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pmc-6067805-1 | A 48-year-old female from Honduras presented to the clinic with chief complaints of breast tenderness and galactorrhea for the past two to three weeks. She had a past medical history of hypertension, latent tuberculosis (TB) and sciatica. Her last menstrual period was three weeks prior to her presentation. Physical examination showed non-tender, diffuse enlargement of the thyroid gland, which was unchanged over the past one year. On palpation, breast examination revealed bilateral tenderness and milky yellowish discharge. The visual field testing and rest of the general physical examination were within normal limits. She was taking hydrochlorothiazide 25 mg and losartan 50 mg daily for hypertension and was on isoniazid (INH) and vitamin B6 for the treatment of latent tuberculosis. She denied the use of tobacco, marijuana, alcohol, illicit drugs, or over the counter medicines. Laboratory investigations are given below (Table ).
She had negative urine pregnancy test. Her mammogram was normal, and magnetic resonance imaging (MRI) of the brain didn’t show any pituitary mass. After looking at her thyroid function tests, prolactin level, and other respective tests, a diagnosis of subclinical hypothyroidism with hyperprolactinemia was made. She was prescribed levothyroxine 50 mcg daily and three months later her galactorrhea and breast tenderness were relieved. Her repeat blood testing showed normal thyroid stimulating hormone (TSH) level 1.4 mIU/ml and normal serum prolactin level of 13.44 ng/ml. |
pmc-6067806-1 | A 25-year-old female presented to the emergency room with a complaint of left-sided body weakness since 12 hours. On clinical examination, the power of the left upper and lower limbs was seen to be limited to just slight movement. Planter reflex was up going on the left side (Babinski positive). Clinical anemia was also present, and the nails showed massive clubbing. According to her parents, she had a history of cyanosis since birth, but they never got treatment for it. There was no history of any psychiatric illness, hypertension, or diabetes.
A CT (computed tomography) scan showed no evidence of a haemorrhage, but some changes in the temporoparietal area were observed, as shown in Figure . Later, an MRI (magnetic resonance imaging) with contrast was advised and performed, which showed an infarct of the right temporoparietal lobe with mild brain atrophy as shown in Figure and Figure . |
pmc-6067807-1 | A 16-year-old girl presented to us with complaints of progressively increasing pain in left thigh for two years. At the time of presentation, the pain was moderately severe in intensity, requiring analgesics on a regular basis. It used to worsen on ambulation, resulting in limitation of her activities of daily living. There was no history of any local swelling or redness. She denied history of local trauma preceding the onset of pain. There was no history to suggest malabsorption or use of anticonvulsant drugs or indigenous medications. She was born out of a non-consanguineous marriage with normal birth and developmental history, and none of the family members had history of bone disease. Nutritional history was notable in the form of only occasional intake of milk and dairy products. The family used to live in an overcrowded basement of a two-storeyed building where exposure to sunlight was inadequate. Besides, patient preferred to remain indoors, moving out briefly only during early morning and evening hours in her premorbid state. For these complaints, she was evaluated in an outside hospital and diagnosed to have an aneurysmal bone cyst of the left femur. She was advised to undergo surgical intervention for the same; however, the anxious family brought her to our center for a second opinion.
Examination revealed a young, lean female with the height of 163 cm, a weight of 40 kg and BMI of 15 kg/m2. She had proximal myopathy involving bilateral lower limbs and walked with an antalgic gait with waddling towards the left side. There were no evident deformities involving the long bones or spine. Rest general and systemic examination were unremarkable.
Laboratory investigations of the patient have been summarised in Table .
Total calcium was 7.9 mg/dl (normal 8.5-10.4), inorganic phosphorous 2.8 mg/dl (normal 2.5-4.5), alkaline phosphatase 1324 IU (normal 240-840), blood urea, creatinine, total protein, albumin, and liver function tests were normal. Tests for complete blood counts, fasting plasma glucose and urine routine examination were unremarkable. Serum intact parathyroid hormone was 840 pg/ml (normal 15-65), 25(OH)D3 <4 ng/ml (normal >20 ng/ml), total T4 8.2 ug/dl (normal 5.1-14.1 ), TSH 3.6 uU/ml (normal 0.27-4.2). X-ray pelvis revealed an expansile lytic lesion involving the trochanteric region of left femur, pseudofractures of bilateral femoral neck along with the widened joint space and irregular margins at the pubic symphysis (Figure ).
Rest skeletal survey did not reveal any other lytic lesions or pseudofractures.
Diagnosis of nutritional osteomalacia with secondary hyperparathyroidism and an expansile lytic lesion of left femur, possibly brown tumor was entertained at this stage. She was started on one gram elemental calcium per day and vitamin D3 (cholecalciferol) 60,000 IU sachet once a week for eight weeks followed by once a month maintenance therapy. She was subsequently followed up at three monthly intervals. At follow-up visits, the patient reported significant improvement in pain and, by six months, she had returned to her premorbid functional sate. Biochemical parameters (Table ) and radiology (Figure ) also showed dramatic improvement with complete disappearance of the lytic lesion in association with correction of secondary hyperparathyroidism.
Although tissue diagnosis was not available, the remarkable clinical and radiological improvement in association with correction of the hyperparathyroid state indicated that the lytic lesion was brown tumor related to parathormone excess. |
pmc-6067809-1 | A 19-year-old female presented to our hospital with complaints of vomiting for one week, along with generalized abdominal pain and weight loss for the last three months. Initial assessment found the patient to be alert and well-oriented, albeit pale, emaciated, and considerably uncomfortable due to the pain. Her heart rate was 103 per minute with a blood pressure of 100/60 mm of Hg, a respiratory rate of 16 per minute, and a temperature of 98.4°F. She had conjunctival pallor. An abdominal exam revealed that she had a distended abdomen with generalized tenderness and a palpable mass in the epigastrium. Her hernial orifices were intact but there were no discernable bowel sounds on auscultation of the abdomen. A digital rectal exam revealed an empty rectal vault.
Laboratory investigations done in the emergency room revealed a low hemoglobin count of 7.2 g/dL, a platelet count of 650,000/µL, and a total leukocyte count of 11,400/µL. Her creatinine was 0.60 mg/dL with a blood urea level of 38 mg/dL. Her potassium level was 4.0 mEq/L and the international normalized ratio (INR) was 1.0. Owing to the patient's abdominal pain, she underwent an abdominal ultrasound scan, which revealed a jejunal intussusception with dilated loops of bowel, while a computed tomography (CT) scan of the abdomen showed a donut intussusception. She also underwent a CT scan of the chest that showed a mediastinal mass with a resultant compression of the trachea.
Due to this clinical presentation, she was admitted for a surgical intervention. A difficult endotracheal intubation, owing to the mass causing tracheal compression, was eventually followed by an emergent laparotomy. A proximal jejunal intussusception with dilated loops of bowel was observed during the procedure, which culminated in an ileotransverse bypass (Figures -).
During the surgery, the patient experienced recurrent episodes of non-ventilation due to tracheal pressure, which improved with repositioning of the endotracheal tube. Following the procedure, she was admitted to the intensive care unit. Her issues with ventilation continued to linger in the postoperative period but her oxygen saturation improved yet again with a repositioning of the endotracheal tube.
Unfortunately, the patient died the following morning due to an episode of sudden apnea. A biopsy of the mediastinal mass revealed an aggressive non-Hodgkin lymphoma of the thyroid gland. |
pmc-6067810-1 | A 67-year-old woman presented to the surgical emergency department with complaints of diffuse, colicky abdominal pain, abdominal distension, obstipation, and multiple episodes of bilious vomiting for six days. Moreover, the patient had a history of recent weight loss and loss of appetite. There was no history of vaginal discharge or IUD insertion or any significant past medical or surgical conditions. On examination, the patient was conscious, oriented, and had tachycardia with normal blood pressure. The abdomen was distended, with diffuse tenderness and guarding. On auscultation, bowel sounds were exaggerated. Abdominal X-ray showed multiple air-fluid levels with loops of distended small bowel. Contrast-enhanced computed tomography (CT) revealed a terminal ileal stricture close to the ileocecal junction together with proximal dilated, and distal collapsed, bowel loops, suggestive of intestinal obstruction. After optimal hemodynamic resuscitation, the patient underwent exploratory laparotomy under general anesthesia. Intraoperatively, we found a granular mass (2×2 cm) at the base of the mesentery and the right ovary with a hard nodular growth mimicking a malignancy (3×3 cm) (Figure ).
A dense fibrotic band extended between the two masses, causing ileal obstruction, and a transitional zone was present 10 cm proximal to the ileocecal junction (Figure ).
Both the mesenteric granular mass and the dense fibrotic band were excised, a right salphingo-oophorectomy was conducted, and resected specimens were sent for histopathological examination. On microscopic examination, the Actinomyces species was identified in the evaluated specimens, and a final diagnosis of abdominopelvic actinomycosis was made (Figures -). |
pmc-6067835-1 | History and physical examination
A 67-year-old male presented to the emergency department with complaints of worsening low back pain and a progressive inability to ambulate as well as to maintain an upright posture. No complaints of fever or bowel and bladder dysfunction were noted. The patient’s past medical history was positive for alcohol abuse and pancreatitis, as well as chronic low back and bilateral leg pain. Relevant past surgical history was positive for prior L4-S1 posterior and interbody fusion performed in 2012 and a recent extreme lateral interbody fusion (XLIF) of L3-4, performed four months prior to his presentation for adjacent segment degeneration and stenosis. The physical exam revealed diffuse weakness, rated 3-4/5 of all bilateral lower extremity key muscles. The workup to rule out infection, including white blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), was negative. Initial diagnostic imaging consisting of a lumbar x-ray showed that the L3-4 implanted cage has developed significant cavitation around it. In addition, new compression fractures were noted at the vertebral bodies of L1 and L2 (Figure ).
Lumbar magnetic resonance imaging (MRI) with contrast demonstrated diffuse edema and enhancement of the L3 and L4 vertebral bodies, strengthening possible infection as the primary etiologic mechanism (Figure ). Finally, abdominal and pelvic computed tomography (CT) for ruling out a possible intra-abdominal involvement was negative.
Surgical treatment and postoperative course
In light of the acute infection resulting in segmental instability, the patient was planned for a two-stage intervention. In the first stage, removal of his existing L4-S1 posterior hardware was followed by spinal canal decompression, which allowed the retrieval of the loose L3-4 interbody loose implant as well as multiple tissue samples for culture and pathology. Spinal stabilization was achieved by placing antibiotic-impregnated temporary polymethyl-methacrylate (PMMA) spacer in the L3-4-disc space and posterior spinal instrumentation from L2 to S1 (Figure ).
In addition, the placement of antibiotic-impregnated PMMA beads allowed for the optimization of local control of the infection, whereas intravenous empirically administered ceftriaxone and vancomycin enabled systemic control. Specimens taken intraoperatively for aerobes and anaerobes cultures and gram stain were negative. Surprisingly, several separate fungus smears have yielded yeast, resulting in adjusting treatment to oral fluconazole only.
Following the uneventful surgery, the patient’s back pain and ambulation had progressively improved and the patient was discharged home. The complete resolution of his symptoms as well as persistently negative CRP and ESR at ambulatory follow-up suggested that his infection had resolved. Four months after the first stage, the patient was taken back to the operating room for a planned second stage. The removal of the PMMA spacer and beads and irrigation was followed by a definite fusion of both the L3-4 segment as well as from T10 to his pelvis (Figure ). |
pmc-6068064-1 | A 46-year-old Japanese female patient was referred to Kochi Medical School Hospital for the treatment of left breast cancer. Her height, body weight, and body mass index (BMI) were 151.2 cm, 55.0 kg, and 24.1, respectively. She had been experiencing vaginal delivery two times. She did not have any past history regarding abdominal diseases or surgery. Disease stage of left breast cancer was diagnosed as T2N0M0, stage IIA, according to the International Union Against Cancer (UICC) TNM classification, by using mammography, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). She underwent left mastectomy with sentinel lymph node biopsy. There was no metastatic lesion in sentinel lymph nodes, and immediate breast construction using left DIEP flap was performed. DIEP flaps were raised in a standard manner which is anastomosed by two perforators located medial of rectus abdominis. We made an incision into anterior sheath longitudinally at the center of the muscle. The rectus muscle was split for dissecting the deep inferior the epigastric vessels during flap harvesting. One branch of the intercostal nerve was sacrificed when the inferior epigastric vessels were harvested. The linea alba of this patient was separated due to two deliveries. She underwent abdominoplasty by suturing the rectus abdominis fascia. The tension of the abdominal wall was not strong after abdominoplasty.
Four days later, she suffered heavy abdominal pain and vomiting after defecation. Abdominal X-ray examination showed niveau imaging (Fig. ), and CT showed bowel herniation into the subcutaneous space (Fig. ). Under a clinical diagnose of postoperative herniation caused by spontaneous rupture of the abdominal wall, we performed emergency operation.
Because there was no finding of bowel strangulation, the small intestine was replaced into the abdominal cavity without bowel resection (Fig. a). Abdominal wall lateral of the rectus abdominis was ruptured measuring 3 cm in diameter, which was located at caudal side of arcuate line (Fig. b). The ruptured abdominal wall was sutured, covering onlay polypropylene mesh after bowel repositioned into the abdominal cavity (Fig. c, d). She got out of hospital without other complication after 11 days later from emergency surgery. After 6 months of following the operation, the patient was asymptomatic and there was no abnormal finding of the donor site (Fig. ). |
pmc-6068367-1 | A 50-yr-old man in the north of China went to Uganda to search for a work on Jul 14, 2016, and returned home on Jul 25. No obvious cause of fever with a temperature of 38.5 °C and occasional cough were found on Jul 30. After intravenous cephalosporin medication in local clinic for 3 d since the night of July 30, his body temperature dropped to normal. The patient became partially unconscious at 18:00 on Aug 2, and was sent to the Second Hospital of Changli County firstly, and then transferred to our hospital due to dangerous condition. Upon admission, the patient was found to have body temperature of 38.5 °C, unconsciousness, irritability, BP of 137/93 mm Hg and heart rate of 122 times/min with the consideration of febrile diseases. After being given intravenous cefoperazone sulbactam symptomatic treatment in the fever clinic, his status showed no improvement and the patient was transferred to intensive care unit for further treatment at 10:30 on Aug 3.
In IUC, physical examination gave the following results as blurred consciousness, irritability, high blood pressure, skin and sclera yellow dye, but few of other positive changes. The patient was treated with sedative, acid suppression, liver protection, clearing mind and anti-infection of meropenem. Considering the falciparum malaria with the warning of local CDC, the patient was transferred to the Third Hospital of Qinhuangdao (the infectious diseases hospital of Qinhuangdao) for continued treatment at 17:00. Considering the patient with cerebral falciparum malaria associated with liver and myocardial damage, more tests were performed and results indicated a lung infection and metabolic acidosis.
The patient was given sodium bicarbonate intravenous drip to correct acidosis, magnesium isoglycyrrhizinate, and reduced glutathione to protect liver, pantoprazole intravenous drip to protect the gastric mucosa, meropenem to anti-infection, diazepam and cockstailytic for sedation treatment, artemether and dihydroartemisinin-piperaquine tablets for anti-malaria treatment. Unfortunately, the patient’s status showed no improvement till 00:20 on Aug 4, and was transferred to ICU of Beijing Ditan Hospital for further treatment at 04:47 on Aug 4. After antimalarial therapy with intramuscular artemether, anti-infection treatment with intravenous cefmetazole and other symptomatic treatment, the disease did not relieve and acidosis became heavier; the patient had already in a deep coma at 15:00 on Aug 5, and then died of septic shock at 20:40.
The study was approved by the hospital.
Blood sample showed hemoglobin of 127 g/l, red blood cell count of 4.29×1012/l, total white blood cell count of 6.71×109/l, 85.5% neutrophil and platelet count of 14×109/l; his liver function test showed hyperbilirubinaemia of 247.68 μmol/l and transaminitis with serum ALT 84.4 U/l, AST 113.4 U/l, LDH 492 U/l, total bile acid 32.46 μmol/l, rglutamyltranspeptidase 431.2 U/l, blood ammonia 35.8 μmol/l and the total protein 62.3 g/l; his serum D- dimmer, fibrinogen and procalcitonin raised to 13.72 μg/ml, 5.38 g/l and 6.23 ng/ml, respectively; bicarbonate was 16.7 mmol/l and plasma protamine paracoagulation was weakly-positive; urine analysis revealed elevated bilirubin, protein, occult blood and ketone.
Red blood cell (RBC) morphology was normal and about 40% of them contained 1–2 mainly or occasionally 3 early trophozoites of Plasmodium falciparum. The early trophozoites were annular and some were located on the edge of RBC, the ring was slender and it accounted for 1/4–1/5 of the diameter of RBC, the ring contained 1–2 nucleuses, which was dark purple, dense, round or oval. Big trophozoite was visible and occasionally schizonts in the smear. The malaria pigment phagocytosed by neutrophils or mononuclear cells was visible occasionally; it showed granular clumps of dark brown or yellowish brown. Finally, infection by P. falciparum was identified. Blood smear examination was performed again at the Third Hospital of Qinhuangdao after 4 h interval, the result showed that approximately 70% of RBC containing early trophozoites, in which three parasites were easy to be seen and 7 rings occasionally, furthermore mixed metabolites of Plasmodium were visible easily ().
Take the patient’s blood samples from our hospital and the Third Hospital of Qinhuang-dao to analyze the RET scatter plots respectively, the results showed RET increased and the percentage of RET to RBC were 5.8% and 9.3% respectively ().
In the Qinhuangdao CDC, the serological detection result supported the mixed infection of P. falciparum by the colloidal gold method. In the Hebei Provincial CDC, dengue real-time polymerase chain reaction (RT-PCR) was positive, serum IgM was positive but IgG against the virus was negative by ELISA. |
pmc-6068370-1 | A 40 year-old female patient applied to our polyclinic with swelling and pain on right axillary which had been continuing for about 2 months. During the breast examination of the patient who had no breast cancer cases in her family history, no features were detected on both breasts and left axillary. On right axillary, well-circumscribed semi-mobile mass lesion was detected. No features were found on biochemical investigations. On mammary ultrasonography (USG), it was reported that both breasts were natural, and there was necrotic lymphadenopathy (LAP) on right axillary that was roughly 10×10 cm sized, and locally included cystic patency. Axillary LAP excision was planned for histopathologic diagnosis. The patient was taken to the operation. By right axillary incision, skin and subcutan were passed. Cystic mass lesion was at axillary area. While trying to take of the lesion, capsule was perforated. Rock water and female vesicles were drained out ().
After it was found out that cyst was hydatic, it was excised with germanium membrane by encircling it with savlon compresses. In order to differentiate primary secondary on postoperative period, the patient was taken to thoracic and abdomen tomography. No cystic lesions were found on tomographies (). Having not any problems on follow-ups, the patient was discharged with recommendations, and with starting albendazol 10 mg/kg on 3 post-op days. |
pmc-6068371-1 | A 40-yr-old female patient was admitted to of Razi Hospital of Qaemshahr City in north of Iran in Nov 2015 with complaint of headache, blurring of vision, dysarthria and acute left-side hemiplegia and right-sided ptosis. Three weeks ago, she had gone to another hospital that after checking she was diagnosed with brain abscess. Magnetic Resonance Imaging (MRI) with intravenous contrast was performed and showed a ring enhancement lesion in the right basal ganglia (). Despite the performed MRI and diagnosis of TE, biopsy of brain was done and the biopsy sample sent to pathologist. In pathology slide, tachyzoite of T. gondii was seen. Observations of tachyzoites show reactivation of parasites considered as indicator of TE ().
In lab data Anti Toxoplasma IgG was positive (other laboratory tests in the below table have been brought) (). HIV antibody test was requested which revealed positive by ELISA method that Western blot method confirmed it. Her husband was an addict and died a few years ago. Toxoplasmosis treatment was done with pyrimethamine, sulfadiazine, folinic acid, and dexamethasone for six weeks that decreased Anti Toxoplasma IgG significantly. Moreover, triple therapy of Anti-HIV drugs (Tenofovir, emtricitabine, and efavirenz) was performed. She was discharged from hospital in relatively good condition. For follow up of this patient, imaging of brain was done in which ring enhancement lesion was eliminated. |
pmc-6068650-1 | A 37-year old homeless male, with a past medical history of peripheral vascular disease, type 1 diabetes mellitus, hypertension, and depression, presented to the emergency department with intermittent chest pain and progressive shortness of breath for a few weeks. The patient denied intravenous drug use, although admitted to the use of recreational marijuana. The patient’s vitals on admission were stable except for low saturation on a pulse oximetry of 86% on room air. On physical examination, the patient was tachypnic and had fine crackles in the bilateral lung fields on auscultation. Laboratory results on admission showed a normal complete blood count and basic metabolic panel, but a urine drug screen test was positive for opioids. Because of persistent hypoxia, a D-Dimer was checked and came back highly elevated. The patient underwent a computed tomography angiography (CTA) of the chest to rule out pulmonary embolism. The CTA was negative for pulmonary embolism, however, it displayed extensive miliary densities throughout the bilateral lung fields (). The patient was admitted to the floor with a differential diagnosis of military tuberculosis versus fungal infection. Human immunodeficiency virus (HIV), fungal, and Quantiferron testing were negative. The cardiac work up and autoimmune serology were also unremarkable. The patient was then started on intravenous steroids and inhaled albuterol, although no improvement was seen. The patient remained hypoxemic despite therapy, and, therefore, underwent a bronchoscopy with a lung biopsy to find out the etiology of the disease process. The lung biopsy showed alveolated lung tissue with a miliary pattern of perivascular foreign body histiocytes containing refractory material suggestive of microcrystalline cellulose material (). There was no evidence of malignancy and there were no fungal or acid fast bacilli organisms identified on special stains. The histological features suggested intravenous injection of foreign material and upon further questioning the patient admitted to injecting oral opiates. The patient was started on intravenous steroids, although his clinical condition continued to decline. The patient developed hypercapnic respiratory failure, which required intubation, and eventually suffered from a cardiopulmonary arrest and passed away. |
pmc-6068752-1 | A 49-year-old male patient presented with acute-onset progressive abdominal cramping pain that had started 1 day previously. He had a medical history of poorly controlled diabetes mellitus and hypertension, as well as renal stone formation after percutaneous nephrolithotomy with double J replacement. There was no history of trauma. Dysuria and mild urgency were noted. He denied having any fever, chills, cough, chest pain, nausea, vomiting, and diarrhea. His temperature was 36.8 °C, blood pressure was 162/89 mmHg, and heart rate was 131/min. On physical examination, a hyperactive bowel sound was noted, accompanied by whole abdominal tenderness, especially at the left quadrant. The Murphy sign was negative, and no tenderness was noted at McBurney’s point. There was no bilateral knocking pain. The laboratory results were as follows: white blood cell count 40,250/µL (band-form neutrophils 2.0%, segment-form neutrophils 86.0%, lymphocytes 5.0%, eosinophils 0.0%, and monocytes 6.0%), hemoglobin 6.7 g/dL, platelet count 645,000/mL, blood urine nitrogen 51 mg/dL, creatinine 1.9 mg/dL, sodium 124 mmol/L, potassium 5.5 mmol/L, glucose 790 mg/dL, alanine aminotransferase 19 U/L, lipase 768 IU/L, total bilirubin 1.00 mg/dL, troponin I <0.01 μg/L, ketone bodies 4.5 mmol/L, and serum osmolarity 336 mOsm/kg. The urinalysis results were as follows: Red blood cell count 10–19/high-power field (HPF), white blood cell count 10–19/HPF, glucose 4+, ketone bodies 1+, bacteria 1+/HPF, and yeast 3+/HPF. The venous blood gas analysis revealed the following results: pH 7.390, pCO2 29.2 mmHg, pO2 44.5 mmHg, HCO3 17.3 mmol/L, actual base excess −6.3 mmol/L, base excess in extracellular fluid −7.6 mmol/L, and O2 saturation 78.9%. The detailed results of laboratory evaluations are listed in . The plain film showed diffuse bilateral opacities over the lung field (A). The kidney, ureter, and bladder (KUB) study revealed gallbladder stone, double J catheter placement from the pelvic cavity to the right renal region, and a heterogeneous mass with air density at the left side (B).
