb level during the following days. He continued to have altered rectal bleeding. On day 3 his Hb dropped to 6.1 gm/dl, despite having received 2 units of packed red blood cells (PRBC). He started to develop a mild fever with a temperature of 37.8 °C, tachycardia with a HR of 140 bpm, and the BP dropping to 70/40 mmHg. He was resuscitated and stabilized with intravenously administered crystalloid fluids and 2 units of PRBC. He did not require any inotropes or vasopressors. Due to this clinical deterioration, he was urgently taken to the operating room for further diagnostic and therapeutic management. The nasogastric tube revealed bile without hematemesis. After initiating general anesthesia, an on-table colonoscopy was performed to identify the bleeding site. There was altered blood within the whole colon and terminal ileum without a definite bleeding site. Therefore, we proceeded to a laparotomy. During the laparotomy, an injured Meckel’s diverticulum was identified as the source of the significant arterial bleeding (Fig. ). Proximal to the diverticulum the small bowel was collapsed and did not show any blood. The bleeding from a branch of the mesenteric artery was stopped, and the Meckel’s diverticulum was resected. Histology revealed vascular injury due to trauma and gastric mucosa within the diverticulum. He required another 2 units of PRBC transfusion during and after the operation, and this increased his Hb to 10.2 gm/dl. He remained stable after that and developed postoperative superficial surgical site infection on day 4. He was discharged home on postoperative day 7 with instructions for wound care at a local clinic and our out-patient department (OPD) follow up after 1 week. No further complications were found during his OPD visit, and he was discharged from our hospital (Fig. , Timeline). |
pmc-6145152-1 | A 49-year-old female presented with a 2-month history of asymptomatic lesions on the left knee found incidentally on routine full skin examination. The patient was otherwise well, with no pulmonary or systemic symptoms.
She had a past history of breast cancer diagnosed 4 years ago, managed by lumpectomy and adjuvant chemoradiotherapy achieving remission. The patient had regular cancer surveillance and was currently on adjuvant tamoxifen, with a planned duration of 10 years. Her other notable medical history included lifelong asthma, gastrooesophageal reflux disease, depression, subacute thyroiditis and previous shoulder, and knee arthroscopies. Her regular medications included tamoxifen, pantoprazole, venlafaxine, budesonide/formoterol, and terbutaline. She was a lifetime non-smoker and rarely consumed alcohol. The patient had no family history of autoimmune conditions.
Examination revealed numerous erythematous-to-brown, non-tender papules occurring on the anterior left knee (). On the right foot, at the site of a scar from prior cryotherapy for plantar warts, the patient had a similar area of firm indurated erythematous-to-brown change. Dermoscopy of both sites showed orange and yellow translucent globules (“apple-jelly” sign). There were no skin lesions detected on full skin examination suspicious for malignancy. There was no lymphadenopathy and systemic examination was otherwise unremarkable.
Skin biopsy showed multiple, variably sized naked sarcoidosis type granulomas scattered throughout the dermis (). Chest radiograph showed bilateral hilar lymphadenopathy and serum angiotensin-converting enzyme was elevated at 107 U/L. Other laboratory tests were within normal limits (full blood count, liver and renal function tests, and calcium and inflammatory markers). Further investigations excluded systemic sarcoidosis (cardiac MRI and CT-PET scan). The CT PET ordered during systemic work-up, however, showed a solitary lesion in the T10 vertebra and subsequent biopsy proved recurrent metastatic breast cancer.
The patient's management was then deferred to a medical oncologist for ongoing care of her metastatic breast cancer. She received stereotactic radiation to her spinal lesion and was commenced on a special access program with ribociclib. Following breast cancer treatment, cutaneous sarcoidal lesions completely resolved. |
pmc-6145163-1 | In 1978, a 41-year-old woman was diagnosed as a hemophilia carrier with a low FVIII level; from the age of 13, she had suffered menorrhagia of up to 8 days each month. In addition, she had suffered five episodes of hematemesis associated with epigastric pain and abundant hemorrhages during the births of her two sons and daughter and after dental extractions requiring red cell transfusions. The two sons had a history of “easy bleeding,” and the daughter did not have such characteristics.
At the age of 12 years, the two sons were diagnosed with hemophilia A; the results of the tests taken in 1978 are shown in . A chromosome analysis showed the normal 46XX karyotype. Both the patients' parents had died but there was no clinical history that the father had suffered from “bleeding problems”. No mutational analysis was carried out to confirm the diagnosis of hemophilia A.
From the time of the diagnosis, she had been treated with cryoprecipiate and later Factor VIII concentrates as necessary for dental extractions and a cholecystectomy. Her hemophilia carrier state with low FVIII level was defined as moderately severe.
In 2006, she was reassessed; the FVIII was 17%, Factor von Willebrand 104%, and Ristocetin CoFactor 110%. Her hemophilia carrier state with low FVIII level was redefined as mildly severe.
The patient presented in 2017 with increasing dyspnea, orthopnea, and tachycardia of 3-week duration. Chest X-ray was consistent with heart failure, and the ECG showed atrial fibrillation with a rapid ventricular response. She had a history of well-controlled hypertension and was taking Losartan 50 mg/day, was not diabetic, and did not have a history of stroke. 3D echocardiography showed a dilated left auricular, 22 mm3 with preserved ejection fraction and no valvular disease. She was treated with amiodarone and a beta-blocker; with an adequate ventricular response, amiodarone was suspended. Renal and liver function tests were normal.
Her CHADS2-VASC (congestive heart failure (C), hypertension (H), age ≥ 75 years (A), diabetes (D), stroke, transient ischemic attack or prior thromboembolic disease (S2) was 3 for age, sex, and hypertension arterial) [], and a HAS-BLED score of 2 (hypertension (H), abnormal renal/liver function (A), stroke (S), bleeding history or predisposition (B), elderly (E), and drugs/alcohol (D)) []. Labile INR score was not included as the patient was being considered for anticoagulation. She was started on aspirin 100 mg/day as well as omeprazole 20 mg/day for the previous history of gastrointestinal bleeding. In this case, pulmonary vein isolation was not accepted by the patient due to its high cost.
At present, with a follow-up of 11 months, there has been no bleeding (stable hemoglobin) or gastric symptoms, and the AF rate is well controlled. |
pmc-6145202-1 | A 20-year-old man with no medical history was referred to the Ear, Nose, and Throat (ENT) emergency room at Shenzhen People’s Hospital on June 17, 2008. He had an extended laceration of his left ear by a shattered beer bottle during a violent fight 3 h ago.
On examination, the external auditory canal of his left ear was amputated transversely, the tragus was lost, the cartilage was exposed, and the auricle was avulsed with only 5-mm skin attachment anteriorly at the crus of helix (Fig. ). Other physical examinations were normal.
After informed consent was obtained, the patient was admitted and taken to the operation room within 3 h for the first-stage surgery under general anesthesia.
First, the amputated ear segment was cleaned with saline, oxydol, and a diluted povidone-iodine solution. The irregular lacerated skin and cartilage were trimmed, and the anterior skin of the amputated segment and the external acoustic pore were sutured appositionally with multiple, interrupted No. 5–0 nylon sutures. Second, the skin on the posterior aspect of the amputated segment was separated from the cartilage with perichondrium preserved (Fig. ). Next, the wound was extended at the posterior sulcus of the auricle longitudinally by 1 cm upward and downward, and the postauricular mastoid skin was elevated about 1 cm to fit the size of the cartilage (Fig. ). Direct suturing was done between the margin and the free edge of the ear, and the wound was closed completely. Then, using an inversion maneuver, the cartilage and the inner side of the posterior skin of the auricle were pushed into the postauricular underlying muscle bed to provide nourishment and blood supply for the cartilage as extensively as possible (Fig. ). A suction drain was placed, and the ear was packed with iodoform gauze and pressure bandage to strengthen the effect of inversion (Fig. ).
Antibiotics consisting of intravenous cefuroxime 1.5 g every 12 h (GlaxoSmithKline Manufacturing S.p.A. Italy, with 1st dose given at the start of surgery), and intravenous metronidazole 0.5 g bid (Jiangsu Hengrui Medicine Co. Ltd., China) were both given for 1 week. Intravenous dextran 40 (Xian Wanlong Pharmaceutical Co. Ltd., China) infusions were given for 7 days. The patient was also given tetanus vaccine.
The nylon sutures were removed on postoperative day 7, and no external auditory canal stenosis or tissue necrosis was observed.
The patient underwent a second-stage procedure 27 days after the initial surgery. On examination, the left auricle healed well without inflammation or skin ischemia; however, the auricular lobule had partial necrosis (Fig. ).
The auricle was released from the postauricular area, and the normal auricle structure was restored (Fig. ). Then, a skin defect (4 × 2 cm2) of the posterior aspect of the ear was noted, and a full-thickness skin grafting of the abdominal wall was applied to reconstruct it. A suction drain was placed, and the ear was covered with pressure bandage (Fig. ). The patient was given dextran 40 (Xian Wanlong Pharmaceutical Co. Ltd.) and vasodilators for 7 days.
The patient had a good recovery with minimal volume loss of the earlobe 15 days after the second-stage surgery (Fig. ). The location and contour were normal. The color and temperature of the left ear were similar to those of the right one. The patient was followed up for nearly a decade, and continued to have good cosmetic and functional outcomes, with the size about 90% of the size of his right ear. The sensation and algesia were a little less sensitive (Fig. , ). |
pmc-6145316-1 | A 22-year-old patient, Para 1, Gravida 2, presented to our Emergency Department of Gynecology and Obstetrics, at 35 weeks of gestation for acute onset of abdominal pain and uterine contraction. It was learned that the patient's history had no follow-up hypertriglyceridemia. On physical exam, her heart rate was at 100 pulses per minute, and her blood pressure was at 110/70 mm-Hg, respiratory rate 18 /min. Her abdomen was defensive. Her cervical os was dilated to 1-2 cm and minimal bleeding. The patient had mild epigastric tenderness. Decelerations were seen in pregnant cardiotocography follow-ups with abnormal abdominal pain and uterine contractions continued and simultaneous wide bleeding area (like abruptio placenta) was seen on the posterior part of placenta in ultrasound. Immediate cesarean section was performed under general anesthesia because of contraction of the tetanic type in the manual contraception. She gave birth to a healthy infant of 2980 g. Amylase, lipase, triglyceride, HDL, and LDL were studied in the patient's blood after emulsion of chylous fluid from abdomen during the cesarean section. Liver enzymes were high: ast: 241, sub. 147. It was observed that blood sample revealed a milky turbid serum. Laboratory finding included a triglyceride at 3297 mg/dl and amylase 827 U/L, lipase 1576 U/L. Abdominal ultrasound showed thickened pancreas without necrosis; acute pancreatitis compatible with diffuse edema was observed on pancreas. Biliary tract was naturally observed. Other causes of cholestasis of pregnancy, such as cholangitis, acute hepatitis, and hemophagocytic syndrome, were ruled out. Oral intake of the patient was stopped; intravenous fluid replacement therapy, antibiotherapy, proton pump inhibitor, insulin, and heparin therapy were started. She was discharged on the 10th day of treatment. Even though the patient did not have previous history of diabetes or gestational diabetes, the baby was born 4 to 3 weeks earlier. It was thought that this condition might be related to maternal hyperlipidemia for newborn's doctors. |
pmc-6145538-1 | A 70-year-old man presented in 2017 after discovery of a hypervascular, expansile, 7 cm pancreatic body mass involving the splenic vein on routine surveillance CT scan (). He endorsed 1 year of diarrhea and steatorrhea that he had not sought medical care for but denied weight loss, appetite changes, fatigue, pain, or jaundice. He had a history of RCC and underwent a left nephrectomy and adrenalectomy in 2002. Additionally, he developed adenocarcinoma of the ampulla of Vater and was treated with pancreaticoduodenectomy in 2003.
He developed pulmonary metastases from the RCC and was treated with right lung segmentectomy in 2006 and three bilateral CyberKnife treatments in 2010, 2011, and 2013. He had surveillance CT scans roughly every 6 months from the discovery of the 2010 lung metastasis until 2015 and then yearly thereafter. He never received any chemotherapy for either the RCC or PDA. He is a former smoker.
Unfortunately, records of his prior malignancies, treatments, and surgeries were limited. His metastatic workup consisted of a CT scan of the head, chest, abdomen, and pelvis, which revealed no other sites of tumor except the 7 cm mass in the body of the pancreas, and testing his carcinoembryonic antigen (CEA) tumor marker level, which resulted as 0.9 ng/mL. The two main differential diagnoses were metastatic RCC versus recurrent PDA. Imaging characteristics, timeline of the mass development, and normal CEA level were the investigations used to determine that metastatic RCC was most likely and supported the decision to resect the mass.
The patient underwent completion pancreatectomy and splenectomy to resect his newly discovered pancreatic lesion. Surgical exploration and dissection revealed that the previous pancreaticoduodenectomy had been completed entirely antecolic. The gastrojejunostomy was able to be left intact throughout the duration of the procedure, whereas the hepaticojejunostomy was reconstructed due to its initial position being too far anterior in relation to the current surgical bed. Due to vascular invasion, a part of the portal superior mesenteric–splenic vein junction was resected with primary venovenostomy. His postoperative course was uncomplicated, and he was discharged on postoperative day 6.
Due to his apancreatic status, he received diabetic teaching, was commenced on parenteral insulin, and referred to an endocrinologist for follow-up. He was also counseled on pancreatic enzyme supplementation and scheduled to have repeat CT scans at 4 months postoperatively, and then, every 3 months thereafter provided no active disease progression. Due to his splenectomy and asplenic status, he received appropriate vaccinations for encapsulated organisms: Pneumococcus, Meningococcus, and Haemophilus Influenzae.
Grossly, a 6.5 × 6.2 × 4.5 cm well-circumscribed mass is located within the pancreatic parenchyma (). On cut surface, it is glistening, red-purple, and slightly lobulated, with foci of hemorrhage. Histologically, the tumor has alveolar and solid growth pattern, with rich network of small thin-walled blood vessels (). At higher power, the lesional cells have clear cytoplasm with distinct cell borders, with large and round nuclei (). The morphological features in conjunction with the history are consistent with a metastatic clear cell RCC. The margins are negative, and 1/6 lymph nodes is positive for metastatic carcinoma.
The patient followed up with his medical oncologist who advised against adjuvant chemotherapy or radiation therapy, opting for imaging surveillance for now despite the one positive lymph node. |
pmc-6145540-1 | A 42-year-old man presented to our pancreas multidisciplinary clinic after a computed tomography (CT) scan (), prompted by a 2-month history of generalized bloating and epigastric discomfort, that demonstrated a 11.2 × 9.6 cm heterogeneous solid appearing mass in the tail of the pancreas. The irregular mass had several small peripheral calcifications and lobulated contours abutting the spleen, stomach, and splenic flexure of colon without any direct invasion. He underwent a distal pancreatectomy and splenectomy with splenic artery lymph node dissection. Intraoperatively the large soft lobular cystic mass at the pancreatic tail was locally contained without any obvious invasion of surrounding structures or gross metastasis. Histopathological assessment of the mass established it as a pT3pN0pMx SPNP (CD56pos nuclear β-cateninpos chromograninneg and synaptophysinneg). Margins were negative without any lymphovascular or perineural invasion. The patient was discharged home after an uneventful period of convalescence in the hospital.
Four years later, he was referred back to our clinic after discovery of a biopsy-proven recurrence in the splenic fossa (). The bulk of the tumor was densely adherent to the splenic flexure and gastric fundus and was resected with wedge gastrectomy and partial colectomy. A 4 cm nodule of tumor adherent to the diaphragm as well as omentum was removed by dividing the omentum and stripping the superficial layer of diaphragm. The tumor was soft, extremely friable, and fractured with minimal manipulation. It remained densely adherent to the left diaphragm, left kidney, and left adrenal gland. Eventually, we were able to dissect down through the Gerota's fat and strip the anterior capsule of the kidney clean to dissect the tumor off the kidney and the adrenal gland. The other end of the mass remained adherent to the diaphragm and was removed along with a portion of the diaphragm.
Final pathology report confirmed the presence of recurrent metastatic SPNP in omentum, diaphragm, accessory spleen tissue, and the gastric fundus. The patient recovered well from his surgery and was discharged home. He underwent CT surveillance at 3-month intervals per his medical oncologist and his first three scans showed stable postoperative changes without any evidence of local recurrence or metastatic spread. However, his next scan showed enlarged retroperitoneal paraaortic nodes that were found to be fluorodeoxyglucose (FDG) avid. He was started on capecitabine with stable disease on recent repeat imaging in April 2018. |
pmc-6145751-1 | A 45-year-old, Caucasian male patient presented with right knee pain that started a year ago and aggravated eight months ago. He was an English teacher and denied a history of any trauma. The symptom sustained despite six months of conservative treatment at another clinic, including intermittent non-steroid anti-inflammatory drug medication, injection (the exact drug is unknown) or physical therapy. He had severe anterior knee pain during stair-climbing or squatting and had been aware of a cystic mass in the posterior aspect of the knee joint that had been progressively increasing in size. On physical examination, mild swelling and effusion of the right knee were seen without localized heat sense. Painful crepitation and moderate tenderness were present around the patellar tendon during knee motion and a large, non-tender cystic mass existed on the posterior aspect of the right knee joint. The crepitation also existed on his left knee, but he had no discomfort on the left side at all. Also, there was no cystic lesion on the left knee. The volume of the right infrapatellar region was greater than normal and felt firm to the touch. Passive full knee range of motion was possible but painful. There was no tenderness on the tibial tubercle or patella.
Plain radiographic examination of the right knee showed a large ossicle locating beneath the patellar tendon and inside the infrapatellar fat pad. A similar-sized ossicle was seen in the left knee, while it was partially fused to the hypertrophied tibial tuberosity (Figure ).
Right knee magnetic resonance images showed about 3.8 x 1.3 x 3.0 cm sized, well-circumscribed ossicle. Several smaller ossicles were also found near the tibial tubercle. Inflammatory changes in synovium, infrapatellar fat pad, and patellar tendon were also seen. A reactive bone marrow edema was found at the anterior aspect of the tibial condyle. Besides, a Baker’s cyst of 7.3 x 4.1 x 14.7 cm size was found (Figure ).
The patient chose to get surgery since the symptom continued after the prolonged conservative treatment. Since the lesion was benign in character and the patient requested to remove the Baker’s cyst simultaneously, arthroscopic surgery was planned to excise the ossicle and decompress the cyst. Right knee arthroscopy was performed through the standard anterolateral and anteromedial portals close to the patellar tendon. Anterior interval release of the hypertrophied fat pad was carefully performed with the mechanical shaver. Then the arthroscopy was inserted through a separate superolateral portal. The knee was held in a 45-degree flexed position and the outline of the ossicle was identified. The overlying fat and fibrous tissues were shaved, and the clear outline of the ossicle was visible (Figure ).
The ossicle was fragmented using an arthroscopic punch or a small osteotome and removed through the slightly extended anteromedial portal (Figure ).
An intraoperative fluoroscopic image was acquired to confirm the complete removal of the ossicle (Figure ).
The knee was held in a 15-degree flexed position and the inflamed retro-patellar tendon surface was debrided. Through the additional posteromedial portal, the Baker’s cyst was decompressed.
Postoperative recovery was uneventful. From the first postoperative day, the patient could walk with full weight-bearing and move his knee. Strengthening exercise for knee extensor muscles was encouraged as tolerable. The patient regained full knee range of motion and returned to his daily activities within two weeks after surgery. The excised tissue was subjected to a histopathological examination. The histology finding was consistent with OSD that mix of osseous and cartilaginous tissue was seen without evident cartilaginous cap (Figure ). At six months after the surgery, the patient’s right knee was normal without any clinical or radiographic sign of recurrence. |
pmc-6145752-1 | A 78-year-old male presented to the emergency room with complains of high fever, and non-bloody non-bilious vomiting. This was associated with a non-productive cough and dyspnea. He had a past medical history of splenectomy following thrombotic thrombocytopenic purpura (TTP) and recurrent pneumonia. On presentation, the patient was febrile to 101.7° F, respiratory rate of 34 breaths per minute and blood pressure of 83/49 mm Hg. Complete blood count showed leukopenia with white cell count of 1.1 x 109 per liter (L), bandemia of 27% and lactic acidosis of 12.3 mmol/l on the venous blood gas. Computed tomography (CT) scan of the chest/abdomen, and pelvis with oral contrast was performed which showed consolidation in the left lower lobe of lung (Figure ).
The patient was admitted in the medical intensive care unit with the preliminary diagnosis of severe sepsis with septic shock. Sequential organ failure assessment (SOFA) score at the time of admission was 10. Sepsis bundle was initiated and intravenous (IV) crystalloid resuscitation at 30 ml/kg was immediately started, blood cultures were drawn and intravenous broad-spectrum antibiotics were initiated. Due to inadequate response to intravenous fluids, a vasopressor agent (phenylephrine) and stress dose steroid (hydrocortisone) was started. Blood cultures grew gram-negative coccobacilli, Neisseria species which was later confirmed by microbiologist as Neisseria cinerea. Antibiotics were narrowed down to IV ceftriaxone 2 gm every 12 hours based on the sensitivity.
During the course of hospitalization, the patient improved clinically and remained hemodynamically stable. Repeat blood cultures did not show any growth and the patient was discharged home after completion of two weeks of intravenous ceftriaxone. |
pmc-6145755-1 | A 19-year-old boy was admitted with a history of recurrent bouts of epistaxis from his right nostril, for a duration of one month. The last episode was severe and uncontrolled, which prompted him to seek medical attention. His past medical history involved a motor vehicle accident four months prior to admission. This event was associated with a brief period of loss of consciousness, vomiting, and associated nasal bleed. He had no history of seizures or any cerebrospinal fluid (CSF) leak, but suffered a complete loss of vision in his left eye. Computed tomography (CT) of the brain revealed a displaced fracture of the left frontal bone with small underlying extradural hematoma with fracture of the orbital roof and spheno ethmoid sinus. He was managed conservatively with antiepileptics, antibiotics and closely observed for CSF leak. Steroids were administered for his left traumatic optic neuropathy and he was discharged after two weeks of observation. On discharge, his Glasgow coma scale was 15 and he had no perceivable vision in his left eye.
On readmission with epistaxis he was severely pale and his hemoglobin levels had dropped to 5.6 g/dL. Medical and endonasal causes for epistaxis were initially ruled out. In view of his previous history of trauma, and the triad of blindness, epistaxis, and trauma a CT angiogram of the brain was performed, which revealed a saccular aneurysm of the left cavernous segment of the internal carotid artery (ICA). It was followed up with a digital subtraction angiogram (DSA) to confirm the flow and cross-circulation across the hemispheres and plan for surgical management. The DSA showed a large left cavernous segment pseudoaneurysm with moderate cross-circulation from the right ICA (Figure ). There was no evidence of any fistulous connection.
The patient was explained about the need for intervention in the form of bypass surgery or endovascular flow diversion. They declined endovascular surgery due to financial constraints. In view of the suboptimal cross-circulation, it was decided to perform a replacement high-flow extracranial-intracranial (EC-IC) bypass and then trap the aneurysmal segment. A left pterional craniotomy and a high-flow EC-IC bypass (common carotid to M2 segment) with saphenous vein graft were performed followed by ligation of the left ICA in the neck (Figure ).
Postoperatively the patient was started on antiplatelets and had no complications. He made good postoperative recovery with daily monitoring of arterial pulsation and Doppler confirmation of the same. An angiogram taken on postoperative day nine revealed good flow across the bypass (Figure ). The patient neither had any worsening of deficits, nor had any improvement in the vision of his left eye. He had no further episodes of epistaxis or any complaints at one year of follow up. |
pmc-6145800-1 | A 47-year-old Caucasian male presented to the emergency department (ED) for diffuse erythema and pruritus of three weeks’ duration. The patient had been followed in dermatology clinic for hand-foot dyshidrotic eczema for approximately three years prior to his admission. The patient’s eczema had been well controlled on low dose weekly oral methotrexate for two years until he reported no longer being able to tolerate the pills. At that time oral methotrexate was discontinued and topical betamethasone was begun. Three weeks prior to admission the patient developed whole body erythema with pruritus. He had been seen in the dermatology clinic twice and received two injections of methotrexate every seven days. He presented to the ED one week after the second injection having failed therapy with a worsening diffuse rash. At the time of presentation to the ED, the patient had diffuse erythema covering >90% of his body (Figures -), generalized exfoliation, and was visibly shaking with chills. Blood cultures and human immunodeficiency virus (HIV) testing were negative. Electrocardiogram (EKG), chest X-ray (CXR), comprehensive blood count (CBC), comprehensive metabolic panel (CMP) and urine analysis (UA) were within normal limits. With skin biopsy results pending, the patient was started on 5 mg/kg/day of intravenous (IV) cyclosporine along with topical triamcinolone cream applied twice a day (BID). Over the course of three days, the patient improved dramatically. A punch biopsy of skin was diagnosed as spongiotic dermatitis. The differential diagnosis included drug eruption, contact hypersensitivity reaction, and other eczematous dermatitis.
A punch biopsy of skin showed hyperkeratosis, parakeratosis, mild irregular acanthosis, and mild spongiosis. The granular layer was maintained, and rare Langerhans cell microabscesses were seen in the epidermis. Spongiosis involving the follicular epithelium was identified. Within the dermis, there was a superficial perivascular mixed inflammatory infiltrate of lymphocytes and scattered eosinophils. These histopathological features are most consistent with spongiotic dermatitis. Spongiotic dermatitis is a reaction pattern that is often seen in patients with erythroderma and is relatively nonspecific for an underlying etiology. Given the patient’s history, an acute exacerbation of the patient’s dyshidrotic eczema with secondary autoeczema progressing to erythroderma was favored. The histologic differential diagnosis also included a drug reaction or contact hypersensitivity reaction. Psoriatic erythroderma often has diminution or loss of the granular cell layer and intraepidermal neutrophils, which were not present in the current biopsy. Pityriasis rubra pilaris may show some epidermal spongiosis but in a classic case will show mild psoriasiform epidermal hyperplasia, follicular plugging, and alternating orthokeratosis and hyperkeratosis in the cornified layer, both horizontally and vertically (so-called “checkerboard pattern”), findings which were absent in this case. The absence of an atypical epidermotropic lymphoid infiltrate argued against the possibility of mycosis fungoides (cutaneous T-cell lymphoma).
The skin biopsy shows parakeratosis (Figure ) with irregular acanthosis and superficial perivascular chronic inflammation. In the lower right aspect of the field, there is a hair follicle with spongiosis involving the follicular epithelium (haematoxylin and eosin (H&E) stain X 40). In the epidermis (Figure ), the granular layer is maintained and rare Langerhans cell microabscesses are identified (H&E stain X 100). The epidermis shows diffuse mild spongiosis. In the dermis, superficial perivascular lymphohistiocytic infiltrate with admixed eosinophils. Atypical lymphocytes with epidermotropism were not present.
The patient followed up approximately a month and a half to dermatology clinic during which time he had clinically improved on his low dose cyclosporine (100 mg twice a day). He continued this dose for a total of four months until his rash had almost completely resolved after which he was instructed to use clobetasol ointment as needed. |
pmc-6145801-1 | A 33-year-old male presented to be admitted as a patient at Case Western Reserve University School of Dental Medicine clinic in Cleveland, Ohio for the purpose of obtaining dental implants. However, the patient complained of pain in his upper jaw bilaterally. His medical history was free from systemic diseases but indicated a past history of acne and recurrent tonsillitis. His vital signs were recorded as 126/85 mmHg blood pressure, pulse of 103 bpm, 15 respirations per minute, height 6.1 ft, weight 196 lb, a calculated body mass index (BMI) of 23.71. No other medical conditions were listed, and the patient did not report taking any medications.