Contrast-enhanced abdominal CT was performed, which revealed several cavitary nodules in both lower lung fields (A,B). A perirenal heterogeneous mass with gas density was found inside the left renal capsule (C). According to the above-mentioned clinical symptoms and images, EPN and multiple septic pulmonary emboli were suspected. The broad-spectrum antibiotics meropenem and teicoplanin were administrated for sepsis. Meropenem was administered for 13 days and teicoplanin was used for 9 days; then, the patient was shifted to ceftriaxone for 3 days. In addition, the patient’s hyperkalemia was treated with insulin in 5% glucose solution and calcium polystyrene sulfonate powder (Kalimate). Transfusion of 2 U packed red blood cells was done for anemia. Famotidine was administered to prevent stress ulcer. Emergency percutaneous nephrostomy was done (D), and pus and urine were collected for culture. The cultures showed E. coli growth in urine and pus. No growth of significant aerobic or anaerobic pathogens in blood was noted. After timely treatment, the sepsis was controlled. The follow-up plain film and abdominal CT revealed a few cavitary nodules and less accumulation of perirenal abscess. The patient was discharged and followed up at the urologic and chest outpatient departments. The follow-up serum creatinine level is summarized in . This study was approved by the Institutional Review Board (IRB) of Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (IRB no. 07-CR-059). |
pmc-6069027-1 | Patient 1 is an 88-year-old white male, a retired pathologist, with a dual diagnosis of melanoma and squamous cell carcinoma of the left ear, neck, and forehead. A small flat patch had been observed since about 5 years. First diagnosed with a small retro-auricular melanotic growth, it grew rapidly and later examination revealed a large fungating mass that was warty, bulky, and elevated in appearance protruding from the left external auditory canal with involvement of the postauricular region and the mastoid area. A positron emission tomography scan demonstrated local spread to cervical lymph nodes without evidence of metastases.
Having been deemed an inappropriate candidate for curative resection due to the size and spread of the primary lesion, the patient was started on 3 mg/kg of the anti-PD-1 inhibitor, nivolumab, administered every other week, which appeared to result in rapid exophytic spread with increased production of blood-tinted (serosanguinous) discharge. A hypothesis of pseudoprogression recommended continuation of nivolumab. At patient’s insistence, aggressive resection/surgical debulking was performed with nivolumab continued perioperatively. Over the next few weeks, treatment with nivolumab resulted in significant shrinkage of the residual tumor, as shown in . |
pmc-6069027-2 | Patient 2 is a 65-year-old white male with melanoma metastatic to the lungs, spine, abdomen, and coccyx. Prior treatment summary included resection of abdominal masses to relieve bowel obstruction, radiation to coccyx, and wedge resection of lung metastases in August 2014, since they were limited in number. Subsequently, he received 4 cycles of the anti-CTLA-4 inhibitor, ipilimumab, with a diagnosis of stable disease. Four months later, he was started on the anti-PD-1 inhibitor, nivolumab. Ten months later, he underwent debulking surgery of enlarging abdominal masses, diagnosed as inoperable, and resection of the coccyx metastasis, respectively. In January 2016, during repair of an abdominal wall defect (with nivolumab continued perioperatively), it was discovered that the tumors disappeared. Positron emission tomography/computed tomography scan demonstrated complete resolution of the abdominal masses and mild residual metabolic activity within the surgical cavity of the coccygeal mass, likely indicative of postsurgical/inflammatory change. |
pmc-6069027-3 | Patient 3 is a 47-year-old white female with squamous cell cervical cancer that originally presented as FIGO (Federation of International of Gynecologists and Obstetrician) stage 1B and was treated with radiation therapy. She subsequently developed recurrence with metastases in the lungs, adrenal gland, and paraspinal tissues and was treated with carboplatin/paclitaxel and bevacizumab and palliative radiotherapy (2700 cGy) to the paraspinal mass. On progression, she was started on a Phase I clinical trial called PRIMETIME (NCT02518958), which involves dosing of nivolumab with the experimental epigenetic and macrophage and cancer stem cell-targeting agent, RRx-001.
At her first 6-week restaging scan, the patient showed stable disease with an approximately 10% reduction in tumor size. Her second 12-week restaging scan demonstrated significant growth of the paraspinal thoracic mass with apparent encroachment of the spinal canal at the level of T5 even while the rest of her lesions continued to diminish in size (). However, most unusually, the patient did not describe any neurological symptoms. In fact, the day before, the patient went for a 3-mile run. Her chief—and only—complaint was back pain for which she took gabapentin (100 mg, PO) and oxycodone (5 mg, PO, PRN). On physical examination, the patient was neurologically intact with normal reflexes, muscle tone, and sphincter functions and negative Babinski signs.
One week later, the patient underwent surgical resection without incident and with postoperative resolution of her back pain. Pathology of the tumor showed the replacement of necrotic tumor cells with collagenous scar. The rest of her lesions continued to diminish in size in the absence of any treatment, possibly due to surgically induced immunogenicity effects. |
pmc-6069036-1 | A 47-year-old African American male with stage III cutaneous T-cell lymphoma with large cell transformation presented to the hospital with shortness of breath, fatigue, and failure to thrive. The patient had progressed through multiple lines of chemotherapy including EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), romidepsin, gemcitabine, brentuximab, and pralatrexate. At inpatient presentation, he had malignant pleural effusions, hypercalcemia, and leukocytosis with eosinophilia. Given the patient’s rapidly worsening clinical course, it was decided to start ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/ on day 2 infused over 24 hours, and carboplatin with an area under curve (AUC) of 5 on day 3. He was alert and oriented prior to and during the infusion but became delirious on day 3 of the regimen, 6 hours after the completion of the ifosfamide infusion. Physical examination did not reveal any stereotypical movements or twitching. His mental status worsened from initial agitation and confusion to drowsiness and eventually stupor. Diagnostic evaluation for acute mental status change including complete blood count, comprehensive metabolic panel, ammonia level, and computed tomography scan of the head was negative. Infectious workup including blood cultures, urine culture, and chest X-ray did not reveal any infectious process contributing to the altered mental status. Thus, the patient’s acute altered mental status was attributed to IME. He was started on hydration, and 50 mg of intravenous MB was given every 4 hours. His mental status began to improve 16 hours after start of MB and was back to his baseline after 48 hours of treatment (received 12 total doses). The one cycle of ICE chemotherapy temporarily improved his disease but due to neurotoxicity, he was not rechallenged. |
pmc-6069036-2 | A 38-year-old African American female with refractory stage IV mycosis fungoides with large cell transformation was admitted to the hospital for initiation of ICE chemotherapy. Patient had extensive cutaneous and muscle involvement of the lymphoma and had failed multiple lines of chemotherapy regimens including romidepsin and rituximab, brentuximab, and gemcitabine. Laboratory testing prior to initiation of ICE therapy was normal except for low serum albumin level of 1.7 g/dL. Patient received ICE therapy with etoposide 100 mg/m2 on days 1 to 3, ifosfamide 5000 mg/m2 on day 2 infused over 24 hours, and carboplatin with an AUC of 5 on day 3. She was premedicated with aprepitant for prevention of nausea. She was alert and oriented prior to and during the infusion but became lethargic, somnolent, and confused within 6 to 8 hours of completion of ifosfamide infusion. Physical examination was significant for random jerky movements of both upper and lower extremities, twitching of the right eye, and somnolence. The patient’s evaluation for sudden neurological changes included complete blood count, comprehensive metabolic panel, computed tomography scan of the head, and infectious workup (blood cultures, urine culture, and chest X-ray), all of which were negative. She received naloxone with no reversal of mental status changes. Based on the timing of the infusion and change in mental status, patient was diagnosed with IME and MB was immediately initiated at a dose of 50 mg every 4 hours. An improvement in the patient’s mental status was noticed within 12 hours of initiation of MB, and the patient was back to her baseline in 72 hours (received 18 total doses). Given the neurotoxicity, patient was not rechallenged with ifosfamide and was switched to a different chemotherapeutic regimen. |
pmc-6069038-1 | A 23-year-old male came to the emergency department with excessive salivation, difficulty in swallowing, and speech immediately after eating some Chinese food. It was associated with retching but no vomiting, abdominal pain, diarrhea, chest pain, cough, or difficulty in breathing. Rest of the review of symptoms was negative. He had no significant past medical history. However, he reported multiple similar episodes in the past for which he had undergone extensive gastroenterological workup, the details of which he did not know at presentation. He was a nonsmoker and did not use any drugs. He had no known drug or food allergy and reported eating the same food from the same eatery multiple times in the past with no reaction. At presentation, his temperature was 98.2°F, pulse was 73 beats per minute, blood pressure was 117/42 mm Hg, and respiratory rate was 22 breaths per minute with oxygen saturation of 97% in room air. Physical examinations were significant for drooling and hyperventilation with diffuse wheezing on chest auscultation. Complete blood counts revealed hemoglobin of 15 g/dL (normal 13-17 g/dL), hematocrit of 45% (normal 39% to 53%), platelet count of 234 000/µL (normal 130 000-400 000/µL), and a white cell count of 13 000/µL (normal 4500-11 000/µL) with a neutrophil of 47% (normal 40% to 70%), lymphocyte of 42% (normal 22% to 48%), eosinophil of 2.6% (normal 0.5% to 5%), and basophil of 0.6% (normal 0% to 2%). Rest of the blood works including blood chemistry and coagulation profile was normal. Chest X-ray was normal. The initial troponin was 0.01 ng/mL, and the electrocardiogram showed normal sinus rhythm with no acute ST or T wave changes (). Urine toxicology screen was negative.
So with the presumed diagnosis of angioedema, he was treated with 125 mg of intravenous methylprednisolone, 50 mg of intramuscular diphenhydramine, and 0.5 mg of intramuscular epinephrine. However, immediately after the administration of epinephrine, he started to complain of palpitation and increasing chest tightness. His pulse jumped to around 150 beats per minute, while his blood pressure dropped to 98/64 mm Hg. Repeat electrocardiogram (EKG) showed ST elevation in V1, V2, and aVR, and ST depression in leads II, III, aVF, and V4-V6 (). Serum troponin jumped to 2.14 ng/mL. He was treated with 1 inch of topical nitroglycerin paste, 325 mg of aspirin, 40 mg of atorvastatin, and intravenous normal saline. His chest pain and palpitation resolved over the next 10 minutes with resolution of his EKG changes (). Echocardiography was done subsequently and showed normal systolic and diastolic function with no regional wall abnormality. Over the course of the next day, his serum troponin rose to 2.30 ng/mL before trending downward to 1.3 ng/mL, and his presenting symptoms of difficulty in swallowing and speech resolved. However, given his low cardiac risk factors and the likely cause for the myocardial ischemia being coronary artery vasospasm rather than atherosclerotic disease, cardiac angiography was not done. During the course of his hospitalization, records of his previous gastroenterological workup were obtained that showed severe tightening of proximal esophageal sphincter with distal esophagitis on enterogastroduodenoscopy and normal gatroesophageal peristalsis on radiocontrast study. In the background of these findings with recurrent similar symptoms in the past and absence of other findings suggestive of allergy, his presenting symptoms were attributed more to his esophageal spasm and less to an allergic reaction. The patient was then discharged home to follow-up as an outpatient. |
pmc-6069501-1 | An 11-year-old Caucasian girl was referred to our hospital ward for the evaluation of right labium majus swelling. History of illness, systemic disease or trauma was denied. On admission, her vital parameters were normal. In her physical examination, there was no abnormality except for the right labium majus, which showed a palpable, painless, soft, non-tender, non-erythematous enlargement measuring approximately 2 cm with indistinct borders. The vaginal introitus and external meatus were normal, with no evidence of clitoral hypertrophy. Laboratory investigations revealed normal complete blood count, liver and renal function tests. Serum levels of acute phase reactants were within normal limits, such as serum levels of FSH, LH, estradiol, total testosterone, and thyroid hormones. Ultrasound showed a mass 23 × 18 × 12 mm in diameter characterized by an increased amount of labial soft tissue on the affected side with a similar echogenicity to the contralateral side.
Surgical excision of the mass was performed. In the histopathological evaluation, the tissue specimens were composed of haphazardly arranged vascular channels, adipose tissue and nervous elements that were compatible with the diagnosis of CALME (). However, all these components are usually constituents of the normal vulvar soft tissue.
Follow-up was performed at 1, 6 and 12 months without evidence of recurrence. |
pmc-6069501-2 | A 6-year-old Caucasian girl presented a post-traumatic painless mass of left labium majus swelling that progressively increased in volume ().
A careful clinical examination was made, with no evidence of other alterations. As in Case 1, laboratory tests revealed no signs of a chronic or neoplastic condition and no endocrine abnormalities. Ultrasound study evidenced an ill-defined heterogeneous echotexture mass 26 × 15 × 10 mm in diameter ().
The area of enlargement blended into the normal labial tissue, and there was no definable capsule. Magnetic resonance imaging (MRI) confirmed these findings, namely, asymmetrical mildly enlarged labial tissue composed of homogeneous hypointense signal on T1-weighted imaging and hypo- to isointense to muscle on T2-weighted images.
Histopathological examination was performed after bioptic sampling evidencing normal constituents of vulvar soft tissue, including fibroblast, collagen, adipose tissue, blood vessels and nerves compatible with CALME (). The immunohistochemistry results were positive for estrogen and progesterone receptors. No evidence of recurrence was found at follow-up visits performed at 1 and 6 months after surgical excision. |
pmc-6069780-1 | A retroperitoneal mass on the left side was found in a 65-year-old-man who was then referred to the Urology Department. He had been receiving methylprednisolone and cyclosporine as treatment for rheumatoid arthritis with vasculitis in the Rheumatology Department of the same hospital. He complained of exertional dyspnea and was hospitalized on suspicion of atypical pneumonia. Blood tested positive for both β-D-glucan and aspergillus antigen. A diffuse nodular shadow across both lungs was seen on chest computed tomography (CT) and a diagnosis of pulmonary aspergilloma was made. Treatment with voriconazole (200 mg twice a daily) was initiated.
On subsequent CT 8 months thereafter, the nodular shadow in the lungs appeared smaller, but a mass in the left retroperitoneum was now seen. Consequently, he was referred to the Urology Department. His past medical history included rheumatoid arthritis with vasculitis, steroid-induced diabetes, hyperlipidemia, and compression fracture of the lumbar vertebrae. He had been receiving methylprednisolone and cyclosporine treatment for 8 years. In addition, he received bezafibrate and his diabetes was controlled with hypodermic insulin and oral sitagliptin. He had no notable family history. The patient’s physical findings were normal, except for chest and joint symptoms related to rheumatoid arthritis with vasculitis.
Blood test results on admission were as follows: white blood cells, 11830/μL; C-reactive protein, 2.16 mg/dL; glucose, 250 mg/dL; total-cholesterol, 230 mg/dL; triglyceride, 642 mg/dL. There was no apparent liver or kidney dysfunction. The aspergillus antigen level was 0.7 (positive, > 0.5) and the β-D glucan level was 240 pg/ml (> 11.0). The frequent occurrence of a diffuse nodular shadow across both lungs on a simple CT image of the chest was noted. Thus, intravenous voriconazole was commenced. On subsequent CT 3 weeks later, a reduction in the pulmonary nodular shadow and improvement of the previous pneumonia was identified (Fig. ). The voriconazole dose was altered for oral application (200 mg/day). He was then referred to the Urology Department once more because a 35-mm mass was found in the retroperitoneal cavity on CT (Fig. ).
The tumor did not exhibit any internal contrast uptake and a film-like layer of contrast was seen around the border on abdominal contrast-enhanced CT. As a result, we believed that the tumor was not a renal angiomyolipoma; however, it was considered possible that it was a lipoma, liposarcoma, or teratoma. We recognized the mixed heterogeneous nature of the high-low signal on abdominal magnetic resonance imaging in both the T2 and T1-weighted images, with signal strength decreasing on the T1 fat suppression images. As liposarcoma could not be ruled out, a left retroperitoneal tumor resection was performed (Fig. ).
We performed a lumbar incision under the left 12th rib with the patient in the jackknife posture during surgery. The mass did not adhere to the surrounding tissues, so there was a small amount of blood loss.
Histological examination identified the contents of tumor as adipose tissue and necrotic debris that were encapsulated by fibrous connective tissue, with a large number of fungal hyphae in the tumor. A blood vessel cavity that passed through the necrotic tissue was identified as the origin (Fig. ). Because the origin showed a Y-shaped divergence with the form of the constituent part, the histopathological diagnosis was aspergilloma. The postoperative course was uneventful and the patient was discharged 10 days after surgery. Thereafter, he continued antifungal therapy and no recurrence was seen on follow-up CT. In the tenth month after the operation, he developed pancytopenia, thought to be related to bone marrow suppression, with Cytomegalovirus infection. He suffered respiratory failure and succumbed. |
pmc-6069820-1 | A 31-year-old man with no medical history was presented to our emergency department (ED) with disturbance of consciousness and generalized seizure. After having a fever, he had been out of contact for 3 days and his colleague found him unresponsive in his apartment. Soon after arriving at the ED, he showed generalized tonic-clonic seizure (GTCS) starting from his left limbs, which ceased after intravenous diazepam 10 mg. Weakness, pyramidal signs, and meningeal irritation signs were not seen. Laboratory examination showed systemic inflammation: white blood cells 26,100/μL and C-reactive protein 8.56 mg/dL. Creatinine was 1.69 mg/dL, urea nitrogen was 41.0 mg/dL, and creatine kinase was 60,264 IU/mL, showing dehydration and rhabdomyolysis presumably due to prolonged impaired consciousness. Lumber puncture was unremarkable except for increased opening pressure (30 cmH2O): cells 2.4/μL, protein 26 mg/dL, glucose 97 mg/dL, and IgG 2.0 mg/dL. Culture of cerebrospinal fluid was negative. Serum HIV, herpes simplex virus, and varicella zoster virus antibodies were negative. Anti-nuclear, anti-double-stranded DNA, anti-glutamic acid decarboxylase, anti-thyroid peroxidase, anti-thyroglobulin, and anti-neutrophilic cytoplasmic antibodies were negative as well. Magnetic resonance imaging (MRI) showed no intracranial lesion or abnormal gadolinium enhancement (Fig. , ). Interictal electroencephalogram showed generalized periodic delta waves predominantly on the bilateral frontal areas (Fig. ).
Despite administering 1000 mg of fosphenytoin for the seizure, he repeated GTCS on day 2. He was intubated and mechanically ventilated on that day due to GTCS accompanied with respiratory depression. Although valproate 900 mg through the nasogastric tube and intravenous propofol was started and the dose of propofol was gradually increased, GTCS recurred on day 5 and levetiracetam 1000 mg and intravenous midazolam was added to control the seizures. Even with these medications he repeated GTCS during day 7 through 14, which obliged us to increase the dose of midazolam to the maximum and levetiracetam to 3000 mg, and also add carbamazepine 400 mg and zonisamide 600 mg. Tracheotomy was performed on day 15 because of prolonged mechanical ventilation. During days 15–19, EEG showed periodic sharp discharges predominantly on the bilateral frontal regions every 0.5–1.0 s even during the patient did not manifest apparent seizure (Fig. d), suggesting the condition of non-convulsive status epilepticus (NCSE). Propofol was transferred to thiopental and its dose was increased to the level that leads to a burst and suppression pattern on EEG during days 20–25.
During this period, repeat head MRI and lumber puncture showed no cause of the status epilepticus. Chest and abdominal computed tomography (CT) and positron emission tomography (PET) did not represent neoplastic lesions. Based on several recent reports, we presumed some occult autoimmune disorders were behind this patient’s refractory status epilepticus and immunomodulative therapy could be effective. The patient received intravenous methylprednisolone (IVMP) on days 25–27 (methylprednisolone 1000 mg/day for 3 days), but his EEG continued to manifest epileptic discharge when the general anesthesia was tapered. We administered plasma exchange (PE) on days 31–35 and intravenous immunoglobulin therapy (IVIG) on days 36–38 (0.4 g/kg for 3 days), under the informed consent of his family (Fig. ). He came to show gradual improvement of consciousness and decreased epileptic discharge on EEG around day 35, making it possible to taper the anesthesia. Mechanical ventilation was discontinued on day 42, and the sedative agents for general anesthesia were withdrawn by day 44.