Upon intraoral examination, badly decayed upper right second molar and highly restored left second molar were noticed with pain on percussion. Dental periapical lesions were suspected. The patient was referred to a private dental imaging center for imaging of the jaws for implant treatment planning. A CBCT scan was taken using a Planmeca Promax X-ray (Planmeca, Helsinki, Finland) unit. Upon reviewing the scan, multiple small nodules of high density were identified as an incidental finding during the interpretation of the patient’s scan (Figure ).
The nodules appear to be dispersed among the layers of the face, which were clearly displayed in more than coronal and axial cuts (Figure ).
The multiple nodules were consistent with the miliary type of OC and his past history of acne as a teenager. The palatine tonsils, in addition, revealed radiopaque masses bilaterally, but more numerous and prominent on the left side. The calcifications were also consistent with the patient history of recurrent tonsillitis as tonsillar stones (tonsilloliths) (Figure ). The patient was advised to visit his dentist and receive a panoramic radiography regularly to follow up the spread of the calcification, especially to the blood vessels. |
pmc-6146110-1 | A 52-year-old woman noticed a right breast mass and underwent a breast examination at a local breast clinic, after which she was referred to our hospital for a further investigation. The patient’s medical history included early gastric cancer and early esophageal cancer, and her family history included breast cancer in a younger sister and gastric cancer in a grandfather. Mammography revealed a 1.5-cm coarse heterogeneously high-density calcified lesion at the upper outer portion of the right breast (Fig. a). Ultrasonography (US) showed a hypoechoic mass containing multiple calcifications with relatively smooth borders. The internal characteristics were unclear due to the calcifications (Fig. ). Fine-needle aspiration cytology of the tumor showed small clusters of either normal or benign epithelial cells without any marked atypia. Since no malignancy was noted, we did not perform a core needle biopsy, and the patient was subsequently followed up.
About 8 months after our first medical examination, mammography revealed a slight enlargement of the coarse calcification (Fig. b), but US showed the same size tumor. About 13 months after our first medical examination, the mass was 2.3 cm in size, and after another 3 months, it had grown to 4.5 cm, and new coarse calcifications that were irregular in shape and different in density from the initial one appeared around the enlarged original coarse calcified tumor on mammography (Fig. c, d). US showed a mass that was covered by coarse calcifications which had remarkably increased in size. MRI revealed a 4.5-cm mass at the upper outer portion of the right breast. Fat suppression (FS)-T2-weighted imaging (T2WI) showed a high signal intensity at the periphery and center of the tumor. Gadolinium (Gd)-enhanced FS-T1WI showed a high signal intensity at the periphery of the tumor but a low signal intensity in the central area (Fig. a–c). A core needle biopsy showed a nodule with bone formation (ossification) that was not malignant. The serum alkaline phosphatase level was 292 U/L (106–322 U/L) at the initial visit but had increased to 548 U/L when the tumor grew. Other hematological findings, including lactate dehydrogenase levels, were within the normal ranges. Extirpation of the tumor was performed. Because the tumor had infiltrated the greater pectoral muscle, we resected a portion of it (Fig. ). The pathological findings were extraskeletal osteosarcoma. Sectioning showed the proliferation of atypical cells with oval to round nuclei and eosinophilic cytoplasm with abundant osteoid and bone formation in the periphery of the tumor. The center of the tumor was composed of hypocellular fibrous maturation, and mitotic figures were frequently seen, but abnormal mitotic figures were not evident (Fig. ). Immunohistochemically, the atypical cells were positive for MDM2, CDK4, and p16 but negative for AE1/AE3, CAM5.2, and p53 (Fig. ). There were no histopathological findings of breast cancer, malignant phyllodes tumor, carcinosarcoma, or dedifferentiated liposarcoma.
After the pathological diagnosis of primary extraskeletal osteosarcoma in the breast was made, the patient received doxorubicin and ifosfamide (AI, three cycles) as adjuvant chemotherapy and then underwent additional resection with latissimus dorsi flap reconstruction at the Department of Orthopedic Surgery. She then resumed AI (two cycles), but at 16 months after the first extirpation procedure, multiple lung metastases appeared, and her treatment was changed to doxorubicin and cisplatin (AP, two cycles). The lung metastatic lesions grew, and the treatment was changed again to trabectedin (seven cycles); however, it had no effect. She is currently receiving eribulin and radiotherapy for multiple lung metastases.
Primary sarcomas of the breast are rare and account for < 1% of all primary breast malignancies []. Among those, extraskeletal osteosarcoma is extremely rare. Extraskeletal osteosarcoma is a malignant mesenchymal neoplasm that produces osteoid, bone, or chondroid material and is located in the soft tissue without attachment to the skeleton []. Although osteosarcomas of the bone occur mostly during the first two decades of life, extraskeletal osteosarcomas are rarely encountered in patients under 40 years of age [, ]. Some studies have reported that a tumor is likely to be caused by a history of trauma to the breast or radiation therapy for a malignant neoplasm [], preceding fibroadenoma or phyllodes tumor []. The most common presentation is a progressively enlarging mass. In our case, the patient had no medical history of breast or preceding fibroadenoma or phyllodes tumor, but a coarse calcified lesion was observed in her breast. The tumor started to grow progressively in the course of follow-up, similar to other cases reported in the literature.
In the present case, changes in the coarse calcified lesion on mammography were remarkable, and the contrast-enhanced MRI findings were characteristic. When the tumor grew, new microcalcifications that were fine and irregular in shape and density appeared on mammography. The characteristics of the calcified lesions differed substantially from those noted at the initial visit. Because the newly appeared microcalcifications surrounded the initial coarse calcified lesion, the new lesion may have originated from a component of the initial one. Other reports have described mammography findings such as “an ill-defined dense mass containing soft calcifications” [] or “an oval, fairly dense, and well-delineated mass” []. In the present case, the mammography findings both at the initial visit and at the new lesion appearance were clearly coarse calcifications. There might be no characteristic findings on mammography for primary osteosarcoma of the breast. This case report was considered to be valuable due to the fact that the calcified lesions had been followed up over a long period of time by mammography.
Extraskeletal osteosarcoma has a very poor prognosis, and approximately 75% of patients die of their disease within 5 years of the diagnosis []. A study reported that the 5-year overall survival probability of primary osteogenic sarcoma of the breast was 38%, and the 10-year estimated survival was 32% []. These data are consistent with the observation that metastases developed in patients within 3 years of the diagnosis, and those patients died of progressive disease within a relatively short time thereafter []. Treatment should include complete surgical removal of the tumor with an adequate margin [, , ]. The local recurrence rate was 67% for patients treated with local excision (a biopsy or tylectomy) and 11% for those treated with mastectomy []. As adjuvant chemotherapy, methotrexate and bleomycin, cyclophosphamide, CDDP, doxorubicin, and ifosfamide have been shown to be effective, as well as a therapy for osteosarcoma of the bone [, , ]. However, no standard regimen has been established for extraskeletal osteosarcoma. In the present case, because the resection margin was close, additional resection and chemotherapy were performed. A diagnosis must be made as early as possible in order to improve the survival of this disease. |
pmc-6146113-1 | A 10-day-old male infant was referred to our hospital because of suspected congenital hypothyroidism. The patient presented with symptoms of airway obstruction, such as an inspiratory stridor and retracted breathing. A hormonal test revealed subclinical hypothyroidism with a free thyroxine level (1.44 ng/dL) within the reference range, although the thyroid stimulating hormone (TSH) level (34.6 μIU/mL) was increased beyond the normal range. Laryngo fiberscopy revealed a lingual mass compressing the epiglottis (Fig. ). Enhanced computed tomography (CT) and thyroid scintigraphy revealed that the mass was an ectopic thyroid with the absence of a normal pretracheal thyroid gland (Figs , ). The patient received oral levothyroxine at a dose of 12 μg/kg/day for 4 weeks to lower the TSH level and reduce the volume of the ectopic thyroid tissue. However, we observed no reduction in the volume of the thyroid tissue and a concomitant progression in his symptoms of airway obstruction. He underwent surgery to relieve the airway obstruction when he was 2 months old. Under general anesthesia, nasotracheal intubation was performed in a sniffing position, and a transverse skin incision measuring 2.5 cm was made at the level of the hyoid bone. We split the hyoid bone at the midline, dissected the base of the tongue towards the foramen cecum, detected the ectopic thyroid mass, and suspended the mass by suturing it to the hyoid bone (Fig. ). We used 5–0 monofilament absorbable sutures and sutured between the lingual thyroid and the hyoid bone. The bite length of both the lingual thyroid and hyoid bone was about 3 mm. The points of suturing were to the lateral side of the lingual thyroid and to the front of it. The total number of suture threads was 3. The degree of suspension of the ectopic thyroid was guided by an intraoperative laryngo fiberscopy to confirm the complete elevation of the epiglottis. The patient was not extubated until postoperative day 4 and needed noninvasive positive pressure ventilation until postoperative day 22. Laryngo fiberscopy performed 6 months postoperatively revealed the complete disappearance of compression of the epiglottis by the lingual mass, and CT performed 8 months postoperatively also revealed the relocation of the lingual thyroid gland towards the hyoid bone (Fig. ). When the patient was 2 years 6 months old, his height was 94.1 cm(1.4 SD), weight was 14.0 kg(1.0 SD), free T3 was 2.97 pg/mL, free T4 was 1.48 ng/dL, and TSH was 4.178 μIU/mL. He was taking daily levothyroxine 4.5 μg/kg/day and had been kept in the euthyroid state. Since we were able to preserve his thyroid gland (which is his only functioning thyroid tissue), the postoperative control of his thyroid hormone status was relatively easy. The surgery was complicated by the development of a salivary fistula that was spontaneously resolved 5 months postoperatively. |
pmc-6146114-1 | A 57-year-old Japanese man was referred to our hospital because of increasing right lower abdominal pain. He had a history of appendectomy at the age of 17 years with no significant family or occupational history.
On initial examination, an abdominal wall tumor (largest dimension, approximately 10 cm in diameter) was detected using transabdominal ultrasound (Fig. ). Laboratory data revealed elevated inflammatory markers (WBC = 14,400 × 109/L, CRP = 11.8 mg/L); major tumor markers (carcinoembryonic antigen, CA19-9, and soluble IL-2 receptor) were within normal limits. Helical computed tomography (CT) also revealed a solid mass (largest dimension, 10 cm in diameter) in the abdominal wall (Fig. ). Magnetic resonance imaging showed a mass that exhibited low intensity on T2-weighted images, slightly high intensity on diffusion-weighted images, and gradual reinforcement on dynamic study (Fig. ). Positron emission tomography–CT revealed fluorodeoxyglucose accumulation in the mass only (SUVmax, 41) (Fig. ). Because clinical and radiographic findings suggested malignant lymphoma, undifferentiated sarcoma, or liposarcoma, he underwent exploratory laparotomy and treatment.
Intraoperative findings at laparotomy were an elastic, hard, milky-whitish mass with a rough surface and capillary growth in the right lower quadrant (Fig. ). On inspection and palpation, a malignant tumor was strongly suspected. No other tumor suspicious of a primary lesion was found in the intraabdominal organs, including the gastrointestinal tract. The mass was completely removed, and the surgical margin secured. The total weight of the mass was 120 g. No complications were observed during the perioperative period, and the patient was discharged on postoperative day 7.
Pathologic examination revealed that these masses were foreign-body granulomas consisting of string-like crystals and a foreign-body giant cell (Fig. , ). Immunohistological staining using anti-CD68 antibody (clone KP1) against the CD68 antigen, which is a known macrophage surface marker, was positive in cells surrounding phosphoglyceride crystals (Fig. ).
The patient underwent regular follow-up abdominal ultrasound examination and CT postoperatively. As of 3 years after the procedure, no signs of recurrence have been detected.
PGDD is a rare disease characterized by deposition of phosphoglyceride crystals, often simulating neoplasm in a scar of soft tissue or bone. It can sometimes form a large mass and be misdiagnosed as a malignant tumor.
Little is known about its etiology and pathogenesis. This deposition disease is apparently triggered by injury and subsequent macrophage aggregation, with a histological picture of deposited crystal radiating from the cell membranes of epithelioid cells. The macrophages themselves may contribute to the formation of a nidus for the crystals. One hypothesis is that localized disturbance of phosphoglyceride metabolism within the macrophages may be initiated by local inflammation, leading to progressive amplification of macrophage infiltration and crystal deposition.
To our knowledge, only 10 cases of PGDD have been reported previously, including our case. The available clinical information on these cases is summarized in Table [–]. The mean age of patients is 57 (range, 37–76) years. There appears to be no gender predilection. No congenital abnormalities or family history of metabolic disorders have been found. Deposition was characteristically noted at intramuscular injection sites or postoperative sites like the gluteal muscles and the deltoid, abdominal wall soft tissue, scapula, spine, myocardium, and pelvic soft tissue. The size of the tumors reported is highly variable, from 3.5 cm to the size of an infant’s head, but in general it is a relatively large tumor with a mean size of 8.9 cm. The time from the initial invasion to confirmation of the tumor was at least 20 years and was 45 years in the longest case. About half of the cases had multiple lesions. In most cases, excisional surgery was performed due to local tumor formation without apparent symptoms of inflammation. Tumors that occurred at postoperative sites were suspected to be true malignant neoplasms or recurrent tumors. In one case, intraoperative rapid pathological diagnosis revealed PGDD, so complete resection was not performed and the patient was observed clinically.
No specific markers exist for PGDD, and differentiating this disease from malignant tumors without pathological examination is difficult. We considered needle biopsy in the present case but decided against it given the risk of needle tract seeding if malignant.
In the present case, exploratory laparotomy, not laparoscopic surgery, was performed for a suspected huge malignant tumor of the abdominal wall, based on radiographic examination. Our patient had a history of appendectomy at the age of 17 years, and local inflammation at the operation site was suspected to have led to progressive amplification of macrophage infiltration and crystal deposition.
Postoperative follow-up has not revealed any findings suspicious of recurrence in our case. However, there are reports in the literature of recurrence at 4 years after surgery []. Few studies have reported on the process of crystallization and deposition of phosphoglycerides and so the mechanism remains unclear. Local injection of a bovine-derived medication has been suggested as causative, yet that alone does not explain PGDD, including the present case. In reviewing previous reports, a few cases suggest that during the process of phosphoglyceride metabolism, a locally invasive procedure increases macrophage activation and leads to phosphoglyceride deposition. Moreover, knowledge of the tendency of PGDD to form at sites of invasion may allow a clinician to clinically observe a similar mass found during routine follow-up, and debulking surgery may be considered as a therapeutic option for symptomatic cases. |
pmc-6146370-1 | A 16-year-old boy with a family history of seizures (mother, cousin) exhibited typical development until the age of 14; this was the point at which he developed generalized epilepsy, which was well-controlled using valproic acid (VPA). He also had a family history of high blood lactate levels (mother) and a history of easy fatigability. At the age of 16, he developed tachypnoea and tachycardia. Serum glucose and lactate levels were elevated to 12.5 and 9.4 mmol/L, respectively. Urine tests for glucose and ketones were positive (3+ and 2+, respectively). Arterial blood gas analysis in room air revealed elevated lactate levels (9.4 mmol/L) and low pH (7.23). His glycosylated hemoglobin A1 (HbA1c) level was 14.60%. He was diagnosed with diabetes, ketoacidosis, and generalized epilepsy. However, his high lactate levels and tachycardia persisted following treatment for hyperglycaemia, fluid resuscitation, and correction of acidosis. Several days later, his tachypnoea returned, and he also developed limb weakness and external ophthalmoplegia. After 1 week, he developed severe respiratory acidosis and respiratory failure type II, for which he required intubation and artificial ventilation. Tracheotomy was performed after several failed attempts to discontinue artificial ventilation.
Upon admission, neurological examination revealed external ophthalmoplegia, mild limb weakness, and pyramidal signs. However, he exhibited no signs of myoclonus or cognitive abnormalities. Laboratory testing revealed an increase in plasma lactate (9.4 mmol/L, normal <2.3), pyruvate (D-3-hydroxybutyrate, 0.35 mmol/L, normal 0.03–0.30 mmol/L), and glucose (12.5 mmol/L, normal <7.0 mmol/L) levels. Fasting plasma insulin and 30 min and 2 h post-prandial insulin values were 112.54, 298.03, and 73.34 μU/mL, respectively. Creatine kinase levels were normal. Arterial blood gas analysis indicated severe respiratory acidosis. His mother also exhibited increase in resting and post-exercise blood lactate levels (2.7 and 9.7 mmol/L, respectively). Cerebrospinal fluid analysis revealed slight increase in intracranial pressure, normal white and red cell counts, glucose levels, and protein levels. Bacterial cultures were negative, and no abnormal cells were detected.
Electrocardiography revealed sinus tachycardia. Normal structure and ejection fraction were observed via echocardiography. Electroencephalography revealed moderate abnormalities, without spikes or sharp waves. Electromyography revealed mild axonal damage and demyelination, as well as abnormal F waves.
High-density computed tomography (CT) signals were observed in the great cerebral vein (arrow in Figure ), sagittal sinus (arrow in Figures ), torcular herophili (arrow in Figure ), and transverse sinus (arrow in Figure ). Thrombus formation had not been excluded at this stage. High-density CT signals were also observed in the cerebral falx (hollow arrow in Figure ), which was suggestive of subarachnoid hemorrhage. However, results of CT angiography taken 2 days after fluid resuscitation were normal.
After 1 month, T2-weighted magnetic resonance imaging (MRI) (Figure ) revealed areas of high signal intensity in the lateral ventricle, periaqueductal gray matter (bilateral hypothalamus and midbrain tegmentum, arrow in Figures ), and medullary tegmentum (arrow in Figure ). There were no evident lesions in the tegmentum of pons at this stage (small arrow in Figure ). After 2 months, T2-weighted MRI (Figure ) revealed hyperintensities in the bilateral thalamus (arrow and hollow arrow in Figure ), tegmental area of the midbrain (arrow in Figure ), pons (hollow arrow in Figure ), and medulla (arrow in Figure ). As shown in Figure , the thalamic lesions had increased in size and new lesions had emerged (hollow arrow in Figures ). There were no evident lesions in the cervical and thoracic spinal cord at this stage (small arrows in Figure ). After 7 months, T2-weighted MRI (Figure ) revealed hyperintensities in the bilateral thalamus (arrow in Figure ), tegmental area of the midbrain (arrow in Figure ), pons (arrow in Figure ), medulla (arrow in Figure ), and the cervical and thoracic spinal cord (new lesions, hollow arrow in Figure ). As shown in Figure , the previously identified lesions had decreased in size because of atrophy. After 8 months, T2-weighted MRI (Figure ) revealed no new developments (arrow in Figures ).
Based on these results, the patient was treated with high-dose corticosteroids and immunoglobulin, although there was no obvious improvement in his severe respiratory insufficiency or limb weakness. Owing to the involvement of multiple systems and the patient's family history, we then suspected mitochondrial disease, following which muscle biopsy and gene detection studies were performed. Levetiracetam also substituted VPA for the treatment of epilepsy.
The patient experienced a gradual worsening of symptoms, developing myoclonus, ataxia, recurrent pneumonia, and hypotension. At this stage, he required sustained ventilator support and intermittent vasopressor treatment. Plasma lactate levels remained elevated. Neurological examination revealed somnolence, severe external ophthalmoplegia, severe limb weakness, myoclonus (evident in the proximal muscles of the upper extremities), ataxia, and pyramidal signs.
Treatment with levetiracetam, L-carnitine (2.0 g), coenzyme Q10 (CoQ10, 600 mg), nicotinamide, idebenone tablets, and vitamin B was initiated after obtaining the results of the genetic study. After 19 months, his symptoms had improved dramatically, and he required only non-invasive ventilator support during sleep. However, he died of recurrent pneumonia at the age of 18.
After 4 and 6 months of hospitalization, the patient underwent biopsy of the left quadriceps muscle. Serial frozen sections (thickness: 10 μm) were stained with modified Gomori trichrome (MGT), succinate dehydrogenase (SDH), and cytochrome C oxidase (COX), in accordance with established protocols ().
After 4 months of hospitalization, muscle biopsy results revealed no remarkable mitochondrial abnormalities (including RRF) following histochemical analysis. However, 6 months after hospitalization, MGT staining of muscle biopsy specimens revealed the presence of scattered RRF (arrow in Figure ), while SDH staining revealed the presence of ragged blue fibers (arrow in Figure ). Histochemical analyses after COX staining revealed a diffuse reduction in the number of fibers (arrow in Figure ). No excess lipid or glycogen levels were noted. Mitochondrial respiratory chain enzyme activity was not measured.
Following hospitalization, total genomic DNA was extracted from the blood and the muscle in accordance with standard procedures. Long-range polymerase chain reaction (PCR) analyses were used to investigate potential rearrangements in the mtDNA, while direct sequencing of the entire mitochondrial genome was performed as previously described (). Amplified PCR products were sequenced using Big Dye Terminator v3.1 (Applied Biosystems, Foster City, CA) and were compared to the revised Cambridge reference sequence (GenBank Accession number NC_012920.1). Quantification of m.8344A>G mutation load by pyrosequencing () was performed using mutation-specific primers.
Molecular analyses were conducted on muscle biopsy specimens from almost all of the patient's maternal relatives. Long-range PCR revealed no DNA rearrangements. Sequencing of the mitochondrial and nuclear genome in the blood and the muscle identified an m.8344A>G mutation. Quantitative pyrosequencing confirmed the presence of the m.8344A>G mutation at very high levels in the patient's blood (95%, IV:4 in Figure ) and muscle (96%).
The patient's mother, who had short stature and increased resting and post-exercise blood lactate levels (2.7 and 9.7 mmol/L, respectively), developed seizures at the age of 30. One of the patient's cousins developed seizures at the age of 8. Seizures are one of the most common symptoms of mitochondrial diseases. The point mutation levels of these two relatives (from blood) were 77% (III:7 in Figure ) and 87% (IV:1 in Figure ), respectively, which were relatively high. Until the time of documentation, most of the other maternal relatives carrying the same mutation had shown no evident symptoms. |
pmc-6146567-1 | An 89-year-old man with a history of Fuchs corneal endothelial dystrophy presented in the left eye with reduced visual acuity and discomfort due to the development of pseudophakic corneal edema following previous uneventful cataract surgery in 2005. The best spectacle corrected distance visual acuity (BSCVA) was 6/18 (20/63) in the right eye and 6/24(20/80) in the left eye. Intraocular pressure was 12 mmHg in both the eyes with central corneal thickness in the left eye of 658 microns, measured using ultrasound pachymeter. The guttae and resulting endothelial dysfunction involved most of the endothelial surface, therefore, a large (9.5 mm) ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) was planned. The graft was prepared following our previously published protocol., However, due to loss of vacuum on the Barron trephine during cutting resulted in an irregular stromal surface (A), which was verified using anterior segment optical coherence tomography (AS-OCT) (SS-1000 Casia; Tomey Corporation, Nagoya, Japan) (B). In order to reduce the corneal wastage, a Descemet membrane endothelial keratoplasty (DMEK) was performed in his left eye using an 8.00 mm donor graft (prepared using SCUBA technique, video 1) placed within a recipient descemetorhexis of about 9.5 mm. Delivery and unfolding of the tissue was achieved without intraoperative complications. Topical prednisolone acetate 1% (Pred Forte, Allergan) and chloramphenicol 0.5% eye drops (chloramphenicol) four times a day were used postoperatively. An early postoperative examination of the graft showed it to be slightly temporally decentred, residual corneal edema in the absence of DM detachment and a well-formed anterior chamber. However, the endothelial graft remained attached and the corneal edema had cleared. After 3 months, AS-OCT (SS-1000 Casia; Tomey Corporation, Nagoya, Japan) confirmed that the graft was completely attached. After 5 months, the patient's BSCVA was recorded at 6/6(20/20) in the left eye, but with complain of mild discomfort. His left cornea was clear in the centre, but it showed a circular ring of corneal edema around the graft (A and B) evident on corneal tomography (Pentacam, Oculus, Germany). Corneal map (C) and AS-OCT (D) for thickness measurement showed decentralization of the transplanted graft with edema observed in the corneal map (C). Endothelial cell density (ECD) of the central cornea assessed using in vivo confocal microscopy (IVCM, Heidelberg Retina Tomographer II with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany) 5 months after surgery was 1506 cells/mm2 at a focal depth of 496 μm with some polymegathism.
Supplementary video related to this article can be found at .
The following is the supplementary data related to this article: |
pmc-6146617-1 | A 52-year-old man presented with intermittent, two-month-duration painless gross hematuria without clot formation and was referred to the Urology Department for evaluation of urologic malignancy. He had multiple bruises and a history of nasal bleeding during childhood. Low platelet levels (34000-38000/μL) and high lactate dehydrogenase titer (244-278 U/L) were found during every blood test he had undergone; however, no further specific examination of thrombocytopenia was performed because he refused to visit a tertiary hospital until ITP and severe unstoppable nasal bleeding were diagnosed at age 45 years. In addition to thrombocytopenia with serum platelets less than 20,000 mg/dL, the patient had underlying diseases such as osteopenia and hypertension without any operative history or family history. The renal function was within the normal range including serum creatinine less than 0.9mg/dL and estimated glomerular filtration rate greater than 90 mL/min/1.73m2.
After cystoscopic examination with urine cytology and computed tomography (CT) imaging for the evaluation of urologic malignancy, a 2-cm protruding solid bladder mass involving the left ureteral orifice and trigone of the bladder with left mild hydroureteronephrosis were detected, suggesting bladder cancer (Figures and ). Transurethral resection of the bladder mass was performed to confirm pathologic amyloidosis involvement of the left ureteral orifice of the bladder after transfusion of five packs of platelet-concentrated plasma and three packs of fresh-frozen plasma (Figures and ). Pathologically amorphous nodular materials were noted in the subepithelial connective tissue and smooth muscle layers. Deposits were noted in resected bladder tissues, including the left ureteral orifice, without any involvement of the periureteral tissues. Mild stromal fibrosis was also seen. Congo red-stained sections of the materials were light green under polarized light. Further immunohistochemistry results were positive for kappa but not for lambda ().
At 2 weeks postoperatively, bone marrow biopsy confirmed polyclonal T-cell receptor gene rearrangement during multiplex polymerase chain reaction and oligoclonal immunoglobin H-chain gene rearrangement during seminested PCR. Four weeks after transurethral resection, the patient still experienced intermittent gross hematuria and left hydronephroureterosis on CT urography. Further left ureteroneocystostomy with excision of the ureterovesical area of the bladder was performed. We made an oblique cystotomy under lower midline incision and dissect the intramural ureter with mass. The mass was delivered through the incision and resected with safety margin from the ureter. The original ureteral orifice was closed. The remaining ureter was reintroduced into the bladder and made neoureteral orifice after submucosal tunneling. The cystotomy site was closed with a standard two-layer manner. Several packs of platelet-concentrated plasmas were infused intraoperatively. A clear resection margin was finally confirmed by pathology. 7 days postoperative, CT cystography confirmed the healed anastomotic site between bladder and ureter () and the patient was discharged. The internal ureteral stenting placed in the ureter was removed under cystoscopy on postoperative 10th day at the outpatient clinics. No further hematuria and hydronephroureterosis were observed during 14-month follow-up. |
pmc-6146624-1 | A 62-year-old woman with HBV-related hepatopathy has been suffering for a few months of pain and a sense of weight in the right hypochondriac site. A CT scan reveals a lesion of about 5 cm between the VI hepatic segment and right colon. Colonoscopy demonstrates near the right colonic flexure an ab extrinseco compression that dislocates the bowel and makes the endoscope's progression difficult. The most significant laboratory tests were AFP = 394.90 ng / ml (normal value <15); CEA = 2.20 ng / ml (normal value <5). Antibodies to HBV were positive. An exophytic, encapsulated neoformation with a diameter of 5 cm, at the level of the VI hepatic segment, is found in the laparoscopic procedure. The segment is resected by ultrasound scalpels. Without complications, the patient is discharged the day after the operation. |
pmc-6146629-1 | A seven-and-a-half-year-old male child was sent to our Pediatric Endocrinology Centre for macrocephaly and right lateralized overgrowth, reported from birth. Parents were not related and no noteworthy diseases were reported in his family history. The pregnancy was characterized by spontaneous abortion of the dizygotic twin at 16 gestational weeks. Fetal ultrasounds were normal. He was born at 35 weeks of gestational age by an emergency caesarean section for acute fetal suffering. Birth weight was 3010 g (1.65 standard deviations [SD]), birth length was 51 cm (2.45 SD) and birth occipito-frontal circumference (OFC) was 36 cm (2.93 SD).
The perinatal period was characterized by hospitalization because of the mild prematurity, neonatal jaundice treated with phototherapy and the findings of hypotonia. In his first months of life he presented a progressive increase of the OFC and was submitted to brain Magnetic Resonance Imaging (MRI) and to neurosurgical evaluation, which permitted an initial diagnosis of isolated benign macrocephaly. The MRI was repeated at the age of 2, revealing ventriculomegaly, Chiari Malformation type I and an arachnoid left temporo-polar cyst. At neurological evaluation, he presented a developmental delay characterized by an acquisition of sitting position at 30 months of life and autonomous walking at 3 years of life and a speech delay with first production of words after 2 years of age. Since he was 3 years old he has been suffering from pain episodes at right lower limb unrelated to physical activity or other specific events, usually characterized by prolonged duration, good response to paracetamol and associated to limb failure and fall to the ground.
At our first physical examination his weight was 24.9 kg (0.54 SD), height 118.3 cm (− 1.42 SD) and OFC 60.5 cm (> 3 SD). He had several capillary malformations on medial axis. His face presented two frontonasal hemangiomas, a hyperpigmented brownish stain on the forehead with telangiectasia, and two on flat hemangiomas the trunk; furthermore, the patient had low-set ears, teeth with serrated edges, diffuse muscular hypotonia, joint hypermobility, and a fine and gross motor dyspraxia associated to a mild intellectual disability. His right lateralized overgrowth involved face, trunk and limbs (mainly legs). In particular, he showed a mild asymmetry of the face and of the facial mime with the right side more represented, different length and diameter of the legs (the right were 66 cm and 40 cm respectively and the left one 63 cm and 36 cm) and of the forearms, measured from elbow to the end of the middle finger (the right were 29 cm and 14 cm respectively, the left one 26 cm and 12 cm).
X-ray, ultrasounds and MRI of lower limbs were performed confirming the asymmetry in length of the legs and showing a musculature and a panniculus adiposus of the right side more represented than the contralateral. Echocardiogram and abdominal ultrasound were normal.
Brain MRI was repeated confirming previous findings of ventriculomegaly, arachnoid left temporo-polar cyst, cerebellar tonsillar ectopia. Furthermore, it revealed a markedly thick corpus callosum (mega-CC), abnormalities of white matter, an area of polymicrogyria, and a pituitary gland with a mild reduction in volume for age (Fig. ). The electroencephalography showed sporadic and isolated paroxysmal abnormalities. The functional evaluation permitted a diagnosis of mild intellectual disability, attention-deficit, hyperactivity disorder and emotional disturbance (Wechsler Intelligence Scale for Children-IV: Total Intelligence Quotient 51).
On the basis of these clinical signs and symptoms we hypothesized an OS and sent the patient to geneticists for specific evaluation. Pediatric geneticists of the Pediatric Department of MBBM Fundation, Monza, Italy, confirmed our diagnostic suspicion and diagnosed a segmental OS. Consequently, the child was submitted to the molecular analysis of 21 selected genes involved in the PI3K/AKT/mTOR pathway (PIK3R1, PIK3R2, PIK3CA, PTEN, PDK1, PDK2, KRAS, AKT1, AKT2, AKT3, RICTOR, MAPKAP1, MLST8, MTOR, IRS1, GAB1, GAB2, THEM4, MAPK8IP1, PTPN11, RPTOR). To identify causative mosaic somatic mutation on these genes the genomic DeoxyriboNucleic Acid (DNA) was extracted from cutaneous biopsy of affected tissue and Targeted Next generation sequencing (NGS) was performed. The pathogenic point mutation c.2740G > A (pGly914Arg) in PIK3CA exon 18 was isolated in the genomic DNA of our patient. It was identified in heterozygosity and was presented as somatic mosaic with a frequency of 31.2%. The identified variant was verified by Sanger sequencing. |
pmc-6146633-1 | A 50-year-old Caucasian man with a remote history of deep venous thrombosis (DVT) at the lower extremities presented with abdominal pain. His medications included acetylsalicylic acid. Physical examination revealed abdominal tenderness and a palpable mass at the left abdominal area. Laboratory exams revealed a normocytic and normochromic anemia, with a hemoglobin of 11.1g/dl (reference range 14–18 g/dl), aPTT and INR prolongation of 78.1 seconds and 1.64, respectively (reference range 25-36 seconds and 0.85 – 1.2, respectively), and elevated urea and serum creatinine values of 68 mg/dL and 1.8mg/dL, respectively (reference range 15–55 mg/dL and 0.7–1.3mg/dL, respectively). An abdominal computerized tomography (CT) revealed a 17x11x8cm3 spontaneous retroperitoneal hematoma due to bleeding of an intraparenchymal branch of the left renal artery (). A repeat hemoglobin after 2 hours was 9.1g/dL and the patient was transfused with 2 units of packed red blood cells and 2 units of fresh frozen plasma, while a central venous catheter, a urinary catheter, and an arterial catheter were placed to allow for hemodynamic monitoring. Left nephrectomy was performed due to inability to embolize the bleeding artery. Pathology of the kidney showed evidence of acute and chronic microangiopathy, renal artery stenosis, and renal vein thrombosis. Antiphospholipid antibodies and lupus anticoagulant were positive twice, while antinuclear antibodies and anti-ds-DNA were negative, suggesting the diagnosis of primary antiphospholipid syndrome. |
pmc-6146636-1 | A 54-year-old Asian American woman presented to her family physician with right side flank pain. She had no other symptoms, and her physical exam was normal. Laboratory testing showed elevated liver function tests including alkaline phosphatase and aspartate aminotransferase. An abdominal ultrasound showed a 1.5 cm hypodense lesion in the left lobe of the liver with associated porta hepatis lymphadenopathy. Computed tomographic (CT) scan revealed a 1.8 × 1.4 cm hypodense mass located in the left lateral section of the liver with minimal peripheral enhancement (). Magnetic resonance imaging (MRI) of the liver showed a T1 hypointense and T2 mildly hyperintense lesion with indeterminate enhancement (). No other abnormalities were found on axial imaging. A CT-guided biopsy showed nodular collections of polyclonal T and B lymphocytes and plasma cells. Tumor markers, including AFP, CEA, and CA 19-9 were within normal limits, and her hepatitis panel was negative. Serum antimitochondrial antibody (AMA) level was normal. She had normal upper and lower endoscopies.
Based on her clinical presentation, imaging, and an indeterminate pathology report, she was seen at the hepatobiliary high-risk clinic and a laparoscopic left lateral sectionectomy of the liver was recommended. The patient had an uneventful hospital stay postoperatively and was discharged home on postoperative day 3.
Her final pathology revealed nodular reactive lymphoid follicular hyperplasia (RLH) and evidence of primary biliary cholangitis (PBC), which was not diagnosed until final pathology was obtained. |
pmc-6146661-1 | A 38-year-old man with past history of hypertension was admitted for a lumbosacral spine surgery. He had been taking Valsartan 160 mg a day for the past 4 years. He underwent two uneventful previous surgeries before diagnosis of hypertension and was not known to have prior drug intolerance or atopy with unremarkable family history. He had no history of nonsteroidal anti-inflammatory drugs in the perioperative period.
The patient was admitted for an elective spinal fusion surgery at L5–S1. His vital signs, airway examination, other physical examination, and laboratory tests were unremarkable. On the next day, the patient was taken to the operating room; anesthesia was induced with intravenous fentanyl and propofol, smooth tracheal intubation was done using atracurium. The patient was turned to prone position and anesthesia was maintained with isoflorane and fentanyl. The patient was given 10 mg morphine and 1 g cefazolin intraoperatively.
At the end of the surgery and turning the patient into supine position, we noticed severe swelling in the neck and the face including the eyes lids, the checks, and the lips, Fig. . Direct Laryngoscopy revealed an edematous tongue, floor of the mouth, glottis, and supraglottic areas without rash association. On auscultation, there were no added breath sounds with normal vital signs. The patient was kept in prone position for 305 min.
A diagnosis of drug induced angioedema was made after exclusion of other causes and intravenous dexamethasone 10 mg, diphenhydramine 25 mg and ranitidine 50 mg were given. He was continuously monitored for progression of the edema and continued to have dexamethasone. The patient remained intubated and was transferred to the intensive care unit. The valsartan was suspected to be the precipitating factor for the angioedema and was therefore discontinued.
The swelling started to regress after 2 h and significantly within 24 h, Fig. . The extubation was done on the second day after a flexible fiberoptic examination revealed normal supraglottic and glottic structures. The facial and neck swelling has resolved completely by the third day, Fig. .
The patient was discharged home on the fifth post-operative day without any complications with no history of further attacks of angioedema during his follow up visits in spine clinic. |
pmc-6146670-1 | A 78-year-old man presented with a slowly growing, painless, immobile right hemiscrotal mass over a nine-month period. An ultrasound study revealed a large right inguinal hernia containing herniated intra-abdominal fat (Figures and ). On surgical exploration, the mass was encasing the right testicle requiring radical orchiectomy for complete resection. Gross examination revealed an 11 × 5.5 cm mass composed of adipose tissue with a lobulated cut surface and thick fibrous septations (Figures and ). The blood vessels exhibited thickened, collagenized walls (). There were scarce atypical, nonlipogenic spindle cells with enlarged, irregular, pleomorphic, and hyperchromatic nuclei within the fibrous tissue (). There was no necrosis, nor mitotic figures. These findings are diagnostic of well-differentiated lipoma-like liposarcoma, grade 1. The margins were involved; thus the patient received radiation therapy. In the follow-up period after resection, the patient was recently examined and found to be disease-free. |
pmc-6146670-2 | A 49-year-old man presented with a painless, nontender, nonreducible, firm, immobile, slowly enlarging right hemiscrotal mass over a one-year period. CT imaging revealed a right inguinal hernia with intraperitoneal fat extending inferiorly into the scrotal sac (Figures –). Subsequently, a 14 × 10.5 cm membranous sac was excised. The hernia sac contained at least nine ovoid, circumscribed, separate, lobulated masses ranging from 2 to 8 cm in size tracking along the spermatic cord. The color varied from light brown to red brown (in contrast to case 1 where the mass was yellow) (). Microscopically, the predominant component was mature adipose tissue. However, the dark red component showed fibrous tissue with myxoid areas and variable numbers of adipocytes with significant variations in size and shape (, bottom). Arborizing capillaries, lipoblasts (vacuolated cells with hyperchromatic scalloped nuclei), and atypical, nonlipogenic spindle cells were found predominantly in the myxoid component (Figures –). This tumor also lacked necrosis and mitotic figures. This tumor was diagnosed as well-differentiated liposarcoma mixed type, lipoma-like, and sclerosing type, grade 1. On follow-up, a PET-scan revealed a nonhypermetabolic fatty mass along the distal anterior aspect of the right psoas, which was considered a retroperitoneal component of the inguinal tumor. |
pmc-6146672-1 | A 40-year-old male presented with complaints of instability and defect in his left knee since 6 months. The patient gave a history of trauma 6 months back and did not take any treatment for this. Clinically, anterior defect was present over the left knee with visibility of intercondylar articulating surfaces of the tibia and femur. Swelling was seen in the anterior aspect of the left distal third thigh, which, on palpation, was the superior part of the patella. The lower pole of the patella was palpable just above the left tibial tuberosity (). The X-ray of the left knee confirmed that the superior fragment of the patella was present in the distal third aspect of the thigh and the lower fragment close to the tibial tuberosity ().
The patient underwent surgery by anterior approach where quadricepsplasty and tension band wiring for the patella were performed after bringing the superior fragment down (). Another tension band wire was passed through the neutralization hole made just posterior to the tibial tuberosity and the retinaculum was repaired.
During the immediate postoperative period, the patient was started on dynamic quadriceps strengthening and active straight-leg-raising exercises. After suture removal, continuous passive motion for his knee was added. On discharge, the range of knee motion was from 5 degrees of extension lag to 40 degrees of flexion. At 6 weeks of postoperative follow-up, the patient had a 5- to 90-degree knee motion. The range of motion improved to 0–110 degrees at 3 months follow-up (). |
pmc-6146677-1 | This is a fifty-five-year-old woman with past appendectomy. She was perimenopausal and had no treatment. Her brother had a rectum neoplasia. She had four children. She suffered from anemia because she had menorrhagia since few months. Ultrasonography examination revealed a polymyomatous uterus and a vascularized polyp of 23x17 mm in the uterine cavity. Mammography and breast ultrasonography were normal. CA125 was high (63,3 U/ml). Total hysterectomy with bilateral ovariectomy was performed because its symptoms lasted for too long. Histological examination showed a subatrophic endometrium with bands of irregular proliferation, slight-to-moderate adenomyosis, and benign subserosal leiomyoma of 34 mm in size. There was also a pedunculated polyp of 25 mm. Macroscopically, this polyp appeared white, fibrous, fasciculated, and focally yellow (). Microscopically, we observed endometrial glands with a stroma composed of smooth muscle and adipocytes (). The zone appearing macroscopically fatty contained mature adipose tissue. No atypia was observed. The adipocytes were positive for estrogen and progesterone receptor. A diagnosis of adenolipoleiomyoma was made. No specific particularities were revealed in the follow-up at two years. |
pmc-6146767-1 | The first case shows a 30 year old female. Clinical and radiographic examination showed a skeletal Class II pattern with an anterior open bite and a transverse maxillary deficiency with a lateral posterior crossbite on the right and the tendency to a lateral crossbite on the left (Fig. ).
The treatment plan involved a first stage of maxillary expansion with SARME to correct the transverse discrepancy followed by the leveling of the dental arches with lingual fixed appliances and finally two jaw surgery to correct the open bite as well as the Class II malocclusion.
Impressions of the upper and lower arches were obtained for the lingual appliances.
During the planning for the production of the lingual brackets, it was noted that a surgically assisted rapid maxillary expansion takes place. In the set-up, therefore, the transverse width of the upper jaw should be adapted to the lower jaw.
Four Benefit mini-implants were inserted: two in the anterior area of the T-Zone and two 12 mm distally on each side of the midpalatal suture. A silicon impression was taken and the laboratory analogues were placed on the transfer caps. The maxillary expansion appliance was manufactured using a Hyrax screw anchored only to the four mini-implants, named the Quadhyrax.
During the same appointment the lingual appliance was indirectly bonded using a dual cured composite (Fig. ) and the Quadhyrax was inserted and attached to the mini-implants using Benefit fixation screws. The first lower arch wire 14 NiTi was placed while the upper brackets were securely ligated with a continuous steel ligature in each quadrant to prevent accidental dislodgement during surgery (Fig. ).
The surgery for SARME was performed on all three patients according to the same procedure: First Le Fort I osteotomy with an oscillating saw. After that, the sutura palatina mediana was chiseled up for the midpalatal split. The tuber region was also mobilized with a chisel for the complete pterygomaxillary disarticulation. The appliance was activated intraoperative to evaluate the individual expansion of both sides of maxilla. After that the aplliance was resetted to reach a final gap of 1 to 1.5 mm.
After surgery and a latency of a few days rapid maxillary expansion commenced with an activation rate of two quarter turns twice a day until the crossbite was corrected []. In all three cases one quarter turn corresponded to 0.2 mm. At four turns a day this was equivalent to 0.8 mm.
A central diastema developed and expansion was complete two weeks after surgery. The Hyrax screw was then blocked for retention. Four weeks after surgery the first maxillary archwire 14 NiTi was placed to begin the alignement and leveling phase. The active closure of the central diastema started at about ten weeks post-surgery once enough bone had started to form for the incisors to move into. Because of the typical mushroom shape of the customized lingual appliances, the archwire has to be swiveled using tandem mechanics in front of the canines until the spaces are closed (Fig. ). The Quadhyrax was removed after six months. One mini-Implant was lost during removal of the expander and the remaining implants served as skeletal retention (Fig. ). The basal expansion of the maxilla worked well however the tooth-bearing segments of the maxilla showed some palatal tipping (Fig. ). After successful leveling and radiographic re-examination the second surgery was performed to correct the open bite and the Class II malocclusion.
The open bite could be closed. The patient has a positive overbite and overjet of 1.5 mm and shows a good transversal and sagittal occlusion. |
pmc-6146767-2 | The second case shows a 53-year-old female. Clinical and radiographic examination confirmed a unilateral posterior crossbite due a transverse maxillary deficiency with a significant mandibular skeletal deviation towards the side of the crossbite (Fig. ). Treatment objectives.
SARME was planned to correct the transverse discrepancy followed by arch leveling with lingual appliances and then a second surgery to correct the mandibular asymmetry.
Similar to case 1 impressions were obtained and this time the lingual appliances were manufactured by DW Lingual Systems (Bad Essen, Germany).
During the planning for the production of the lingual brackets, it was noted -similar to case 1- that a surgically assisted rapid maxillary expansion takes place. The transverse width of the upper jaw should be adapted to the lower jaw.
Two trans sagittal Benefit mini-implants were inserted in the T-Zone. A silicon impression with the transfer caps was taken. The impression was given to the laboratory together with the lingual molar bands. A Hybrid Hyrax [] was then made and laser welded to the molar bands (Fig. ). Similar to case 1, the lingual appliance was indirectly bonded with a dual cured resin and the maxillary expansion appliance was inserted. In this case the molar bands were cemented with a dual cured resin and the hybrid hyrax was fixed to the mini-implants using the Benefit fixation screws. The first lower arch wire 12 NiTi was inserted while in the upper the brackets were secured with a continuous steel ligature in each quadrant (Fig. ). SARME was performed with an activation rate of two quarter turns twice a day until crossbite correction was achieved at two weeks post-surgery (Fig. ). The Hybrid Hyrax was then blocked. The first upper archwire (12 NiTi) was placed four weeks after surgery (Fig. ). After complete leveling and radiographic re-examination the surgery to correct the asymmetry was performed.
The patient has a positive overbite and overjet now. The patient shows a good transversal and sagittal occlusion. |
pmc-6146767-3 | The third case shows a 30-year-old male. Clinical and radiographic examination confirmed a concave profile, a skeletal Class III pattern with a complete anterior and posterior crossbite. Transverse deficiency of the maxilla was evident with compensatory labial tipping of the upper incisors (Fig. ).
Firstly SARME was planned to correct the transverse deficiency. Decompensation was then planned by retraction of the anterior teeth using distalization of the posterior segments and proclination of the lower incisors by leveling. Finally the surgery to correct the Class III malocclusion.
The insertion-procedure of the mini-implants was similar to case 2. The lingual appliance was also manufactured by DW Lingual Systems (Bad Essen, Germany).
During brackets planning, similar to the previous cases, the transverse width of the upper jaw should be adapted to the lower jaw.
In addition two distalizing-screws were attached between the Hybrid Hyrax and the molar bands (Hybrid Hyrax Distalizer) [] (Fig. ). SARME was completed in two weeks with an activation rate of two quarter turns twice a day. The Hybrid Hyrax was then blocked (Fig. ). Four weeks after surgery leveling was commenced simultaneously with distalization. A 12 NiTi wire was inserted in the upper arch and activation of the distalization screws started at a rate of one quarter turn a week. The active closure of the central diastema started at about ten weeks post-surgery and it was closed one month later (Fig. ).
A half year post-surgery radiographic re-examination was made and there was a sufficient distance of repositioning for the jaws (Figs. + + ) (Tab. ). The surgery to correct the Class III malocclusion could be performed.
The patient has a positive overbite and overjet now. The patient shows a good transversal and sagittal occlusion. |
pmc-6146902-1 | A 20-year-old female patient was admitted to the Department of Restorative Dentistry, Faculty of Dental Medicine, Kırıkkale University, with aesthetic concerns. The anamnesis did not specify any systemic illnesses of the patient. After the clinical and radiographic examinations, hypomineralization was identified in the maxillary anterior teeth except the right canine tooth. An external discoloration was also identified in the left canine tooth. Moreover, the right canine tooth was identified as a Turner's tooth according to the patient's anamnesis. ().
A minimally invasive and aesthetically satisfactory treatment plan was made with the consent of the patient. The resin infiltration technique (Icon, DMG, Hamburg, Germany) was applied to the maxillary anterior teeth except the right canine. A rubber dam was implemented to protect the soft tissues and create a clean and dry working environment. The teeth were then cleaned with a cleaning pad, and the resin infiltration technique was applied step by step as follows. (1) A gel comprising 15% HCl, water, silica, and other additives was applied for 2 min with a special apparatus to ensure its homogenous application. Then, the acid gel was washed with a water spray for 30 s. (2) An ethanol drier was applied for 30 s to remove water in the lesion area and make the microporosity of the enamel surface more visible. (3) Finally, a low-viscosity resin infiltrate was applied for 3 min. Excess materials were removed with a cotton roll and a dental floss. Finally, a light curing accessory was used for polymerization and polishing for 40 s. ().
Later on, the left canine tooth was identified to have a darker color and hence bleaching treatment was applied. First, the color of the left canine tooth was determined as A3 on the Vita scale. Then, a gingival protective gel was applied to the contours of the gums following the manufacturer's protocol and polymerized with an LED light accessory. Two components of the whitening agent (Opalescence Boost PF, Ultradent, YT, USA) were mixed following the manufacturer's protocol and applied to the aforementioned area. The application took 40 min in one session, and the color of the tooth was determined as A2 on the Vita scale ().
A laminate veneer restoration was planned for the upper right canine, which was a Turner's tooth according to the patient's anamnesis. The tooth was prepared (Komet Ceramic Veneer Kit, Komet Dental, Hamburg, Germany). The overlapped preparation was applied to exceed the incisal enamel contours by 2 mm. The gingival retraction was achieved using a combination of mechanical and chemical retraction methods. The prepared tooth and the opposite teeth were digitally measured with an intraoral scanner (TRIOS A/S, 3Shape Trios, Copenhagen, Denmark). The designed laminate veneer was produced with a CAM system (Coritec 550i, imes-icore, Eiterfeld, Germany) using lithium disilicate glass ceramic blocks (IPS e-max CAD, Ivoclar Vivadent, Schaan, Liechtenstein). The restorations were glazed in the laboratory and then cemented with adhesive cement (Panavia V5 Clear, Kuraray Noritake Dental, Tokyo, Japan) following the recommendations of the manufacturer ().
Incisal irregularities on the maxillary central incisors were restored with a nanohybrid composite resin (Filtek Ultimate A2 Body, 3M ESPE, St. Paul, MN, USA). Following the treatment, a satisfactory aesthetic restoration was achieved. The examination of the restorations after 1 year did not reveal any clinical failures (). |
pmc-6147009-1 | We present a case of a female aged 33 with a diagnosis of NFI. She presented with a longstanding history of bilateral nipple skin tags. No family history of NFI was documented. She had a history of hypothyroidism, epilepsy, and learning difficulties.
On clinical examination, bilateral, pedunculated, polypoid, and fleshy lesions were noted on both nipple-areolar complexes (). The right nipple lesion measured 60x55x35mm and left measured 25x25x25mm.
Microscopically, both specimens showed dermal proliferations of bland spindle-shaped cells with elongated wavy dark nuclei (Figures –). No atypia, pleomorphism, necrosis, or mitotic activity was seen. Spindle cell proliferation extended close to a mammary duct (); however, it must be noted that these lesions did not arise from the breast parenchyma but included smooth muscle fibres of nipple and were in close proximity to mammary ducts. This can pose a diagnostic challenge when differentiating between spindle cell lesions arising from breast parenchyma which can also extend to the nipple.
Immunohistochemistry (IHC) supported the neural differentiation of the spindle cells with immunopositivity for S100 and neurofilament (Figures –). Neurofilament usually stains axons in peripheral situations and not spindle cells. The proliferation was negative for a panel of cytokeratins including AE1/3 and p63.
Interestingly, large amounts of smooth muscle bundles were dispersed within the lesion. Desmin () and smooth muscle myosin on IHC highlights the florid component of associated smooth muscle. This is thought to be a reactive process in response to the development of the neurofibroma. |
pmc-6147040-1 | The patient was a 64-year-old man, who had bilateral ptosis, diplopia and exercise intolerance. His early development had been normal and currently he had no regular medication. Ocular symptoms had started to develop at the age of 54 years, the right eye had been operated due to squint at the age of 58 years and ptosis surgery had been performed on the right at the age of 63 years. He had right clubfoot, which had been regarded as a complication of vaccination at the age of two years. There was muscle atrophy in the right leg and the leg movements were restricted. His parents, his seven siblings and his son were healthy. Patient’s maternal uncle had ocular symptoms and, interestingly, uncle’s granddaughter had ptosis and a 7.5 kb deletion in mtDNA.
On neurological examination, the patient limped slightly because of the right clubfoot. Ptosis was moderate on the right and mild on the left. Vertical gaze paresis and a slight restriction in horizontal movements was noted in both eyes. Otherwise, muscle examination was normal. Ankle reflexes were absent, while other tendon reflexes were normal.
Routine laboratory values including creatine kinase were normal. Blood lactate was 1.16 mmol/l (reference values 0.33–1.33 mmol/l) and pyruvate was 84 μmol/l (reference values 30–80 μmol/l). Brain MRI showed minimal nonspecific white matter lesions in the frontal lobe. Polyphasic units in frontal and nasal muscles were found in electromyography. Myasthenia gravis was first diagnosed at the age of 60 years and pyridostigmine was initiated. Because the treatment did not alleviate symptoms and all myasthenia studies were negative, treatment was discontinued. Lambert-Eaton myasthenic syndrome was excluded and PABP2 gene test for repeat expansion causing dominantly inherited oculopharyngeal muscle dystrophy was negative.
Muscle biopsy from vastus lateralis was compatible with mitochondrial myopathy (Fig. ). Ten percent of the muscle fibers were COX-negative and few RRFs were found as well. Ultrastructural examination revealed an increased number of mitochondria and changes in the internal structure of mitochondria.