The patient gradually regained his ability of daily life and showed well-preserved memory function and his computer skills for the job, but mild anterograde amnesia, irritability, and difficulty in concentration remained. Although the patient was discharged home on day 189, refractory focal onset seizures with impaired awareness were seen every 2–3 days which required valproate 1200 mg, levetiracetam 3000 mg, zonisamide 400 mg, lamotrigine 200 mg, and clobazam 7.5 mg. |
pmc-6069825-1 | A 54-year-old male, with alcohol-related liver cirrhosis and a calculated Model for End- stage Liver Disease (MELD) score of 28, presented for deceased donor LT. ESLD was complicated by hepatic encephalopathy, ascites, spontaneous bacterial peritonitis (SBP), and esophageal varices. A preoperative transthoracic echocardiogram (TTE) performed 10 months before transplantation demonstrated normal size and systolic function of both ventricles (RV and LV), no valvular or regional wall motion abnormalities, normal pulmonary artery pressures, and a left ventricular ejection fraction (EF) of 65%. The TTE did, however, demonstrate bi-atrial dilatation, and evidence of diastolic dysfunction with an E/A ratio of 0.9, a deceleration time (DT) of 278 ms, and tissue Doppler early diastolic velocities of 8 cm/s at the annulus and 12 cm/s at the septum indicating impaired relaxation. References for degree of diastolic dysfunction are provided in Table . A dobutamine stress echocardiogram (DSE) was negative for ischemia and an electrocardiogram (EKG) performed at the same time as TTE demonstrated normal sinus rhythm with a prolonged QTc interval of 476 ms.
Shortly after the beginning of pre-anhepatic phase, transesophageal echocardiography (TEE) demonstrated an EF of 40–45% with no wall motion abnormalities. The surgical procedure was complicated by blood loss of 5.5 l with the patient receiving 3 L of crystalloids, 1 L of 5% albumin, 16 units of fresh frozen plasma (FFP), 15 units of packed red blood cells (PRBC), 3 units of platelet concentrate, and 3 units of cryoprecipitate. Despite the significant blood loss and reduction in EF, hemodynamic stability was maintained throughout the case with minimal vasopressor support (norepinephrine (NE) infusion 0.02–0.05 mcg/kg/min with intermittent boluses (10–20 mcg) during reperfusion). Hemodynamics and arterial blood gas data is presented in Table .
The patient was admitted to the Surgical Intensive Care Unit (SICU) for postoperative management in stable condition.
In the SICU, the patient initially remained intubated and sedated with propofol and fentanyl infusions titrated to a Riker Sedation Score of 3–4. Weaning attempts failed due to episodes of agitation and hypertension. Despite a normal postoperative hepatic Doppler study and both laboratory and clinical improvement in liver function, the patient’s neurological status did not improve. A brain MRI performed on post-operative day (POD) 3 was normal. On POD 5, the patient’s mental status improved significantly and he was successfully extubated. A few hours after extubation, however, the patient complained of difficulty breathing and became hypoxic with chest X-ray findings consistent with acute pulmonary edema. This episode resolved with aggressive diuresis and continuous positive airway pressure (CPAP). On POD 6, a similar episode occurred but was only minimally responsive to escalating doses of diuretics and CPAP.
TTE performed at that time demonstrated diffuse LV hypokinesis, an EF of 25%, dilated left and right atria, and a dilated RV with globally reduced function. EKG demonstrated a prolonged QTc of 510 ms with no new ST-T changes. Three sets of cardiac enzymes performed 4 h apart were negative. Later that day, the patient developed new onset atrial flutter with episodic arterial desaturation requiring re-intubation and mechanical ventilation. A pulmonary artery catheter (PAC) was placed and a dobutamine infusion was started with a goal to keep the mean arterial pressure (MAP) above 65 mmHg (PAC data in presented in Table ). Over the next few days, the patient developed progressively worsening hypotension, requiring escalating doses of vasopressors. Daily TTE demonstrated continuing deterioration of cardiac function with an EF as low as 10%. The patient’s renal function deteriorated and continuous renal replacement therapy (CRRT) was begun.
Due to worsening cardiogenic shock, the patient was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) on POD 10. Despite ECMO support, the LV remained distended and globally hypokinetic. An Impella® device (Abiomed, Danvers, MA, USA) was placed to provide ventricular decompression. Over the course of the next few days, inotropic support was weaned and TTE demonstrated decreased LV dilation and an improvement in function (EF of 40%). The Impella® device was discontinued and a low dose epinephrine infusion was started. The patient tolerated a clamp trial and VA-ECMO was weaned. At the same time, however, liver transaminases began to increase. Liver Doppler evaluation demonstrated thrombosis of the left portal vein and decreased flow in the hepatic arteries. This was despite being maintained on a heparin infusion with a target activated partial thromboplastin time (aPTT) of 50–60 s. His clinical condition continued to deteriorate requiring an escalation of vasopressor support.
Postoperatively, this patient received 20 U PRBC (not more than 2 U/day), 1 U of FFP (on POD 0), and 8 U of platelets. Crystalloids were used as maintenance and fluid management was directed using TTE. After extensive discussions with the family, care was withdrawn and the patient expired on POD 31. |
pmc-6069825-2 | A 47-year-old male, with alcohol-related liver cirrhosis and a calculated MELD score of 39, presented for deceased donor LT. His ESLD was complicated by esophageal varices, upper gastrointestinal bleeding, and SBP. This patient’s abnormal laboratory studies included a serum iron level of 144 mg/dl (normal range 49–181 mg/dl), ferritin of 3670 ng/ml (normal range 17.9–464 ng/ml), and iron saturation of 85% (normal range 20–55%). As a result of these abnormal lab results, genetic testing was performed to determine if there was any genetic predisposition to hemochromatosis. Genetic testing did, in fact, reveal that the patient was heterozygous for HFE (HFE-H63D) and alpha-1 antitrypsin (PiSZ), predisposing him for hemochromatosis. Preoperative TTE performed 2 months prior to LT demonstrated mild left ventricular hypertrophy with an EF of 55%, mild bi-atrial dilatation, and a dilated RV with normal systolic function. There were no valvular abnormalities and pulmonary arterial pressures were normal. In addition, the TTE demonstrated some degree of diastolic dysfunction (impaired relaxation) with an E/A ratio of 1.1, a DT of 228 ms, and tissue Doppler early diastolic velocities of 6 cm/s at the annulus and 9 cm/s at the septum. EKG demonstrated a prolonged QTc of 479 ms. Myocardial Perfusion Scintigraphy (MPS) performed 3 weeks before LT demonstrated an EF of 54% with no evidence of ischemia or infarction.
The surgical course was uneventful with an estimated blood loss of 1.6 l. Intraoperatively, the patient received 5 units PRBC, 2 units of platelet concentrate, 1 L blood from cell saver, 2000 mg of fibrinogen (RiaSTAP), 1000 units of prothrombin complex concentrate (Kcentra), and 1 L of crystalloid. Intraoperatively, this patient required NE administration (0.02–0.08 mcg/kg/min with 0.2 mcg/kg/min for a short period of time during the anhepatic phase). Hemodynamics and arterial blood gas results are presented in Table . Intraoperative TEE demonstrated normal cardiac function with an EF of 55% and no valvular abnormalities. The patient was admitted to the SICU for postoperative management where he was extubated on POD 1.
On POD 4, the patient’s mental status decreased significantly and had an increasing oxygen requirement. Auscultation of the lungs demonstrated wheezing in all lung fields and chest X-ray findings were consistent with acute pulmonary edema. TTE at that time demonstrated a mildly dilated LV with diffuse hypokinesis and severely reduced systolic function (EF 20%). The left atrium was severely dilated and there was a moderate degree of mitral regurgitation. The RV was severely dilated and diffusely hypokinetic with reduced systolic function. Troponins were mildly elevated (0.024 ng/ml (normal< 0.010 ng/ml)) and brain natriuretic peptide (BNP) was significantly elevated (7625 pg/ml (normal < 125 pg/ml)). EKG demonstrated sinus tachycardia with no ST-T changes. The patient received aggressive diuresis along with CPAP. A beta-blocker and heparin infusion was started. Coronary angiography was performed which was unremarkable.
Over the next few days, the patient’s cardiac function remained unchanged (as assessed by serial bedside TTEs), however, his hemodynamics continued to deteriorate. A PAC was placed and dobutamine and NE infusions started with a goal to keep the MAPs above 65 mmHg (please see PAC data in Table ). After the administration of catecholamines, the patient continued to deteriorate and was re-intubated. He also developed a severe metabolic acidosis, supraventricular arrhythmias requiring cardioversion, and acute renal failure requiring CRRT. His liver function continued to deteriorate and he became progressively encephalopathic. An abdominal CT scan demonstrated a hepatic artery thrombosis. A heparin infusion was started and titrated to target an aPTT of 50–70 s. In view of a continued decline in cardiac and hepatic function, the decision was made to withdraw care on POD 22.
Postoperatively, this patient received 5 U of PRBC and 2 U platelets. Cardiac function was evaluated by daily TTE performed by a certified ICU physician. Fluid administration was also directed by TTE.
Microscopic examination of the explanted liver demonstrated signs of alpha-1 antitrypsin deficiency (globules within hepatocytes) as well as very large amounts of iron deposits within the hepatocytes; a sign of hereditary hemochromatosis. Postmortem pathology demonstrated an enlarged heart (490 g), RV hypertrophy, dilation of all valves, and minimal atherosclerotic changes of the left main coronary artery, left anterior descending artery, and aorta. Microscopic examination of cardiac tissue demonstrated stainable iron within both the myocytes and cells of the conduction system. |
pmc-6069825-3 | A 64-year-old male patient, with cryptogenic liver cirrhosis and hepatocellular carcinoma with calculated MELD score of 21, presented for a deceased donor LT. His ESLD was complicated by recurrent ascites, non-bleeding esophageal varices, portal hypertensive gastropathy, and hepatic hydrothorax. His other medical problems included a prior myocardial infarction (3 years prior to LT) treated with a bare metal stent, Grave’s disease, and asthma. A TTE performed 3 months prior to LT revealed a small LV cavity with normal systolic function (EF of 63%), no valvular or regional wall motion abnormalities, a small pericardial effusion, and normal pulmonary artery pressures. The E/A ratio in this case was 0.74 with a deceleration time of 289 ms. Tissue Doppler early diastolic velocities were 8 cm/s at the annulus and 11 cm/s at the septum indicating impaired relaxation. Preoperative EKG demonstrated a prolonged QTc of 467 ms. MPS performed 3 months before LT demonstrated an unchanged fixed deficit in the infero-lateral wall.
The patient’s surgical course was complicated by blood loss of 5 l, primarily during the pre-anhepatic stage due to significant adhesions from repeated paracentesis. He received 24 units of PRBC, 24 units of FFP, 3 units of platelet concentrate, 1000 mg of fibrinogen (RiaSTAP), and 4.5 L of crystalloid. Despite the significant blood loss, hemodynamics was maintained within a normal range with minimal vasopressor support (NE was administered 0.03–0.7 mcg/kg/min with 0.3 mcg/kg/min for a short period of time during the anhepatic phase). Hemodynamics and arterial blood gas analysis are presented in Table . Intraoperative TEE demonstrated an EF of 65%. The patient was admitted to the SICU for postoperative management and was extubated on POD 1.
On POD 2, he developed acute respiratory distress with hypoxemia (SpO2 < 90%) and an increasing oxygen requirement. Chest x-ray demonstrated acute pulmonary edema with bilateral moderately sized pleural effusions. TTE at this time revealed a mildly dilated left ventricle with severely reduced systolic function (EF of 20%) and diffuse hypokinesia. The RV was also dilated with reduced systolic function. Pulmonary artery pressures were mildly elevated and there was no valvular dysfunction. Other laboratory results obtained on the same day demonstrated an elevated troponin (0.182 ng/ml) as well as a markedly increased BNP (greater than 35,000 pg/ml). EKG demonstrated normal sinus rhythm with a prolonged QT of 488 ms. Troponins peaked at 0.463 on POD 3 and then trended down. With aggressive diuresis and ventilator support, the episode resolved. Repeat TTE performed 3 days later demonstrated improving LV systolic function (EF of 40%) and normalization of pulmonary artery pressures. The patient was discharged from intensive care on POD 8, liver enzymes normalized by POD 13, and LV size and function returned to normal (EF 55%) on POD 32. Postoperatively, this patient received 1 U FFP on POD 6. TTE was routinely performed to assess cardiac function and direct fluid administration. |
pmc-6069874-1 | A 57-year-old female presented to the clinic with severe dyspnea at mild exertion (NYHA III) and a history of lymphocytic myocarditis. Her comorbidities included stage III chronic kidney disease (CKD), chronic gastritis and Hashimoto thyroiditis. Because of recurring episodes of sustained monomorphic ventricular tachycardia and repeated pre-syncopal events she had received an implantable cardioverter defibrillator in 2009, followed by a cardiac contractility modulation (CCM) – system in 2012. Despite optimal medical treatment (high dose ACEI, ß-Blocker, diuretics and MRA), the patient experienced a severe worsening of dyspnea and quality of life, with a progressive left ventricular ejection fraction (LV EF) reduction and LV dilation during the following years. A coronary heart disease and a recurrence of myocarditis had been excluded by coronary angiography and a repeated endomyocardial biopsy, respectively. For this reason, the patient was enrolled in the waiting list for heart-transplantation and, at the beginning of 2017, a CardioMEMS™ was implanted (Fig. ). In the first 3 months, she underwent 2 diuretic dose adjustments. A month later, the CardioMEMS™ documented a rise in pulmonary artery pressure (PAP, 34/24/17 mmHg, Fig. ). Therefore she was admitted to the hospital. A transthoracic echocardiogram showed her long-standing dilated cardiomyopathy picture with severe global LV hypokinesia and an ejection fraction of 30%. After excluding any potential cause accounting for the acute presentation, a 24-h infusion of calcium sensitizer levosimendan was administered. At hospital discharge, her basic hemodynamics had improved, as shown by a drop in estimated systemic and pulmonary vascular resistance (1375 and 338 dyn sec cm− 5 vs 1167 and 178 dyn sec cm− 5 respectively, before and after the infusion). These changes were accompanied by an increased cardiac output (4.5 vs 3.8 l/min). Pulmonary artery mean pressure at 1 week dropped after levosimendan infusion (− 13.5 mmHg x days, calculated as area under the curve change, Fig. ), and was correlated with symptomatic improvement. A single-beat view of the PAP before and after levosimendan administration clearly showed a decreased pulmonary mean pressure, as well as a decreased pulmonary pulse pressure at an unchanged heart rate (Fig. ). However, despite the initiation of an angiotensin receptor neprilysin inhibitor (ARNI, Sacubitril-Valsartan), which replaced the ACEI, a quick relapse and rise in PAP was observed. Given clinical and hemodynamic worsening despite Levosimendan administration and heart failure therapy optimization, we saw the indication for LVAD-Implantation. A few weeks later the patient underwent a LVAD Heart Mate III implantation as a bridge to heart transplantation. The procedure was uneventful and the patient was discharged home. Since LVAD-implantation, her NYHA class improved to class II, and her hemodynamic parameters have stabilized at lower pulmonary pressures over 7 months (mean PAP constantly below 20 mmHg, Fig. ). |
pmc-6069874-2 | A 74-year-old male with a history of dilated cardiomyopathy presented to the outpatient clinic with severe dyspnea at rest (NYHA IV). The patient’s comorbidities included arterial hypertension, dyslipidemia, GOLD stage II COPD, stage III CKD, type II-Diabetes, ulcerative colitis and Barrett’s esophagus. His cardiovascular history started in 2008 with recurrent atrial fibrillation episodes and ventricular ectopies of LBBB morphology. He underwent cardioversion and pulmonary vein isolation procedures. A coronary angiography in 2012 revealed a single vessel coronary artery disease, managed conservatively. In 2014 the patient underwent a MitraClip implantation for severe mitral regurgitation. Given the worsening of the patient’s symptoms, recurrent decompensation events, and a severely reduced LV function (LV EF 27%), an implantable cardioverter defibrillator was implanted for primary prevention in June 2015. In February 2016, a baroreceptor simulator was implanted and, given no NYHA class improvement, his medication was implemented with Sacubitril-Valsartan in April 2016. Another decompensation event followed in January 2017 and subsequently a CardioMEMS was implanted. In early 2017, the patient required a diuretic dose adjustment. As shown in Fig. , towards the middle of March 2017, PAP peaked (60/44/30 mmHg), and the patient was suggested to adjust the diuretic dose, allowing an effective reduction in PAP within 3 weeks (37/27/18 mmHg, a single-beat view is shown in Fig. ). Given the lack of NYHA class improvement and the sudden PAP rise, a month later the patient was admitted to the hospital for levosimendan infusion. On hospital admission, an echocardiogram was undertaken before inotrope infusion and revealed his previously known dilated LV with severely impaired LV systolic function (EF 27%) and global hypokinesia. After levosimendan administration we observed an improvement in his ejection fraction (LV EF 35%), associated with a mean PAP reduction from a peak of 33 mmHg to 25 mmHg (− 36 mmHg x days, calculated as area under the curve change at 1 week from infusion, Fig. ). Two supplemental clips with a 4-chamber-view from the echocardiographic examination before and after levosimendan infusion are available as online supplement (Additional files 1 and 2). |
pmc-6069874-3 | A 53-year-old male presented to our outpatient clinic with severe dyspnea at rest (NYHA IV) and a history of idiopathic dilated cardiomyopathy. His cardiovascular history included the occurrence of paroxysmal atrial fibrillation and ventricular arrhythmias (non-sustained ventricular tachycardia) that were managed with two previous catheter ablations. In 2015, he underwent a coronary angiography as well as left ventricular endomyocardial biopsy sampling that excluded coronary artery disease and myocarditis, respectively. In the same year, a cardioverter defibrillator was implanted (primary prophylaxis of sudden cardiac death). A year ago, he underwent a mitral valve repair with annuloplasty, and percutaneous patent foramen ovale (PFO) closure. Following recurrent hospital admissions with severe decompensation events poorly responded to optimal medical treatment (valsartan 80 mg twice daily, torasemid 5 mg twice daily, bisoprolol 2.5 mg twice daily, eplerenon 25 mg once daily), a CardioMEMS system was implanted in June 2017.
During CardioMEMS implantation a LV end-diastolic pressure of 14 mmHg and a cardiac index of 2.4 l/min were measured. A week post hospital discharge, he had another decompensation event (severe dyspnea and 3 kg weight gain), correlated with a sudden rise in PAP (59/45/35 mmHg) leading to a further hospital readmission. During this hospital stay, his systemic pressure profile and volume status improved on Sacubitril-Valsartan 24/26 mg twice daily and intravenous furosemide 30 mg twice daily respectively, while PAP showed slight improvement (46/33/25 mmHg), (Fig. ). The mid-term benefit of switching this patient with recurrent hospitalizations to the ARNI Sacubitril-Valsartan is shown in Fig. . In November 2017, ARNI dose has been increased to 49/51 mg twice daily. Since the first introduction of ARNI, both the patient’s subjective condition, his ejection fraction (LV EF increased from 29 to 39%, LV ESV from 146 to 133 ml, LVEDV from 205 to 219 ml from July to November) and his hemodynamics (a single-beat view from November 2017 is shown in Fig. ) have consistently improved, avoiding further hospitalizations. NT-pro BNP decreased from 76,733 ng/l in July 2017 to 1533 ng/l in November 2017. |
pmc-6069878-1 | A 68-year-old male was diagnosed with severe HEMA in early childhood, with less than 0.001% factor VIII activity. The brother of the proband also suffered from severe HEMA, thus the mother must have been carrier of the causative mutation. The children of the proband were male, and consequently, in this part of the family the mutation has not been passed on. Due to the distant past of the diagnosis, no genetic tests had been performed to identify the causative mutation. Around 30% of patients with severe HEMA develop inhibitors during their treatment with factor VIII, especially patients with large deletions and intron inversions. Thus, genetic factors can influence inhibitor development, and different treatment approaches are chosen according to risk of inhibitor development []. However, the proband never developed factor VIII inhibitors, possibly suggesting a smaller and less frequent mutation in F8 than the large intron inversion. Following blood transfusion, the proband was tested positive for HIV-1 and hepatitis C virus in the late 1980s and early 1990s, respectively. The patient was cured for his Hepatitis C infection, but never received any treatment for his HIV-1 infection, since he remained with normal CD4 T cell count over time and was considered an HIV long-term non-progressor (LTNP).
To identify the HEMA causative mutation (as well as possible mutations explanatory for his HIV LTNP phenotype), a blood sample was drawn in EDTA tubes (FLUKA), and peripheral blood mononuclear cells (PBMCs) were isolated over ficoll gradient (GE-healthcare). Integrating HIV DNA in CD4 T cells might result in false positive (somatic mosaic) mutations, or disturb the quality of sequencing. Therefore, CD4 T cells were depleted by magnetic purification (miltenyi biotec). DNA from non-CD4 T cells was purified using allprep DNA/RNA mini kit (Qiagen). Whole exome sequencing (WES) was performed employing Kapa HTP Library preparation and Nimblegen SeqCap EZ MedExome Plus kit and analysed using Nextseq v2 chemistry (2 × 150 bp). SNPs were called relative to hg19. Variant call files (VCF) were uploaded to Ingenuity Variant Analysis (IVA, Qiagen) and variants were compared to population frequencies of variants in the Allele Frequency Community (AFC) database and to frequencies in the 1000 Geneomes project. One hundred thirty thousand six hundred eighty-seven variants were identified in 16,957 genes in the patient, of which seven were located in the F8 gene. Two variants did not pass quality control, thus five variants could be possibly causative (see Table ). Four of the remaining variants had an allele frequency much higher than the disease frequency and were therefore judged as being irrelevant. Therefore, one variant (c.5411_5412delTCT, p.F1804del) remained a potential cause of disease (Fig. ). The mutation was verified in the raw BAM file (Additional file : Figure S1). Ingenuity did not provide any dbSNP ID or frequency for this variant, which is thus denoted as novel. Moreover, the variant was not reported in Coagulation Factor Variant Databases EAHAD.CFDB (), which provides all 5418 known transcript variants in the F8 gene, confirming that the c.5411_5413delTCT, p.F1804del must indeed be novel. |
pmc-6069891-1 | A 45-year-old woman presented to our hospital with multiple lung nodules. She had a history of poorly differentiated thyroid carcinoma, diagnosed 7 months prior to admission, at an outside hospital. The patient was healthy otherwise and reported no radiation exposure or any family history of thyroid cancer. The initial work-up at the time of discovery of the right thyroid nodule included fine needle aspiration and core biopsy, with findings consistent with poorly differentiated thyroid carcinoma. The patient then underwent a total thyroidectomy and central neck lymph node dissection. The pathologic diagnosis from the outside hospital reported a 2.8 × 2.4 × 1.1 cm tumor in the right thyroid without extrathyroidal extension or lymph node metastasis. However, both capsular invasion and extensive vascular space invasion were noted. Based on the tumor size, tumor extension and lymph node status, the tumor was designated as Stage II (pT2 pN0 pMx). IHC staining showed that the tumor cells were positive for thyroglobulin and thyroid transcription factor 1 (TTF1). An immunostain for p53 was also performed at the outside hospital and showed a small focus (< 1 cm) with p53 positivity, suggesting a diagnosis of anaplastic thyroid carcinoma.
At our institution, the diagnosis was revised, based on review of both the primary thyroid tumor and the current lung metastases. Both tumors were remarkable for biphasic malignant components: the carcinoma and the sarcoma. The carcinoma component showed a poorly differentiated microfollicular type thyroid carcinoma, composed of sheets and islands of tightly packed thyroid follicles with dense colloid. The tumor nuclei were small and round with vesicular chromatin, resembling those of typical poorly differentiated follicular thyroid carcinoma. Admixed with the epithelial component were malignant spindle cells with small round blue cell type morphology. Focally, rhabdomyosarcoma-like cells with eosinophilic cytoplasm were appreciated. No heterologous cartilage or bone components were identified. The IHC staining performed at the outside hospital showed that the thyroid carcinoma (epithelial) component was positive for thyroglobulin, PAX8 and TTF1 (Fig. ). The sarcoma (spindled) component was negative for all thyroid carcinoma markers (TTF-1, thyroglobulin and PAX8), but was positive for vimentin and focally positive for myogenin (supporting skeletal muscle differentiation) consistent with mesenchymal differentiation. Interestingly, the foci of vascular space invasion contained both epithelial and mesenchymal components as well.
The patient received Taxol with Carboplatin for 7 weeks followed by radiation therapy. Her thyroglobulin level rose from 1.2 ng/mL to 25.40 ng/mL 5 months after completion of the chemo-radiation therapy, suggesting progression of the disease. A follow-up CT scan of the chest showed multiple newly developed nodules (ranging from 1 to 2 cm) in the right lung, highly suspicious for metastases. The patient underwent a right thoracotomy, right lung resection/metastasectomy. The surgery was uneventful with negative resection margins. However, the patient’s general condition deteriorated and she succumbed to the disease 4 months later.
Histological examination of the lung nodules revealed similar tumor morphology and tumor differentiation when compared to the original thyroid tumor, which is somewhat unusual for a biphasic carcinosarcoma (Fig. ). Tumor necrosis was also present. Mutational analysis using a next-generation sequencing based assay showed that the neoplastic cells from the lung metastasis were devoid of genomic alterations for known thyroid cancers, including BRAF, RAS family (KRAS, NRAS and HRAS), EGFR, PTEN, TERT, PI3Kinase or RET. BRAF or RAS family are known as the most commonly altered genes in papillary thyroid cancers. Other molecular mutations reported in the development of anaplastic thyroid carcinoma include p53, PAX8/PPAR gamma rearrangement []. None of the mentioned gene mutations were identified in our patient.
However, an interesting finding in this case is the presence of a point mutation in DICER1 (E1705K) that has previously been associated with differentiated thyroid carcinoma [, ]. Whether the DICER1 (E1705K) mutation is the underlying genetic event leading to the initiation of tumorigenesis or is downstream to other gene alterations in tumor development is largely unknown. Additional mutations of unknown significance were also detected in this tumor including FLCN (R239H), POLD1 (Q684H) and SYK (R217L). These variants have not been adequately characterized in the scientific literature and their prognostic and therapeutic significance is unclear. |
pmc-6069949-1 | A 24-year-old woman with Asian eyelid underwent bilateral upper lid blepharoplasty and levator tucking with skin approach for double lid formation 7 years ago. After the first surgery for cosmetic purpose, her eyelid level in the right eye was over-corrected, and thus she underwent several surgeries performed by another plastic surgeon to correct the lid level. First, she underwent removal of the levator tucking suture, but then the upper conjunctiva was prolapsed and ptosis occurred in the right eye. Prolapsed conjunctiva was resected. Subsequently, the patient underwent levator resection with skin approach for ptosis correction in the same eye. After this surgery, the patient immediately complained of vertical diplopia in the primary position that worsened in upgaze. Vertical diplopia persisted, and 2 months later, she was referred to our clinic for evaluation of strabismus.
The patient underwent complete ophthalmic examination including prism and alternate cover test. We found a 25-prism-diopter (PD) right hypotropia and a 4-PD intermittent exotropia in the primary gaze, increasing to a 30-PD right hypotropia in upgaze as a consequence of the restricted upward movement of the right eye (− 2 degrees) (Fig. ). CT scan was performed immediately, and revealed suspicious enlargement and enhancement of the right SR muscle, considered as possible damage from trauma (Fig. ). The infiltration around the SR muscle insertion was observed to be increased, and the insertion of the SR muscle was not clearly shown in the CT. The patient was prescribed 50 mg of oral prednisolone tapered over 7 weeks. Five months later, CT was repeated; however, there was no significant change. Since there was no improvement of her hypotropia and CT scan, we elected to explore the SR muscle. Preoperatively, mild (1+) restriction in the IR muscle on the forced duction test and weakness of the SR muscle on the forced generation test were observed.
Intraoperatively, there was neither remnant muscle fiber nor muscle capsule at the insertion site. Instead, some SR muscle fibers were attached at the posterolateral location of the original insertion of the SR muscle (Fig. ). The superior oblique (SO) muscle was intact. There were severe adhesions around the SR muscle. Normal muscle fibers of the SR muscle were identified when tendon tissue containing radial fibers obscured the view of the muscle hook underneath it. After exploration and scar tissue removal, for nonadjustable procedures, two single-armed absorbable 6–0 polyglactin 910 sutures were passed in full thickness, double loop, locking fashion at the both margins of the remnant SR muscle fibers and perimuscular connective tissue at the anomalous attachment site. The SR muscle was sharply disinserted from the sclera and was advanced maximally to the original insertion. The muscle was sutured to the sclera at the new insertion site. Aiming to achieve initial postoperative alignment of orthotropia to 4PD right hypotropia, we additionally performed 5.5 mm IR muscle recession with a 6–0 polyglactin 910 double arm suture. No other inflammation was observed. Topical antibiotics and steroids were used postoperatively for 2 weeks.
On postoperative 1 day, a 6-PD intermittent exotropia of the primary gaze was observed and vertical diplopia was diminished. At 2 months after surgery, orthotropia was maintained in the primary gaze and there was a 2-PD right hypotropia in upgaze. Upgaze restriction of the right eye was greatly improved. There was no postoperative improvement in ptosis. At 6 months after surgery, orthotropia was observed in upgaze as well as primary gaze. At 12 months after surgery (last visit), orthotropia in all gazes was maintained. |
pmc-6069954-1 | A fifty-five-year-old man with hypertension and who used regular medications for anxiety came to the Emergency Room in Malmö, Sweden, complaining of dyspnea in 2009. He had arrived to Sweden by plane from Sri Lanka five days prior, where he resides a large part of the year. Upon exiting Sri Lanka, he was put into custody for almost 6 weeks under unhygienic conditions.
Already in Sri Lanka, but aggravated upon the return to Sweden, the patient experienced throat pain and shortness of breath. At the emergency room the patient presented with severe shortness of breath and fever of 39 °C. Throat inspection revealed swelling and greyish membranes. The patient deteriorated quickly with hypoxia and hypercapnia. He was intubated and put under ventilator support. Bronchoscopy showed greyish membranous plaques covering the larger part of the bronchus and partly occluding the left major bronchus. Serial X-rays showed progressive atelectasis of the left lung (Fig. ). The membranes could mechanically be removed from its underlying layer and repeated bronchoscopies with lavage were performed.
Culture specimens were sent from larynx and bronchoscopy specimens as well as from a 1 cm2 skin ulceration. Due to suspicion of diphtheria, Loeffler’s tellurite media was used for culture. On day four from admission, the results from cultures showed growth of toxin producing C. diphtheriae, subsequently typed to non-gravis, both from the ulcer and from the respiratory tract. Serologies for Human Immunodeficiency Virus (HIV), hepatitis B and C and syphilis returned negative, as well as urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila. The diphtheria strain was susceptible to both cefotaxime and erythromycin, which the patient was receiving since admission. It was in this situation judged too late for administration of DAT in relation to possible side effects and the duration of symptoms, and the patient was never administered this treatment. In the following weeks (day 5–14), the patient showed signs of improvement in infection control with decreasing C-reactive protein (CRP) and was afebrile, however the left lung remained deflated. The patient was under ventilator support for one month through tracheostomy performed on day seven. The prolonged time in ventilator was due to inability to recruit the left lung, despite repeated bronchoscopy and cleaning of greyish debris from the airways. A pleural catheter was also placed in the left inter pleural space with clearance of about one liter of transudative fluid. Bacterial cultures from the pleural fluid were negative.
Between day 14 and 16 the patient had changes in the electrocardiogram with T-wave inversions and short periods of ventricular tachycardia as well as elevated cardiac enzymes that resolved spontaneously (Fig. ). An echocardiogram was performed with no significant pathology. Additionally, a passing increase in serum creatinine was noted during this period. No clear reasons for these adverse organ effects were identified and were judged to be Diphtheria toxin related. On day 19 the patient deteriorated with fever and increased purulent secretions from the airways. This was considered due to Ventilator Associated Pneumonia (VAP) with Methicillin Resistant Staphylococcus aureus (MRSA) which was successfully treated with intravenous vancomycin for two weeks. In the fourth week, the patient improved and could gradually be weaned off of the ventilator. The tracheostomy tube was removed on day 46 from admission and the patient was mobilized in the following week with physical therapy and was prepared to be discharged to a center for rehabilitation.
On day 55, however, the patient developed a gradual onset of neurological symptoms. First he got increasingly weaker voice and shortly thereafter weakness of the extremities, and increasing difficulties to breathe. From day 58, the patient quickly deteriorated with a complete paraplegia and respiratory failure ensued, requiring reintubation. Repeated neurographic examinations showed severe polyneuropathy with mixed demyelination and axonal loss. The pattern was not deemed to be consistent with Guillain-Barré, nor Critical Illness and was judged to be due to toxin effects of diphtheria toxin thus no neuroimaging was considered necessary. Furthermore, lumbar puncture showed no significant pathology.
On day 56, surveillance Bronchiole Alveolar Lavage (BAL)-culture was sent for extensive testing and culture due to respiratory deterioration. This subsequently showed growth of Mycobacterium tuberculosis (MTB) fully sensitive to rifampicin, isoniazide, pyrazinamide and ethambutol. MTB-PCR was negative. Bronchoscopy specimens for MTB culture and PCR had previously been sent for investigation on day two from admission, but was negative at that time. The patient was started on combination therapy for pulmonary tuberculosis (TB) on day 70.
The patient gradually regained motor function from day 80 and the patient could once again be weaned off of the ventilator. The sensory functions likewise gradually returned from the center to the periphery (Fig. ). After an extended stay for mobilization, the patient was discharged to a rehabilitation clinic on day 91 from admission. On follow up after three and six months, the patient continued to improve in motor and sensory functions, The patient was followed for three years reporting only minor polyneuropathic symptoms in his feet, but had resumed his daily activities with no motor impairments. |
pmc-6069986-1 | A 34 year old male patient, a worker in the salt mines, presented to us complaining of diminished vision in both eyes since the past 10 years. He also complained of diminished night vision which was stationary and non-progressive. His vital parameters and general physical examination was noted to be within normal limits.
Ocular examination revealed a visual acuity of 6/36 (OD) and FCCF (OS). The pupillary reactions were sluggish in both eyes. The remainder of the anterior segment examination was noted to be normal. Fundus examination (Fig. a, b) showed presence of widespread outer retinal atrophy with visible choroidal vessels and peripheral sub-retinal scarring. The left eye shows evidence of foveal atrophy. A small peripheral rim of normal retina, around 1 disc diameter in size, was noted on indirect ophthalmoscopy.
We initially considered a diagnosis of choroideremia, retinitis pigmentosa and scarred posterior uveitis. There was no family history of nyctalopia and an evaluation of his siblings revealed a normal retina. The blood-work on uveitis also came out to be negative.
We once again reviewed the past medical history and upon detailed inquisition the patient divulged a history of a suicide attempt 10 years ago. He stated that he had consumed the chemical used in the iodination of salt after which he noted the diminished vision in both eyes.
We carried out an OCT evaluation (Fig. c, d) of the patient which showed evidence of outer retinal atrophy with associated sub-foveal scarring which was more pronounced in the left eye. A thinning of the choriocapillaris was evident in the OCT scans along with disruption in the continuity of the retinal pigment epithelium (RPE) in the left eye at the fovea. An examination of the medical records revealed an old fundus fluorescein angiogram, from 10 years ago, which showed prominent areas of choroidal hyperfluoresence due to extensive window defects, indicative of RPE damage (Fig. e, f). An electro-retinogram of the patient noted a flat response in both eyes on scotopic stimulation. |
pmc-6070054-1 | A 48-year-old, African-American female patient presented for treatment of acne vulgaris and was incidentally found to have 40 - 60 hyperpigmented, fibrotic, depressed, round, 5 to 15 mm papules and plaques on the forearms and lower legs (Figures -). The patient revealed that these lesions were sites where she had injected heroin and that she had a 10-year history of heroin and other illegal drug use. She reported a history of recurrent abscesses and cellulitis on her extremities. Based on her clinical history and characteristic skin findings, the lesions were diagnosed as skin popping scars. She was counseled regarding her condition. She reported being drug-free for the past 20 years. No biopsy was performed, and blood tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. |
pmc-6070057-1 | A 26-year-old man with no history of genital dermatoses developed new penile lesions; he was evaluated on several occasions by his primary care physician. The clinical impressions of his lesions included both condyloma acuminata and molluscum contagiosum. On separate occasions, he was treated with either topical imiquimod 5% cream or cryotherapy with liquid nitrogen. Two months later, he noticed new lesions on his penile shaft and sought medical evaluation by a dermatologist.
Clinical examination showed three 1-2 mm asymptomatic, flesh-colored papules located on the proximal portion of the dorsal penile shaft: proximal, middle, and distal, respectively (Figure ). The site was cleaned with an alcohol swab, the lesions were circled, and lidocaine HCl 1% with epinephrine 1:100,000 was injected locally. The lesions were elevated with Adson forceps and subsequently removed with Metzenbaum scissors. Hemostasis of the biopsy sites was achieved with the application of 20% aluminum chloride. The biopsy sites were treated with topical mupirocin 2% ointment three times daily until the wounds healed.
Microscopic examination was performed; hematoxylin and eosin-stained slides of the lesions were inspected with light microscopy. The most proximal lesion revealed focal dermal fibrosis. In addition, there were multiple large, round intraepidermal pale cells presenting singly and in clusters (Figure ). The cells resembled those seen in extramammary Paget’s disease, containing condensed pyknotic nuclei with perinuclear halos of clear cytoplasm. Additionally, they demonstrated premature keratinization without acantholysis or parakeratosis.
The middle lesion revealed a dilated follicular ostium as well as similar changes of pagetoid cells with premature keratinization (Figure ). The distal lesion only demonstrated sparse superficial dermal fibrosis with mild perifollicular lymphocytic inflammation. The light staining pagetoid cells were not present. Immunoperoxidase staining with p16 was negative within the lesional keratinocytes of all three lesions, making a human papillomavirus infection unlikely.
There has been no recurrence or new lesions in the subsequent six months. |
pmc-6070067-1 | Our patient is a 43-year-old ambidextrous male with a 20-year history of intractable seizures. His seizure semiology typically included a hot flash and other sensory auras with evolution into focal motor activity predominately on the right. Workup for seizure etiology included magnetic resonance imaging (MRI) revealing the large midline lipoma, partial callosal agenesis, and an adjacent lesion in the left frontal lobe presumed to represent a glial neoplasm based on the radiographic appearance. The left anterior medial frontal lobe lesion consisted of nodular calcification with peripheral enhancement and extensive FLAIR signal changes involving bilateral cingulate gyri and the left frontal lobe (Figure ).
Medical management efforts had failed to control his seizures and he was referred for surgical treatment options. The enhancing lesion was noted to progress with additional imaging and the extent of edema also expanded. The concern for progressive glial neoplasia and poor seizure control prompted a recommendation for surgical resection. The decision was made to proceed with neuronavigation-guided resection of the left frontal enhancing mass and partial frontal lobectomy utilizing intraoperative electroencephalogram (EEG), cortical mapping, and somatosensory evoked potentials (SSEP) monitoring.
Intraoperative samples sent for frozen pathology were found to have Rosenthal fibers and focal calcification and felt to likely represent glial neoplasm. Permanent pathologic evaluation revealed a lipoma and focal cortical dysplasia, Palmini Type IA, in the adjacent brain. The mild cortical architectural abnormalities and associated white matter gliosis can be seen on hematoxylin and eosin (H&E) and glial fibrillary acidic protein (GFAP) stains and neurofilament protein (NFP) staining in the areas of gliosis shows no evidence of dysmorphic neurons, giant neurons or balloon cells (Figure ).
Post-operative imaging (Figure ) shows a near-total resection of the peripherally enhancing lesion in the left frontal lobe and cingulate gyrus. A significant reduction in vasogenic edema was noted on FLAIR imaging. The midline lipoma was unchanged.
Post-resection recovery included a moderate supplementary motor area syndrome including hemiparesis, delayed speech, and changes in effect. These changes gradually resolved and the patient was found to be neurologically intact at outpatient follow-up. Seizure control occurred immediately after resection. Antiepileptic agents were continued and gradually removed over subsequent months without recurrence. The patient remained seizure-free three years post resection. 18-month follow-up imaging found stable T2/FLAIR changes with small unchanged areas of perilesional enhancement (Figure ). |
pmc-6070280-1 | This case involved a 59-year-old male patient with OAD that started 6 years ago. The patient also showed DISH and OPLL with tendency of diffuse ligament ossification. Conservative treatments were unsuccessful, and surgical treatment was recommended. Preoperative VFSS revealed obstruction at the C5/6 osteophyte level. Postoperative VFSS showed normal movement of the esophagus, and reduced symptoms of dysphagia (FOSS 3 to 1) (). Radiographic follow-up showed osteophytes at the C3/4 and C5/6 levels that demonstrated gradual regrowth at 9 and 17 years postoperatively (). |
pmc-6070448-1 | A 33-year-old man was diagnosed as having Crohn’s disease 15 years previously and had undergone a left semi-colectomy and colostomy surgery 2 years later because of an anastomotic stenosis. Unfortunately, an abdominal wall abscess caused by multiple colonic fistulas formed around his stoma several years after the surgery. His physician recommended a second surgery, but the patient refused to consent to the procedure for more than 10 years. Finally, the stoma stenosis progressed, and the patient’s condition became uncontrollable. At that time, the patient agreed to be transferred to our hospital and underwent an operation.
Abdominal computed tomography (CT) scans showed the formation of a massive abscess in the rectus abdominis and outer oblique muscle around his ascending colonic stoma and edematous changes in the intraperitoneal and abdominal wall fat tissues (Fig. –). Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a fecal culture examination. However CT scans showed signs of progressive inflammation, we decided to perform conservative treatment before the planned surgical treatment to avoid excessive destruction of the abdominal wall because of the presence of Crohn’s disease. After 2 weeks of conservative treatment with fasting, parenteral nutrition, and antibiotic therapy, a CT scan indicated a considerable improvement in the inflammation around the stoma, though the abdominal wall abscess had persisted (Fig. –). In addition, almost all the laboratory findings were within the normal ranges including the C-reactive protein (CRP) level, with the exception of anemia (hemoglobin, 9.9 g/dL) and malnutrition (albumin, 3.0 g/dL). Based on these results, we expected to be able to perform the surgery safely.
Colostomy closure, ileocecal resection, abdominal wall abscess and fistula debridement, and ileostomy construction were performed through a 15-cm-long midline incision. The patient’s general condition was classified as class 2 according to the American Society of Anesthesiologists (ASA) physical classification, and the wound was stratified as class IV according to the Centers for Disease Control and Prevention (CDC) classification. The ascending colonic stoma with multiple fistulas was firmly adhered to the surrounding tissue, and the operation required 4 h and 16 min to complete. In addition to the dirty, infected condition, the long operation time also increased the risk of SSI. Furthermore, the skin defect after the resection of the ascending colonic stoma was 10 cm long × 5 cm wide. We were able to close the rectus sheath and the abdominal oblique muscle using an antiviral absorbable suture, but closure of the edematous body surface was challenging. Accordingly, we left the body surface open and covered the wound with wet gauze.
As soon as the patient returned to his room, we removed all the wet gauze and started NPWT (Fig. ). In the present case, we performed NPWT using the V.A.C. (vacuum-assisted closure) system (KCI USA, Inc., San Antonio, TX, USA). The dressing was changed once every 2 days, and the skin defect wound was closed using sutures from both edges in a stepwise manner each time the dressing was changed. As prophylactic antibiotics, 1 g of cefmetazole was intravenously administered once every 12 h for 7 days after the surgery. Because the postoperative course was uneventful, the intraperitoneal drainage tube was removed on postoperative day (POD) 5, and bacterial and mycotic cultures of the drained fluid confirmed the absence of infectious organisms. The condition of the wound, including the skin defect area, improved daily (Fig. –), and the surgical site was successfully closed without any signs of infection on POD 14 (Fig. ). The patient was discharged from the hospital on POD16. A pathological examination of the surgical specimen revealed colonic stenosis and chronic inflammation, but no malignant changes were observed.