DNA of blood leucocytes and buccal epithelial cells was extracted by using QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) and that of muscle by using Wizard® Genomic DNA purification kit (Promega Corporation, Madison, WI). Mitochondrial DNA was amplified and sequenced in twelve overlapping fragments. The amplification reactions were done by using Phire Hot Start II DNA polymerase (Thermo Fisher Scientific, Waltham, MA, U.S.A.) according to the provided protocol. Sequencing was carried out at Biocenter Oulu sequencing core facility.
The muscle sample for histological staining was fresh-frozen and cryostat sections (5 μm) were stained with routine histochemical techniques []. The stainings included hematoxylin and eosin and combined cytochrome c-oxidase and succinate dehydrogenase (COX-SDH). Laser-capture microdissection of COX-SDH stained frozen sections was done using Carl Zeiss P.A.L.M. microscope (Microlaser Technologies GmbH, Bernried, Germany) in Turku Centre for Biotechnology, University of Turku and Åbo Akademi University. Ten COX-negative and ten COX-positive fibers were collected into Carl Zeiss AdhesiveCap tubes (Carl Zeiss Gmbh, Göttingen, Germany) and DNA was released incubating fibers 30 min in 65 °C in lysis buffer containing 200 mM potassium hydroxide and 50 mM dithiothreitol followed by neutralization step with 900 mM Tris-HCl, pH 8.3. Amplification was carried out using Phusion High-Fidelity DNA polymerase (Thermo Fisher Scientific). Heteroplasmy was determined by cloning using CloneJET PCR Cloning Kit with blunt-end cloning protocol and DH5α competent cells (Thermo Fisher Scientific). Colony screening was done by using FastDigest XmiI (Thermo Fisher Scientific). XL-PCR for whole mtDNA amplification was carried out using Phusion High-Fidelity DNA polymerase with GC Buffer according to the original protocol (Thermo Fisher Scientific).
We found the m.15923A > G mutation in MT-TT in the skeletal muscle of the patient. The heteroplasmy was determined and, interestingly, the mutation was undetectable in the blood of the patient, while it was present with a 33% heteroplasmy in the skeletal muscle and with 2% heteroplasmy in the buccal mucosa. In pooled COX-negative fibers, the heteroplasmy was 92% while it was 43% in biochemically normal fibers. The investigation of mtDNA deletions remained negative. |
pmc-6147263-1 | In November 2008, a 61-year-old man was admitted to the Ear, Nose and Throat (ENT) and Cervico- facial Surgical Department of Salah Azaez Oncology Institute for the treatment of T2N0M0 squamous cell carcinoma of the right hemi larynx. The patient was a heavy smoker, a consumer of alcohol and had a long history of dysphonia and complained of recent slight dyspnea. Suspension laryngoscopy showed a white burgeoning formation invading the right true and false vocal cords, the right laryngeal ventricle of Morgagni and the anterior commissure. The patient underwent SCPL-CHEP with bilateral neck dissection followed by adjuvant radiotherapy.
In March 2016, after 8 years of being disease free, the patient reported a painless protrusive swelling in the right side of the neck. Cervical examination found an elastic mass measuring 2×3 cm in the right side of the neck, more prominent when coughing. Suspension laryngoscopy was normal and ruled out any local relapse. Computed tomography (CT) showed a hypodense formation measuring 35 mm on the right side of the neck that began opposite the first tracheal ring. No signs of malignant recurrence were noted ().
The patient was operated on following an external approach. A total excision of the mass was performed, and found intraoperatively to be a 2-cm round renitent mass with a smooth surface (,). Histological examination of the specimen concluded a laryngocele, filled with glandular mucus without any suspicious signs malignancy. |
pmc-6147265-1 | A 52-year-old male patient presented with a history of a change in the voice over 3 months, with neither sore throat nor fever. Physical examination revealed right-sided grade IV and left-sided grade III tonsillar enlargement with prominent vessels ().
Serology was negative for human immunodeficiency virus (HIV), and other preoperative blood investigations were also normal. He was known to have been diagnosed with type II diabetes mellitus for 15 years, and was treated with oral hypoglycemic medications. Clinical features were not suggestive of chronic tonsillitis, and the possibility of lymphoma was considered due to the asymmetric tonsils and their abnormal surface nodularity and vascularity. Hence, the patient underwent bilateral tonsillectomy by dissection and the snare method. There was no extra tonsillar spread, and no excess bleeding was encountered.
On microscopy, the left-side tonsil predominantly showed numerous reactive follicles of various sizes spread throughout the tonsillar tissue. The sections of the right side showed reactive follicles with germinal centers having a darker zone, giving way to a lighter one harboring tingible body macrophages, a polymorphous population of cells including centrocytes, centroblasts and immunoblasts. Some follicles had a broadened mantle cell layer encroaching upon the germinal centers. The mantle layer consisted of a monotonous population of small-to-medium sized lymphoid cells with irregular nuclear contours, condensed nuclear chromatin, inconspicuous nucleoli and scant cytoplasm. A few of the follicles had their germinal centers completely replaced by the mantle-zone cells, imparting a nodular pattern with fairly uniform sizes ().
Based on these findings, the initial histopathological report suggested chronic tonsillitis with areas suspicious of atypical lymphoproliferative disorder. Immunohisto- chemistry (IHC) was advised for confirmation of the same. With the clinical suspicion of lymphoma already in place, IHC was promptly performed. The neoplastic cells were positive for Bcl2, CD20, CD5 and Cyclin D1. CD10, Bcl6 and CD3 were negative (); thus confirming a diagnosis of MCL in both the mantle-zone and nodular patterns. As the patient lived far away from our hospital and wished to take further treatment at an oncology-center close to his home, he was lost to follow-up. |
pmc-6147267-1 | A 21-year-old male student presented to the emergency department with severe headache for 15 days, periorbital swelling, pain and double vision in the right eye for 10 days, fever for 7 days and left lower limb weakness for 5 days ().
His past history was unremarkable, and no significant family history was found. The patient was conscious, oriented, febrile, and his vital parameters were normal. Severe ptosis was noticed in the right eye, although visual acuity was normal in both eyes. Fundoscopy was also normal in both eyes. All cranial nerve function was found to be normal. On examination of the lower limb, it was evident that the tone of the muscle was normal, with grade-4 muscle strength. The patient had a typical hemiplegic gait with foot drop due to the weakness of the flexor muscles of the leg and foot on the left side. Ocular movement was restricted on right lateral gaze. The patient’s eye lid was swollen, tender and fluctuant on palpation. Diagnostic nasal endoscopy (DNE) revealed bulging of the right lateral wall of the nose and mucopurulent discharge in the middle meatus. The oral cavity and oropharynx were normal, and examination of the neck revealed no palpable lymph node. Contrast enhanced computer tomography (CECT) of the nose and paranasal sinus demonstrated bilateral pan sinusitis with right subperiosteal abscess ().
An MRI of the brain revealed ring-enhancement lesion in the parasagittal area of right frontal lobe without significant displacement of the midline ().
Prompt conservative treatment was started covering gram positive, negative and anaerobes, assuming an infective etiology. Vancomycin (I/V 500 mg twice daily), metronidazole (I/V, 500mg thrice daily) and ceftriaxone (I/V 2g twice daily) was given along with supportive treatment (I/V mannitol and dexamethasone).
After 48 h of treatment, there was no significant improvement in the orbital and intracranial symptoms. Endoscopic orbital decompression was undertaken after 48 h, when it did not respond to medical management. The subperiosteal abscess was drained by breaking the lamina papyracea and was sent for microbiological study for antibiotic sensitivity.
Pus culture was consistent with alpha hemolytic streptococcus, which was sensitive to imipenem and later was continued.
The fever subsided after 48 h of surgery, and neurological symptoms began resolving after 7 days. The patient subsequently underwent regular physiotherapy for foot drop. A repeat CT scan was advised after 2 weeks, and revealed a reduction in the size of the abscess. The patient was discharged after 28 days of medical treatment with complete resolution of the intracranial abscess and foot drop. The patient remained on close follow-up for last 12 months in the rhinology clinic and was found to be completely asymptomatic, both clinically and radiologically (,). |
pmc-6147272-1 | A 30-year-old woman was referred to our clinic with a 2-month history of epistaxis and necrotizing lesions of her nose with a background of chronic sinusitis and rhinorrhea. Ear, nose, and throat (ENT) examination of the patient indicated a defect in her nasal septum.
The coronal and axial cut of computed tomography (CT) reconstructions of nasal soft tissues and paranasal sinuses revealed mucosal thickening in the right maxillary sinus and a defect in the anterior aspect of the nasal septum with an approximate diameter of 13 mm (). The nasal septum biopsy revealed respiratory mucosa with ulceration, acute inflammation, and granulation tissue formation ().
Kidney function and chest X-ray were normal. Laboratory findings were leukocyte count 13,600 per μl (normal range 4,500 to 11,000), which was mildly elevated; hemoglobin 13 g/dl; platelets 373,000/mm³; high erythrocyte sedimentation rate (ESR) 35 mm/h (normal range up to 20); elevated C-reactive protein (CRP) 45 mg/L (normal range up to 6); perinuclear ANCA (p-ANCA) 1/320 (normal range up to 1/10) with positive antigen-specific ANCA directed against proteinase 3 (PR3) and negative myeloperoxidase (MPO), cytoplasmic ANCA (c-ANCA), antinuclear antibody (ANA) and rheumatoid factor. All tests for HIV virus, hepatitis C and hepatitis B viruses, FTA-ABS and venereal disease research laboratory (VDRL) were negative. Purified protein derivative (PPD) test was not reactive. Leishmaniasis and blastomycosis serology were also negative.
When asked, the patient denied being a drug abuser. Thus, the combination of clinical, serologic and histologic findings, including ulceration, inflammation, and granulation tissue formation () led to the diagnosis of ANCA-associated vasculitis, most likely limited GPA.
Her treatment with prednisolone (50 mg/day), sulfamethoxazole and trimethoprim was started, followed by adding methotrexate (15 mg/week). After 3 months, with no evidence of improvement clinically or serologically, and considerable weight gain due to the high-dose steroid, rituximab was administered to the patient, but with only a minor improvement in the symptoms. At this point, the patient admitted the ongoing nasal use of cocaine. Subsequently, the causative effect of cocaine was suspected, and the patient was advised to stop cocaine abuse. During 3 months of further clinical follow-ups, no additional new problems related to CIMDL were identified. Written informed consent was obtained from the patient in order to publish her case. |
pmc-6148720-1 | A 54-year-old Chinese woman with a 5-year history of multiple nodules under the subcutaneous tissues on the right auricle () was referred to their hospital in April 2009. The patient also suffered from itching and occasional tingling in the right auricle. Topical corticosteroids and oral antihistamines were prescribed, but the condition repeatedly recurred. On examination, erythematous or violaceous papules and nodules were present in the right dermis and subcutaneous tissues, and auricle swelling was observed. No regional lymphadenopathy or other pathological findings were evident.
Laboratory data, including eosinophil count and total serum immunoglobulin (Ig)E, were within normal limits. A biopsy was performed on the lesion, and the pathological diagnosis was ALHE ().
After the patient presented to their department, brachytherapy with 32P simple-drug membranes was performed on the lesions. The patient underwent 32P brachytherapy treatment five times. The 32P brachytherapy involving simple-drug membranes of brachytherapy began by diluting a 32P solution (Beijing Atoms High-Tech Ltd. Co.) with 0.9% NaCl solution to produce a radioactivity of 69.2–74.7 MBq/mL (1.87–2.02 mCi/mL). The lesion area was covered with transparent plastic film and cellulose qualitative filter paper (Grade 1) as a medicine film. The size of the 32P simple-drug membranes was determined using carbon paper, and the membranes were prepared by evenly applying the diluted 32P to filter paper, which was then allowed to dry. Electric soldering was used to close the transparent plastic film. The treatment area was disinfected using iodine tincture, and the prepared 32P simple-drug membranes were pressed tightly to the lesion. The drug membranes were removed between 48 and 72 h after application, and the membranes were properly disposed of as radioactive waste. There were intervals ranging from 65 to 72 d between the membrane application periods, and the last treatment was in June 2010. After the 32P brachytherapy, follow-up results over the course of 8 years were promising. The regional symptoms disappeared, the right preauricular swelling decreased, the subcutaneous nodules decreased in size, the exudate disappeared, and the skin appearance improved (). |
pmc-6148735-1 | A 9-month-old baby girl from the Adamawa Region of Cameroon was brought to the out-patient department of our hospital by her mother for a reddish, “snake-like” rash on the child’s abdomen that appeared 3 days prior to consultation. The mother suspected the lesions were pruritic because her child was irritable and seemed restless during sleep hours. She reported that the lesions increased in length by approximately 2 cm each day, and they had gotten longer since she first noticed them 3 days prior to consultation. The child had no fever, cough, or other systemic symptoms. They had no pet dogs or cats but our patient’s mother reported that stray dogs usually visit their courtyard. Even though the mother did not allow her children to play in the dirt, she admitted to drying her children’s clothes on the grass in the courtyard. Our patient’s twin sister was symptomless.
On physical examination, the child was conscious, calm, and in no form of distress. She had a temperature of 37.4 °C, pulse rate of 92 beats per minute, respiratory rate of 24 breaths per minute, and weighed 9 kg. An examination of her skin revealed multiple erythematous, raised, and “thin” serpiginous lesions of varying lengths over her trunk and extending to the proximal portions of her arms (Fig. ). The lesions did not appear to increase in length throughout the examination.
A diagnosis of CLM was made and she was placed on albendazole syrup (15 mg/kg per day) for 3 consecutive days and chlorpheniramine syrup 1 mg/ml for 3 days. A follow-up visit 3 days later was marked by absence of irritability but the persistence of a few serpiginous lesions. She was prescribed topical ivermectin cream with a total resolution of the lesions at follow-up, 1 week later. |
pmc-6148795-1 | The patient is a 16-year-old boy, born at term by natural delivery from unrelated healthy parents. The mother and father were 38 and 43 years old at time of birth. Prenatal NT at ultrasound examination and karyotype on amniocytes, performed because of advanced maternal age, were referred as normal. Patient birth weight was 3950 g (90th percentile), length 51 cm (50-75th p), and occipital frontal circumference 34.5 cm (50-75th p). Apgar scores were 9/9. The patient started walking autonomously at 13 months, pronounced his first words at 11 months, and then has shown neither developmental delay (DD) nor ID. Neuropsychological evaluation at 9 years using WISC-III [] evidenced mild learning disabilities, namely dysgraphia. At the last follow-up at the age of 13, the phenotype was very mild, mainly characterized by obesity (weight > 97th p), a normal height (150.5 cm, 50-75th p), hyperactivity, dysphagia, sleep disturbance, and minor dysmorphic features such as round face, bushy eyebrows, and stubby hands. Brain MRI and angiography showed an altered signal near both the capsular lenticular structures and the head of the caudate nucleus, implying the presence of a hamartoma. He was referred to our lab for Smith-Magenis syndrome (SMS)-like phenotype without SMS molecular diagnosis (neither a 17p11.2 deletion nor RAI1 mutations were formerly identified). |
pmc-6148997-1 | A 55-year-old woman was referred to the Peking Union Medical College Hospital in September 2015 for rectorrhagia and intermittent abdominal pain lasting 6 months. The patient had a past medical history of ovarian endometriosis and had undergone excision of bilateral ovarian chocolate cysts in 1988 when she was 30 years old. Histological examination showed benign bilateral endometriosis of the ovaries. The patient was not treated with any hormonal therapy following hysterectomy. She has a familial history of endometriosis comprising her mother, one sister and one aunt.
Physical examination of the patient was unremarkable, except for the tenderness of the left lower quadrant of the abdomen.
Serum CA125, CEA, and CA199 were within a normal range. A colonoscopy was performed (Fig. ), which revealed an ulcerated fleshy neoplasm that was 15 cm from the anal margin and blocked 50% of the passage of the endoscope. It was possible to pass the endoscope beyond the lesion. The mass appeared to bleed relatively easily and had a diameter of 2 × 3 cm. The surface of the lesion was irregular, and the margin was unclear. The surrounding colonic mucosa was rough. The results of the scan also revealed a 0.8 cm sessile polyp in the ascending colon. Multiple endoscopic biopsies were taken. Pelvic ultrasound showed multiple uterine leiomyomas, which presented as multiple heterogeneous internal echoes. A computed tomography scan revealed eccentric thickening of the wall of the recto-sigmoidal junction (Fig. ). A whole body FDG-positron emission tomography (PET) was requested (Fig. ). F18-FDG PET/CT imaging showed local thickening and narrowing of the recto-sigmoid colon wall and hypermetabolic lesions. FDG-PET/CT also found enlarged pelvic lymph nodes with pathologic FDG-uptake. Since the pathology obtained from the colonoscopy showed evidence of a metastatic adenocarcinoma, and the lesion was confined to the pelvic cavity, laparoscopic surgery was performed on October 20, 2015. During the procedure, a 3.5-cm ulcerated mass was identified above the peritoneal reflection with multiple adhesions to the uterine wall. The surgeons examined the pelvic cavity carefully and found apparent adhesions in the pelvic cavity due to the previous surgical procedures. The adhesions present between the tumour and the uterus were severed. There were no obvious tumours on either of the ovaries. A rectal anterior resection with lymphadenectomy was performed. The lymph nodes around the common, internal, and external iliac arteries, the middle rectal artery root, and the obturator space were dissected. Hysterectomy and bilateral salpingo-oophorectomy were performed. There was no residual macroscopic tumour present at the completion of the surgery.
The endoscopic biopsy specimens were fixed in 10% buffered formalin and embedded in paraffin. Four μm sections were stained with standard haematoxylin and eosin (H&E). Immunohistochemical stains were performed using the following antibodies: CK7, CDX-2, CA-125, Villin (Dako); CK20 (OriGene Technologies); PAX-8, WT-1(XiYa Biology); P16, ER, PR (VENTANA); P53 (Maixin Biotech. Co., Ltd.). The H&E slides and immunohistochemical stains were reviewed by two pathologists. The excised bowel was sent for histological analysis. The pathologic specimen consisted of an ulcerated mass with grey, solid, friable cut surface. The mass measured 3.5 × 2 × 1.2 cm and was attached to the wall of the colon. The mass involved the muscularis propria macroscopically. Microscopic sections revealed a high-grade serous carcinoma extending through all of the layers of the intestine (Fig. ). Tumour cells appeared as irregular tubular structures, moderately differentiated, with no sign of atypical adenomatous hyperplasia. The section margins were free of tumour, but the circumferential resection margin (CRM) was positive. Eight out of 30 lymph nodes that were collected were positive. The uterus and the ovaries were free of cancer. According to the preliminary pathological diagnosis, the TNM staging was determined to be pT4bN2bM0 (IIIC) based on the AJCC Staging System. The final histology was confirmed after discussion between several pathologists who diagnosed the patient with pronounced focal atypical endometriosis in the intestinal wall and the right ovary (Fig. ). The immunohistochemical profile showed CK7 positivity and CK20 negativity, as well as negative CDX2 (Fig. ). The case was positive for CA125, PAX8, P16 and mildly positive for oestrogen receptors. The Ki67 index was 30%. Based on the immunohistochemical characteristics of the primary intestinal adenocarcinoma, it was determined that the lesion was an endometrial carcinoma deriving from colorectal endometriosis.
The patient received adjuvant chemotherapy consisting of 175 mg/m2 Taxol and AUC5 carboplatin for eight cycles. The patient experienced reversible chemotherapy-induced myelosuppression and gastrointestinal reactions during chemotherapy. The timeline of the process was shown in Table .
At 23-months, the patient had a follow-up appointment and reported difficult defecation at the 22nd month. The CT scan, PET-CT and colonoscopy showed local recurrence in the lower rectum, which was confirmed by pathological diagnosis. The patient has received Taxol and carboplatin chemotherapy again and will receive another surgery after two cycles of chemotherapy. |
pmc-6149011-1 | A male patient, 26 years old, sought care at the dental clinic with fractures of the left maxillary central incisor resulting from a sudden strike three months earlier. The patient had no clinical symptoms during this period (Fig. ). A clinical examination revealed that the left maxillary central incisor was fractured in the middle third of the crown and that this fracture involved the enamel and dentin with no pulp exposure and no signs or symptoms of a concussion or contusion. A routine cold vitality test of the tooth revealed that it was associated with the same reaction as the reference tooth. Additionally, the patient had a defect in the incisal area of the right maxillary central incisor that resulted from eating melon seeds, and a routine cold vitality test of the tooth revealed a positive reaction. Finally, the relationship between the anterior teeth overbite and overjet was normal. A radiographic examination of the central incisors was conducted, and an analysis of radiography of the maxillary left central incisor revealed that there were fractures in the middle third of the crown, but no abnormalities, such as damage to the remaining roots, were observed (Fig. ).
A 3D-printed template was fabricated using intra-oral scanning, CAD, virtual modeling and 3D printing. Briefly, a digital registration of the dentition was performed using a CEREC AC Omnicam intra-oral scanner (CEREC AC D3492, Sirona Dental Systems GmbH, Fabrikstr, Bensheim, Germany). The inlay in the machine was selected, and the system automatically generated a prosthesis using the contralateral tooth as a reference. From the analysis performed using the software, the occlusal contact of the intercuspal occlusion of the patient was concentrated in the middle third of the cervix, and it was therefore appropriate for composite resin restoration. An occlusal adjustment was made to eliminate anterior contact in the occlusion and to avoid contact with the prosthesis (Fig. ). We showed a picture of the result to the patient, and he was satisfied with it. The data were then imported into Freeform (Geomagic Freeform, 3D Systems, Morrisville, North Carolina, USA), a software program that is widely used to design 3D models. Using the Freeform program, a template can be designed through a process similar to drawing a picture, and a dentist can design a repaired palatal template in only minutes (Fig. ). The digitally designed template is prepared for export using the “stl check” command, exported as a stl-file and then sent to a 3D printer (3D System 3510HB, 3D Systems, Morrisville, North Carolina, USA). Finally, the 3D-printed template is fabricated (Fig. ).
Before treatment, the 3D-printed template was detached and soaked in disinfectant. Then, the template was positioned on the patient’s dentition, and a correct and reproducible fit was verified. Initially, the anterior teeth were isolated using a rubber dam (Hygienic Elasti rubber dam, Switzerland). The teeth were carefully cleaned using prophylaxis paste (SS white prophylaxis paste, England), dried, and submitted to minimal tooth preparation using a diamond bur (Mani SF-41, Japan) to produce an improved alignment for the bond. Both surfaces of the connection were etched using acid gel (Ultra-Etch® 35% Phosphoric Acid, Ultradent, USA), rinsed, and gently dried. Single bond (Adper™ Single Bond 2, 3 M ESPE, USA) was applied first. The surface was then air-dried for 5 s and exposed to light-activation for 10 s. Subsequently, the 3D template, which had been detached and soaked in disinfectant, was positioned on the back of the anterior teeth (Fig. ). It was convenient to construct the palatal surface using an opaque enamel shade (E2, Ceram*X duo, DENTSPLY, Germany) with the aid of a 3D printing guide. After polymerization, the palatal wall is sufficiently strong to support the next stratification steps. Reconstruction was performed using an opaque dentin shade (D2, Ceram*X duo, DENTSPLY, Germany) to construct the dentin body (Fig. ). The enamel shade E2 was used to match the superficial enamel, and each composite increment was light-cured for 20 s. Additionally, tooth 11 was restored using enamel shade E2 in the incisal area and on the buccal surface. The final step consisted of performing an additional 20 s of polymerization at each site. After excess composite material was removed, an occlusion test was performed using carbon paper, and the restorations were shaped to a proper anatomic morphology (Fig. ). Next, finishing and polishing procedures were performed using diamond fine coating burs and a polishing system (One-step diamond micro-polisher, Germany) (Fig. ). |
pmc-6149011-2 | A 61-year-old female patient was referred to the clinic with dental caries of her left maxillary central incisor. The patient had no clinical symptoms (Fig. ). A clinical examination revealed that the left maxillary central incisor had caries in the middle third of the crown, which involved the enamel and dentin with no pulp exposure. A routine cold vitality test revealed that the tooth was sensitive. Finally, the relationship between the anterior teeth overbite and overjet was normal. A radiographic examination of the central incisors was conducted, and a radiographic analysis of the maxillary left central incisor revealed that there were caries in the middle third of the crown. (Fig. ). A 3D-printed template was fabricated using intra-oral scanning, CAD, virtual modeling and 3D printing as in the first case. Finally, the 3D-printed template was fabricated (Fig. ).
Before treatment, the 3D-printed template was detached and soaked in disinfectant. Then, the template was positioned on the patient’s dentition, and a correct and reproducible fit was verified. Initially, the anterior teeth were isolated using a rubber dam. The teeth were subjected to minimal tooth preparation using a diamond bur (Mani SF-41, Japan) to produce an improved alignment for the bond (Fig. ). Both surfaces of the connection were etched using acid gel (Ultra-Etch® 35% Phosphoric Acid, Ultradent, USA), rinsed, and gently dried. Single bond (Adper™ Single Bond 2, 3 M ESPE, USA) was applied first. The surface was then air-dried for 5 s and exposed to light activation for 10 s before the appropriate enamel composite (E3, Ceram*X duo, DENTSPLY, Germany) was placed on the defect area of the 3D template. Subsequently, the 3D template was positioned on the back of the anterior teeth (Fig. ) and exposed to light activation for 20 s (Fig. ). The palatal surface was then constructed. After polymerization, the palatal wall was sufficiently strong to support the next stratification steps (Fig. ). The integration of A2 (Ceram*X duo, DENTSPLY, Germany) was used to match the functional aesthetic bevel. Reconstruction was performed using an opaque dentin shade (D2, Ceram*X duo, DENTSPLY, Germany) to construct the dentin body (Fig. ). The enamel shade E3 was used to match the superficial enamel, and each composite increment was light cured for 20 s. The final step consisted of performing an additional 20 s of polymerization at each site. After excess composite material was removed, an occlusion test was performed using carbon paper, and the restorations were shaped to the proper anatomic morphology (Fig. ). Next, finishing and polishing procedures were performed using fine diamond-coated burs and a polishing system (One-step diamond micro-polisher, DENTSPLY, Germany). Figure shows the final appearance of the restorations as follows: labial view (Fig. ) and lateral view (Fig. ). |
pmc-6149070-1 | A 49-year-old, previously healthy, Caucasian man, a motorcyclist, was referred to our Emergency Department (ED) after a high velocity frontal collision with a car. He was married and worked as a car body repairer. He had no tobacco smoking or drinking history and was not taking any medication. A prehospital primary survey assessment according to ATLS protocols revealed a hemodynamically stable patient with blood pressure (BP) of 136/82 mmHg and heart rate (HR) of 65 beats per minute (bpm) without airway or breathing alterations. He was oriented and conscious and reported pain in the symphyseal region and left arm. Cervical spine immobilization and intravenous access were obtained and a pelvic binder was applied by paramedics (SAM® Pelvic Sling™ II, Fig. ).
At arrival in our ED, he was alert without any relevant cardiorespiratory dysfunction: body temperature 36.8 °C, HR 65 bpm, BP 132/80 mmHg, oxygen saturation 100%, and Glasgow Coma Scale of 15. A secondary survey revealed a deformation of his left wrist, and painful palpation of the pubic symphysis and sacral region. The pelvic binder was maintained and a total body CT scan with two-dimensional MPR and three-dimensional reconstruction was performed. Laboratory findings revealed mild normocytic anemia (133 g/l) and liver and renal functions were normal. The chronologic timeline of patient management and investigations is provided in the Additional file .
No relevant pelvic anomaly was detected (Figs. and ) including after three-dimensional reconstruction (Fig. ) and the pelvic binder was removed.
Because of the high velocity of the crash and persisting symphyseal pain, plain anteroposterior pelvic radiography was ordered shortly after the CT. Pelvic radiography revealed a non-osseous pelvic disruption, with an opening of the pubic symphysis (more than 2.2 cm) and of the left sacroiliac joint (type 61-B2.3d according to the 2018 revision of the AO/OTA fracture and dislocation classification compendium; type APC-2 according to the Young and Burgess classification) [–] (Fig. ).
He was admitted to the operating room for surgical pelvic stabilization, and external fixation of his left wrist and was discharged on the tenth day after admission. Full recovery of the pelvic disruption was observed after 6 months and ablation of the left wrist osteosynthesis material was performed at 7 months because of residual pain. |
pmc-6149227-1 | The pedigree of the family is shown in Fig. . The proband (Ib in Fig. ) was a 47-year-old female of Han Chinese ethnicity (with family from Shandong province, China), who was admitted to our hospital with a chief complaint of “fatigue and chest tightness for 7 days”. She never had a similar episode before. She had neither intellectual disability nor a history of seizures. Her blood pressure was 135/85 mmHg. Physical examination revealed typical facial angiofibromas (adenoma sebaceum) and multiple periungual fibromas (Fig. ), and obvious abdominal distention. Her biochemical laboratory test demonstrated renal insufficiency (serum creatinine levels: 3.1 mg/dL, normal values 0.5–1.1 mg/dL; estimated glomerular filtration rate: 17.1 ml/min/1.73 m2, estimated by CKD-EPI formula) and moderate anemia (hemoglobin of 8.6 g/dL, normal values 11–15 g/dL). Ultrasonography of her both kidneys manifested a heterogeneous mass with a large echogenic fatty component and a less echogenic soft-tissue component with prominent vessels within it, which was suggestive of giant bilateral renal angiomyolipomas (AML) (Fig. ). Highly vascular fatty masses were seen on Color Doppler scans (Fig. ). Ultrasonography of the left eyes demonstrated a hyperechogenic lesion with posterior shadowing due to calcifications (Fig. ). Fundus photograph showed a hamartoma with central calcifications and a surrounding translucent zone in the left eye, suggesting the retinal hamartoma (Fig. ). Thereafter, non-contrast-enhanced computed tomography (CT) of the abdomen confirmed the ultrasonography diagnosis of giant bilateral renal AMLs with prominent fatty components and internal prominent vessels. Multiple variable-sized air-filled cysts throughout the parenchyma were noted in both lungs consistent with lymphangioleiomyomatosis (LAM) on lung CT. And brain CT revealed multiple calcified subependymal nodules. Images of spine displayed multiple patchy sclerotic lesions (Fig. ).
Therefore, we considered that the patient fulfilled the diagnostic criteria of TSC []. The patient accepted the treatment with the mTOR inhibitor everolimus (10 mg/d) because her AMLs nearly invaded all tissues of bilateral kidneys which could not be removed completely. Two months later, the patient felt a significant alleviation in the feeling of abdominal swelling. Regrettably, she had to discontinue her treatment because of financial difficulties. After half a year follow-up, the patient remained in a stable condition. Besides, she had a son (IIc) who died of epilepsy at the age of six. Her daughter (IIa) also had the presentation of typical facial angiofibromas and multiple periungual fibromas, but she denied further imaging examination. Her husband (Ia) and granddaughter (IIIa) did not show any significant symptoms or abnormalities on testing. To further confirm the diagnosis of TSC, mutation analysis of the TSC1 and TSC2 gene and bioinformatics analysis were performed by the methods in Additional file . The CARE guidelines were followed in reporting this case.
By the next generation sequencing, the proband was found to carry a heterozygous guanine to adenine substitution of the last nucleotide in exon 29 of TSC2 (c.3610G > A), resulting in a single amino acid substitution from Glycine to Arginine at amino acid position 1204 (p.Gly1204Arg) (Fig. ). Sanger sequencing validation of all family members revealed that the proband’s daughter (IIa) carried the same heterozygous p.Gly1204Arg mutation in TSC2 gene, whereas other family members and 100 unrelated controls did not harbor this mutation. No mutation was identified in TSC1 gene.
The c.3610G > A variant was considered as novel since it was neither present in ExAC, 1000G, nor in HGMD databases (HGMD Professional 2017.4). However, another substitution at the same codon (c.3611G > A, p.Gly1204Glu) has been reported to be related with TSC [].
The p.Gly1204Arg alteration was predicted as deleterious by three different softwares (i.e. MutationTaster, SIFT and PolyPhen-2). Moreover, the p.Gly1204Arg variant is highly conserved among 8 different species (human, Callorhinchus milii, Macaca mulatta, chimpanzee, house mouse, rat, xenopus tropicalis and zebrafish) by using Vector NTI Advance 10-Align.
It was noteworthy that the c.3610G > A was a nucleotide substitution at the last position of exon 29, which was located at the upstream close neighbor nucleotide of classical donor splicing site (GT) of intron 29. Therefore, this position may play an important role as splicing modulator. The BDGP and the NetGene2 splice prediction programs were then employed to test whether this mutation could alter the splicing of the TSC2 transcript. Both predictions resulted in the abolishment of the donor splice site. Finally, the in silico analysis by ASSP software showed that the splice donor site strength remarkably decreased from a score of 8.434 to 4.895 (cut off: 4.5).
The mini-gene assay performed to study the effects at the transcript level of the novel c.3610G > A variant showed that the wild-type gave rise to a 476 bp PCR product containing exon 29, the empty pSPL3 control gave rise to a 263 bp PCR fragment missing exon 29 of TSC2 gene. However, the c.3610G > A mutant construct produced two transcripts corresponding to 263 and 476 bp PCR fragments, respectively (Additional file : Figure S1). We then investigated whether the mutation c.3610G > A really led to exon 29 skipping in an actual patient. The cDNA was reverse transcribed from total RNA extracted from peripheral blood leucocytes of the proband. By cDNA sequencing, the exon 29-excluded transcript was identified only in the proband and not in a not-mutated individual. Approximately 44% of the cDNA products inserted into the pGEMT Easy vector were missing exon 29, whereas 56% were in-frame cDNA with the single nucleotide change c.3610G > A (Fig. ). |
pmc-6149836-1 | A 42-year-old Caucasian female with pseudoxanthoma elasticum, who had been diagnosed with bilateral AS and CNV secondary to AS in the left eye (OS), was treated with 12 intravitreal injections (IVIs) of ranibizumab (0.5 mg [50 µL]) over a period of 13 months. Despite the intensive treatment with ranibizumab, no significant functional or anatomic change was observed. One month after the last administration of ranibizumab, best-corrected visual acuity (BCVA) was 10/10 in right eye (OD) and remained stable (3/10) in OS. Fundoscopy demonstrated peau d’orange fundus appearance and AS as multiple irregular linear branching subretinal streaks, emanating radially from the optic disc without sparing the fovea. An elevated gray-yellow subretinal lesion compatible with CNV was observed in the fovea in OS, adjacent to a large fibrotic lesion. Fluorescein angiography clearly showed streaks around the optic disc and leakage of the dye originating from the CNV, while staining of the fibrotic element of the foveal lesion was observed (). Optical coherence tomography (OCT) imaging revealed signs of active CNV in OS with intraretinal and subretinal fluid accumulation ().
It was at that point a switch of treatment to aflibercept was agreed (administered by IVI), using the proposed treatment regimen for age-related macular degeneration (AMD). Following the signing of an informed consent form, the patient received a loading dose consisting of 3 consecutive IVIs of aflibercept (2 mg [50 µL]) monthly, followed by bimonthly aflibercept administration at the same dose. The 3 loading doses of aflibercept led to an improved BCVA of 6/10 in OS, while OCT demonstrated resolution of the subretinal fluid with reduction of the intraretinal fluid (). Two months after the third dose of aflibercept, BCVA decreased to 3/10 and ceased to improve thereafter. After a 12-month treatment period and 7 IVIs of aflibercept, BCVA remained at 3/10 in OS, while OCT demonstrated further morphologic improvement as indicated by reduction of the intraretinal fluid (). |
pmc-6150707-1 | Female patient aged 11 years and 2 months, previously diagnosed with agenesis of tooth #32, was referred by the pediatric dentist for orthodontic evaluation. The patient reported dissatisfaction with “misaligned lower teeth and very narrow smile” (). The medical and dental histories were uneventful, and anamnesis revealed no familial occurrence of hypodontia.
The facial analysis evidenced symmetry in frontal view, straight nasolabial angle, lack of lip seal, everted lower lip, balanced dimensions of the lower facial third and convex profile (). The functional analysis demonstrated adequate exposure of maxillary incisors during speech and smile. There were no sounds or symptoms of temporomandibular disorder, nor deviations in mandibular movements.
The occlusal analysis revealed that the patient was in the permanent dentition stage, with absence of tooth #32 confirmed by panoramic radiograph (). The patient presented Angle Class II division 1 malocclusion with 8-mm overjet, deep bite, coincident maxillary and mandibular midlines, positive tooth-size discrepancy of 5 mm in the mandibular arch and negative of 2 mm in the maxillary arch, and slight constriction at the region of maxillary premolars. The patient presented good oral hygiene without restorations or carious lesions ().
Cephalometric analysis confirmed the skeletal Class II pattern with ANB of 5o, convexity angle of 7o, adequate mandibular plane and adequate axial inclinations of maxillary and mandibular incisors. Analysis of maturation of cervical vertebrae indicated that the patient could be on onset of the pubertal growth spurt (). |
pmc-6150744-1 | A 68-year-old male presented to the emergency department with left-sided abdominal pain, early satiety, fatigue and 7 lbs weight loss for seven weeks. His past medical history was significant for hypertension, emphysema and HCV with an undetectable HCV ribonucleic acid (RNA) following treatment with sofosbuvir and ribavirin. Vital signs were stable and clinical examination was unremarkable, except for left-sided abdominal tenderness. His labs showed a hemoglobin of 16.4 mg/dL, white blood cell count of 6.31 k/uL, and platelet count of 101 k/uL with normal liver function tests. Abdominal ultrasound showed splenomegaly and three heterogeneous hypoechoic masses in the spleen. Magnetic resonance imaging (MRI) of the abdomen confirmed splenomegaly with multiple hypoenhanced lobulated masses in the spleen; no evidence of lymphadenopathy or hepatomegaly (Figure , ). Single-photon emission computerized tomography (SPECT) identified heterogeneous splenic uptake with areas of photopenia related to splenic masses.
Since the patient had a history of HCV, we needed to rule out liver disease leading to splenomegaly. His liver biopsy showed chronic hepatitis of mild activity with focal bridging fibrosis. Bone marrow biopsy revealed no evidence of lymphoma. Janus Kinase 2 (JAK 2) mutation was negative. Hence, liver disease was not the main cause, and thrombocytopenia was attributed to hypersplenism. Therefore, splenic biopsy was performed by interventional radiology, which showed DLBCL. The patient was started on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The decision was made to delay splenectomy due to massive splenomegaly and a possible bleed inside the spleen as the patient was recently started on warfarin for new onset atrial fibrillation. After six cycles of R-CHOP, repeated imaging with CT abdomen and positron emission tomography (PET) scan showed complete remission on PET and decrease in spleen size. Subsequently, after six months, he presented with left lower quadrant pain and splenic biopsy showed a relapse of DLBCL. Due to his poor performance status, he was not a candidate for autologous stem cell transplant and was started on palliative lenalidomide and rituximab. |
pmc-6150745-1 | The patient is a 73-year-old male, with only a past medical history of bilateral cataracts and hyperlipidemia. He had complained of one year of left-sided radiating neck pain into the shoulder, arm and the second digit, with numbness in the second digit. He was noted to have a palpable left anteromedial upper arm mass one year ago, which was subjected to needle biopsy and determined to be a “benign schwannoma”. Initially, the mass was painless, without a Tinel’s sign. Upon initial presentation to our clinic, his radicular pain was worsening. He also developed pain in the upper arm around the palpable mass, with shooting pain into the hand with percussion. There was a positive Tinel’s sign, with the percussion of the mass leading to pain and paresthesias in the left hand. On exam, the patient had 4/5 weakness in the left triceps, 4+/5 weakness in pronation, and a mild “benediction” sign, with incomplete voluntary flexion of the second and third digits. Sensory examination revealed reduced sensation to pinprick in the left palmar index finger and thumb. All deep tendon reflexes were diminished, but symmetric. Magnetic resonance imaging (MRI) of the cervical spine revealed a prominent left C6-7 foraminal disc protrusion, causing C7 nerve root compression as shown in Figure . An MRI of the left humerus revealed a circumscribed ellipsoid mass along the anteromedial distal upper arm, contiguous with the median nerve as demonstrated in Figure . Electromyography (EMG) and nerve conduction velocity (NCV) study of the upper extremities revealed acute and chronic denervation changes in the left flexor carpi radialis (FCR) with reduced recruitment in the triceps and the cervical paraspinal muscles.
The patient was counseled and offered a staged surgical approach, with resection of the upper arm mass first, followed by a C6-7 anterior cervical discectomy and fusion (ACDF). The resection of the upper arm mass was performed under general anesthesia; through a linear anteromedial distal upper arm incision, the tumor capsule was identified and contiguous with the median nerve. Intraoperative monitoring and stimulation were performed and a capsular incision was made in a region on no activity. The tumor was resected with a fascicle entering and exiting the tumor, without nerve action potential transmission. After resection, the epineurium was closed with 6-0 prolene, and the skin was closed in a layered fashion. Post-operatively, the patient’s motor examination was unchanged, but his pain had significantly improved. He returned to the operating room two weeks later for the C6-7 ACDF, which included a full discectomy and division of the posterior longitudinal ligament, with direct decompression of the left C7 nerve root, performed with use of sensory and motor evoked potentials, and EMGs via intraoperative monitoring.
Pathological examination of the nerve sheath mass revealed a circumscribed spindle cell lesion demonstrating hypercellular areas alternating with hypocellular areas (Antoni A and B regions), in addition to Verocay bodies shown in Figure . S100 red immunostaining confirmed the diagnosis of a peripheral schwannoma, as depicted in Figure .
By four weeks post-operatively, his triceps function returned to full strength, as did his strength in the finger flexion of his index finger. Numbness persisted in the left thumb and index finger, although it improved in its intensity. The neck and radiating arm pain resolved completely. The only complication was post-operative hoarseness of the voice, which also improved by three months post-operatively. |
pmc-6150749-1 | A 36-year-old female with past medical history significant for schizophrenia presented to the hospital after experiencing arthralgia for nine days followed by an evanescent rash for three days accompanied by persistent high-grade fever. Her symptoms were associated with pleuritic chest pain. The rash was non-pruritic and non-painful spreading over the neck, trunk, and all four extremities. The patient was diagnosed with schizophrenia five years before to her admission, and has been receiving olanzapine 20 mg daily for the last six months. She admitted noncompliance with her medication recently, due to developing diabetes mellitus and weight gain while being on olanzapine.
In the emergency department, her initial vital signs were as follows: temperature, 103.7°F (39.8°C); blood pressure, 111/55 mmHg; heart rate, 141 beats/minute; and respiratory rate 22 breaths/minute. The patient looked anxious and diaphoretic. Skin examination revealed salmon-like, blanchable, maculopapular rash of various shapes and sizes, most prominent over bilateral extremities. Soft, tender and mobile lymph nodes were palpated in the left cervical and left submandibular chains. Joint examination revealed reduced range of motion of both shoulders, right elbow, left wrist and right third proximal interphalangeal (PIP) joints. Her cardiac and pulmonary examination discovered no abnormalities.
Table describes the laboratory examination results at the presentation.
On admission radiograph of the chest revealed normal cardiac silhouette without any pleural effusions or pulmonary infiltration. Vancomycin and ceftriaxone were empirically started which were discontinued soon after the admission because the symptoms were not consistent with a bacterial infection, the patient then was managed symptomatically with acetaminophen and intravenous fluids. Over the next 36 hours, the patient continued to have spiking fevers with negative blood/urine cultures. Abdominal ultrasound revealed hepatomegaly and echocardiogram revealed trace pericardial effusion. On hospital day three, empiric gatifloxacin was started. Spiking fever persisted on following days four, five and six. Numerous lab studies including blood cultures and urine culture were performed to rule out infectious possibilities, e.g., antibody assays for rubella, mumps, cytomegalovirus, Epstein-Barr virus, parainfluenza, Coxsackievirus, adenovirus, influenza, human herpesvirus 6, parvovirus B19, hepatitis B and hepatitis C, Mycoplasma pneumoniae, Chlamydia pneumoniae, Borrelia burgdoferi, Quantiferon test, Pneumococcal and Legionella urinary antigens, Chlamydia, Mycoplasma and HIV. All of which proved to be negative. Lymph node biopsy has been done, reactive benign lymphadenopathy was reported. Infectious diseases consultation advised initiation of vancomycin despite lack of infectious source.
Table describes laboratory examination as per rheumatology consultation.
Based on Yamaguchi criteria, the patient was diagnosed to have AOSD, hence steroids with 50 mg Solu-Medrol intravenously started. Over the next four days, fever, rash and arthralgia resolved and serum ferritin levels decreased to 1085.2 ng/mL. The patient was discharged apyretic, in good clinical condition on oral prednisone and advised to follow up in outpatient clinic. |
pmc-6150750-1 | The patient is a 46-year-old right-handed female with a past medical history of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus type two (DM2), obesity, and hemorrhagic stroke who was transferred from an outside facility to be evaluated for CNS vasculitis. She was admitted to this outside facility for a four-week period prior to being transferred to the primary facility for further evaluation over a subsequent 23-day period. Total duration of hospitalization at both the facilities was close to 7.5 weeks. Approximately one week into the initial four-week admission, her family found that she was very lethargic with diminished responsiveness and pronounced difficulty speaking. In the emergency room (ER), her blood pressure was measured at 243/129 mmHg with a blood glucose value greater than 400 mg/dL. She was started on aggressive antihypertensive therapy and underwent a series of diagnostic tests. Dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel was initiated in combination with high-dose atorvastatin. With respect to her lethargy and fluctuating cognition, there was concern that she may be experiencing complex partial seizures, so lacosamide was also started.
A baseline computed tomography (CT) scan of the head without contrast showed multiple indeterminate lacunar infarcts involving the head of the right caudate nucleus and left corona radiata. The same day, a magnetic resonance imaging (MRI) was performed and elicited similar findings with the addition of bilateral punctate infarcts of the left thalamus, right periventricular white matter, and right centrum semiovale. Magnetic resonance angiography (MRA) done on the following day showed high-grade stenosis of the left middle cerebral artery (MCA), in addition to markedly diminished caliber of the right MCA and high-grade stenosis involving the left posterior inferior cerebellar artery (PICA). Bilateral carotid ultrasounds showed very mild plaques. An angiogram exhibited an occluded left posterior cerebral artery (PCA) distally and was also suggestive of advanced intracranial atherosclerosis (more so than would be expected in CNS vasculitis). There was no evident change from day two to day six of this hospital course. A spinal tap performed at the end of the first week demonstrated elevated protein and IgG synthesis rate (16.4), which was concerning for CNS vasculitis. Appreciating the contrast between the imaging and spinal tap findings, CNS vasculitis could not be ruled out. The patient was started on intravenous (IV) corticosteroids briefly, however, the medication was discontinued due to worsening hyperglycemia that was progressively difficult to control. Near the end of the third week of hospitalization, a repeat MRI showed a new small stroke in the left subcortical parietal white matter.
The patient was transferred to the primary facility after this initial month of hospitalization, at which time the patient had a National Institutes of Health Stroke Score (NIHSS) of seven. She was alert and oriented to person only and able to follow simple commands. Significant findings on subsequent blood testing revealed leukocytosis (12.2), elevated absolute neutrophil count (ANC) at 11.3, hyperglycemia (314 mg/dL), HbA1c of 9.6%, mildly elevated erythrocyte sedimentation rate (ESR) at 36, positive herpes simplex virus type one (HSV1), and the presence of IgG and hepatitis B core antibody (HBcAb). Workup for hypercoagulable state was negative for Factor V Leiden and antithrombin deficiencies, though notably protein C was elevated. A repeat spinal tap on hospital day one showed elevated levels of protein (122), but also demonstrated an elevation in myelin basic protein (6.09). Otherwise, the patient was afebrile and hemodynamically stable on admission. On hospital day two, rheumatology was consulted. In order to confirm the suspected diagnosis of CNS vasculitis, the specialist recommended a leptomeningeal biopsy and IV corticosteroids in the interim. Although angiography is very sensitive, it is nonspecific as it cannot distinguish between vasculitis and reversible cerebral vasoconstriction syndrome (RCVS). Consequently, the angiography that the patient had undergone earlier in her hospital course could not provide us with a definitive diagnosis, thus warranting the biopsy of the brain.
A baseline transthoracic echocardiogram (TTE) obtained on hospital day three revealed a left ventricular ejection fraction (LVEF) of 57 +/-5 percent with mild dilation of the left atrial cavity. Repeat imaging showed much of the same findings, however, radiology recommended further workup for underlying CNS vasculitis. Over hospital day four to six, the working diagnosis was “multifocal bihemispheric strokes with no clear etiology with an encephalopathic process.” The patient’s cardiovascular risk factors continued to be treated and monitored (lipids, blood pressure, and sugars), and a more extensive rheumatological workup was ordered. Continuous electroencephalogram (EEG) monitoring on hospital day eight also showed evidence of diffuse encephalopathy although there were no epileptiform changes or seizures recorded. Over the second week of hospitalization, a new left cerebellar infarct was detected on MRI, at which time steroids were tapered down and a transesophageal echocardiogram (TEE) was ordered. The results of this echocardiogram were unchanged in comparison to the baseline TTE. There was no thrombus detected in the left atrium, ruling out cardioembolic etiology of the new stroke. The CT studies of the chest and abdomen were negative for any findings pertinent to the patient’s chief complaint.
During the third week of hospitalization, a repeat head CT without contrast revealed additional recent infarcts. A four-vessel angiogram showed 50% stenosis in the petrous and cavernous segments of the left internal carotid artery (ICA), a completely occluded M1 segment of the left MCA, and multiple alternating foci of narrowing within the M2 and M3 branches of the right MCA as well as the P2 and P3 branches of the PCA. In consideration of these findings and given the fact that there is a considerable overlap between the imaging appearance of vasculitis and atherosclerotic disease, neither diagnosis could be excluded. A second rheumatology consult recommended that a leptomeningeal biopsy be considered prior to starting cyclophosphamide, effectively ruling in CNS vasculitis versus ischemic stroke. The neurosurgery team agreed to conduct the biopsy of the meninges and brain. However, after discussing the details of the procedure with the patient's family, her family decided against her having the procedure due to the risks associated with brain surgery and the debilitating neurologic deficits already suffered by the patient. |
pmc-6150751-1 | A 30-year-old male with no past medical history moved from Puerto Rico three weeks prior to admission. He was found unresponsive at home with foamy secretions around his mouth. Paramedics found him apneic and pulseless. Cardiopulmonary resuscitation (CPR) was initiated and he had the return of spontaneous circulation after prolonged CPR. He was admitted to ICU and started on therapeutic hypothermia. His urine toxicology revealed cocaine, benzodiazepines and cannabinoids and most likely etiology for his cardiac arrest was thought to be due to overdose. Antibiotics (vancomycin and piperacillin-tazobactam) and vasopressors were initiated for septic shock along with mechanical ventilation and intubation for respiratory failure. His significant laboratory studies were as below in Table .
He remained unresponsive on discontinuation of propofol but he showed muscle twitching. Electroencephalogram (EEG) showed encephalopathy without seizure activity (Figure ).
On day three he had repeated episodes of twitching, decerebrate posturing, eyes rolling for which propofol was restarted. Repeat EEG showed similar results to prior EEG. Magnetic resonance imaging (MRI) brain showed diffuse injury and restricted diffusion involving both basal ganglia, bilateral frontal and occipital cortices (Figures , ).
He continued to have repeated episodes of decerebrate posturing, rhythmic jaw movements, sweating, fever, and tachycardia. He ultimately required tracheostomy and gastrostomy tube placement. After initial antibiotic treatment of one week, his sputum cultures grew Pseudomonas aeruginosa which resolved with a course of gentamicin nebulizers.
Infectious disease was consulted for repeated fevers. He had negative blood cultures, sputum cultures, and urine Legionella antigen. His urinalysis was negative for infection and no diarrhea, decubitus ulcers or rash was identified. Thyroid function tests (TFT) did not show hyperthyroidism, and ultrasound (US) of the abdomen was negative for acalculous cholecystitis. Hepatitis B and hepatitis C serologies, interferon-gamma release assay, and human immunodeficiency virus (HIV) were negative. He had constant lip smacking resulting in gum bleeds, but no evidence of oral infection was noticed. Tagged white blood cell scan showed uptake in the region of cecum and ascending colon but colonoscopy did not show any evidence of inflammatory bowel disease or colitis.
While getting this workup he was started on acetaminophen for fever and baclofen for rigidity. At this point in time, he was diagnosed with PSH as the workup described above was negative. He was initially started on the regimen of bromocriptine and propranolol but his response was poor. Clonidine and diazepam were added to the regimen which eventually helped with his symptoms. He was then discharged to an LTC facility after a prolonged hospital course. Currently, he has improved and is slightly responsive. He was able to say a few words to his family and identify his family members, but continues to be bed bound. |
pmc-6150752-1 | A 79-year-old African American male was admitted for evaluation of two episodes of melena within one day. No associated abdominal pain, nausea, weight loss, appetite changes, diarrhea, hematemesis, or hematochezia was reported. His past medical history was significant for chronic obstructive pulmonary disease (COPD), heart failure with reduced ejection fraction of 25%, coronary artery disease, dementia, and a recent large left middle cerebral artery (MCA) stroke that had led to aphasia and residual right hemiparesis.
The patient was admitted a year ago for evaluation of hematemesis with a hemoglobin level of 6.9 g/dL. At that time, esophagogastroduodenoscopy (EGD) had shown a large submucosal, ulcerated mass in the area of major duodenal papilla with histology suggestive of benign small intestinal mucosa without any atypical changes (Figure ). A subsequent computed tomography (CT) scan of abdomen and pelvis confirmed a 6.7 cm x 5.5 cm mass at the pancreatic head invading the duodenum. It had led to a pancreatic duct dilatation of 11 mm seen as a cut-off sign on CT. Endoscopic ultrasound (EUS) to characterize the mass had to be terminated prematurely due to hypotension at the beginning of the procedure. He was eventually discharged after stabilization of his vitals and hemoglobin for a repeat outpatient EUS within a week. He failed to follow up with his appointment.