A number of clinical practice guidelines or articles have been published as part of efforts to reduce the incidence of SSI [–]. Nonetheless, the incidence of SSI remains high for surgical wounds classified as class IV. According to the Japanese Nosocomial Infection Surveillance System (JANIS), the incidence of SSI for colorectal surgery with a stoma construction classified as having a risk index (R.I.) of 2 or 3 was as high as 31.2% (816 incidents among 2611 cases) in 2016. The classification of JANIS’s R.I. was based on the surgical wound classification, the ASA physical status classification, and the operation time. Basically, JANIS’s R.I. is comparable to that of the National Nosocomial Infections Surveillance System (NNIS) [], but the cutoff value for the operation time was uniquely set in reference to JANIS’s database.
In our department, we induced NPWT in the treatment of exudative wound in September 2012 at first time and experienced the dramatic effect. Accumulating a successful experience, we gradually expanded the indications for NPWT. And in November 2013, we applied NPWT from just after the abdominal surgery. Because we could confirm the safety and usefulness of the wound treatment applying negative pressure from just after abdominal surgeries, we decided to induce this method in patients with inflammatory bowel disease.
The conventional treatments, including subcutaneous drain or nylon drainage, can also drain exudate. However, the procedure in the present case achieves the appropriate wound bed preparation with continuous negative pressure and promotes wound healing far more efficiently as compared with conventional methods.
In addition to the basic mechanisms responsible for the action of NPWT, such as macrodeformation, microdeformation, fluid removal, and an increase in angiogenesis, the detailed molecular mechanism has also been elucidated: the expression profiles for cytokines, chemokines, and growth factor induced by NPWT promote wound bed preparation and healing [–]. In the present case, NPWT was performed without primary closure, and this method enabled the uniform application of a negative pressure over the entire cross section of the wound. Compared with closed-incision NPWT, this procedure enabled a more efficient promotion of wound bed preparation and might be even more effective than closed-incision NPWT, which is a breakthrough wound care, taking into account the principle of this procedure. Though whether this procedure can be stratified as prophylactic NPWT is controversial, the procedure is expected to be effective not only for patients with Crohn’s disease, but also for all patients suffering from chronic SSI, particularly those with a high risk of SSI or a thick abdominal wall. On the contrary, we consider that we should avoid to apply this method to those who with low risk of SSI, from the viewpoint of cost-effectiveness.
On the other hand, the method we performed in this case requires frequent foam exchanges and stepwise closure of the wound site. After contaminated abdominal surgery, a large amount of exudate generates from the wound site with this method, applying NPWT without primary skin closure, and surgeons need to respond promptly to troubles such as obstruction of the foam tube or bleeding. For the wound site is closed with dressing, once the bacteria proliferate in the wound site, the foam and drainage tube easily becomes obstructed and the condition of the wound site gets worse and this method rather promotes infection. In order to avoid complications, surgeons need to observe the wound site carefully and frequently. However, if appropriate countermeasures such as increasing the frequency of foam replacement are taken, these troubles can basically be overcome. In facilities that newly introduce NPWT, it is necessary to experience success cases with treatment for exudative wound and expand the indication gradually.
The wound margin can achieve a soft and infection-free condition through the appropriate use of NPWT. After the completion of wound bed preparation, skin defects can then be closed from both ends in a stepwise manner, as in the present case. Without NPWT, defect closure would likely be difficult because of tissue stiffness and subsequent infection.
The abdominal wall has numerous important functions as an organ, such as the protection of the intra-abdominal organs; the maintenance of an upright posture; the support of the spine; assistance when coughing, urinating, or defecating; and the creation of a feeling of fullness to trigger the endpoint of hunger. The absence of an intact abdominal wall results in the loss of all these functions [, ]. Since patients with Crohn’s disease often undergo multiple abdominal surgeries during their lifetimes, the prevention of SSI is especially important for young patients with Crohn’s disease to maintain the function of the abdominal wall, not only because Crohn’s disease itself is reportedly an independent risk factor for SSI []. The usefulness of NPWT for surgeries related to Crohn’s disease has already been reported [, ], and the procedure used in the present case might also contribute to the effective prevention of SSI in highly contaminated surgery in general. |
pmc-6070452-1 | A 62-year-old woman was admitted to Onomichi General Hospital in 2017 with a suspected pancreatic tumor. Her medical history included hilar cholangiocarcinoma (poorly differentiated adenocarcinoma, intermediate type, INFß, pat Bp, ly1, v0, pn0, hinf2, hm0, dm0, em2, 3 cm × 2 cm × 2 cm, T3N0M0 stage IIA, UICC version 6) at the age of 53 years and cervical cancer at the age of 55 years. Each of these was curatively resected. PJS was diagnosed by the presence of hamartomatous polyps in the gastrointestinal tract and melanin pigmentation on the hands 20 years ago (Fig. ). Family history revealed that her son was also diagnosed with PJS. There was no chief complaint. Level of the tumor marker carcinoembryonic antigen (CEA) was elevated at 6.7 ng/ml; squamous cell carcinoma antigen, carbohydrate antigen 19–9, and laboratory data were within the normal limits. Contrast-enhanced computed tomography (CT) revealed a cystic tumor consisting of mural nodules at the pancreatic head; the maximal diameter was 15 mm. The tumor border was enhanced in the early phase, and the inner portion of the tumor showed low density (Fig. ). Tumor enhancement was prolonged in the delayed phase (Fig. ). Magnetic resonance imaging (MRI) showed the tumor with low intensity on T1-weighted images, high intensity on T2-weighted images, and heterogeneously high intensity on diffusion-weighted images (Fig. ). Endoscopic ultrasound sonography (EUS) showed a high echoic tumor at the pancreatic head (Fig. ). Fine-needle aspiration biopsy confirmed adenocarcinoma. Endoscopic retrograde cholangiopancreatography showed no dilation of the papilla of Vater, or mucin production. There was no connection between the tumor and the main pancreatic duct (Fig. ). The preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC; T1N0M0, stage IA). Subtotal stomach-preserving pancreaticoduodenectomy was duly performed (operation time, 697 min; bleeding volume, 1200 ml). The pathological diagnosis was IPMC, and the final tumor stage was TisN0M0, stage 0. The patient was subsequently discharged without any complications 20 days after the surgery. There was no recurrence over the 11 month follow-up period. |
pmc-6070557-1 | A 17-year-old male from Misiones, Argentina who was born to healthy, non-consanguineous parents. After an uneventful pregnancy, he was referred for genetic testing after being diagnosed with ALS as an infant; he presented with a normal karyotype and CGH array test results. After years of being misdiagnosed, a genetic counselor suspected he might have been affected with MWS due to his facial features, congenital cardiomyopathy and the presence of generalized refractory epilepsy. He also presented with bilateral hearing loss, hypoplasia of the corpus callosum, and severe neurodevelopmental delay with the absence of speech. |
pmc-6070557-2 | A 7-year-old male from Lobos in Buenos Aires, Argentina who was born to healthy, non-consanguineous parents. The relevant clinical features included a severe intellectual disability (ID), severe speech delay, and convulsive seizures. The patient presented with earlobe features that are characteristic of MWS. There was no reported family history of ID in the patient’s mother or in other known relatives. Previous testing included a 15p11.2-q13 methylation test, which was normal. This patient was initially diagnosed with ALS during infancy, when the typical phenotypic features were not clearly present.
Blood samples were extracted after informed consent was obtained from the parents of each patient. DNA was then extracted from the blood samples using the High Pure PCR template purification kit (Roche S.A.Q.EI, Buenos Aires, Argentina) according to the manufacturer’s instructions. The DNA quality and concentration were assessed using an Implen NanoPhotometer (Biosystems SA, CABA, Argentina).
Next generation sequencing (NGS) of the whole exomes of each of the subjects was conducted according as follows. Prior to the preparation of the libraries, the DNA quality was assessed using a 2100 Bioanalyzer DNA chip (Analytical Technologies SA, Buenos Aires, Argentina). The samples were prepared using the Nextera Rapid Capture Exome Sequencing panel (Illumina, San Diego, USA). The libraries were sequenced with a NextSeq 500 System (Illumina, San Diego, USA) using a high-throughput kit and a configuration with a read length of 2 × 150 base pairs (bp) and dual indexing. All of the exomes were sequenced with 160 × coverage, with at least 93% of the sequences having a minimum of 20 × coverage.
To identify the germ-line variants present within the NGS data, which consisted of the sequences of the exons within the ZEB2 gene (GRCh37/hg19 chr2:g.145141048:145282747) and the adjacent intronic regions ( ± 10 bp), a proprietary bioinformatics analysis was performed that utilized a protocol based on that of the GATK (Genome Analysis Toolkit) from the Broad Institute. We included all variants with a minor allele frequency of at least 20% and with at least 4 reads that represented the alternative allele in our analysis. These variants were subject to comparison with entries in several databases and to analysis using in-sílico prediction programs. The classification of the variants was made according to guidelines published by the American College of Medical Genetics and Genomics (ACMG). The Copy Number Variants (CNVs) that were identified from the WES data were verified by a comparative genomics hybridization (CGH) array using an Innoscan710 instrument (Innopsis, Santa Clara, CA, USA) according to the manufacturer’s instructions.
After obtaining the WES data for both patients as well as the parents of patient 1, the subsequent analysis identified a novel truncation variant (NM_014795.3:c.2177_2180delCTTT, NP_055610.1:p.Ser726TyrfsTer7) in patient 1 that was determined to be a deleterious mutation according to the variant interpretation guidelines of the ACMG (Fig. ). This variant was not present in unrelated healthy controls that were obtained from the exome sequence databases ExAc Browser () and gnomAD Browser (). The novel 4-bp INDEL that leads to the frameshift p.Ser726TyrfsTer7 (Fig. ) was confirmed as de novo using Sanger sequencing. No other mutations were found in other genes in patient 1 that are known to be associated with ALS, confirming the diagnosis of MWS and putting an end to years of misdiagnosis. However, no pathogenic mutations, including SNVs or INDELs, were identified in patient 2 in either ZEB2 or other genes associated with ALS.
The WES data for both patients were also screened for possible CNVs using a proprietary bioinformatics analysis protocol based on the eXome-Hidden Markov Model v1.0 (XHMM; ). The screening analysis of CNVs in patient 2 identified a novel deletion of at least 0.573 Mb (GRCh37/hg19 chr2:g.144704611-145277958) that was predicted to lead to the complete loss of the ZEB2 gene, resulting in haploinsufficiency (Fig. ). This mutation was confirmed by a CGH array to be a novel 1.08 Mb heterozygous deletion (arr[GRCh37] 2q22.3(144569168_145648045)x1) that encompasses the 0.568 Mb deletion that was detected during the WES data analysis (Fig. ). The deleted region also encompasses the neighboring genes GTDC1, which is unrelated to MWS, and TEX41, which is a non-protein coding gene of unknown function (). This deletion is not present in the Human Gene Mutation Database, version 2016.2 (HGMD; ), or in ClinVar (), which suggests that it is a novel pathogenic variant. Two other larger deletions encompassing the same region as this variant but with different breakpoints, ID 2566 (4.30 Mb) and ID 251811 (2.65 Mb), were found in the Decipher database (). Inheritance of the deletion by patient 2 cannot be excluded, as a DNA sample from the father was not available, but it is reasonable to assume that it is a de novo deletion due to its pathogenic classification and the absence of any phenotypic features of MWS in either of the parents. Our genomic analysis confirmed suspicions of MWS in patient 2, despite an initial misdiagnosis of ALS. In contrast, no CNVs were identified from the WES data obtained from patient 1.
In summary, WES was performed on genomic DNA extracted from blood samples obtained from two patients and their parents, when available, after informed consent was obtained. Subsequent analyses revealed the presence of a novel pathogenic truncation variant (NP_055610.1: p.Ser726TyrfsTer7) of the ZEB2 gene in patient 1, which led to the loss of the CID and Zinc-finger 2 protein domains and resulted in haploinsufficiency (Fig. ). Interestingly, in patient 2, no disease-causing SNVs or INDELs were identified; however, we were able to detect a heterozygous deletion of the entire ZEB2 gene due to a large-scale deletion of the region encompassing GRCh37/hg19 chr2:g.144704611-145277958. We were able to verify this deletion using a CGH array, which detected the presence of a larger chromosomal deletion (arr[GRCh37] 2q22.3(144569168_145648045)x1) that encompassed the deleted region that was identified via WES. The confirmed heterozygous deletion of a portion of chromosome 2 encompasses a gene that is upstream of ZEB2, GTDC1 (MIM 610165), which encodes a glycosyltransferase-like domain-containing protein 1, as well as a downstream gene, TEX41, that does not encode a known protein and is of unknown function. As the Illumina Exome Capture kit does not screen for the TEX41 gene, it was not detected during the WES CNV analysis. No association was reported in the literature between the large-scale GTDC1-TEX41 deletion and any pathogenic phenotypes; thus, it is not possible to speculate whether these genes contribute to additional phenotypes in this patient other than those associated with MWS (). It is of note that we were able to correctly re-diagnose these patients as having MWS after both were misdiagnosed during infancy with ALS because the phenotypic features of MWS were not yet present.
The successful use of WES/CES as a first-tier single assay test for MWS has recently been highlighted as evidence that it can also be used for differential diagnosis of a wide variety of neurodevelopmental disorders. Using WES as a first-tier test in two patients with an early clinical diagnosis of ALS and normal 15p11.2-q13 methylation test results, we were able to identify two novel mutations that have not been previously described (a 4 bp deletion and a > 0.573 Mb deletion) that unequivocally differentiate MWS from other ALS. As a result, we propose that WES/CES can be used as a cost-effective first-tier assay to diagnose and differentiate MWS from ALS, which is caused by SNVs, INDELs, CNVs, or other factors, in newborns, infants, and young children with suspected ALS who also have a normal 15p11.2-q13 methylation test result. |
pmc-6071094-1 | 28 years old Caucasian male, single and unemployed, living alone, with a positive forensic history and a diagnosis of Paranoid Schizophrenia. The patient had a 4 years’ history of psychosis with frequent relapses (5 admissions in 4 years). He was transferred to an acute treatment ward from a psychiatric intensive care unit (PICU). At the time of the transfer the patient was stable and on treatment with Risperdal Consta 37.5 mg fortnightly + Olanzapine 10 mg daily + Pregabalin 100 mg daily. The PANSS score was 73/210 and his psychopathology was mainly characterized by positive symptoms: delusional mood, persecutory and grandiose delusions and second and third person auditory hallucinations. The UDS was initially negative but, one week after the transfer, Mr A’s mental state deteriorated suddenly and he became very agitated and verbally and physically aggressive. He presented with a bizarre and repetitive behaviour consisting of stopping and remaining immobile for a few minutes and then running fast along the ward corridor. He also had second and third person auditory hallucinations, persecutory delusions and thought disorganization. He started to fear the hospital ward’s electronic fire alarms. He believed that the fire alarms were cameras that were spying on him and he was very preoccupied with specific members of the staff whom he believed were there to kill him. The hallucinations also became very severe and he was responding to internal stimuli constantly throughout the day. The total PANSS score was 109/210 and the UDS was positive for SCRAs. We decided to increase Olanzapine to 20 mg, daily and to add Clonazepam 8 mg, daily to manage the agitated behaviour and the psychotic symptoms. We also increased the level of monitoring of his vital measures by completing the NEWS scores twice a day. NEWS scored 2 with increased heart rate and fluctuating blood pressure. We considered a transfer to PICU but since the patient was starting to respond well to the new treatment plan and the reason for the relapse was evident (NPS intake), we decided to continue to treat the patient on the acute ward. Mr. A responded well to the change/increase of medications, his symptoms improved in 24 h and within 7 days from the acute intoxication the PANSS scores reduced to 74/210. |
pmc-6071094-2 | 32 years old Caucasian woman, single and unemployed, living alone, with no forensic history and a diagnosis of Schizoaffective Disorder and poly-substance misuse (mainly crack cocaine and heroin). Ms T was stabilized on a combination of Aripiprazole 30 mg, daily + Lithium carbonate 800 mg, at night. The PANSS score was 95/210 and the UDS was negative for all illicit substances. Four weeks later, the patient’s mental state deteriorated suddenly. She became physically and verbally very aggressive with severe features of sexual disinhibition. The patient presented with delusional mood and with complex grandiose and persecutory delusions such that she believed she was part of a secret army and she had powers to kill people with her thoughts. She also believed she was being chased by the Albanian mafia and had to fight for her life. The patient also became very aggressive with members of staff and on four occasions it was necessary to call the emergency team to provide extra sedation. The PANSS score was consistent with the deterioration of her mental state, scoring 115/210 and the UDS tested positive for both SCRAs and THC. The clinical team felt that the patient needed a more robust pharmacological treatment plan and therefore Haloperidol 10 mg daily + Clonazepam 8 mg daily were added. The patient remained acutely unwell for more than 72 h. Ten days after the intoxication Ms T remained still irritable and agitated. The PANSS score was 115/210, 10 points higher than the baseline, and the UDS continued to test positive for SCRAs. NEWS were increased to twice a day but the score was always within range (0 or 1) with tachycardia being the only altered parameter. Meanwhile, other patients on the ward tested positive for SCRAs and it was suspected that Ms T was bringing SCRAs to the ward. At that stage, leave was suspended and a stricter search policy was enforced on the ward. The patient’s mental state improved further and ten days later her urine tests were negative for SCRAs. |
pmc-6071094-3 | 20 years old Black-Caribbean male, single and unemployed, living with friends and with no forensic history, was quickly re-admitted to a treatment ward following the sudden onset of bizarre behaviour after an earlier discharge from another ward. The diagnosis was First Psychotic Episode in the context of poly-substance misuse. On admission, Mr Y was on Haloperidol Decanoate 50 mg, monthly + Haloperidol 10 mg, at night (on reducing regime). He appeared severely thought-disordered, sexually disinhibited and aroused, approaching other patients for sex or suddenly becoming physically aggressive by spitting on others. The PANSS score was 116/210 with prominent positive symptoms (positive symptoms subscale 40/49). He presented as being severely disruptive, chaotic, and intrusive into other patients’ care, attacking staff and other patients, urinating on the floor and spitting at other people’s faces. Mr Y was therefore treated with Aripiprazole 9.75 mg three times a day + Clonazepam 6 mg daily in divided doses. Observation levels were increased to 2:1 arms’ length to reduce risks of retaliation from others due to sexually inappropriate and aggressive behaviour. NEWS monitoring was increased to hourly to monitor any possible deterioration in physical health. UDS were positive for benzodiazepines and SCRAs. The patient remained unwell. Observation levels were maintained at 2:1 arms’ length and NEWS monitoring decreased to TDS once physical outcomes remained stable for 12 h. After 72 h the clinical condition improved with a reduction of PANSS score to 98/210. Eventually, because of the continued high risk of retaliation from others Mr. Y was transferred to a Psychiatric Intensive Care Unit (PICU). |
pmc-6071094-4 | 39 year old Asian British man, married and unemployed, living with his family and with a long forensic history. Mr G had a long-standing history of Bipolar Disorder since the age of 28. He had a history of numerous admissions, was non-compliant with his medications, and engaged poorly with his community team. He presented with a long-term history of poly-substance misuse (e.g., alcohol, cocaine, MDMA, cannabis, “legal highs”). He had previously been treated with a mood stabilizer (Sodium Valproate); Zuclopenthixol and Risperidone Depot (both stopped due to sexual dysfunction); Olanzapine and Quetiapine (both stopped due to poor response). At the time of his admission to Highgate Mental Health Centre, he was administered Abilify Depot 400 mg, monthly with no or little efficacy. He was transferred from another ward on due to a manic relapse, with no leave and a diagnosis of Bipolar Affective Disorder (BPAD, current episode manic). Mr. G had a long history of violence towards staff and patients (he broke a nurse's nose and stabbed another patient with a pen). At the time of the admission, he was very agitated, aggressive and intimidating, banging his fist on the table and threatening staff with a glass bottle. He also showed bizarre behavior, e.g., wearing sunglasses whilst indoors, holding pieces of paper with some incomprehensible notes on Hitler, quantum physics and aliens. He was thought disordered with grandiose delusional beliefs regarding him being the King of Egypt and able to cause a nuclear war. It proved very difficult to verbally de-escalate him and he did not agree to change his medication regime as he believed that he should be treated “only with love”. The PANSS score was 108/210. Abilify was withdrawn and Zuclopenthixol started whilst he continued the rest of his medications. On admission, UDS was negative for both NPS and TPS. A week later, UDS was positive for both benzodiazepines and SCRAs, and NEWS was increased to TDS. Two weeks later, UDS continued to be positive to SCRAs, no changes to his leave status were made, with garden leave being maintained. Three weeks after admission, UDS was positive for benzodiazepines and THC and four weeks later the admission UDS was positive for THC and SCRAs. After admission, his mental state remained unsettled with refractory manic positive symptoms and a poor response to medication. The PANSS score was 123/210. Hence, his leave was stopped and, a week later, his UDS became negative for all substances, SCRAs included. His positive symptoms started to improve with a reduction of PANSS to 66/210. Over the following four weeks Mr. G appeared well kempt and settled on the ward, with no grandiose delusions and no further episodes of aggression. He showed a satisfactory response to Zuclopenthixol 300 mg, weekly + Sodium Valproate 1200 mg. UDS was negative for all substances and, therefore, Mr. G was safely discharged to the community team. |
pmc-6071335-1 | A 33-year-old male patient presented to a tertiary care hospital with intermittent abdominal pain, nausea, vomiting, constipation and numbness of bilateral lower limb extremities, of 3 days duration. He was conservatively managed in a surgical unit as partial intestinal obstruction and was awaiting diagnostic laparoscopy. The patient developed confusion and found to have systemic hypertension, and, therefore, was transferred to a medical ward for further management. He is a non-diabetic and did not have a previous history of hypertension. The drug history revealed usage of over-the-counter analgesics for 6 weeks.