Examination on this admission revealed an ill-appearing, aphasic, thin male with hypotension and tachycardia. Initial testing showed a hemoglobin level of 9.9 g/dL, a blood urea nitrogen (BUN) level of 30, an international normalized ratio (INR) of 1.1, and a total bilirubin level of 0.3. After initial resuscitation with intravenous fluids and red blood cell transfusions, an emergent EGD was performed using front- and side-viewing endoscope. A fungating, polypoid mass was seen within the ampulla of Vater with blood oozing out of the duodenal papilla that failed to be controlled with epinephrine injection (Figure ). A hypervascular mass was seen within the second part of duodenum and pancreatic head with active hemorrhage from the supplying vessels including the superior pancreaticoduodenal branch of gastroduodenal artery (GDA) on the following arteriogram. Successful coil embolization of GDA was able to control bleeding and the patient did not require any further transfusions.
A biopsy specimen taken during endoscopy showed ‘invasive adenocarcinoma’ on histopathology (Figure ). CA 19-9 level was within the reference range 15.6 U/mL (0-37 U/mL). Based on the clinical picture, imaging and pathology data, he was diagnosed with adenocarcinoma of the ampulla of Vater.
Due to his poor performance status and multiple comorbidities, he was not considered as a candidate for surgery or aggressive chemotherapy. He refused any aggressive measures and was discharged to a nursing facility with an outpatient oncology follow up for consideration of palliative radiotherapy. |
pmc-6150755-1 | A 47-year-old female with an active substance use disorder involving intravenous (IV) heroin, amphetamines, benzodiazepines, and a known history of asthma and chronic obstructive pulmonary disease (COPD) was found cyanotic at home in a prone position. She was hypoxemic on room air with oxygen saturation of 50% but emergency medical services (EMS) were unable to intubate her so she arrived at the emergency room (ER) on 100% supplemental oxygen through a bag and mask ventilation. Once in the ER, she was intubated and treated with albuterol and ipratropium nebulizations.
Physical exam revealed bilateral rhonchi, a pulse of 89 beats per minute, and a blood pressure of 120/58. Laboratory values included a white cell count of 12,000 k/mm3, hemoglobin 13 g/dl, d-dimer 6,481 ng/ml, blood urea nitrogen 90 mg/dl, creatinine 0.96 mg/dl, lactic acid 2.5 mmol/L, and an arterial blood gas with a pH of 7.29, partial pressure of carbon dioxide of 46 mm Hg, partial pressure of oxygen of 110 mm Hg on 35% fractional inspired oxygen, and a peak end-expiratory pressure of 5. Her urine drug screen was positive for methamphetamines, benzodiazepines, and opiates, and a chest radiograph showed a right lung infiltrate. Blood cultures were drawn which showed no growth.
She was diagnosed with acute hypoxic and hypercapnic respiratory failure secondary to asthma exacerbation with possible aspiration pneumonia. She was treated with intravenous steroids and antibiotics and was placed on a substance withdrawal protocol with lorazepam, clonidine, Robaxin, and as needed Seroquel.
The patient self-extubated 24 hours after admission and became agitated and tachycardic. She then had a brief run of high-grade (advanced) atrioventricular block (AVB) with a 9:1 conduction abnormality and 2:1 AVB.
Subsequent electrocardiography (EKG) showed a sinus rhythm with no conduction abnormalities. Echocardiography revealed no regional wall motion abnormalities, valvular dysfunction, or vegetations. She remained hemodynamically stable. Electrophysiology was consulted and recommended a permanent pacemaker placement. Review of her electronic medical records stated the risks of pacemaker placement were discussed with the patient and her family and they consented. Details of the conversation were not recorded. The pacemaker was placed with anesthesia support without complications, and periprocedural antibiotic coverage was provided.
Information regarding drug rehabilitation was provided by the psychiatry team, along with recommended follow-up with an addiction specialist as an outpatient. This information was provided both before and after the procedure. The patient initially agreed to an inpatient drug rehabilitation program but later refused and was discharged home. At follow-up two weeks post-pacemaker placement, she was doing well without substance abuse relapse. |
pmc-6150760-1 | A 26-year-old male patient with a past medical history of asthma and marijuana use presented to the emergency room with a one-week history of shortness of breath. The patient believed his shortness of breath was associated with his asthma and he did not seek help earlier. The patient reported having exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and blood-tinged sputum upon further questioning. He denied chest pain, palpitations, cough, fever or dizziness. The patient stated that he has moved recently from Washington State and is trying to establish care with a physician locally. The patient denies any surgeries, family history of medical conditions but endorses occasional alcohol use, daily marijuana use and no tobacco use. The patient lives with his sister and works as a cook at a local restaurant. He is sexually active with women, but not at the time of presentation. The patient states he has previously prescribed some medications but does not remember what they were, and reports that he has not been taking them. On physical exam, he appeared to be in moderate distress. His vital signs were abnormal with an elevated blood pressure of 182/110, increased pulse at 120/minute and increased respiratory rate at 24/minute with use of accessory respiratory muscles noted. The patient's body mass index was 23.4. Pulmonary examination revealed scattered wheezes in all lung fields and no crackles. The cardiovascular exam revealed a non-displaced point of maximal impulse. Cardiac auscultation was noted for tachycardia with no murmurs, rubs, or gallops. Examination of the head and neck showed dry mucous membranes, with minimal jugular venous distension. The gastrointestinal exam was largely normal with no hepatomegaly, splenomegaly, or tenderness to palpation. There was one plus edema noted on the extremities during the musculoskeletal exam. Laboratory investigations done showed that his creatinine at this time was 3.4 mg/dl. Further workup for his shortness of breath revealed elevated brain natriuretic peptide (BNP) at 2534 pg/mL. Echocardiogram followed, which revealed an ejection fraction (EF) of 10–15% and a diagnosis of LVNC was made with the help of image resolution, focusing in the apical region with a non-compaction to compaction ratio >2.3 as shown in Figures -.
The EF was reassessed with the multiple-gated acquisition (MUGA) to be 27%. His acute kidney injury (AKI) was worked up and it resulted in a pre-renal etiology due to the cardio-renal syndrome. The patient was diuresed with furosemide 40 mg three times a day, which resulted in significant improvement of respiratory symptoms. However, renal function remained impaired throughout hospitalization. Creatinine peaked at 4.6 mg/dl but was trending down upon discharge. The patient was discharged on furosemide and carvedilol and was encouraged to follow fluid and salt-restricted diet. A life vest was acquired for home use, potentially as a bridge to automated implantable cardioverter-defibrillator (AICD). |
pmc-6150762-1 | A 24-year-old male presented with severe throbbing pain extending from the distal half of his left thigh to his left foot. The pain initially began four years prior, was mild, and was triggered by walking one-half to one mile. The pain progressed and is now triggered by walking one block and relieved by several minutes of rest. He delayed medical evaluation, because he believed he was having muscle cramps. He denied any history of chest pain, palpitations, shortness of breath, lower extremity swelling, skin discoloration, trauma, or prenatal/birth complications. He had no personal or family history of hypertension, hyperlipidemia, diabetes mellitus, deep vein thrombosis, hypercoagulability, malignant neoplasms, or autoimmune disorders. The family history was also negative for PAD and myocardial infarction. He was taking no medications at the time of evaluation. He does not consume alcohol and has never smoked cigarettes or used illicit drugs.
Physical examination revealed a heart rate of 72 beats per minute, left brachial blood pressure of 114/74 mmHg, and body mass index of 25.1 kg/m2. Lower extremities showed no pigment changes, edema, tenderness, and had full range of motion. The right femoral, popliteal, and posterior tibial pulses were palpable 2+. The left femoral artery was palpable 1+. The left popliteal, posterior tibial, and bilateral dorsalis pedis pulses were nonpalpable. The left popliteal and posterior tibial arteries had a weak, biphasic Doppler signal and the bilateral dorsalis pedis arteries had no appreciable Doppler signal. No carotid or abdominal bruits were noted, and the remainder of the physical exam was unremarkable. Laboratory values were within the normal range: total cholesterol 161 mg/dL, high-density lipoprotein 58 mg/dL, triglycerides 52 mg/dL, low-density lipoprotein 90 mg/dL, hemoglobin (Hb) 16.1 g/dL, platelet 218,000/uL, creatinine 0.79 mg/dL, glucose 80 mg/dL, HbA1c 5.2%, prothrombin time 12.8 seconds, and international normalized ratio 1.0. Left ABI was 0.76 at rest and 0.40 after five minutes of exercise. Arterial duplex demonstrated biphasic waveforms from the left common and profunda femoris arteries with no stenosis. The left superficial femoral artery had bi/monophasic waveforms with >75% stenosis at the proximal thigh. The popliteal and tibial arteries had bi/monophasic flow without stenosis. A computed tomography (CT) angiogram with contrast and bilateral lower extremity runoff demonstrated normal arteries of the abdomen and right lower extremity (Figure -C). The left common femoral artery was significantly smaller than the right but otherwise normal. The left proximal to mid superficial femoral artery was severely diseased with extensive calcifications causing near-complete occlusion with distal reconstitution (Figure -C). The left proximal profunda femoris artery was completely occluded with lack of flow for the first 45 mm with distal reconstitution (Figure -F). The left popliteal, tibial, peroneal, and dorsalis pedis arteries were normal with excellent runoff. There were no signs of embryological abnormalities.
Surgical exploration confirmed that the left common femoral artery was diminutive but soft with a palpable pulse. The origin of the profunda femoris artery was obstructed with a smooth, hard lesion (Figure ), which was removed with local endarterectomy and confirmed by pathology as a calcified plaque. The distal profunda femoris was followed and was found to be extensively full of the calcified plaque with no back bleeding, so a profundaplasty or complete profundal bypass was decided against, and a bovine pericardial patch was placed. Next, the left great saphenous vein was harvested and used for a left femoral to left above-knee popliteal artery bypass. A 2+ palpable pulse was noted in both the graft and the left above-knee popliteal artery. A 1+ weak pulse was noted at the left posterior tibial artery. The patient recovered excellently, beginning to walk in the unit by the next morning, and was discharged later that evening. Doppler on follow-up two weeks later demonstrated continued patency of the bypass graft and improvement in symptoms. His consent was obtained for publication of this report. |
pmc-6150764-1 | A 70-year-old male, known case of diabetes mellitus, hypertension and coronary artery disease, presented with complaints of increased appetite, weight loss, palpitations and heat intolerance. Physical examination revealed 4 cm thyroid nodule in the left lobe on palpation. His blood pressure was 130/85 mmHg, and resting pulse was 102/min with sinus rhythm. His TSH suppressed 0.29 uIU/mL (Reference range: 0.40–4.00 uIU/mL) while free thyroxine (FT4) 2.1 ng/dL (0.8–1.9 ng/dL) and free triiodothyronine (FT3) 4.2 pg/mL (1.5–4.1 pg/mL) elevated. In Figure , the radioiodine uptake scan showed the abnormal focus of hot uptake in the left lobe, suggestive of a hyperfunctioning toxic thyroid nodule.
The patient had classic signs and symptoms of hyperthyroidism. The possibility of the benign nature of hyperfunctioning thyroid nodule discussed, but the patient requested further workup to rule out any remote possibility of thyroid cancer. A fine needle aspiration (FNA) performed, and the cytology report was suggestive of thyroid carcinoma. The patient then underwent total thyroidectomy. The pathology report confirmed the fine needle aspiration cytology (FNAC) finding and revealed a solitary tumor measuring 3.5 cm in diameter. The architecture was predominantly follicular, and papillary cytological features were best seen in an area of 1 cm consistent with a follicular variant of papillary thyroid carcinoma. No other cancerous tissue found in the remaining thyroid gland. Due to the small size of the tumor no ablative radioiodine therapy performed. Post surgery, the patient received levothyroxine to prevent hypothyroidism and to stop TSH stimulation. Serum TSH and serum thyroglobulin were checked regularly. On follow-up visit, radioactive iodine whole-body scan did not reveal any distant metastasis. This case is a rare example of FVPTC arising within a toxic nodule. |
pmc-6150765-1 | A 24-year-old female patient presented to the otolaryngology clinic with a six-month history of progressive hoarseness of voice. In addition, she has a recent history of mild dyspnea on exertion and dry cough. The patient did not have any weight loss nor dysphagia. The patient was a cigarette smoker of around one pack per day for five years. There was no past family history of cancer, and she did not have any medical illness of significance. The patient also did not have any prior history of radiotherapy. In the clinic, fiberoptic nasoendoscopy showed a right vocal fold mass reaching the anterior commissure. The vocal fold mobility was normal. The neck examination was unremarkable. Our clinical impression, at this stage, was that the patient had early glottic laryngeal cancer. Consequently, the patient had a computed tomography (CT) scan showing the mass with no cervical lymphadenopathy (Figure ).
The vocal fold mobility was normal. The neck examination was unremarkable. The patient underwent a laryngotracheoscopy under general anesthetic, with a biopsy taken from the lesion, which appeared to be arising from the right vocal fold without a subglottic extension. The initial histopathology report confirmed sarcomatoid carcinoma and subsequent immunohistochemistry was positive for epithelial membrane antigens (EMA), cytokeratin CK 5/6, and cytokeratin AE1/AE3AE 1/3 (Figures -).
The patient’s spindle cell (sarcomatoid) carcinoma stage was T2N0M0 according to the AJCC cancer staging system for laryngeal carcinomas. The options for management were evaluated by the head and neck multidisciplinary team, who preferred a transoral surgical excision as a modality of treatment. We discussed the treatment options with the patient, who refused surgical intervention. Consequently, she received intensity-modulated radiotherapy (IMRT). The patient had followed up at a six-month interval, and she remains free of the disease (Figure ). |
pmc-6150766-1 | A 60-year-old Caucasian male known to have a bicuspid aortic valve was admitted with a three-day history of cough, altered mental status, and left upper extremity weakness. He did not have any other significant medical or surgical history. At presentation, he was confused and afebrile. His Glasgow Coma Scale (GCS) score was 8/15 (E2V2M4), blood pressure was 124/70 mm Hg, respiratory rate was 22 breaths/min, and oxygen saturation was 86% at room air. He was intubated for airway protection and respiratory support. Cardiac auscultation revealed 3/6 systolic murmur in the right second intercostal space, whereas lung auscultation revealed left lower zone crepitation. The abdominal examination was normal; he did not have any scars to suggest splenectomy. A complete neurologic assessment was not feasible, as the patient was intubated.
The initial laboratory investigations showed a white blood cell count (WBC) of 14.7 K/UL (reference range, 4.0 to 11.0 k/UL) with 90.9% neutrophils, and the platelet count was 34 k/UL (reference range 145-400 k/UL). His erythrocyte sedimentation rate (ESR) was 71 (reference range, 0-22 mm/hr for men). Blood cultures collected before the initiation of antibiotics grew Streptococcus pneumoniae, which was sensitive to ceftriaxone and penicillin. His urine was positive for the Streptococcus pneumoniae antigen.
A chest radiograph and computerized tomography (CT) scan of the head done on admission demonstrated areas of consolidation over his left lower zone and the dilation of the lateral and third ventricles, respectively (Figure ).
Treatment for bacterial meningitis was initiated with intravenous (IV) ceftriaxone, ampicillin, and dexamethasone empirically. Lumbar puncture was deferred due to the high risk of brain stem herniation secondary to hydrocephalus noted on head CT and high bleeding risk due to thrombocytopenia (platelet count 34 k/UL). On day two of admission, magnetic resonance imaging (MRI) of the brain revealed scattered bilateral cerebral punctate infarcts suggestive of septic emboli along with hydrocephalus (Figure ). A transesophageal echocardiogram (TEE) revealed caseous calcification of the bicuspid aortic valve and fusion of valve commissures with no vegetation.
Over the course of hospitalization, his condition improved. Antibiotics were de-escalated. On day five of admission, he was successfully extubated. He remained cognitively impaired, which improved gradually.
On day nine of admission, he started complaining of right shoulder pain and had an elevation of leukocyte count (17.2 K/UL) with low-grade fever (99.9F). He underwent right shoulder arthroscopy and debridement for right shoulder septic arthritis. Gram staining of the synovial fluid showed few polymorphs, and the culture was negative. He was subsequently discharged home on a six-week course of IV ceftriaxone 2 g every 24 hours and a plan to get an aortic valve replacement.
Eight weeks after his initial presentation, he had a persistently elevated leukocyte count despite adequate medical management, prompting a treating physician to repeat the echocardiogram. A TEE was performed and documented aortic valve vegetations. Urgent cardiac surgery was performed.
Intraoperative findings include severe pericarditis, a bicuspid aortic valve, and multiple vegetations on the aortic valve leaflet, a 3x3 cm aortic root abscess, and an approximately 10x10 cm retro aortic abscess. He underwent a debridement of the retro-aortic abscess, pericardial patch repair, and aortic valve replacement. A valvular gram stain showed a few polymorphs and negative cultures.
He remained stable in the postoperative period and was subsequently discharged on intravenous penicillin to complete a course for another six weeks.
On a follow-up two months after discharge home, he remained stable with no significant anatomic or functional heart abnormalities and no neurological deficits. |
pmc-6150767-1 | A 70-year-old African American male was seen in the emergency department for acute anxiety and paranoia. He reported that his son gave him melatonin to help him sleep, but he felt the medication was poisonous. He also reported that he was struggling with the death of his partner of 40 years and was feeling anxious. The patient was prescribed risperidone and lorazepam and was discharged shortly thereafter. Twenty-four hours later, he was seen again in the emergency department for worsening anxiety, psychosis, suicidal ideation, and command hallucinations. The patient's son reported that his father “had not slept in weeks.” The son reported progressive agitation, paranoia, and bizarre behavior. Due to the worsening psychosis, he was admitted to the medical floor for further work-up. He reported feeling as though people were watching him and that someone was going to harm him. When questioned about his reported suicidal ideation, he blamed that thought on his post-traumatic stress disorder; but would not elaborate on the event. The patient was given a one-to-one sitter due to his suicidal ideation.
This patient lives with his family of seven children. He has a history of prolonged incarceration. His past medical history is significant for hypertension and negative for seizure disorders. The patient had never been hospitalized for psychiatric issues prior to this visit. He denied past suicidal behavior and any history of physically or sexually aggressive behavior. The patient reported a history of excessive alcohol abuse for more than a year following the death of his partner. He reported that he stopped drinking “cold turkey” five months prior to this visit. The patient's family history is significant for a son with an anxiety disorder. He denied a history of physical or sexual abuse in the past.
The patient's mental status exam was significant for an anxious affect with referential and paranoid ideations. He denied any thought broadcasting, insertion, or withdrawal. He had some paranoid and persecutory delusions. Insight, judgment, and impulse control were poor.
The patient's initial physical exam revealed an inability to ambulate and overall weakness. Further neurological examination revealed mental disorientation with bilateral muscle wasting, sensory deficit, and hyporeflexive ankles. Additionally, the patient exhibited stance and gait abnormalities. A later eye exam revealed bilateral light-near dissociation with accommodation but no reaction to light. Otherwise, all other neurological components were intact and within normal limits.
Initial routine testing was positive for the Treponema pallidum antibody, suggesting prior infection, but the distinction between treated and untreated syphilis cannot be made as the Treponemal-specific immunoglobulin G (IgG) may remain elevated throughout life. An RPR was then ordered to help distinguish between acute or chronic infection and a Treponema pallidum particle agglutination test was ordered to distinguish between syphilis infection and a false positive screening test. The RPR returned nonreactive but the Treponema pallidum particle agglutination returned reactive, indicating a prior infection of Treponema pallidum. The initial differential diagnosis workup included testing to exclude thiamine, folate and B12 deficiency, insomnia, hypocalcemia, hypothyroidism/hyperthyroidism, HIV encephalopathy, dementia, stroke, drug or alcohol intoxication, and normal pressure hydrocephalus.
Further labs showed white blood cell count, sodium, potassium, calcium, anion gap, creatinine, glomerular filtration rate, glucose, mean corpuscular volume, and thyroid stimulating hormone within normal limits. Urinalysis, toxicology screening, alcohol levels, and HIV antibody were also negative. Imaging included a head computed tomography (CT), which showed no abnormalities, a brain magnetic resonance imaging (MRI) that showed cortical atrophy, and an electroencephalogram within normal limits. |
pmc-6150771-1 | A 60-year-old male patient presented to the dermatology outpatient department (OPD) with a two-month history of diffuse facial erythema, itching, and burning sensation. Raised skin lesions were noted on the forehead, nose, and left cheek. He also complained about the exacerbation of lesions upon exposure to the sun. On dermatological examination, well-defined annular erythematous lesions over the forehead, with a sharp margin and a raised edge, and scaly plaques with papular to papulopustular lesions involving both the eyebrows, the nose, and the left cheek were revealed, as shown in Figure .
The patient gave a history of myocardial infarction and cardiac surgery and was on antidiabetic and antihypertensive drugs. He gave a history of sharing linen and admitted to the habit of sleeping outside the house in the open air during the summer season. The patient also informed about a rodent infestation in his immediate surroundings and frequent animal contact. A history of previous nail infection on the right great toe, which was otherwise normal upon examination, was noted. No other concomitant infections were observed. The patient denied any application of topical corticosteroids or any self-medication. An intramuscular injection of dexamethasone was given 10 days before by a local practitioner, which gave temporary relief from erythema and tingling.
Processing of the specimen for a mycological/microbiological examination
Skin scrapings were taken under aseptic precautions from the extending and raised margins of the lesion on the forehead. Potassium hydroxide preparations revealed more than five Demodex folliculorum mites measuring ~ 0.3-04 mm in a scraping of 1 cm2 area along with a moderate number of hyaline septate hyphae, with a few hyphae breaking into chains of arthroconidia under 40X magnification of the microscope.
The mite was semitransparent, with an elongated body formed by two fused segments. The first segment had four pairs of legs and a hairless and colorless body surface. The second or posterior segment had secondary striations. The longer posterior segment at the opisthosomal end was round, differentiating it from D. brevis, which has a short and pointed opisthosomal end, as shown in Figure [].
Repeated slit skin smear examinations were negative for acid-fast bacilli. A diagnosis of Pityriasis folliculorum with concomitant dermatophytosis (Tinea faciei) was made.
The specimen was later inoculated on a dermatophyte test medium (DTM) agar base with a dermato supplement and Sabouraud’s dextrose agar (SDA) with 50 mg chloramphenicol and 0.05% cycloheximide (HiMedia, India) and incubated in ambient air at 28°C (Biological Oxygen Demand/Biochemical Oxygen Demand (BOD) incubator).
Growth started to appear after five days of incubation, which was later subcultured on to potato dextrose agar (PDA).
Routine slide culture, microplate culture, and adhesive tape preparations for the phenotypic identification of the dermatophyte fungus along with a urease test and a hair perforation test were performed.
Phenotypic identification and morphological description of T. mentagrophytes
The surface texture of the colonies on DTM agar base initially showed downy, later turning into pleomorphic and powdery, growth with a flat surface after two weeks of further incubation. When subcultured on to PDA, a pale brown to buff or yellow surface producing a characteristic stellate powdery surface growth was observed after two weeks of incubation. The reverse showed a dark red pigment rather than the usual light yellow or brown-tan color. When grown on cornmeal agar (CMA), there was no reverse pigment.
Macroconidia were demonstrated only in the early colonies grown on the DTM agar base and PDA, which were noted to be thin, smooth-walled and cigar-shaped, with a few of them bearing narrow attachments to the vegetative hyphae. Microconidia were spherical to pyriform and arranged in grape-like clusters.
Older cultures exhibited pleomorphism with antler-like hyphae and peridial hyphae with the terminal branches bearing two or three cells with an abundance of spiral hyphae, as shown in Figure .
The isolate was positive for the urease and hair perforation tests and was phenotypically confirmed as T. mentagrophytes. Due to its variable morphological and cultural attributes, the isolate was submitted for confirmation and antifungal susceptibility data to the national reference centre, National Culture Collection of Pathogenic Fungi (NCCPF), an Indian Council of Medical Research (ICMR), New Delhi, sponsored center at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Confirmation of Trichophyton interdigitale by molecular identification
Molecular identification of the culture with submission identification (ID) nccpf IL-2878 was performed at the national reference center by amplifying the DNA and sequencing the internal transcribed spacer (ITS) region of rDNA using the ITS1 and ITS2 primers. T.interdigitale was confirmed by comparing the sequence in Centraalbureau voor Schimmelcultures (CBS), Utrecht, The Netherlands, the Dermatophytes database [], and the National Center for Biotechnology Information (NCBI) GenBank database, respectively, which showed a 99.61% similarity with the type strain CBS 130940 T.interdigitale.
GenBank direct submission and accession ID: The T.interdigitale ITS sequence was deposited in GenBank ITS databases and published in the NCBI database on 16/5/2018 with accession number MH327513 and name T.interdigitale - IL2878/333.
Antifungal susceptibility testing
Antifungal susceptibility testing (AFST) was performed following the Clinical Laboratory Standards Institute (CLSI) guidelines (M38-A2). The broth microdilution (BMD) method was used to determine the minimum inhibitory concentrations (MICs) of the test isolate against various antifungal drugs, which included itraconazole, sertaconazole, terbinafine, griseofulvin, and amorolfine. All the antifungal drug powders were reagent grade and were procured directly from Sigma Aldrich (Missouri, United States) by PGIMER/NCCPF, Chandigarh, India. RPMI-1640 (HiMedia, India) with L-glutamine, without bicarbonate, buffered at pH 7.0 with 0.165 M morpholine propane sulfonic acid (MOPS buffer) was used for inoculum preparation and to perform broth microdilutions. All the antifungal powders tested were dissolved in dimethyl sulphoxide (DMSO). Three quality control strains, including Candida parapsilosis American Type Culture Collection (ATCC) 22019, Candida krusei ATCC 6258, and Aspergillus flavus ATCC 204304 were included. Inoculum suspension and dilutions were performed as described by Adimi et al. []. Endpoint determination and interpretation of MICs was done according to CLSI M38-A2 and from the recent AFST studies [-].
The results of the antifungal susceptibility testing of five antifungal agents are shown in Table .
Antifungal and acaricide therapy
The patient was treated with oral terbinafine 500 mg once daily for four weeks. Combination topical therapy involving a cleanser containing selenium sulfide 2.5% lotion followed by the application of 2% sertaconazole twice daily and 1% metronidazole gel for three weeks was initiated. The patient had an uneventful recovery. |
pmc-6150772-1 | A 40-year-old man with a history of end-stage renal disease on hemodialysis, hypertensive cardiomyopathy, and poorly controlled hypertension presented to the emergency department with a sudden onset of 48-hour right visual blurring and headache. On physical examination, he was alert, oriented to time, place and person, with a blood pressure of 200/124 mmHg, and a heart rate of 88 beats/minute. Neurologic examination was only significant for decreased right visual acuity. The electrocardiogram revealed normal sinus rhythm.
Computed tomography of the head revealed focal area of hypoattenuation in the left cerebellar hemisphere (Figure ).
Magnetic resonance imaging of the brain revealed multiple new regions of restricted diffusion within the left frontal, parietal and occipital lobes, consistent with an embolic stroke (Figure ).
A carotid duplex ultrasound was unremarkable for carotid artery stenosis. A two-dimensional transthoracic echocardiography revealed a large calcified mass measuring 24.5 mm x 16.0 mm (Figure , asterisks; Video ).
A three-dimensional transesophageal echocardiogram of the mitral valve revealed two discrete nonmobile calcified masses, with central areas of echolucency consistent with CCMA (Figure , asterisks; Video ).