The past medical and surgical history revealed similar neurovisceral attacks requiring five acute hospital admissions over 2 years, which ended up in questionable diagnoses. The sixth acute attack raised the suspicion of an acute porphyria. The first attack in January 2013 led to a diagnosis of appendicitis. Because the symptoms worsened following the surgery an emergency laparoscopic exploration was done. But the exploration revealed no cause to explain the worsening symptoms. The second attack was managed as sinus tachycardia and he was started on beta adrenergic blockers. The third attack which was associated with a fever was conservatively managed for a questionable renal colic. Forth attack was complicated with transient hyponatremia and transiently high serum creatinine levels. These complications were attributed to a questionable interstitial nephritis based on the fact that patient had used 50 mg of diclofenac sodium twice a day for 6 weeks, repeating the prescription given by a general practitioner. Another attack in 2015 was managed as partial intestinal obstruction and diagnostic laparoscopy was done. In all these presentations, findings from the ultra sound scans and diagnostic laparoscopy did not support a diagnosis of intra-abdominal pathology.
On examination he was thin built (BMI = 20 kg/m2) and pale. Brachial blood pressure was 160/90 mmHg. There were scars of previous appendectomy and laparoscopy surgeries on the abdominal, but, otherwise, the abdominal examination was unremarkable. Muscle power was 4/5 in all four limbs (could not move against a good resistance).
The laboratory investigations performed during this admission showed severe hyponatraemia of 115 mmol/L (136–145) with serum osmolality of 255 mOsmol/Kg (275–295) and urine osmolality of 460 mOsmol/Kg (50–1200 mOsmol/Kg). Serum creatinine concentration was 106 µmol/L (80–115) with blood urea level of 20 mg/dL (6–20). Hemoglobin concentration was 8.2 g/dL (13.5–17.5) and the red cell morphology was normochromic and normocytic. The total cholesterol level was 282 mg/dL (5th to 95th centile; 142–258) with LDL fraction of 225 mg/dL (5th to 95th centile; 78–185). Serum ferritin level was 646 ng/mL (20–250). Arterial blood gas analysis was suggestive of a metabolic acidosis. Echocardiogram showed evidence of left ventricular hypertrophy. There were no significant radiological findings in abdominal X-ray film or abdominal ultrasonography. Blood lead concentration was 3 μg/dL (< 5 μg/dL).
A urine sample collected during the acute attack was sent to the Department of Chemical Pathology for biochemical analyses. On standing the urine sample gradually turned dark brown. The Watson and Schwartz test for urinary porphobilinogen (PBG) was positive (Fig. ). Spectrophotometry of urine for total porphyrins showed a “Soret band”. Urine total porphyrin level, calculated using Allen corrected absorbance of the urine sample was 5505.5 nmol/L (< 300 nmol/L). Genetic studies were carried out in an overseas laboratory. The full analysis of HMBS gene was performed by PCR amplification of extracted DNA followed by exon specific primer extension analysis of all exons, exon intron boundaries and promotor regions. The gene analysis revealed a previously reported missense mutation, c.517C>T encoding p.R173W in the HMBS gene. Targeted mutation analysis was performed by PCR amplification of extracted DNA followed by allele specific primer extension analysis, in five first-degree relatives. Among these, four were heterozygous for the same HMBS gene mutation (Fig. and Table ).
Since heme arginate is not available in Sri Lanka the patient was managed only symptomatically. Carbohydrate loading with intravenous dextrose and oral carbohydrates was the only feasible option. All the medications used for symptomatic management were checked for safety in acute porphyrias. Patient was discharged from the ward after symptoms gradually improved over 6 days to a degree that he can be managed as an out-patient. Response to treatment could not be assessed due to unavailability of quantitative tests to measure urinary aminolevulinic acid (ALA) and PBG in Sri Lanka. The patient was educated regarding precipitating factors of acute porphyria. A diagnostic card with information regarding medications to avoid was provided to the patient. Patient was followed up at the clinic with regular renal functions, hemoglobin and blood pressure monitoring. Follow up of the patient over 1 year following diagnosis revealed that patient suffered from two mild attacks which didn’t require in-patient management. Nerve conduction studies were not carried out because neurological symptoms were not observed in-between acute attacks.
Pre-symptomatic relatives who inherited the HMBS mutation were also advised to avoid the trigger factors of acute attacks such as certain medications, fasting, alcohol and hormones. The brother of the proband was counseled regarding the risk of his children inheriting the HMBS mutation and recommended targeted mutation analyses for both children. |
pmc-6071372-1 | A 36-year-old man presented with urinary frequency for 6 months. He had no significant urologic abnormality and no palpable abdominal mass on physical examination. He denied abdominal pain, vomiting, anorexia, or bowel disturbances. There were no specific laboratory abnormalities. The abdomen and pelvis computed tomography scans showed a 20 × 11 cm, well-defined, fatty mass in the abdominal cavity. A mass was located between the abdominal wall muscles and the peritoneum and compressed bladder (Fig.). We performed surgery, firstly. The reasons are as follows: (1) the mass was just beneath the abdominal wall, (2) the patient had symptom (urinary frequency), and (3) the mass was considered benign from well-demarcate mass with homogenous features on CT scan. We performed a laparoscopic mass excision with preservation of the parietal peritoneum. Two 11-mm ports were inserted, one supra-umbilically, and the other in the left lower abdomen. A 5-mm port was inserted in the right lower abdomen. A huge, freely mobile, soft mass in the external peritoneal layer with no connection to other organs was seen in the lower abdomen (Fig.). After demarcating the mass, we excised the parietal peritoneum through the marked line with a monopolar instrument. Next, we dissected the mass from the peritoneum (Fig. ). The mass which was excised completely, was placed in a large plastic endopouch-type bag, and extracted through the extended left port site. Finally, the preserved peritoneum was fixed to the abdominal wall using a fixing material with a closed suction drain (Fig. ). The operative time was 90 min, with no estimated blood loss. The resected specimen size was 22 × 16 × 7.5 cm3, and the weight was 942 g. The pathological diagnosis was reported benign lipoma with clear resection margin. The patient was discharged without complications on post-operative day 6. |
pmc-6071436-1 | A 50-year-old Chinese man with no prior illnesses presented with a history of one month of fever, headache, and vomiting. Magnetic resonance imaging (MRI) of the brain showed multiple varying sizes of ring-enhancing lesions scattered in both cerebral and cerebellar hemispheres. An initial diagnosis of metastatic brain tumour or infection was made. Computer tomographic (CT) scan of the thorax revealed a 6.5 cm × 4.5 cm right upper lobe mass that extended to the right hilum, radiographically suspicious for primary lung malignancy (Fig. A).
There was mild leucocytosis of 11.7 × 103/uL and a normal C-reactive protein of 1.5 mg/L. Lumbar puncture demonstrated raised intracranial pressure of 26 cm H2O with drainage of clear cerebrospinal fluid (CSF). There was an elevated cell count of 260 cells/mm3 of fluid with 90% lymphocyte predominance, low glucose of 1.9 mmol/L, and raised protein at 1.15 g/L. Initial mucicarmine and India Ink staining did not demonstrate organisms on staining. Subsequently, CSF cryptococcal antigen was detected by qualitative testing, and CSF fungal culture grew C. gattii. Blood cryptococcal antigen was detected at a titre of 1:1280. Of note, human immunodeficiency virus testing was negative.
Bronchoscopy was performed for evaluation of the right upper lobe mass. Bronchoalveolar lavage showed thick-walled fungal yeast forms with narrow-based budding, morphologically consistent with Cryptococcus yeasts. These were highlighted by mucicarmine special stain (Fig. A). Bronchoscopic biopsies showed non-specific chronic inflammatory infiltrates in the submucosal stroma of the bronchial wall epithelium and lung parenchyma.
The patient received induction anti-fungal therapy with four weeks of amphotericin B and two weeks of flucytosine. This was followed by maintenance therapy with oral fluconazole. Therapeutic lumbar punctures were performed for the treatment of raised intracranial pressure. On outpatient review, brain imaging showed cerebral cryptococcomas completely resolving at five months of therapy. CT chest performed for monitoring of right upper lobe cryptococcoma demonstrated reduction in the size of consolidation. However, at 15 months of anti-fungal therapy, new ground-glass opacities were seen in all lobes, with focal areas of crazy-paving pattern seen in bilateral upper lobes (Fig. B). This occurred in tandem with the complaint of a new cough. Differential diagnoses include drug pneumonitis, interstitial pneumonias, and new opportunistic pulmonary infections.
Flexible bronchoscopy was repeated for evaluation of new opportunistic infections, but there were none detected. Bronchoalveolar lavage returned turbid fluid, occasional alveolar macrophages were seen, and periodic acid Schiff (PAS) stains did not reveal any abnormalities or fungal elements. Transbronchial lung biopsies yielded normal lung parenchyma.
A decision was made to use video-assisted thoracoscopic lung wedge biopsy. Histological examination of the lung parenchyma showed intra-alveolar accumulation of foamy macrophages and airspaces containing PAS-positive amorphous eosinophilic material with strong immune positivity for surfactant A (Fig. B). This was consistent with a diagnosis of PAP. At the time of this report, the patient has preserved spirometric values, lung volumes, and corrected diffusion capacity of the lung for carbon monoxide (DLCO) of 90%. Plans have been made for monitoring of pulmonary function, with a view to commence therapeutic whole-lung lavage when required. |
pmc-6071571-1 | Here we describe a newborn female who was delivered via vaginal delivery at 40 wks 5 d gestational age to a 29-yr-old mother after an uncomplicated pregnancy. The physical exam at birth was unremarkable, and all growth parameters were proportionate and appropriate for her gestational age. She was enrolled in the well-baby cohort of the BabySeq Project and randomized to undergo whole-exome sequencing with analysis limited to genes strongly associated with pediatric-onset disorders. There were no major health concerns, surgeries, or hospitalizations between her well-baby nursery discharge and the time genomic results were reported at 2.5 mo of age. Both maternal and paternal families were of European ancestry, with no known consanguinity. Family history was significant for a 17-mo-old brother with severe eczema and two distant paternal relatives reported to have alopecia (one of whom had onset as a teenager). |
pmc-6071948-1 | On May 23, 2013, a 55-year-old female was admitted to Mudanjiang Forestry Central Hospital, a sentinel hospital for tick-borne diseases located in Heilongjiang Province, Northeast China, with a chief complaint of dizziness, gait disturbance, and headache. Two weeks before admission, an engorged adult tick was removed from her supraclavicular fossae (). Eleven days after tick removal, she sought help at a local clinic due to fever (39.0 °C) and headache, where she received supportive treatment with compound paracetamol tablets for two days with no clinical improvement and persistent high fever up to 42.0 °C.
Upon admission, a routine exam showed a body temperature of 39.5 °C, a blood pressure of 125/70 mm Hg, a pulse rate of 60 beats/min, and a respiration of 18 breaths/min. The neurological check revealed moderate nuchal rigidity. No ulceration or exudation was observed around the tick bite location, nor were any erythematous lesions found on her trunk. A routine blood test showed that white blood cell (WBC) (7.6 × 109/L) and red blood cell (RBC) (4.6 × 1012/L) levels were both in normal range, while the neutrophil—granulocyte proportion was substantially elevated (91.6%), along with 64.136 mg/L of C-reactive proteins (CRPs), indicating an inflammatory response. Laboratory tests of blood showed 53.1 U/L for alanine aminotransferase, 54.3 U/L for aspartate transaminase, and 78.0 U/L for gamma-glutamyl transferase in the blood that was collected on the day of admission, with 0.15 g/L protein detected in urine. Cerebrospinal fluid (CSF) tests revealed 0.4 g/L of protein, 4.28 mmol/L of glucose, and 125.3 mmol/L of chloride chloridate, with no WBC or RBC in the CSF, which was collected at four days after hospitalization and presented visually crystal clear and faint yellow. The routine test for the antibody of Borellia spp. and tick-borne encephalitis virus (TBEV) in CSF was routinely conducted in hospital once they collected the CSF sample for patients with recent tick bite history. The patient tested negative for TBEV but positive for immunoglobulin G (IgG) antibody against Borrelia burgdorferi sensu lato (sl) at titer of 1:256 in the serum, leading to a presumptive diagnosis of Lyme disease.
During her 10-day admission, the patient was administered doxycycline (100 mg/twice daily) []. Samples, including blood and CSF, were stored in liquid nitrogen and were transported to the Beijing Institute of Microbiology and Epidemiology at the end of July 28, 2013, for further testing. Specific PCR assays targeting B. burgdorferi sl, Babesia spp., Anaplasma spp., Ehrlichia spp., and Rickettsia spp were conducted for both blood and CSF samples. Except for the PCR assay targeting Babesia spp. in the CSF sample, all were negative. Furthermore, the recovered 1,627-bp sequence did not closely match any known characterized Babesia species []. Phylogenetic analysis revealed the nucleotide sequence was relatively close to Colpodella spp. with 89.0%–90.0% similarity (). The sequence was submitted to GenBank under accession No. KT364261, and we provisionally nominated it Colpodella spp. Heilongjiang (HLJ) strain. On April 15, 2015, almost two years after initial infection, no Colpodella spp. HLJ strain was detected, indicating no chronic or relapsing infection.
In addition, we conducted a screening for Colpodella spp. in 474 host-seeking adult Ixodes persulcatus collected in woodlands around the patient’s living area in the Mudanjiang area in 2015 with the same PCR assay, followed by direct sequencing, and subsequently found two I. persulcatus ticks positive for Colpodella spp. The positive amplicon was then cloned and sequenced. After sequence analysis, we identified two distinct sequences (GenBank accession No. KT600661, KT60062) that were 93.8% identical to each other, providing the first evidence of Colpodella spp. in I. persulcatus ticks found in China. Compared to the Colpodella spp. HLJ strain from our suspected clinical case (accession No. KT364261), the tick strains only shared an 88.0%–89.0% identity (). The detection of Colpodella spp. DNA in both the CSF of a patient with tick bite history along with isolation in ticks from the same region warrants deeper investigations. |
pmc-6072312-1 | A 49-year-old male presented with a sudden onset of severe, left-sided abdominal pain radiating to the groin for one day. He is a nonsmoker with a nonsignificant past medical and surgical history. His family history is contributory for factor V Leiden mutation in his brother and factor XII deficiency in his half-sister. On examination, his vital signs were afebrile, with a blood pressure (BP) of 150/90 mmHg, pulse 55/min, respiratory rate (RR) 22/min, and an unremarkable physical examination except for generalized abdominal pain on palpation. A computed tomography (CT) scan of the abdomen and pelvis showed poor opacification of the upper and interpolar segments of the left kidney, which were concerning for a renal infarct (Figure ). To rule out an embolic source, transthoracic echocardiography was performed, which showed no evidence of a thrombus in the heart. To further delineate the underlying pathology and for revascularization, a renal artery angiography was planned. The angiography showed FMD with a clot in the anterior branch of the left renal artery (Figure ). The patient was started on apixaban for the clot and amlodipine for hypertension. In the outpatient setting, renal artery duplex showed 0-59% stenosis of the left renal artery. Carotid and abdominal visceral arterial ultrasounds were unremarkable. Apixaban was discontinued after one month of therapy as the patient was asymptomatic with a BP of 120/82 mmHg. In the following six months, he underwent repeat imaging with a CT angiography (CTA) of the abdominal vasculature, which showed resolution of the clot and a beading pattern suggestive of FMD. |
pmc-6072448-1 | A 12-year-old girl presented seeking treatment for unerupted permanent right maxillary central incisor. She reported very low self-esteem as she was constantly bullied due to her unesthetic smile. The patient was otherwise physically healthy and had no history of any medical illness. Neither the parents nor the patient could recall any history of trauma to the teeth or jaws. |
pmc-6072454-1 | A 21-year-old Hispanic male reported to the orthodontist office with the primary complaint of not feeling comfortable with the bite and chin projection (). A subsequent clinical examination showed that the profile had worsened since a previous orthodontic treatment.
Systemically, he referred controlled Diabetes Mellitus Type I. The extraoral examination showed concave facial profile, with a slight maxillary hypoplasia, significant chin projection, upper lip retrusion and adequate nasolabial angle (). Dentally, the patient presented a Class III malocclusion with proclined upper incisors and retroclined lower incisors, edge to edge bite, lower proper alignment and spacing of 2mm in the upper arch (Figs 1, 2, and 3A).The panoramic radiograph showed mild different ramus lengths (B). Skeletally, Class III pattern with mandibular prognathism and macrognathism was observed (A, 3C).
The treatment objectives were to correct the Class III skeletal pattern, to improve profile, to increase overjet and to improve facial aesthetics. The treatment options presented were presurgical orthodontic treatment followed by mandibular setback surgery and SFA with mandibular setback followed by fixed appliances to align, level and stabilize the occlusion. Considering that the patient’s chief concern was his facial esthetics, it was decided to proceed with SFA, because the patient wanted immediate facial change. This approach would avoid deterioration in his profile and malocclusion during presurgical orthodontics, and would also take advantage of the biological potential of the regional acceleratory phenomenon (RAP).
A computed tomography (CT) (Bright Speed Elite, General Electric, and Fairfield, Connecticut, USA) was taken for the construction of a model of the skull with Proplan CMF (Materialise, Plymouth, MIs). The surgical plan was mandibular setback (Fig 4). The virtual design was transferred to the CAD/CAM software for production of surgical splints. The intermediate splint was physically generated by a 3D printer (Fortus 250mc, Stratasys, Eden Prairie, MN, USA) with hybrid epoxy-acrylate polymer.
The first step in the Insignia system (Ormco Corporation, Orange, CA) for custom-designed orthodontics is to send precise polyvinyl siloxane impressions as well as photographic and radiographic information to the manufacturer. The brackets chosen were Insignia self-ligating (SL) brackets, which are the customized version of Damon Q SL brackets (Ormco Corporation, Orange, CA). The final set-up for the patient was approved with an overcorrection of lower incisors positive torque, ensuring optimal expression of the lower incisors decompensation exploiting the massive RAP after orthognathic surgery (Fig 5). The selected sequence of wires was CuNiTi 0.014-in, CuNiTi 0.014 x 0.025-in, CuNiTi 0.018 x 0.025-in, TMA 0.019 x 0.025-in and stainless steel 0.019 x 0.025-in (Ormco Corporation, Orange, CA). The brackets were bonded three days before surgery and no archwire was placed.
In the day of the surgery, immediately before intubation assisted by a fiber optic probe, CuNiTi 0.014-in (Ormco Corporation, Orange, CA) archwires were placed (). After mandibular setback surgery by sagittal osteotomy, under brain activity monitoring, and once a suitable rigid fixation and postoperative occlusion were established, ¼ 3.5 oz intermaxillary elastics were applied with Class III vector.
After 15 days, 1/8 3.5 oz intermaxillary elastics were used () and the archwires were changed to 0.014 x 0.025-in CuNiTi (Ormco Corporation, Orange, CA). One month after surgery 0.018 x 0.025-in CuNiTi archwires (Ormco Corporation, Orange, CA) were placed and Class III intermaxillary elastics were continued. Then, 0.019 x 0.025-in TMA arches (Ormco Corporation, Orange, CA) were placed six weeks later. The orthodontic treatment was completed five months after mandibular setback, showing great improvements in facial profile, Class I occlusion with ideal overjet and overbite (Figs 8, 9, and 10). The 24-month posttreatment photographs show excellent stability of the treatment results (). |
pmc-6073078-1 | A 35-year-old male Ugandan presented to Mbarara University Referral Hospital Eye Centre (MURHEC) in June 2017 with a 10-day history of a painful, red left eye. There was no history of trauma, contact lens or TEM use. He was not aware of his HIV status at the time of presentation, but thought that he was HIV negative. He described a somewhat similar eye problem in his teenage years, which followed trauma, was treated and had healed. He had experienced no further ocular problems until this new presentation.
On this admission (day0),the left visual acuity was hand movements only, with no improvement on pinhole. There was a dense white paraxial supratemporal corneal infiltrate (2.0 mm × 1.5 mm), an overlying epithelial defect (2.0 mm × 1.5 mm), 80% corneal thinning and a 3.5 mm hypopyon (a). Additionally, the left cornea had an old inferior vascularized scar (7 mm × 6 mm). The right eye had an unaided visual acuity of 6/5 and normal ocular examination.
Corneal scrapings were collected for microscopy (Gram stain, Potassium Hydroxide [KOH] stain, Calcofluor White [CFW] stain, Lactophenol Cotton Blue stain[LPCB]) and culture (Blood Agar [BA], Chocolate Agar [CA], Potato Dextrose Agar [PDA] and Brain Heart Infusion [BHI]). Initial CFW slide revealed fungal elements. The Gram, KOH and LPCB tests were negative. However, Candida spp. grew on BA, PDA, CA and BHI subculture within 48 h.
The patient was started on hourly Natamycin 5% eyedrops (Zonat Sunways India) as well as Ofloxacin 0.3% eyedrops (Biomedica Remedies-India) 4 times/day and Atropine eyedrops. By day3, the eye had rapidly deteriorated (b) and hourly Chlorohexidine 0.2% eyedrops (locally formulated) was added to his treatment. By day7 the cornea had thinned further and was threatening to perforate (c). Corneal tissue for transplantation is currently unavailable in Uganda. On day8, a conjunctival flap procedure was performed (d), in conjunction with a subconjunctival injection of Fluconazole 2% (0.5 ml). On day21, he returned with a total corneal and conjunctival flap melt (e). At this stage further active treatment was considered futile and a decision was taken with the patient to perform an evisceration. Subsequently, a prosthetic shell was fitted.
It is our routine practice to offer HIV counselling and testing to all people presenting with MK. This individual accepted the offer and was found to be HIV positive. He was referred to HIV services and started anti-retroviral therapy. His CD4 count was 352 cells/µL around the time treatment was initiated.
Five months later, he returned to MURHEC with a 4 day history of a painful right eye. Again, there was no history of trauma, contact lens or TEM use. On this day0 for the righteye presentation, visual acuity in the right eye was 6/12. Slit lamp examination showed a supra-temporal dense corneal infiltrate (3.1 mm × 2.8 mm), a. Corneal scrape samples were collected and sent for microbiological investigations, as outlined above. Gram stain showed pseudo-hyphae. CFW and KOH reported fungal hyphae and all culture plates (BHI subculture, BA, CA, PDA) grew Candida spp. The same first line protocol as previous (Natamycin, Ofloxacin and Atropine) was started. At this point, we were concerned that he might have a source of Candida elsewhere, that had led to the sequential corneal infections. He reported no systemic symptoms; specifically he did not have dysuria. As part of the assessment a urine sample was cultured, which also grew Candida spp.
By day3 we noted a moderate deterioration (b). Therefore, we added hourly Amphotericin B 0.15% eyedrops (locally formulated with a hyper methylcellolose base) and oral fluconazole 200 mg twice a day to his treatment. By day21, the ocular pain had greatly reduced and the infiltrate had transitioned into a scar extending to the visual axis (7 mm × 4 mm). He developed a small para-central perforation. This self-sealed with iris plugging; the anterior chamber was deep and Siedel's test was negative (c). By 3 months (day90) the scar size had reduced slightly (6 mm × 3.2 mm), and his right visual acuity was 6/24. |
pmc-6073164-1 | This 18-year-old male patient presented at the Oral and Craniomaxillofacial Surgery Clinic to consider surgical treatment options for reducing an enlarged tumor of the back. The patient had more than six café au lait spots on the trunk and extremities, axial and inguinal freckling and several cutaneous tumors that were slightly raised above the level of the skin. The patient had no physical discomfort, no motor or sensitive deficits. The patient stated that he had been operated 2 years earlier on a tumor of the back in another hospital. More detailed information was not available. Despite this previous treatment of the tumor, the remaining tumor mass disturbed him both physically and in his self-perception. The patient stated that the tumor had been growing again since the first operation.
On the back there was a tumorous protrusion of the intact skin with a maximum above the spine, which extended from the lower thoracic region close to the edge of the pelvis (Figure 1 A ). The tumor was clearly prominent under tight-fitting clothing. The skin in this area was darker pigmented throughout the lumbar region and showed hirsutism. The tumor was insensitive to touch and pressure, showed no fluctuation on palpation, and the covering skin moved with the tumor.
B-scan ultrasound revealed an inhomogeneous mass with focal, partly string-like reflections inside the space occupying lesion. Borders were poorly defined and the tumor mass reached to the spinous processes of the spine. The tumor appeared as solid mass and contained no cavities suggestive of necrosis. The tumor was resected in general anesthesia. When the lesion was exposed, a black pigmentation became apparent, which was partially arranged in a stripe-like pattern and frayed at the edges (Figure 2 ). The tumor was resected and the contour of the back reshaped. Despite dense suturing of the wound margins a hematoma developed, which was emptied. Secondary wound healing took 21 days and led to a stable healed wound (Figure 1 B ). There was no movement restriction of the patient after the wound had healed.
Upon neuropathological investigation a spindle-shaped, 22x9x2 cm3 large skin sample with centrally located 6 cm long scar was seen. Cutting the skin exposed white and slightly greasy tissue on both sides of the scar with spotty brown-black pigmentation.
Histological examination revealed a diffusely grown neoplasia of medium to high cellular density in the subepidermal connective tissue, consisting of roundish and oblong cells with delicate cytoplasmic extensions and slightly pleomorphic, small, round-oval, sometimes comma-shaped nuclei. The cells showed different degrees of pigmentation. Repeatedly, pseudo-Meissner corpuscles were observed. There was no evidence of mitoses and no Turnbull-positive hemosiderin pigment was detected. Immunohistochemistry demonstrated labeling of the tumor cells with antibodies against S100-protein and melan-A and to a lesser extent also with antibodies against HMB45. The Ki-67-proliferation index was less than 3%.
A subepidermal diffusely grown pigmented (melanotic) neurofibroma WHO grade I was diagnosed (Figure 3 ). |
pmc-6073424-1 | A 50-year-old male patient with a history of nightly lower abdominal pain for three months was transferred to the emergency room at Erlangen University Hospital. First routine examinations revealed that heart, spine, liver and kidney showed no pathological changes. The patient had no diarrhea, no fever and no apparent changes in blood values. Gastroscopy revealed a moderately chronic slightly active H. pylori gastritis as determined by Warthin silver staining and culturing. After collecting a sample by endoscopy, a conventional triple antibiotics therapy for 7 days was prescribed to eradicate gastric H. pylori. As the nightly colics continued for the next three weeks, ultrasound diagnostics was performed revealing a thickened gallbladder wall and signs of inflammation, suspicious for cholecystitis. Two gallstones measuring up to 1.5 cm were detected before removal of the gallbladder by standard laparoscopic surgery. Histopathology suggested a microbial infection as the etiology for the observed pathological changes of the gallbladder. |
pmc-6073498-1 | The child described here was first seen at the Paediatric Unit of the Santa Maria Hospital, Terni, Italy, when he was 3 years old. The hospital admission was required by parents for further evaluation of an already diagnosed EIEE. The child was born from eutocic delivery after a 39-week regular gestation. Neurological problems emerged during the first days of life when a significant hypertonus of the lower limbs was clearly evident. In the following weeks, repetitive, difficult-to-treat seizures occurred. Moreover, neuromotor and psychic development was very poor. At admission, the clinical manifestations included epileptic encephalopathy with tonic and myoclonic seizures and spasms refractory to polypharmacy, severe cognitive disability, and severe postural spastic paresis with a dystonic-myoclonic component (both cortical and truncal myoclonias at rest and in action). Magnetic resonance imaging (MRI) showed complex brain malformations such as pontocerebellar hypoplasia, corpus callosum atrophy and simplified cortical architecture (). These characteristics were also associated with a posterior laryngomalacia. The child underwent tracheotomy and percutaneous gastrostomy because of his low aptitude for swallowing. Congenital cardiac cardiopathies were not observed at the cardiological consultation, and no congenital alterations were seen in renal ultrasound.
The patient has continued to show repeated daily critical episodes, characterized by a polymorphic tonic semeiology with an inconstant clonic component, tonic spasms in extension, tonic deviation of the head on the left and inflection adduction of the right upper limb, and clonus of the head and upper left limb. The electroencephalogram (EEG) showed a poorly organized pattern for the age of the subject. On the centro-temporal derivations of the two hemispheres, theta-delta band rhythms were present, followed by intermittent repetitions of sharp waves, mainly evident on the left hemisphere where they assume a subcontinuous morphology. The cortical electrical anomalies were evident in the centro-temporal areas of both cerebral hemispheres, especially on the left side (). |
pmc-6073672-1 | A 58-year old lady was diagnosed with OS kappa light chain (KLC) myeloma in June 2014 after a history of worsening back pain over the preceding four months. At admission, a CT scan showed multi-level crush fractures at T8, T9, L1 and L2; (a sestamibi scan later confirmed avid uptake in the axial skeleton). She was hypercalcaemic at presentation (Ca2+ corrected 3.33 mmol/L), with mild renal impairment (Creatinine 133 μmol/L) and a haemoglobin of 110 g/L. Circulating plasma cells (PC) were seen (22% of 10.1 × 109/L total white cells) on the peripheral blood film, consistent with PCL. No PP was detectable and KLC were only modestly elevated at 112 mg/L. The LDH and albumin were normal and beta-2-microglobulin (B2M) was elevated at 4.4 mg/L. A BM biopsy was diagnostic of MM with a marrow burden of 80% PC infiltration. FISH studies subsequently demonstrated a 17p deletion.
The patient was treated with 4 cycles of Bortezomib/Cyclophsophamide/Dexamethasone (VCd) followed by a melphalan (200 mg/m2) conditioned autograft in November 2014. This resulted in a modest reduction in BM PC burden from 80% to 20%. Given the high-risk MM features and the availability of a HLA matched unrelated donor, the patient underwent a fludarabine/TBI (2 Gy) conditioned allograft in February 2015. Cyclosporin and mycophenolate were used for post-transplant graft verus host disease (GvHD) prophylaxis.
No meaningful disease control was achieved post-allograft. At day 42, KLC rose to 641.2 mg/L. As there were no features of GVHD, a rapid wean of her immunosuppression was instituted. The patient had mixed CD3 chimerism at day +60 with 79% being donor derived. The reduction in immunosuppression temporarily halted the progressive increase in KLC but at the cost of mild hepatic and cutaneous GvHD. Low level systemic immunosuppression was thus reintroduced with a corresponding rebound in KLC. A BM biopsy at 6 months post allograft in August 2015 showed extensive PC infiltration and the KLC had increased to 840 mg/L. At this point, immunosuppression was weaned again and thalidomide (T) 100 mg daily was commenced. The patient remained symptomatically well.
The combination of T and the withdrawal of immunosuppression led to a reduction in KLC to 148 mg/L in February 2016, 1 year post allograft, though moderate BM involvement persisted. CD3 chimerism had improved to 100% by day +180 and remained complete at 12 months. However, despite ongoing biochemical control (KLC 150 mg/L), the patient presented to hospital with a pathological clavicular fracture in April 2016. A PET-CT confirmed widespread skeletal disease and the patient was switched to lenalidomide (R) (). She presented again in late July 2017 with progressive lower limb weakness. MRI demonstrated T12 spinal cord compression from extra-osseous disease. A repeat PET-CT showed differential response of the widespread FDG-avid lesions since the commencement of the R (). KLC remained suppressed −165.8 mg/L. She was treated with radiotherapy and dexamethasone (d) and regained full mobility with continuation of R treatment.
Biochemical control was maintained on Rd until November 2016 when she presented with new thoracic wall disease and by early mid-December 2016, KLC had risen to 347 mg/L. PET-CT scan showed clear progression with numerous subcutaneous deposits (). The patient became cytopenic and a repeat BM biopsy demonstrated effacement of normal haemopoiesis by PC. Both the BM and EM-sternum (EM-S) biopsy were subject to genomic analyses along with a matched PB sample (315) for ctDNA assessment. In an attempt to systemically target the EM disease, she was commenced on a combination of panobinostat, bortezomib and Dex (PAN-Vd), but this failed to arrest disease progression. By February 2017, KLC were 1200 mg/L despite modest reductions in the size of some cutaneous plasmacytomas. Salvage treatment with pomalidomide (P), C and d (PCd) was commenced. This led to a slight, reduction in light chains (1200 mg/L to 600 mg/L) but the EM disease progressed and she experienced further spinal cord compression in April 2017. This was again treated with palliative radiotherapy. Over the next few months she required radiotherapy to multiple cutaneous plasmacytomas.
In May and July 2017, the patient received two donor lymphocyte infusions (DLI). Dexamethasone was withheld but P was continued during this period. The DLIs caused a fleeting reduction in KLC, but, again the patient had EM progression and presented with further spinal cord compression in July 2017, again requiring further palliative radiotherapy. Additional cfDNA samples were obtained in July and September 2017 (435 and 485). Carfilzomib (K) and daratumumab (Dara) were accessed and combined with Pd (KPd-Dara); though the quadruplet achieved a degree of biochemical control (nadir 107 mg/L, late September 2017), the patient’s EM disease remained resistant to treatment with PET-CT showing clear progression with numerous subcutaneous deposits in November 2017. Biopsy from 3 different regions of an axillary nodal EM-plasmacytoma (EM1, 2 and 3) were obtained along with a matched cfDNA sample (504). She presented again in December 2017 with cord compression; further radiotherapy was delivered but the patient deteriorated, becoming increasingly obtunded. She was palliated and died shortly thereafter. |
pmc-6073990-1 | A 39-year-old Ethiopian man, temporarily in Italy for professional reasons, with a recent diagnosis of human immunodeficiency virus (HIV) infection, on antiretroviral therapy (cART) with emtricitabine–tenofovir disoproxil fumarate and lopinavir/ritonavir, presented to the emergency department of our hospital with a month history of vomiting, abdominal pain, and diarrhea. His medical history included peripheral T-cell lymphoma located in the ethmoid and maxillary sinuses, treated with local radiation.
On admission, he was febrile (up to 38 °C), with severe dehydration, tachycardia (heart rate of 100 beats/min) and hypotension (blood pressure of 90/50 mmHg). Initial laboratory tests showed an elevated white blood cell count of 14,790/mm3 with a normal eosinophil count of 260/mm3 (reference range <500/mm3), C-reactive protein level of 348.5 mg/L, hypoalbuminemia (1.9 g/dL), and acute renal failure (serum creatinine 5.45 mg/dL). Liver enzymes were slightly abnormal (aspartate aminotransferase 63 U/L and alanine aminotransferase 84 U/L) with a normal total bilirubin value (0.22 mg/dL). CD4 count was 402/mm3, and HIV-RNA was <20 copies/mL. A chest X-ray revealed bilateral areas of increased parenchymal density. The computer tomography (CT) scan of the chest and abdomen with intravenous contrast showed bilateral ground-glass opacities and areas of consolidation with pleural effusion, and small bowel wall thickening without distension. Blood, urine, and stool samples were collected for cultures. The patient was transferred to the intensive care unit (ICU), where supportive treatment and empiric broad-spectrum antibiotic therapy with trimethoprim/sulfamethoxazole, metronidazole, and ceftriaxone were started; cART was temporarily interrupted.
The following day, he developed altered mental status, progressive respiratory distress (PaO2 61 mmHg), and persisting hypotension requiring vasopressors and endotracheal intubation. Due to severe stomach and abdominal distension, a nasogastric tube was placed, with a high gastric output (800–1200 mL/day). Bronchoscopy with bronchoalveolar lavage (BAL) for microscopic examination, cytology, and cultures was performed, with no significant finding on visual inspection. Microscopic examination of the BAL and stool showed parasitic organisms morphologically consistent with Strongyloides larvae. Serology for Strongyloides stercoralis by enzyme-linked immunoassay was positive. Administration of ivermectin 200 µg/kg daily by nasogastric tube was immediately started. Due to persistent fever, new urine and blood cultures were taken, and empiric antibiotic therapy was escalated to meropenem and vancomycin with discontinuation of ceftriaxone, metronidazole, and trimethoprim/sulfamethoxazole.
Despite intensive support care and antimicrobial therapy, the patient progressively deteriorated, developing paralytic ileus. After 22 days of antihelmintic treatment, BAL and stool specimens continued to demonstrate larvae and eggs of S. stercoralis. Given the persistence of larvae in the body fluids and malabsorption syndrome, emergency approval for the use of veterinary preparation of parenteral ivermectin (Ivomec® 1% injection, licensed for veterinary use only) was obtained from the Local Therapeutic Committee, and subcutaneous injection of 16 mg (200 μg/kg) was administered. Subcutaneous administration was repeated at 48 h, without local or systemic reactions. After two days, larvae were no longer detected in the BAL and stool, and the patient’s symptoms improved. The concentrations of ivermectin in plasma were determined by high performance liquid chromatography (HPLC), using a previously-published extraction method []. The linear range of the calibration curve was 0.20–400 ng/mL from 0.20 mL plasma ().
Five days later, the patient was transferred from ICU to the infection diseases ward. All cultures (blood, urine, stool, BAL) were persistently negative for bacteria, mycobacteria, and fungi, and antibiotic therapy was therefore discontinued. A systemic lymphoma was excluded with hematological evaluation, maxillofacial CT scan, and positron emission tomography/computed tomography (PET/CT) scan. cART and rehabilitation program were started. At the 9-month follow-up visit, the patient was still asymptomatic with no medical problems, and direct stool examinations remained negative. |
pmc-6074057-1 | We report the case of a 6-month-old male infant admitted to our clinic for persistent fever and a generalized polymorphous rash. The onset of the disease, with fever, rhinorrhea, and cough was ~7 days before the admission. Therefore, he was admitted to a regional hospital where he benefited from antibiotics and antipyretics, but there was no improvement. He also presented with a generalized polymorphous rash and bilateral nonexudative conjunctival injection and was transferred to our clinic with suspected KD.
The clinical exam revealed the following pathological elements at the time of admission: influenced general status, pallor, a polymorphous rash on the limbs and face (Figure ), bilateral conjunctival hyperemia, painless right cervical lymphadenopathy, and a productive cough.
The laboratory tests on the day of admission revealed leukocytosis (34,590/μl) with neutrophilia (28,000/μl), anemia (Hb: 7.5 g/dl, Htc: 23.5%, MEV: 73 fl, MEH: 23.3 pg), thrombocytosis (648,000/μl), hypernatremia (154.1 mmol/l), hypoalbuminemia (2.48 g/dl), elevated CRP (311.33 mg/l), and ESR (65 mm/h). The urinary exam and blood culture were negative. The initial echocardiography showed good ventricular contractility, diastolic dysfunction, mild mitral regurgitation and moderate dilatation of LAD (the internal diameter was 3.49 mm and Z score + 7.62). (Figure ). The abdominal ultrasound revealed a right renal cyst without pathological elements. Based on all these findings, we established the diagnosis of KD.
Due to the echocardiographic findings, we initiated IVIG in a dose of 400 mg/kg/day for 5 days accompanied by intravenous pulsed methylprednisolone at 30 mg/kg/day for 3 days and high doses of aspirin at 100 mg/kg/day. We also administered substitution with erythrocyte mass and human albumin.
The clinical symptoms and laboratory parameters improved within the first days after the initiation of the above-mentioned treatment, but unfortunately, after ~1 week from the cessation of IVIG treatment, the fever and the bilateral conjunctival injection reappeared. The echocardiographic re-evaluation showed an aneurysm of the LAD with internal diameter 6.2 mm, Z score + 16.45 (Figures , ) with a hyperechoic image inside raising the suspicion of a thrombus or a thickening of the coronary lumen. The cardiologist recommended the initiation of low-molecular heparin in the treatment, and the lowering of the aspirin dose at 5 mg/kg/day in a single dose. We performed an angio-CT scan that confirmed a potential thrombus. We also repeated the laboratory parameters and found increased levels of CRP. Therefore, we decided to administer another IVIG in a single higher dose of 2 g/kg, but the inflammatory biomarker remained elevated. Based on all these findings we decided to re-initiate intravenous methylprednisolone, but in a lower dose, of 1.5 mg/kg/day twice a day for ~1 week. The ESR values started to decrease progressively, and therefore we switched to oral methylprednisolone tapering the dose gradually for ~3 weeks. The echocardiographic re-evaluation did not reveal any improvement, and for this reason, the cardiologist recommended the continuation of the low-molecular heparin for ~6 weeks and aspirin for 3 months. After ~2 months, the infant's status generally improved, but the echocardiography underlined a persistent dilation of the left coronary artery with an aneurysmal portion of ~6 mm and a tendency of stenosis below this portion. |
pmc-6075479-1 | An 18-year-old male presented to the emergency department (ED) with a complaint of severe abdominal pain for three days along with painful urination, vomiting, diarrhea and subjective fever and chills. The patient reported brief, severe, colicky episodes of mid and left upper quadrant (LUQ) abdominal pain that radiated to his testicles. He vomited several times because of the pain, which he stated began suddenly while he was lying down. Notably, the patient had recently got over a diarrheal illness a few days prior, followed by constipation, and had recurrence of one loose stool on the day of presentation. He denied any flank pain or back pain, and had never experienced anything like this current illness before.
The patient had no prior medical or surgical history, and had no known family history. His family lived in Honduras, but the patient was currently incarcerated. He was previously a one-pack-per-day smoker, drank alcohol one to two times per month, but denied drug use. Review of systems was negative for weight loss, headaches, chest pain, shortness of breath, melena, hematemesis, rashes, or joint swelling.
The vital signs were as follows: temperature 37.0°C orally, pulse 103 beats per minute, respiratory rate 11 breaths per minute (bpm), blood pressure 122/67 mmHg, and oxygen saturation 100% on room air. Physical examination revealed an alert young man intermittently doubled over in pain with spontaneous resolution. The heart was tachycardic and regular without murmurs, rubs or gallops. The lungs were clear bilaterally with normal work of breathing and no wheezes, rhonchi or rales. His abdomen was soft and non-distended with normoactive bowel sounds, but he demonstrated diffuse tenderness and guarding to palpation. He had no midline or costovertebral angle tenderness, and no ecchymoses were present on inspection of his back. His skin was warm, dry and without any obvious rashes. His neurological examination was grossly intact throughout. The patient was uncircumcised, and his right testicle was lying higher than his left, but neither was tender or swollen. No masses or inguinal hernias were appreciated in the groin.
Laboratory studies were ordered (–), and a point-of-care focused assessment with sonography for trauma (FAST) exam and gallbladder ultrasound were normal. The patient had a formal scrotal ultrasound performed. ().
The patient’s pain was initially well controlled with hydrocodone/acetaminophen and non-steroidal anti-inflammatories; however, as more laboratory and imaging studies resulted, the patient continued to have intermittent pain episodes requiring morphine for analgesia. After two to three hours, the pain crises appeared more severe and the patient became more tachypneic to 18 bpm. It was at that point that an additional study was ordered, and the diagnosis was subsequently made. |
pmc-6075480-1 | An 11-year-old male presented to the emergency department (ED) with abdominal pain of one night duration causing difficulty with sleeping and ambulation. Of note, the patient denied loss of appetite, vomiting, and fever. Past surgical history was significant for appendectomy 19 months prior after presenting with similar symptoms and being diagnosed with appendicitis sonographically. There were no reported operative or postoperative complications.
Upon presentation the patient had not had a bowel movement in several days, and the initial leading differential diagnosis was constipation. Physical examination was significant for fever and localized peritonitis. Pertinent laboratory investigations at current presentation included leukocytosis of 13,300 per cubic millimeter (reference range 4,500–13,000), neutrophilia of 9,870 per cubic millimeter (reference range 1,700–7,500), and an elevated C-reactive peptide to 1.4 milligrams per deciliter (reference range <0.5). After antipyretics, repeat assessment showed a reduction in fever; however, the patient still had severe abdominal pain. A point-of-care ultrasound showed a normal-appearing gallbladder and no dilation of the common bile duct but demonstrated an aperistaltic mass in the right lower quadrant (RLQ).
After consulting with the pediatric surgery team, contrast-enhanced computed tomography of the abdomen and pelvis was performed and demonstrated surgical changes of appendectomy with staple lines at the blind end of the appendiceal stump. A high-density appendicolith was obstructing the base of the appendiceal stump, which was surrounded by mesenteric fat stranding (). Thickening of the appendiceal wall and the peritoneal reflection of the RLQ were additional findings consistent with acute appendicitis. There was no pneumoperitoneum. The patient was admitted and taken for laparoscopic surgery the next day. Surgical exploration revealed an inflamed appendiceal stump with pus in the right paracolic gutter. The appendiceal wall was very friable, and the stump required piecemeal removal during which time two appendicoliths were discovered in the lumen. The base was stapled flush with the cecum ensuring that no residual appendicoliths were present. The patient was discharged on postoperative day 3 and reported good recovery at follow-up appointments.