As no other potential sources of embolism were identified, CCMA lesion was postulated as the possible source of embolism. Dual antiplatelet therapy (aspirin 81 mg daily and clopidogrel 75 mg daily) and high-intensity atorvastatin 80 mg daily were initiated. Surgical excision of the CCMA lesion was considered but not performed immediately due to the potential risk of hemorrhagic conversion of the ischemic stroke. |
pmc-6150885-1 | A 38-year-old gravida 1 para 0010 female presented with infertility of 15 years duration. The patient was initially referred 9 years earlier by her gynecologist and underwent a laparoscopy and hysteroscopy with findings of stage I endometriosis, patent right fallopian tube, and intrauterine synechia. The patient’s obstetrical history was significant for a left cornual ectopic pregnancy, for which she underwent an exploratory laparotomy with left cornual resection 16 years ago. She had irregular menses since menarche at age 13 years old and typically has spotting for about 5 days every other month. The patient had no allergies and was not on any medications. On initial evaluation, she underwent a transvaginal ultrasound which was significant for a 7 × 5 cm solid homogeneous appearing ovoid mass of her left ovary, which was suspicious for a granulosa cell tumor. The patient had an elevated baseline AMH of 14.3 and normal CA-125 of 13. Referral to Gynecology Oncology resulted in a laparoscopic left salpingo-oophorectomy and lysis of adhesions without complications. Surgical pathology revealed a granulosa cell tumor. Post-operatively, repeat AMH fell to 0.64 ng/mL, and inhibin B to 14 pg/mL. Six months later, the patient underwent ovarian stimulation for IVF and conceived an intra-uterine pregnancy, which unfortunately ended in a first trimester loss. Further infertility treatment is ongoing. |
pmc-6150971-1 | A 33-year-old female nonsmoker with a 4-month history of intermittent chest pain and dyspnea at rest, which recurred every 2 weeks, was admitted to our hospital at 31 weeks of gestation. Four months ago, she had been admitted after experiencing these symptoms for the first time. A chest radiograph at that time revealed left hydropneumothorax with 90% lung compression. The patient received closed chest tube drainage (CTD). However, left pneumothorax recurred during rest or minimal activity in the 20th, 25th, 28th, and 30th weeks of gestation. For every recurrent episode, she was admitted to a local hospital, where she received CTD and was discharged only after radiographic confirmation that the pneumothorax had completely resolved. At the current admission, arterial blood gas analysis indicated type I respiratory failure with a partial pressure of oxygen (PaO2) of 51 mmHg. The patient was treated with supplemental oxygen and continuous CTD. Between the 31st and 32nd weeks of gestation, abdominal ultrasound revealed that the umbilical cord was twisted around the neck of the fetus. At 33rd weeks, the patient underwent a cesarean section and successfully delivered a baby with a low birth weight of 1720 g and normal Apgar scores. High-resolution computed tomography (HRCT) revealed small, thin-walled cystic lesions diffused throughout all lung fields. The serum level of vascular endothelial growth factor-D (VEGF-D) was 6608 pg/ml. The patient was diagnosed with LAM, and she began treatment at a dose of 2 mg/day from 28 days after delivery. At 18 months after treatment initiation, the patient’s exercise capacity and quality of life exhibited considerable improvement, and she was able to resume work. She was followed up for 3 years and had not experienced recurrent pneumothorax at the time of writing this report. She could perform all daily activities, including jogging, housekeeping, and routine work. The only sirolimus-associated adverse effect was mucositis, which gradually ameliorated and resolved with time during the course of sirolimus treatment. A follow-up pulmonary function test (PFT) revealed a forced vital capacity (FVC) of 2.20 l (75.3% predicted), FEV1 of 1.85 l (66.3% predicted), and an FEV1/FVC ratio of 84.1% (100% predicted). Moreover, she could cover a distance of 480 m in a 6-min walk test (6MWT). Her baby showed normal growth and remained healthy without breast milk.
A 23-year-old female nonsmoker was admitted to our hospital with 6 days of dyspnea. The chest radiograph revealed bilateral hydropneumothoraces (50% and 80% compression in the left and right lungs, respectively). Two months ago, a large intraperitoneal mass had been detected during prenatal examination, and the patient underwent laparatomy with abdominal mass resection and left nephrectomy. Postoperative pathological examination with hematoxylin and eosin (H&E) staining demonstrated that the renal mass consisted of malformed blood vessels, fusiform smooth muscle bundles, and adipose tissue. Immunohistochemical staining revealed positive expression of human melanoma black 45 (HMB45), smooth muscle actin (SMA), and cluster of differentiation 34 (CD34). She underwent bilateral CTD and when her lungs markedly re-expanded, chest HRCT was performed and revealed multiple, diffuse, round, thin-walled cysts in both lungs. TSC gene mutation was not seen. The patient opted for a conservative management strategy with observation and intermittent supplemental oxygen administration after complete resolution of the pneumothorax. However, 4 months later, the patient developed left followed by right pneumothorax. She was hospitalized for over 30 days, and after complete resolution of the pneumothoraces, she began sirolimus treatment. The plasma sirolimus level was maintained at 4–5 ng/ml in repeated measurements. The patient was followed for > 1 year without pneumothorax recurrence, and she could perform all types of ordinary exercises, including running, mountain climbing, cycling, housekeeping, and other outdoor activities. The only sirolimus-associated adverse effect was a mildly intermittent menstruation disorder. A follow-up PFT revealed an FVC of 2.08 l (61% predicted), an FEV1 of 2.04 l (70% predicted), an FEV1/FVC ratio of 98% (87% predicted), a diffusing capacity for carbon monoxide (DLCO) of 4.70 mmol/kPa/min (75% predicted), and a total lung capacity of 3.13 l (68% predicted). She could cover a distance of 550 m in 6MWT. However, the patient discontinued sirolimus after 1.5 years without seeking advice from her physicians because she was planning to conceive for the second time. Three months later, she presented with left chest pain and an uncomfortable feeling in her chest on movement. She received supplemental oxygen support at home for 5 days, following which a chest radiograph revealed left pneumothorax with 30% lung compression. Over the next 2 months, she experienced two episodes of right pneumothorax. She was hospitalized again and remained unable to work or perform regular activities.
A 31-year-old female nonsmoker presented with chest pain and dyspnea at rest. Chest HRCT revealed right pneumothorax with 90% lung compression and multiple bilateral pulmonary bullae. The patient received CTD and oxygen supplementation, followed by bullectomy in the right upper lung lobe. Postoperative H&E staining of lung tissue revealed small spindle-shaped cells distributed alongside bronchioles, blood vessels, and lymph vessels. Immunohistochemical staining demonstrated positive expression of HMB45, SMA, estrogen receptor (ER; 80%), and progesterone receptor (PR; 80%). Considering her age and the fact that it was her first episode of pneumothorax, sirolimus therapy was not initiated. During the following 6 months, the patient presented with unilateral pneumothorax with 30% lung compression and was unable to resume work, and she expressed concern about the recurrence. Nine months later, she was readmitted with bilateral pneumothoraces (compression of the right and left lungs: 95% and 70%, respectively). She successively received supplemental oxygen support, CTD, and left chemical pleurodesis with 50 ml high-sugar + 5-ml lidocaine infusion and autologous blood for sclerification. Eventually, the chest tube was successfully removed, and the patient opted to begin sirolimus treatment at 2 mg/day. Follow-up plasma sirolimus levels ranged from 6 to 10 ng/ml. At the time of writing this report, the patient had been followed up for 2.5 years without recurrence, had resumed her job, and was able to perform ordinary exercises, including jogging, running, mountain climbing, and badminton. A follow-up PFT revealed an FVC of 2.24 l (72.7% predicted), FEV1 of 2.23 l (73.6% predicted), and FEV1/FVC ratio of 99% (118% predicted), and she could cover a distance of 555 m in 6MWT.
A 38-year-old female nonsmoker with an 8-year history of recurrent dyspnea and hemoptysis, which had been aggravated since a week, was admitted to our hospital. She had experienced right chest pain and mild dyspnea following a sneeze 8 years ago, and chest radiography at that time confirmed right pneumothorax. Chest HRCT revealed bilateral, diffuse, round, thin-walled cysts with varying sizes. She was clinically diagnosed with tuberculosis and received anti-tuberculosis therapy for 6 months. Two years later, the patient underwent pleurodesis under video-assisted thoracoscopic surgery (VATS) because of recurrent pnuemothoraces and for further evaluation of the thin-walled cystic lesions. Postoperative pathological examination of lung tissue revealed the characteristics of pulmonary LAM. Immunohistochemical examination demonstrated positive expression of HMB45, SMA, ER, and PR. Over the next 3 years, she experienced recurrent pneumothorax, mainly in the right lung. At the current admission, the chest radiograph revealed right pneumothorax with 60% lung compression. Two days later, the patient exhibited severe dyspnea with cyanotic lips and nails, and unconsciousness. Arterial blood gas analysis revealed type I respiratory failure with a PaO2 of 45.5 mmHg, while a chest radiograph showed massive bilateral pneumothoraces. On resolution of the pneumothoraces, the patient opted to begin sirolimus treatment at 2 mg/day. She was diagnosed with recurrent tuberculosis at the same time, and anti-tuberculosis therapy was also initiated. The plasma sirolimus level was 3.9 ng/ml. Following anti-tuberculosis treatment for 1 year, her respiratory symptoms completely resolved, and the treatment was discontinued. One month later, she presented with swollen, painful ankles and fingers. The plasma sirolimus level at that time was > 15 ng/ml. The findings of rheumatological and immunological examinations were unremarkable. The ankle and finger pain was considered a side effect of sirolimus treatment; therefore, the dose was reduced to 1 mg/day. The ankle pain resolved; however, the patient developed slight fever, and clinical examinations revealed that the tuberculosis had relapsed. Accordingly, anti-tuberculosis therapy was restarted. Four months later, she experienced recurrent dyspnea and right pneumothorax; the plasma sirolimus level was 0.01 ng/ml. The sirolimus dose was increased to 2 mg/day, and she additionally received supplemental oxygen support. Two months later, the plasma sirolimus level was 2.97 ng/ml, and a chest radiograph revealed complete resolution of the pneumothorax. Sirolimus-associated side effects included mild mucositis, joint pain, and menoxenia. At the time of writing this report, the patient had been followed up for > 3 years, with gradually improved respiratory symptoms. She exhibited an improved quality of life and was able to perform daily activities such as housework, jogging, cycling, and mountain climbing. A follow-up PFT revealed an FVC of 3.39 l (120.2% predicted), FEV1 of 2.38 l (90.5% predicted), and FEV1/FVC ratio of 70.2% (86.2% predicted). The distance covered in 6MWT was 510 m.
A 30-year-old female smoker presented with a 3-year history of recurrent pneumothorax, chest pain, and dyspnea on exercise. Chest CT obtained after the first episode of pneumothorax 3 years ago revealed left pneumothorax with 50% lung compression and bilateral, multiple, thin-walled pulmonary cysts. The patient underwent left pulmonary bullectomy and intrapleural fixation. However, the patient still experienced frequent left or right pneumothorax at rest or on minimal activity, although it showed spontaneous resolution. A year ago, the patient was admitted to a local hospital with severe pain in the right chest and dyspnea. A chest radiograph revealed right pneumothorax with 30% lung compression. She also developed recurrent lower abdominal pain accompanied by nausea and vomiting. Abdominal magnetic resonance imaging revealed multiple retroperitoneal cystic masses (15.6 × 20.2 cm), a cystic mass at the right uterine attachment (6.2 × 3.6 × 7.0 cm). She underwent retroperitoneal tumor resection, and postoperative pathological examination of the retroperitoneal mass revealed a large number of spindle-shaped cells distributed alongside blood vessels and lymph vessels. The cells showed no obvious heterotypic features, necrosis, and mitosis. Immunohistochemical examination demonstrated positive expression of SMA, HMB45, ER, PR, and D2–40. The serum VEGF-D level was 2685.88 pg/ml. Considering the possibility of recurrent pneumothorax, the patient agreed to begin sirolimus therapy at 1 mg/day. At the time of writing this report, the patient had been followed up for 5 months without recurrent pneumothorax or abdominal pain. A follow-up PFT revealed an FVC of 3.12 l (93.6% predicted), an FEV1 of 2.35 l (81.4% predicted), an FEV1/FVC ratio of 75.54% (84.06% predicted), a DLCO of 5.35 mmol/kPa/min (61.4% predicted), and a total lung capacity of 4.31 l (93% predicted). The plasma sirolimus levels in the first and third months of treatment were 5.28 and 7.25 ng/ml, respectively. The distance covered in 6MWT was 480 m. Mild mucositis was the only sirolimus-associated adverse effect. |
pmc-6151028-1 | The second case was a 41-years-old female with a WHO°II diffuse Astrocytoma (IDHmt, no LOH 1p19q, mMGMT) that underwent gross total resection (GTR) and also was in an excellent physical status (KPS 90%). This case represents a high-risk Astrocytoma situation based on the inclusion criteria of the RTOG 9802 trial []. |
pmc-6151028-2 | The third case was a 31-year-old female with a WHO°II diffuse Astrocytoma without IDH1 mutation, without LOH 1p19q, and without MGMT promoter hypermethylation. The patient underwent GTR and was in an acceptable physical Status (KPS 80%), yet there was some minor hemiparesis present after surgery. According to the RTOG 9802 inclusion criteria, this is a low-risk-case []. However, the molecular pattern of the tumor reflects a high-risk situation with a prognosis that is closer to Anaplastic Astrocytoma or even Glioblastoma [, , ].
The questionnaire was piloted by members of the departments of radiation oncology, neurology, and neurosurgery and reviewed by all authors for understandability. An ethical vote was not necessary, as there were no clinical data included and the survey is a pattern of care analysis.
The survey was generated as an online-based questionnaire at and invitations for the survey were send by e-mail to all 326 Members of the “Neuroonkologische Arbeitsgruppe” (neurooncological working group, NOA) of the “Deutsche Krebsgesellschaft” (German Cancer Society, DKG) as well as to all German Speaking Members of the European Low Grade Glioma Network (22 persons). The survey was open from December 12th, 2016 to January 30th, 2017.
We counted 150 visits resulting in 38 completed surveys. 35/38 responders worked at tertiary care hospitals, and the remaining three responders worked at major regional hospitals (Fig. , left panel). Most responders worked in high-volume centers with > 10 LGG cases per year (15/38; 39,5%), > 20 LGG cases per year (9/38, 23.7%) or > 30 LGG-Cases per year (4/38, 10.5%). These numbers were educated guesses in 23 cases (60.5%) and numbers from a database in 12 cases (31.6%). The departments employed 23.5 physicians (median). Only specialists in their field answered the questionnaire, all (100%) of them answered that interdisciplinary oncologic boards provide treatment recommendations at their centers. 2/38 (5.3%) were specialists, 18/38 (47.4%) attending physicians, 10/38 (26.3%) senior consultants and 8/38 (21.1%) chairmen (Fig. , middle panel).
The majority of the responders were neurosurgeons (18/38, 47.4%), followed by neurologists (12/38, 31.6%), radiation oncologist (6/38, 15.8%) and medical oncologists (2/38, 5.3%) (Fig. , right panel).
The dataset is not representative of the members of the NOA. However, e-mail-communications by several of the responders suggest that in the majority of centers, only one person per center responded to the survey.
We asked for the technical abilities of the centers concerning imaging and radiation therapy. MRI with advanced sequences (Diffusion Weighted Images (DWI), Perfusion Imaging, Diffusion Tensor Imaging, etc.) was available at all centers. Positron Emission Tomography combined with computed tomography (PET-CT) or MRI (PET-MRI) were available at 86.8% and 21.1%, respectively. 25 responders gave answers for radiation oncology devices, one person did not answer this question at all, and 12 patients responded not to be able to answer this question. The majority of the remaining responders reported about providing advanced radiation oncology techniques, comprising 22/25 (88%) with intensity modulated radiotherapy (IMRT), 12/25 (48%) with image-guided radiotherapy (IGRT), 13/25 (52%) with frame-guided stereotaxia, 17/25 (68%) with frameless stereotaxia, 5/25 (20%) with MRI-Linear accelerators and 4/25 (16%) with particle therapy.
We then asked, which imaging as well as which radiation techniques are used for the target definition and treatment of LGGs. 13/38 responders stated not to be able to answer the question about the imaging used for treatment planning. From the remaining 25, MRI was used in all cases, PET-CT in 6/25 (24%), PET-MRI in two cases and SPECT in 1 case. Advanced MRI techniques, such as spectroscopy (3/25, 12%) and advanced sequences, such as DWI or Perfusion images were used by 8/25 (32%). 23 responders answered the question about the radiation techniques used for LGG patients. The majority used at least 3D conformal radiotherapy (20/23; 87%), 13 (57%) used IMRT or 3D-conformal techniques, and 2 (9%) used at least IMRT. One center stated to apply only frameless stereotaxia for the treatment of LGG patients. Particles were available in the centers of 4 responders; however, patients were either treated with photons or with particles in these centers. The centers mostly prescribed a dose of 54 Gy (median, range 50,4–60 Gy) in single doses of 2,0 Gy (median, range 1,7–2,7 Gy) centers.
The responders follow up their patient by MRI every three months (median, range 3–6 months) for two years (median, range 1–5 years), after that the imaging interval is prolonged.
All responders answered the questions to the 3 cases. In case 1 (Fig. ), 61% would recommend radiotherapy followed by six cycles of PCV (RTOG 9802 regimen), 13% a radiochemotherapy with concomitant and adjuvant Temozolomide (TMZ-RCT). 10% would recommend monotherapy with either chemotherapy or temozolomide (TMZ). Further 11% would recommend a wait-and-scan policy. Asked for the treatment recommendation that would have been given in 2015 (i.e., before publication of the final results from RTOG 9802), only 31% would have recommended an RTOG 9802 regimen, but the majority of participants would have supported a mono-therapy with either chemotherapy or radiotherapy. A wait-and-scan policy was prescribed in 24% in 2015. In total, 14/18 (37%) reported that their treatment regimen was different in 2015 as compared to the end of 2016.
In case 2 (Fig. ), the recommended treatment in 2016 was wait-and-scan by 41% as compared to 58% in 2015. The RTOG 9802 regimen was recommended in 19% in 2016 as compared to 16% in 2015. A TMZ-RCT was recommended in 16% in 2016 as compared to 5% in 2015. Monotherapies were recommended in 13% in 2016 as compared to 18% in 2015. The recommendation differed from 2015 in 7/38 participants (18%). |
pmc-6151035-1 | The authors report two Moroccan cases of dermoscopy in skin metastasis of breast cancer with two different clinical presentations; the dermoscopic examination was performed using a Dermatoscope Delta® 20 (Heine; Herrsching, Germany) with polarized light and without immersion.
Case 1 was a 51-year-old Moroccan woman diagnosed as having infiltrating ductal carcinoma of the left breast. Case 2 was a 65-year-old Moroccan woman diagnosed as having infiltrating ductal carcinoma of the right breast. They underwent mastectomy and axillary node dissection followed with adjuvant hormone and chemotherapy. After a remission period of 14 months (Case 1) and 10 months (Case 2), they were referred to our hospital for painful lesions on the surface of their trunk, chest, and back.
For Case 1, a physical examination revealed irregularly distributed pink nodules of various sizes with a large firm, indurated skin on and around the mastectomy scar of her left chest (Fig. ). For Case 2, a physical examination revealed a diffuse well-demarcated erythema and edematous cellulitis-like skin on the right side of her chest wall and her back, with a central ulceration on her abdominal wall (Fig. ) and palpable lymphadenopathy in her bilateral anterior cervical and supraclavicular chains. Dermoscopic examination of the two cases revealed a pink-orange background, yellow central areas, linear irregular and polymorphic vessels, whitish bright lines, whitish structureless areas, and linear irregular fissure-like depressions. A recurrence of ductal carcinoma was confirmed with skin biopsies, and the patients were referred to the oncology department for further investigations and appropriate management (Figs. and ). |
pmc-6151044-1 | A 21-year-old man complained of transient muscle stiffness since 10 years. He experienced difficulty in initiating movement and felt muscle weakness after rest. However the symptoms typically improved after repeated contraction (warm-up phenomenon). The symptoms tended to aggravate during cold weather. He was unable to open his eyes immediately after washing his face with cold water. He had non-consanguineous parents and there was no significant family history. Further, the patient showed normal growth and development. Medical examination showed generalized muscle hypertrophy and normal muscle strength as assessed with the Medical Research Council (MRC) sum score. Deep tendon reflexes were attenuated. No nerve dysfunction or sensory deficit was noted. The serum creatine kinase level was 2-fold higher than the upper limit of the normal reference level. Electromyogram showed myotonic discharges. Biceps muscle biopsy specimen was obtained after written informed consent of the patient. The specimen was precooled with isopentane and frozen in liquid nitrogen. A section of muscle biopsy specimen was stained with hematoxylin-eosin (HE) and modified Gomori’s trichrome (MGT). Activity of oxidative enzymes such as succinate dehydrogenase (SDH), NADH-tetrazolium reductase (NADH-TR), and cytochrome c oxidase (COX) were normal. Next generation sequencing of the DNA sample of this patient identified a novel splice mutation (c.1401 + 1G > A) (which was inherited from his father) and a known mutation (c.1657A > T, p.Ile553Phe) (which was inherited from his mother) (Fig. ). The novel splice mutation was not detected in Human Gene Mutation Database or any of the 200 healthy controls. The splicing site, analyzed by Human Splicing Finder, is implicated in the alteration of the wild-type donor site and most probably have an impact on splicing. Mutation Taster software predicted the effects of the mutation to be ‘disease causing’. The patient was prescribed mexiletine 100 mg three times per day for about 6 months. The patient responded well to the treatment and was completely relieved of his symptoms. |
pmc-6151052-1 | A 3-year-old boy presented to our hospital with a 3-month history of foamy urine. He was born at gestational age of 36 weeks 6 days to a young couple with no history of consanguinity. Prior history was significant for decreased amniotic fluid volume, which was detected since gestational age of 5 months. According to the mother, fetal ultrasonography at that time was suggestive of renal malformation without exact details. Otherwise, he had been free of any significant illnesses including hepatitis B, tuberculosis, IgA vasculitis or systemic lupus erythematosus. His father had been diagnosed with “nephritis and kidney failure” at the age of 20 and had an allograft kidney transplantation for 10 years. Upon presentation, his vital signs and physical examinations, including eye examinations, were normal. The results of relevant investigations were depicted in Table . In summary, he had proteinuria, elevated levels of BUN and creatinine, hyperparathyroidism, acidosis and bilateral renal atrophy. Genetic study showed a heterozygous mutation in the PAX2 gene. Further studies on the family showed that the patient inherited the mutated gene from his father although no similar mutation was detected in paternal grandparents. The pedigree was shown in Fig. and the gene mappings were shown in Fig. .
The child was managed medically by correcting the metabolic derangements secondary to chronic kidney diseases and by monitoring the progress. At last follow up at 1 year, all his initial metabolic changes normalized and his GFR did not deteriorate. |
pmc-6151189-1 | A 48-year-old Caucasian man was admitted to our emergency ward. His medical history included an episode of depression and some disabilities in reading and writing. From the age of 1 to 8 years, he had recurrent episodes of seizures associated with vomiting and loss of unconsciousness, which had been interpreted as febrile seizures. Ten years earlier he was diagnosed as having a peptic ulcer of the stomach after episodes of modest gastrointestinal bleeding. He had independently excluded protein from his diet during several periods of his life.
He presented at the emergency room (ER) at 8 a.m. with complaints of headache, backache, and a sensation of pressure in his ears since the previous evening. He had felt nauseous and vomited several times during the night. Late in the night he developed altered sensorium and his wife brought him to the hospital. In the ER, he initially answered monosyllabically to questions (Glasgow Coma Scale (GCS) 11) but within 15 minutes he lost consciousness (GSC 8). He was afebrile and his circulatory/respiratory systems were stable. On neurological examination he was motorically agitated, moved all extremities, and presented slight miosis and saccadic eye movements. The Babinski sign was positive bilaterally. Routine hematological and biochemical blood tests, including blood cell counts, electrolytes, liver parameters, intoxication screening, glucose, and C-reactive protein (CRP), turned out normal. Arterial blood gases showed a lactate concentration of 2.1 mmol/L and a pH of 7.5. A computed tomography (CT) scan of his brain was normal.
During the 12 hours after admission, he was still unconscious but could breathe autonomously and was circulatory stable. A lumbar puncture revealed a slight rise in lactate (3.7 mmol/L), but no signs of infection or inflammation. An electroencephalogram (EEG) showed suspected encephalopathy with pronounced pathological activity but no focality, asymmetry, or epileptic activity. Broad-spectrum antibiotic and antiviral treatment was given despite no obvious signs of central nervous system (CNS) infection. Twelve hours after admission, he had hematemesis and due to respiratory instability he was transferred to our intensive care unit (ICU), anesthetized, and intubated. Concerns regarding a possible inflammatory lesion in his CNS led to administration of betamethasone. Acute magnetic resonance imaging (MRI), including in-flow angiography, phase-contrast angiography, and diffusion series, was normal.
The following morning, 24 hours after admission, the cause of unconsciousness was still unclear. The contribution by the relatives of our patient here became essential. His sister called for attention regarding her suspicion that her brother might suffer from a UCD. She explained that the relatives had discussed the possibility that her brother might be suffering from a congenital neurological disorder based on his seizures, cognitive difficulties, and dyslexia since childhood. Because of the acute severe illness, they made a search on a web search engine using a combination of his symptoms, which was vomiting, unconsciousness, and seizures (in Swedish, kräkningar, medvetslöshet, kramper). The web search resulted in the suspicion of OTC deficiency, which belongs to the group of UCDs. Our patient’s plasma ammonia concentration was therefore analyzed and turned out to be 213 μmol/L (reference level 11–32 μmol/L), diagnostic for a UCD in the absence of hepatic failure. Continuous renal replacement therapy (CRRT) was initiated to eliminate plasma ammonia.
Approximately 48 hours after admission, our patient became circulatory unstable. Acute gastroscopy revealed a severe upper gastrointestinal hemorrhage from a peptic ulcer of his stomach. The ulcer was treated locally through gastroscopy and he needed repeated erythrocyte and plasma transfusions (Fig. ). Heparin was suspended during CRRT. Despite this treatment, his ammonia rose to 497 μmol/L and he developed recurrent partial seizures (Fig. ). Sodium benzoate, an ammonia scavenger, was given as a bolus infusion of 250 mg/kg for 120 minutes, followed by continuous maintenance infusion of 250 mg/kg per day with addition of carnitine and arginine substitution. During the following 30 hours, he suffered from recurrent gastric bleedings from his peptic ulcer which were repeatedly treated locally through gastroscopy. He received a total of 25 units of erythrocytes, 20 units of plasma, and 3 units of thrombocytes, in addition to intravenously administered fluids. The total volume of blood lost through bleeding was estimated to be 10 liters.
On day 3, biochemical analysis confirmed the diagnosis of HHH syndrome. In addition to elevated levels of ammonia, the plasma concentration of ornithine was 420 μmol/L (reference 30–110 μmol/L) and homocitrulline in urine was detected (23 mmol/mol creatinine; normally not detected). Further analysis of plasma amino acids also showed elevated glutamine (1321 μmol/L; reference 355–725 μmol/L), whereas citrulline (30 μmol/L; reference 15–50 μmol/L), arginine (33 μmol/L; reference 30–125 μmol/L), and lysine (221 μmol/L; reference 20–221 μmol/L) were in the normal range. Orotic acid in urine was 156 mmol/mol creatinine (reference < 1.0 mmol/mol creatinine). The concentrations of several essential amino acids were low.
Intravenously administered glucose and lipids were given to keep a preset blood glucose level, in order to stimulate insulin secretion and prevent catabolism. Total nutrition level was aimed at 115% of normal needs and no proteins were given. At the end of the third day his ammonia level was in the normal range.
Late on day 4, a wake-up call was attended, which revealed deep unconsciousness with stereotypic extension of limbs. He was again anesthetized and a CT scan of his brain showed considerable, general cerebral edema (Fig. ). He was transported to a neurological ICU. Continuous monitoring showed increased intracranial pressure (ICP) and he was treated with deeper sedation. He developed epileptic convulsions and was given levetiracetam. MRI on day 5 showed generalized cytotoxic edema in cortex and subcortical white matter; the edema was symmetric and more prominent in insula, gyrus cingula, and hippocampus compared to the basal ganglia and infratentorially (Fig. ). This pattern is considered typical for hyperammonemic encephalopathy []. The ICP gradually decreased. CRRT was discontinued on day 15 and the ammonia concentration remained normal. He was treated with protein-reduced food, sodium benzoate, arginine, citrulline, and substitution of essential amino acids. On day 21 he was transferred back to the general ICU, where he was treated for another 9 days. MRI of his brain on day 31 showed regression of edema (Fig. ).
He remained hospitalized for another 9 months, mainly for rehabilitation. He suffered from considerable impressive and expressive aphasia (monosyllabic), perception difficulties (visual, auditory, and spatial), spastic paraparesis, and dystonia. He could move his head autonomously, but could not control his arms and legs. Despite a few bacterial infections, aspiration pneumonia, and urine tract infections, no hyperammonemia was observed. MRI of his brain after 7 months showed considerable atrophy, general gliosis, and wide ventricles (Fig. ). During the rehabilitation the severity of the spastic paraparesis was progressive.
Ten months following admission he was discharged from our hospital after his home had been adapted to his needs. The treatment with ammonia scavengers (sodium benzoate) was continued as well as substitution with citrulline, arginine, and essential amino acids. His protein intake was reduced to a level of 0.7 (0.6–0.8) g/kg per day, in accordance to minimum protein intake for adult male based on World Health Organization (WHO) guidelines []. His ammonia concentration has remained within normal ranges or discretely elevated at times of acute illness (an episode of gastroenteritis and urinary tract infection).
Fifteen months after his first admission to our hospital, he has started to eat unassisted and use his legs to move his wheelchair around in his apartment. He has also begun to use more words in his speech (still monosyllabically).
Sequence analysis of the SLC25A15 gene (Center for Genomics and Transcriptomics, Tübingen, Germany) detected two heterozygous mutations: a c.337G>A (p.G113S) mutation in exon 4 and a c.712C>T (p.Q238X) mutation in exon 6. Our patient’s mother and daughter were heterozygous carriers only for the c.712C>T mutation whereas his sister was a heterozygous carrier of the c.337G>A mutation confirming that our patient carried the two mutations in trans. The c.712C>T mutation in exon 6 leads to a premature stop codon and thus a truncated and probably inactive protein. The mutation c.337G>A (p.G113S) in exon 4 is listed in the Single Nucleotide Polymorphism Database (dbSNP; rs199894905) with an allele frequency of 0.1%. This missense mutation affects a phylogenetically highly conserved amino acid residue and in silico analysis with different prediction programs (for example, PolyPhen-2 and SIFT) classifies the mutation as pathogenic. Another mutation affecting the same residue (p.G113C) has also been described in another patient with HHH []. |
pmc-6151194-1 | A 52-year-old postmenopausal female of Filipino origin presented to hospital with a three-day history of increasing abdominal bloating, vomiting, and fevers. She denied urinary or bowel symptoms. This patient had no significant past medical or family history and was a nonsmoker. She moved to Australia from the Philippines in 2015 and worked as a nurse in both countries.
On admission, she had a temperature of 39.9°C, a heart rate of 127, and a respiratory rate of 35. Her abdomen was markedly distended. There was a palpable tender mass in the right lower quadrant, with guarding and rebound tenderness.
Initial investigations showed mildly deranged liver enzymes, an elevated CRP, and slightly elevated CA-125 and CA-19.9 (). CT scan showed a 22 × 13 cm multiseptated cystic lesion almost certainly of ovarian aetiology, as well as omental fat hazing, raising the possibility of an acute omental infarction (Figures and ).
She was admitted for observation and intravenous antibiotics. Her fever resolved, and she was discharged home with a plan to follow-up in outpatient clinic for elective ovarian cystectomy.
Ten days later, the patient re-presented to hospital with severe abdominal pain and ongoing fevers. Repeat laboratory results showed worsening liver enzymes and a further rise of CRP (). A repeat CT scan showed the large ovarian cyst had likely ruptured with new generalised ascites and peritoneal enhancement, concerning for disseminated disease (Figures and ).
The patient underwent emergency laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and appendectomy. The cyst had a small leak, and 3.5 L of fluid was drained from the cyst and sent for histology (). A further 200 ml of ascitic fluid was collected. Inflammatory changes on the surface of the pelvis, and multiple inflammatory deposits overlying small bowel mesentery were noted (). Histology of the cyst showed a benign mucinous cystadenoma. The uterus, ovarian cyst, omentum, and appendix contained florid granulomatous inflammation and caseous necrosis. Peritoneal fluid cultured Mycobacterium tuberculosis. A chest CT confirmed lymph node calcification consistent with previous tuberculosis, with no evidence of active infection. Her postoperative recovery was uneventful, and she was commenced on isoniazid, rifampicin, ethambutol, and pyrazinamide under guidance of the Infectious Disease team. The patient remained well at a recent 3-month follow-up. |
pmc-6151198-1 | A 31-year-old African American female was found to have severe anemia on laboratory work performed by her gynecologist. The patient reported fatigue and dyspnea on exertion for about two months. She also had a two-week history of gum bleeding while brushing her teeth. She denied any other bleeding, weight loss, chills, or fevers. She had occasional blurry vision for about two weeks. Physical examination was unremarkable except for proptosis of the left eye. Visual fields and acuity were normal. A complete blood count showed a white blood cell count of 18 × 109/L with 50% blasts, hemoglobin of 5.7 g/dl, and a platelet count of 18 × 109/L. Bone marrow aspirate showed myeloblasts (64.2%) by flow cytometry. The myeloblasts were positive for CD13, CD33, CD34, MPO, and HLA-DR and negative for CD20 and CD19 on immunophenotyping. Fluorescent in situ hybridization (FISH) analysis revealed translocation t(8;21). Testing for FLT3 (Fms-like tyrosine kinase 3), CEBPA (CCAAT/enhancer-binding protein alpha) and NPM1 (nucleophosmin 1) was negative. Cerebrospinal fluid analysis was negative for involvement by leukemia. MRI of the brain demonstrated bilateral orbital masses measuring 2.6 cm on the right and 1.2 cm on the left (). The left orbital mass spanned the intraconal and extraconal compartments and displaced the optic nerve superomedially. The right orbital mass was in the right orbital apex extending along the roof of the orbit. Both masses were separate from the optic nerve and the ocular globe. Both masses compressed the optic nerve at the apex. There was mild proptosis on the left and only minimal proptosis on the right. There was an enhancing dural-based lesion in the right posterior fossa measuring 11 × 3 mm (). Nodules measuring around one centimeter were noted in the omentum, retroperitoneal space, and the left ischiorectal fossa on computed tomography (CT) scan of the abdomen ().
The patient was treated with cytarabine 200 mg/m2 and daunorubicin 90 mg/m2 (7 + 3 regimen) induction chemotherapy. Radiotherapy (RT) to the orbital MS was administered due to visual symptoms. The first treatment was on day 2 of chemotherapy. The treatment consisted of 50 cGy fractions using opposed lateral fields and half-beam blocks using 6 mV photons to both orbits. The planning was done in such a way that the lens was not in the radiation field, and the conus was included in the radiation field. Two days later, MRI of the brain showed interval resolution of the enhancing mass in the right orbital apex, decreased proptosis of the left eye secondary to decreased size, and enhancement of the orbital mass which had diminished in size to 1.5 × 1.0 cm compared to 2.6 × 1.9 cm on the prior scan (). The dural-based mass in posterior fossa had nearly resolved. The patient had an improvement in blurry vision after two doses of RT. The patient received a total of 150 cGy to the right orbit and 200 cGy to the left orbit in four fractions over a week. The RT treatment details are shown in . There were no acute toxicities of RT. Complete hematologic and cytogenetic response was achieved on day 28 after the induction chemotherapy.
One month later, MRI of the brain showed a decrease in enhancement of the left orbital mass likely representing residual scar and complete resolution of MS in the right orbit and brain (). Her visual symptoms and proptosis had resolved. There was also resolution of the dural-based posterior fossa lesion (). CT scan of the abdomen and pelvis showed resolution of all the nodules in the abdomen and pelvis (). She was evaluated for stem cell transplantation and was deemed to have low-risk disease. The patient proceeded to receive consolidation chemotherapy with high-dose cytarabine for four cycles. The patient remained in complete remission eighteen months since diagnosis. No chronic adverse effects of RT were reported. |
pmc-6151199-1 | A 73-year-old Caucasian male presented with three weeks of dyspnea, headache, and lower extremity edema. Initial labs were significant for marked leukocytosis with increase in myeloid precursors and rare blasts: white blood cell (WBC) 156 k/μL, neutrophils 103 k/μL, monocytes 7.1 k/μL, eosinophils 1.6 k/μL, basophils 0, and blasts 12 k/μL. Other cell lines were normal with hemoglobin of 12.6 gm/dL and platelets of 242 k/μL. Uric acid was elevated at 9.0 ml/dL, and lactate dehydrogenase was 860 units/L.
A bone marrow biopsy was performed and revealed a chronic myeloproliferative neoplasm. H&E stained slides of the core showed marked hypercellularity (99%) with profound myeloid hyperplasia and complete maturation to segmented neutrophils. Immature myeloid cells of all stages were appropriately present, without dysplasia or increased blasts. A moderate amount of reticulin fibrosis was seen. Giemsa stain of the aspirate confirmed the biopsy findings with blast count of less than 5%. By flow cytometric analysis, myeloid cells in the blast gate expressing CD34 accounted for less than 1% of total cells. Molecular diagnostic testing of the aspirate indicated the presence of the BCL-ABL1 p210-type transcript by RT-PCR with an international scale-normalized (ISN) copy number of 35.27%. Fluorescence in situ hybridization (FISH) testing for BCR-ABL1 fusion was present in 89% of cells. Together, these findings were consistent with a diagnosis of chronic phase-CML.
Given the symptoms of intermittent dyspnea in the absence of anemia, the patient underwent further evaluation. Stress echocardiogram indicated a normal left ventricular ejection fraction. Computed tomography (CT) chest with contrast enhancement revealed mediastinal, cervical, and supraclavicular adenopathy, without evidence of pulmonary embolism.
The patient subsequently underwent an excisional biopsy of the cervical lymph node, which revealed involvement with CML and FL (). Atypical follicles with abnormal germinal centers and paracortical expansion by maturing pan-hematopoietic elements without blastic groups were noted. Immunohistochemistry (IHC) analysis showed that the atypical germinal centers expressed the pan-B cell marker CD20 and the germinal center marker CD10. There was coexpression of BCL2 and BCL6. The findings were consistent with low-grade follicular lymphoma, with fewer than 15 centroblasts per high-power field. PCR analysis for immunoglobulin heavy chain and kappa light chain gene rearrangements indicated monoclonality. Fluorescence in situ hybridization detected the IGH-BCL-2 translocation confirming follicular lymphoma.
IHC and flow cytometric analysis of the paracortical pan-myeloid hyperplasia showed no evidence of increased myeloblasts. Qualitative RT-PCR of the node detected the presence of the CML-type Mbcr (p210) fusion protein, and quantitative RT-PCR showed an ISN copy number of BCR-ABL transcripts of 0.642%, confirming nodal involvement by chronic phase-CML. Given the unusual presentation of concomitant CML and FL, further testing was done to evaluate for other abnormalities. PD-L1 expression was low (10%) using the 22C3 clone (Dako), and EBV was negative both by IHC for the viral latent membrane protein 1 (LMP1) and by Epstein–Barr encoding region in situ hybridization (EBER). |
pmc-6151203-1 | A 58-year-old female was found unresponsive after a house fire, with the primary cause of death anoxic brain injury. Despite a short period of asystole, her renal function was preserved with an admission creatinine of 0.88, peak creatinine of 1.24, and a final creatinine of 1.04. The Kidney Donor Profile Index (KDPI) was 64%. On gross examination, severe organ discoloration was noted (), and biopsy results were significant for the presence of oxalate crystals. Kidney pump pressure was set at 35 mmHg, resulting in a flow of 133 mL/min with a resistance of 0.23 (). The organ recipient was a 53-year-old male with end stage renal disease secondary to hypertensive nephrosclerosis on hemodialysis three times per week for a total duration of 52 months. His cPRA was 0% with no evidence of gray zone DSA (). A complement dependent cytotoxicity (CDC) T cell cross match was performed and negative.
Following transplantation, induction immunosuppression consisted of alemtuzumab 30 mg and solumedrol 500 mg, followed by a maintenance regimen of tacrolimus, mycophenolate 500mg twice daily and prednisone 10 mg daily. Early in the perioperative period, the patient's hospital course was complicated by severe hyperkalemia and delayed graft function requiring HD on postoperative day (POD) 1, 2, 4, and 6. Each session was performed without incident. On POD 7, in the setting of ongoing oliguria and worsening abdominal distention, laboratory and imaging studies revealed a large pelvic fluid collection consistent with an acute perinephric hematoma. The patient was taken emergently to the operating room for reexploration and evacuation of the hematoma. Subsequently, the patient's urine output began to improve and serum creatinine started to decrease. Ultimately, the patient was discharged to home on POD 13.
Approximately 3 weeks after transplant, the patient presented with an elevated creatinine to 4.70 mg/dL (previous nadir 2.60 mg/dL). A biopsy of the renal allograft revealed acute T cell mediated rejection (Banff category 2A) as well as acute antibody-mediated rejection. A C4D stain was positive in more than 30% of the peritubular capillaries. A Human Leukocyte Antigen (HLA) antibody screen revealed a class II (DQ) DSA at 8000 mean fluorescence intensity (MFI). Institutional protocols for rejection were followed, and the patient was initially treated with solumedrol 500 mg x3 doses. Despite this, his creatinine continued to rise and he remained oliguric. Subsequently, anti-thymocyte globulin 1 mg/kg x 3 doses was administered, followed by plasmapheresis and IVIG x 5 doses (2g/kg ideal body weight). During this 2-week hospital readmission for rejection, 4 additional sessions of HD were required, and again, there were no complications. A repeat biopsy 6 weeks later did not reveal any signs of ongoing rejection, and all prior oxalate crystals had disappeared. The patient's creatinine improved and plateaued in the 1.9-2.0 range. Eighteen months after transplant, the patient has a stable graft function with creatinine levels near 2 mg/dL (). |
pmc-6151203-2 | A 57-year-old male found unresponsive after a house fire subsequently developed pulseless electrical activity (PEA) arrest with the primary cause of death documented as anoxic brain injury. The donor met criteria to be considered public health services (PHS) high risk given his recent history of incarceration. Overall, renal function was preserved with a creatinine on admission of 1.60, peak creatinine of 1.60, and final creatinine of 1.40. The KDPI was 75%. On gross examination, severe organ discoloration was noted (), however, renal biopsy did not reveal the presence of oxalate crystals. Kidney pump pressure was set at 35 mmHg, resulting in a flow of 94 mL/min with a resistance of 0.30 (). The organ recipient was a 78-year-old male with ESRD secondary to hypertension and diabetes undergoing HD three times a week for a total duration of 25 months. The cPRA was 0%, however, a single gray zone DSA against HLA A29 was identified (). All crossmatch tests were negative.
Induction immunosuppression consisted of anti-thymocyte globulin (total dose of 5mg/kg) administered over 5 doses and solumedrol 500 mg, followed by a maintenance regimen of tacrolimus, mycophenolate 500 mg twice daily and prednisone 10 mg daily. The patient had an overall uneventful postoperative course with immediate graft function and progressive downtrend in creatinine levels. On POD 7, the patient was discharged to a short-term rehabilitation facility. Six months after organ transplantation, the patient continues to experience a stable graft function with baseline creatinine of 1.14 (). |
pmc-6151209-1 | A 73-year-old woman presented with the complaint of left ankle pain that had exacerbated with walking for the previous month. She had a limping gait and complained of a limited walking ability of 5–10 minutes with a cane because of pain. She originally had limited walking ability due to a cerebral infarction 10 years prior that was classified as least-limited community walker according to the classification by Perry et al. []; however, she had been able to walk without a cane for 30 minutes prior to symptom onset. An examination revealed bilateral hindfoot valgus and flatfoot deformities, and both feet were rigid and not reducible. The physical examination revealed localized swelling and tenderness on the distal fibula about 5 cm proximal to the tip of the left lateral malleolus.
An anteroposterior (AP) weight-bearing view of the left ankle joint revealed the fracture of the distal fibula, valgus talar tilt with joint space narrowing at the lateral tibiotalar joint, and collapse of the lateral talar dome (). An AP weight-bearing view of the right ankle joint revealed similar findings on the contralateral side excluding the fracture of the distal fibula (). Lateral weight-bearing views of both feet demonstrated severe arch collapse and increased radiodensity of the body of the talus (Figures and ). Magnetic resonance imaging (MRI) of the left ankle revealed a vertical crack in the talar body extending from the center of the talar dome to the subtalar joint and a lateral talar body fragment with low signal intensity on both T1-weighted and short T1 inversion recovery images suggestive of osteonecrosis (Figures and ). A computed tomography (CT) scan of the left ankle clearly demonstrated that the fracture lines extended from the talar dome to the subtalar joint with the comminuted lateral talar body fragments and the fracture of the distal fibula with callus formation (Figures and ). MRI of the right ankle also revealed a depressed lateral talar dome and some cyst formations surrounded by bone marrow edema in the talar body suggestive of a previous talar dome fracture; however, the lateral talar body fragment maintained the same intensity as those of other bone marrow on T1- and T2-weighted images, negating osteonecrosis in contrast with the left ankle (Figures –). A CT scan of the right ankle demonstrated the continuity of the bone trabeculae in the suspected area of the fracture suggesting bony union ().
She could not recall any trauma or unusual activity that may have caused this problem. She denied any history of smoking, alcohol abuse, or corticosteroid use. A blood test was negative for rheumatoid factor, anticyclic citrullinated peptide antibody, and antinuclear antibodies. Radiographs of other joints including the hip, knee, and shoulder revealed no osteonecrosis. Dual-energy X-ray absorptiometry measurements showed that the bone mass was 82% of young adult mean (YAM) in the lumbar spine and 81% of the YAM in the femoral neck without any use of drugs affecting bone metabolism, which did not meet the criteria for osteoporosis.
The fibular stress fracture was treated successfully in 2 months with a walking boot and limited weight-bearing with crutches. After the fibular stress fracture healed, the patient could perform her activities of daily living as before the fibular fracture without wearing any devices or using any analgesics for pain control. At the time of the most recent follow-up, 2 years after the first visit to our hospital, the patient maintained the performance described above without complaint, although the comminuted lateral talar body displayed nonunion on radiography and CT evaluations. |
pmc-6151219-1 | A 44-year-old woman was diagnosed with iron deficiency anemia but showed no abnormalities on gastrointestinal tract endoscopy 5 years prior to the current presentation. A blood test for health screening showed anemia with hemoglobin 7.6 g/dL, and uterine fibroids were suspected on abdominal ultrasonography. She was diagnosed as having an intra-abdominal tumor on magnetic resonance imaging (MRI) for detailed examination and was referred to our hospital.
The abdomen was flat and soft, with an elastic mass of poor mobility which was the size of an infant's head was palpable below the umbilicus to above the pubis. There were no blood test abnormalities; CEA, CA19-9, SCC, and the interleukin 2 receptor level were within normal limits. Abdominal MRI revealed a homogeneous and well-demarcated 74 × 98 × 122 mm mass near the cranial end of the uterus, with a low signal intensity on T1-weighted image, and mostly low signal intensity and partially high intensity on T2-weighted image (Figures and ). Abdominal-enhanced computed tomography (CT) showed a well-demarcated and contrast-enhanced oval mass with a smooth margin in the pelvis. The tumor was supplied by the superior mesenteric artery, and the surrounding lymph nodes were enlarged (Figures and ). Upper gastrointestinal tract endoscopy showed an easily bleeding tumor with an ulcer in the third part of the duodenum, involving half the circumference (). The biopsy results were inflammatory exudates and granulation tissues. FDG-PET/CT showed heterogeneous uptake inside the tumor with SUVmax 6.3 (Figures –). A slight 18F-FDG uptake was observed in the enlarged lymph nodes with SUVmax 2.6. Along with the facts that there were no malignant cells detected by endoscopic biopsy and the CT image showing enlarged surrounding lymph nodes, the patient was suspected of nonepithelial malignancy of the duodenum such as gastrointestinal stromal tumor (GIST) and malignant lymphoma. As we could not make a definite diagnosis preoperatively, she underwent surgery for an accurate diagnosis and treatment.
Surgery was performed under general anesthesia; laparotomy was performed via midline incision from 5 cm above the umbilicus to above the pubis. There was a 12 cm tumor centered on the third part of the duodenum, extending to the fourth part. The tumor extended into the pelvis and pulled the duodenum and the ligament of Treitz caudally (). There was no infiltration of the tumor into the pancreas or the small intestine. The duodenum was transected at the third part of the duodenum on the oral side. On the anal side of the tumor, the jejunum immediately after the ligament of Treitz was transected, and the tumor was resected. The enlarged lymph nodes sampling were also performed. In reconstruction, end-to-end duodenojejunostomy was performed (). She had an uneventful postoperative course and was discharged 9 days after surgery.
Pathological findings showed a solid tumor growing from the muscle layer of the duodenum through the serous membrane. The duodenal mucosa was invaginated at the site of the tumor, forming a deep ulcer (). The tumor showed uniform growth of long and spindle-shaped cells in an intricate manner, and the number of nuclear divisions was 1 or less per 50 visual fields (). There were no evidence of calcification, hemorrhage, or degeneration within the tumor. On immunostaining, α-smooth muscle actin was positive, while S-100, c-kit, and CD34 were negative (Figures –). The MIB-1 index was low at 3% maximum, and there were no neoplastic lesions in the enlarged lymph nodes. Based on these findings, a leiomyoma was diagnosed. Since then, no relapse has occurred for two years and six months. |
pmc-6151220-1 | This patient, a 63-year old male, was referred with MDS by an indication of MDS with excess blasts. Chromosomal analysis showed a karyotype of 46,XY,der(15)t(1;15)(q12;p11.2)[4]/46,XY,der(22)t(1;22)(q12;p11.2)[2]/46,XY[7]. FISH analysis using dual color probes for the CDKN2C gene at 1p32.3 and CKS1B gene at 1q21.3 confirmed three copies of 1q in 5.5% of bone marrow cells. Over the next six months, the percentage of abnormal cells increased despite two rounds of chemotherapy and the patient progressed to AML. A transit clone with the der(15)t(1;15) and a deletion at 11q was noted. The last chromosome analysis revealed a karyotype of 46,XY,der(15)t(1;15)(q12;p11.2)[13]/46,XY,der(22)t(1;22)(q12;p11.2)[2]. FISH detected three copies of 1q in 94% of bone marrow cells. This patient died eight months after the initial finding of the jumping translocations of 1q. |
pmc-6151222-1 | A previously healthy 35-year-old African American male presented with a one-month history of worsening lower back and bilateral lower extremity pain, intermittent night sweats, and 32 kg unintentional weight loss over the course of a year. He did not have saddle anesthesia or urinary or fecal incontinence. He was initially seen in a primary care clinic and was diagnosed with sciatica. As symptoms continued to worsen, he underwent a computed tomography (CT) scan of the lumbar scan as an outpatient that was concerning osseous spinal metastasis. He was started on prednisone 10 mg daily and was referred to the oncology clinic at our center. Prednisone gave him minimal symptomatic relief. While waiting to be seen in the oncology clinic, the patient had an episode of leg weakness with near-fall prompting him to present to the emergency department of our hospital and was admitted for further evaluation. His vital signs were stable. He had no palpable cervical, supraclavicular, axillary, or inguinal lymph nodes. Neurological exam was normal with intact strength and sensation in both lower extremities.
His complete blood count and serum electrolytes were normal including a normal serum calcium level at 8.1 mg/dL. He tested negative for human immunodeficiency virus 1 and 2 antibodies. Magnetic resonance imaging (MRI) of the cervical, thoracic, and lumbar spine showed several enhancing lesions in T11, T12, L3, L4 vertebral bodies, right sacrum, and ilium that were concerning metastatic disease. There was effacement of the right lateral recess and right neural foramen at the L3-L4 and effacement of the left lateral recess and left neural foramen at the L4-L5 due to tumor retropulsion (Figures –). In addition, a small epidural tumor was noted at the T5 vertebral level without significant spinal canal stenosis or cord compression. Imaging was also concerning osseous metastasis involving the sternum and multiple ribs. Incidentally, narrowing of the neural foramen at left T2-T3 and right C7-T1 and T5-T6 levels was also noted. Since the findings were concerning diffuse metastatic disease, a CT scan of the chest, abdomen, and pelvis were performed and showed bilateral hilar and mediastinal adenopathy, mild cardiomegaly, and dilated main pulmonary artery measuring 3.6 cm (Figures and ). Enlarged liver measuring 18.1 cm, enlarged spleen measuring 12.4 cm, and multiple bilateral enlarged pelvic sidewall, external iliac, and inguinal lymph nodes concerning lymphoma or metastatic disease are shown in . Ultrasound of the scrotum did not reveal any testicular masses.
He underwent extensive screening for hematologic and solid tumor malignancies including serum protein electrophoresis, urine immunofixation, beta-human chorionic gonadotrophin hormone levels, and fecal occult blood test that were all negative. He subsequently underwent a CT-guided core needle biopsy of the left iliac crest lesion that was significant for noncaseating and necrotizing granulomas. Histochemical stains for Grocott's methenamine silver (GMS) and Ziehl-Neelsen stains were negative for fungal elements and acid-fast bacilli, respectively. Due to high suspicion of malignancy, he also underwent an endoscopic bronchial ultrasound with transbronchial needle aspiration of the inferior mediastinal lymph node which found non-necrotizing granulomas but did not reveal any malignant cells (Figures –). Fungal culture and acid-fast bacilli culture from the transbronchial aspirate were again negative. Serum ACE level was 62 U/L (normal 14–82 U/L).
Neurosurgery was consulted, and they did not recommend any acute neurosurgical intervention. The patient was discharged with follow-up in pulmonology clinic. Since there was concern that his steroid therapy prior to admission could have masked lymphoma, he had a left inguinal node excisional biopsy, a month later, that showed necrotizing and non-necrotizing granulomatous lymphadenopathy and was negative for acid-fast or fungal microorganisms. Since there was concern for a process with high metabolic activity, he also had an 18F-labeled fluorodeoxyglucose (18F-FDG) positron electron topography (PET) scan that was significant for extensive hypermetabolic osseous and nodal disease (). |
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