Pathology confirmed that the stump was necrotic, in two 2 cm long portions, with one portion containing a large appendicolith. |
pmc-6075480-2 | An 11-year-old female patient with a past medical history significant for appendicitis treated with laparoscopic appendectomy two months prior presented to a local ED with a one-day history of epigastric and right-sided abdominal pain, poor oral intake, and emesis. Prior to transfer to the university hospital, contrast-enhanced computed tomography of the abdomen and pelvis demonstrated a fluid collection in the right pericolic gutter at the site of surgical changes of appendectomy. The collection contained small stones () and small foci of extraluminal air. There was also a small amount of frank pneumoperitoneum consistent with rupture of the appendiceal stump or dehiscence of the sutures.
Upon transfer, the patient was febrile and tachycardic. She was taken for laparoscopic appendectomy during which an inflamed, approximately 5 cm-long stump was encountered with an obvious appendicolith at its base adjacent to the cecum. The site of perforation was not readily evident, but there was evidence of recent peritoneal spillage and contamination. The previous staple line was readily apparent at the end of the stump. The appendectomy was completed by passing a stapling device proximal to the appendicolith and resecting the stump.
Pathology confirmed an inflamed, 5 cm appendix containing two large fecoliths. After gradual clinical improvement, she was discharged on postoperative day 4. Residual postoperative pain was well controlled with acetaminophen. |
pmc-6075482-1 | A 34-year-old female was brought to the emergency department (ED) by family with a chief complaint of severe epigastric pain. Her symptoms, which had begun five days earlier, consisted of general malaise, self-reported low-grade fevers, and a non-productive cough in addition to her epigastric pain. She had taken off work for the prior three days due to her symptoms. She reported one instance of nausea and vomiting the day prior to her ED admission. She denied any history of dysuria, hematuria, headache, or neck stiffness. Past medical history was significant for polycystic ovarian syndrome and attention deficit hyperactive disorder. Past surgical history was notable for a remote appendectomy and cholecystectomy. Social history revealed that she had quit smoking 10 years prior and drank one alcoholic beverage on average per day. She denied any recreational or intravenous (IV) drug abuse.
Triage temperature was 97.5°F, heart rate was 71 beats per minute (BPM), blood pressure measured at 136/93, respiratory rate was 20, and her oxygen saturation was 98% on room air. Approximately 20 minutes after triage, the patient remained afebrile but her heart rate had increased to 125 and blood pressure decreased to 96/56. She appeared fatigued and slightly diaphoretic. Her oropharynx was clear and moist, neck was supple with full range of motion, cardiac examination revealed no evidence of a murmur, and she displayed normal respiratory effort without any signs of distress or wheezing. Her abdomen was soft and non-tender without rebound or guarding. Urinalysis showed a specific gravity of 1.024, trace ketones, 0–2 white blood cell count per high power field (HPF), 0–2 red blood cells per HPF, and 16–20 hyaline casts. Urine pregnancy test, mycoplasmal immunoglobulin M, and influenza A/influenza B rapid screen were all negative. Chest radiograph was negative for pathology and showed a heart size and vascularity within normal limits, with clear and fully expanded lungs. Blood test results are displayed in the below.
Fluid resuscitation was started upon arrival to the ED. Despite infusing four liters of normal saline over the course of four hours, the patient’s blood pressure never increased above a systolic pressure of 100 and she remained borderline hypotensive. Her admitting diagnosis was systemic inflammatory response syndrome (SIRS) due to a presumed viral but undetermined etiology with hypovolemia. At the time of admittance, her vital signs were a temperature of 97.5°F, a heart rate of 116 BPM, a respiratory rate of 18 breaths per minute, and a blood pressure of 94/67. She received ondansetron for nausea.
The next morning, the patient complained of worsening symptoms of malaise and weakness while denying any shortness of breath, cough, chest pain, headache, diarrhea, or anxiety. Except for her blood pressure, which had dropped to 80/50, her vitals were stable. She was given a seventh liter of fluid with modest improvement of her blood pressure, but she remained clammy and required a central line placement in the intensive care unit (ICU). Physical examination was significant for mild epigastric tenderness and acrocyanosis. At this time, she was diagnosed with dehydration secondary to severe sepsis with septic shock. She was given ceftriaxone, vancomycin, and doxycycline to cover meningococcus, methicillin-resistant Staphylococcus aureus, and rickettsia. Additionally, blood cultures and an electrocardiogram (ECG) were ordered and revealed questionable 0.5mm ST-segment elevation of lateral chest leads (). Troponin I was elevated at 0.47 ng/ml.
The patient was sent for abdominal computed tomography (CT) to look for a cause of sepsis. The imaging showed some atelectasis/bibasilar infiltrates with small bilateral pleural effusions as well as patchy enhancement of the kidneys concerning for pyelonephritis, but no significant pulmonary edema or cause of sepsis. After completing the CT, the patient decompensated into pulseless ventricular tachycardia and eventual death despite attempts at resuscitation. A postmortem influenza smear was negative for influenza A, parainfluenza A1–A4, and positive for influenza B. This finding, coupled with inflammation of the myocardium on the autopsy, led to the diagnosis of fatal myocarditis caused by influenza B. |
pmc-6075483-1 | A 38-year-old female presented with right foot, ankle, and calf pain. Her past history was remarkable for a 55-pound weight gain in the prior six months due to being sedentary, and she had a history of meralgia paresthetica of her right lower extremity after a motor vehicle collision. The patient stated that she had completed a 10K race (6.2 miles) two days prior to presentation and a half marathon (13.1 miles) one day prior to presentation when she noticed her right calf started “seizing up” during the second race. She then started to experience pain on the dorsal aspect of her right foot. The pain progressively worsened over the next 24 hours until she could no longer bear weight on the right lower extremity without severe pain. The pain was worse on the posterior/lateral leg and lateral ankle with associated foot numbness and burning in the sensory distribution of L2-S1. Her sensation was intact to light touch in the sensory distribution of L2-S1 and throughout her lower extremity, despite perceived numbness to the dorsal aspect of her foot and lateral calf. The pulses in her leg were 2+ in femoral, dorsalis pedis, and posterior tibial locations. She also cited intermittent pulling and tightness at rest and with active motion.
She had attempted her normal post-race remedies including ice, hot baths, ibuprofen and hydrocodone/paracetamol. Nothing improved her pain. Stepping on the leg, moving, or touching the leg was extremely painful. Physical exam showed normal vital signs and was significant for an uncomfortable appearing, overweight woman. She allowed a limited physical exam; however, she refused to move the extremity actively or passively.
A radiograph did not show a fracture and ultrasound did not show a deep venous thrombosis. Her creatinine kinase was 5533 (30 – 223 U/L). Intravenous fluid resuscitation was immediately initiated. Given that her pain seemed out of proportion to the exam, orthopedic surgery was consulted. Upon orthopedic evaluation, the patient was diagnosed with compartment syndrome based on the physical exam. She was taken to surgery for emergent lateral/anterior/superficial and deep posterior compartment (four-compartment) fasciotomy. Vacuum-assisted closure was placed on the fasciotomy wounds. A delayed primary closure of all of her wounds was done on postoperative day three. She was discharged the following day. |
pmc-6075485-1 | A 26-year-old female presented to a Level I trauma center after a motorcycle crash in which she was the unhelmeted passenger thrown from the vehicle. The patient did lose consciousness and was noted to be briefly confused on scene. Her right shoulder had a palpable deformity and she had difficulty moving the right upper extremity, but she denied other symptoms and was transported to our facility via ground emergency medical services. Upon arrival, the patient was in no distress, alert and oriented, and reported only pain in the right shoulder.
Initial vital signs were temperature of 36.7° Celsius, heart rate 107 beats per minute, blood pressure 102/57 mmHg, respiratory rate 18 breaths per minute, and 100% oxygen saturation on room air. She was evaluated by standard trauma protocol. Computed tomography (CT) imaging of the head, cervical spine, and chest/abdomen/pelvis were significant only for a right anterior shoulder dislocation. The patient was treated symptomatically and preparations were made to perform procedural sedation to reduce the shoulder dislocation. Prior to sedation, the patient developed an abrupt change in mental status. Her right pupil became fixed and dilated. She became aphasic, and her right side became flaccid. The patient was immediately intubated based on Glasgow Coma Scale (GCS) of 7 and rapid deterioration of her clinical status.
A repeat CT head was obtained and revealed a hyperdense left middle cerebral artery (MCA). Neurosurgery and neurology were both immediately consulted. CT angiography (CTA) of the head and neck revealed a left internal carotid dissection with tandem embolus to the proximal left MCA. A tandem occlusion is defined by injury that results in cervical carotid artery dissection, as well as embolic occlusion of a large intracranial artery. This type of vascular occlusion typically does not respond well to thrombolysis. Given the confirmed presence of a tandem occlusion in our patient, a discussion regarding the utility of thrombolytics was held. Neurosurgery opted to perform endovascular mechanical thrombectomy and stenting of the internal carotid artery. Diagnostic cerebral angiogram revealed complete revascularization of the distal left MCA territory. The patient was subsequently admitted to the intensive care unit. There, her course was uncomplicated, and by discharge on hospital day 18 the patient had regained a significant amount of independent function. |
pmc-6075486-1 | An 80-year-old woman with a history of hypertension presented to the emergency department (ED) with blunt facial trauma including a four-centimeter laceration of the right upper eyelid sustained during a ground-level mechanical fall. Upon arrival to the ED, she was confused, repetitive, and amnesic to events surrounding the fall. Computed tomography (CT) of the brain and orbits was rapidly obtained, and upon return from CT she reported new visual loss of the right eye with the ability to see only light. On exam, her globe was noted to be increasingly firm, full to palpation, and swollen shut. Physical examination also revealed new ophthalmoplegia, proptosis, subconjunctival hemorrhage, and afferent pupillary defect. Intraocular pressure (IOP) measured 50 mmHg in the right eye and 12 mm Hg in the left eye. CT demonstrated a hematoma within the right orbit impinging on orbital contents, confirming the diagnosis of orbital compartment syndrome (OCS). An emergent bedside lateral canthotomy and cantholysis (LCC) was performed by the emergency physician with reduction of her IOP and restoration of vision. |
pmc-6075487-1 | A nine-year-old Hispanic female with a past medical history of autism and global developmental delay presented to our emergency department (ED) complaining of a one-year history of pain in her extremities. The pain initially started in the right leg causing her to limp, trip, and fall. She was evaluated by her primary care physician and referred to a physical medicine and rehabilitation clinic that prescribed supramalleolar/ankle foot orthosis (SMAFO). The leg pain resolved, but she developed episodic pain in her bilateral upper extremities a month later. Initially manifesting as pain in her left arm, it was managed with nonsteroidal anti-inflammatory medications; then as this resolved she developed pain in her right arm. The episodic chronic pain in her extremities prompted laboratory evaluation and eventually her referral to the ED because of an elevated alkaline phosphatase (1,847 international units/liter [L]) and low serum calcium (6.4 milligrams [mg]/ deci-liter [dL]). Her past medical history was significant for autism and developmental delay. She did not have a family history of frequent fractures, bone pathology, or calcium problems.
On exam, she was non-verbal but followed commands and was comfortable with no acute distress. Her weight and height were less than the third percentile for age with minimal subcutaneous fat but normal body mass index (twelfth percentile). She had angular deformity and diffuse tenderness in the right and left arms and proximal forearms. She was able to bear weight but had lower extremity pain and difficulty with ambulation. The rest of her physical exam was normal. We noted no spine tenderness, brachydactyly or other dysmorphic features.
Initial laboratory findings were remarkable for hypocalcemia and elevated alkaline phosphatase (). Radiographs of her extremities revealed multiple healed and healing fractures (), initially raising concern for non-accidental trauma. Further review of films with radiology revealed generalized bony demineralization, widened growth plates and metaphyseal fraying and flaring consistent with the diagnosis of rickets (). No vertebral compression fractures were noted, nor was rachitic rosary noted on chest radiographs. An elevated intact parathyroid hormone level (PTH) and extremely low serum 25-hydroxyvitamin D (25-OH vitamin D) concentration () confirmed a diagnosis of severe hypocalcemic rickets due to vitamin D deficiency.
Endocrinology was consulted and elicited on history that she was a picky eater, only eating rice, fries and potato chips. She drank homemade green juices and smoothies but had limited dairy intake. On further review of systems, the family had not noticed any muscle spasms, seizures or twitching. Physical exam by the endocrinologist revealed widened wrists and ankles and rachitic rosary-prominent costochondral junctions of the ribs. She had no symptoms of neuromuscular irritability (negative Chvostek sign) despite ionized calcium of only 0.93 millimoles/L, highlighting the chronicity of the presentation.
The patient received calcium carbonate and calcitriol therapy followed by gradual supplementation of vitamin D3. She experienced significant improvement of pain and gait issues one month after initiation of calcitriol, calcium carbonate, and vitamin D3 supplementation along with orthotics. She was followed by endocrinology and was taken off calcitriol with normalization of calcium and serum 25-OH vitamin D concentrations in a month. One year after the diagnosis, calcium supplementation was also stopped with complete normalization of her calcium (10.1 mg/dL), PTH (38.6 picogram/mL), alkaline phosphatase (355 units/L) and vitamin D (48.7 nanogram/mL). All fractures were well healed except for a malaligned right humerus with no functional disability. She had improved dietary calcium intake with supplemental nutritional shakes and remained on 2,000 IU of vitamin D3 daily. |
pmc-6075488-1 | We present a 31-year-old male who sustained an isolated stellate corneal laceration associated with an open globe injury. The patient presented with mild, right eye pain one hour after glass was sustained to the face during a motor vehicle collision. Visual acuity was 20/100 (baseline 20/20), but no obvious facial or ocular trauma was noted. Extraocular movements were intact. Slit lamp examination revealed a central stellate corneal laceration, peaked 4mm non-reactive pupil, flat anterior chamber, and a falsely negative Seidel sign (). Intraocular pressure was not measured given the nature of the injury. Computed tomography (CT) orbits revealed a flat anterior chamber (). The patient was placed in an eye shield, treated for nausea/pain, initiated on antibiotics with levofloxacin, and updated on tetanus; ophthalmology then completed a surgical repair. |
pmc-6075489-1 | A previously healthy 55-year-old female was evaluated in urgent care for easy bruising for three weeks’ duration. After she was found to have abnormal laboratory results, she was directed to a community ED for further treatment and care.
The patient presented to a community ED the following day. She denied trauma, fever, chills, headaches, or abdominal pain. Upon initial evaluation, the patient had a temperature of 98.5º F, pulse of 87/minute, respiratory rate of 18/minute, and blood pressure of 170/75 mm/Hg. Pulse oximetry showed 100% saturation on room air. Physical exam was unremarkable, except for ecchymosis to the upper and lower extremities bilaterally. Initial laboratory data was significant for a white blood cell (WBC) count of 51.7×109/L, with 89% monocytes and 5% segmented neutrophils, platelets of 16×109/L and hemoglobin of 11.3 g/dL. Prothrombin time (PT) was 17.3 seconds, and international normalized ratio (INR) was 1.6. Complete blood count was negative for blasts; however, Auer rods were present, and the specimen was sent for peripheral smear and flow cytometry. The EP consulted oncology by phone for suspicion of acute leukemia, and the patient was scheduled for an outpatient follow-up two days later, with instructions to return if her symptoms worsened.
Early on the day of her scheduled oncology consultation, the patient returned to the ED complaining of bilateral lower extremity pain and multiple new bruises. She had pain in her lower extremities, from thighs to feet, and occasionally buttocks. She denied tingling, numbness, bladder or bowel incontinence, back pain, or headache. Review of systems was positive only for gross hematuria. Other than mild tachycardia, vital signs at triage were within normal limits. Similar to the prior visit, her physical exam showed ecchymosis over all four extremities, but was otherwise unremarkable. Neurologic examination was within normal limits.
Hematological studies showed significant dysfunction of multiple cell lines, including WBCs of 110.8×109/L, platelets of 60×109/L, hemoglobin of 10 g/dL, 0% neutrophils, and blasts now at 22%. Additional labs found a PT of 18.7 seconds, INR of 1.6, and a d-dimer of 27.9 mg/L FEU. Initial analysis of peripheral smear showed multiple blast forms with convoluted nuclei and monocytoid features. Flow cytometry results from the previous visit were consistent with AML, while a lack of cluster of differentiation antigen 34 (CD34) and human leukocyte antigen – antigen D related (HLA-DR) was suggestive of APL. After ruling out deep vein thrombosis by lower extremity ultrasound, the patient was transferred by ambulance to a tertiary care center. At the recommendation of the receiving oncologist, 30mg of ATRA was administered prior to transfer to prevent DIC.
While en route to the tertiary care facility, the patient became acutely altered and lost consciousness. Upon arrival, her pulse was 68/minute, blood pressure was 231/96, respiratory rate was 15/minute, and oxygen saturation was 99% on 15L by non-rebreather mask. The patient’s Glasgow Coma Score was 1-1-1, her left pupil was fixed and dilated, and she was intubated for airway protection. She was given 50g mannitol. The right pupil became fixed and dilated shortly thereafter, and another 50g mannitol was administered.
Computed tomography (CT) demonstrated a 7.2 centimeter parenchymal hematoma with associated edema and a 10mm midline shift, causing leftward uncal herniation (). Trace subarachnoid hemorrhage was also noted. The patient was emergently evaluated by neurology and neurosurgery and was treated with 60ml (30ml × 2) 23.4% sodium chloride. Neurosurgery evaluated the patient’s CT and reported that mortality associated with ICH of this size was 72%, and that full recovery, if she survived at all, would be unlikely. Although there was no advanced directive in place, the patient’s family members agreed that the patient would not have wanted surgical intervention if her chances of significant recovery were unrealistic.
Over the next 24 hours, the patient’s diagnostic studies demonstrated continued derangement across multiple parameters, with blast forms increasing to as high as 83%, fibrinogen dropping to 77 mg/dL, and platelets paradoxically oscillating from 60×109/L, to 13×109/L, to 88×109/L in a matter of hours. Aspartate aminotransferase was measured at 64 units/L and alanine aminotransferase at 61 units/L, while creatinine increased from 0.9 mg/dL at initial presentation to 1.3 mg/dL, and troponin I was measured at 7.70 ng/mL at its peak. The patient died within 24 hours of arrival at the tertiary care center. |
pmc-6075490-1 | We present the case of a 56-year-old female with history of syncope due to third degree atrioventricular heart block presenting initially with onset of stroke symptoms six days after pacemaker placement and two days after hospital discharge. At 5 PM she developed abrupt onset of left facial droop along with left upper and lower extremity weakness. The patient was initially treated at an outlying hospital and received alteplase at 6:35 PM for treatment of acute ischemic stroke.
A chest radiograph performed at the outlying hospital prior to alteplase administration demonstrated an enlarged cardiac silhouette when compared to prior radiographs showing only borderline cardiomegaly. Upon administration, the patient reported mild chest pain and was given nitroglycerine and morphine. Her chest pain resolved and she was transferred to our comprehensive stroke center for admission. The patient presented to our emergency department at 10:10 PM with a heart rate of 122 beats per minute (bpm) and a blood pressure of 109/41 millimeters of mercury (mmHg).
At 11:20 PM the patient went for a computed tomography angiogram (CTA) after an initial assessment by the emergency physician in consultation with the stroke-team attending physician. After CTA at 10:28 PM, she was documented to have a blood pressure of 49/25 mmHg and heart rate of 109 bpm. She was returned to the resuscitation bay for re-evaluation. Cardiac tamponade was suspected due to the extreme hypotension in the setting of thrombolytic administration after recent pacemaker placement.
On reassessment, the patient had become confused with a Glasgow Coma Scale of 14. The emergency physician performed a POCUS, which demonstrated a pericardial effusion with features of cardiac tamponade including diastolic collapse of the right ventricle (). At that point the diagnosis of cardiac tamponade was made. The patient was alert and responsive, so an intravenous bolus of normal saline was given while a stat surgical consult was obtained. The surgical team evaluated the patient at the bedside within minutes and was able to review the POCUS findings. As the patient was conscious, they elected to take her immediately to the operating room rather than perform a bedside pericardiocentesis.
While in the operating room, approximately 400 milliliters of coagulated blood were evacuated from the pericardial sac with 150 milliliters of surgical bleeding. The operative report notes resolution of tachycardia following this intervention with heart rate trending down to a range of 80–90 bpm with concomitant improvement in blood pressure. She was discharged two days post-operatively with a pericardial catheter in place. Echocardiogram performed on day of discharge noted a small, residual pericardial effusion. |
pmc-6075491-1 | A 69-year-old male with no significant past medical history presented to the emergency department (ED) after accidental ingestion of hydrogen peroxide. He used concentrated hydrogen peroxide as a home remedy. Intending to drink water, he had accidentally grabbed the incorrect bottle and ingested “multiple gulps.” He soon started to experience multiple symptoms including eructation, flatulence, nausea, non-bloody vomiting and generalized abdominal pain. His computed tomography is shown (). During his stay in the ED he started to complain of headache, blurry vision and was found to have a left homonymous hemianopia, dysmetria and hyperreflexia. He was emergently transferred to a tertiary care hospital for hyperbaric therapy. |
pmc-6075492-1 | A 30-year-old male presented to the emergency department (ED) with sudden, painless, decreased vision in the left eye after an episode of severe vomiting. He noted a gray area in the center of his vision and was only able to distinguish objects’ outlines with the affected eye. His visual acuity was 20/200 in the left eye vs. 20/50 in the right. Intraocular pressures were 18 millimeters of mercury (mmHg) in the left eye and 16 mmHg in the right eye. Point-of-care ultrasound (POCUS) (, ) showed findings consistent with retinal pathology and hemorrhage. No further workup was obtained in the ED. Ophthalmology was consulted with the ultimate diagnosis of pre-retinal hemorrhage due to Valsalva action. |
pmc-6075493-1 | A 57-year-old female presented to the emergency department (ED) with periumbilical and left upper quadrant abdominal pain. The pain began abruptly 12 hours prior to presentation and was worsening. Her pain increased with supine position and was associated with nausea and vomiting. Her past medical history was significant for hypertension, gastroesophageal reflux disease and obesity. Prior to presentation in our ED, she underwent a laparoscopic Roux-en-Y procedure for weight loss 10 years prior at an outside hospital. On arrival, pertinent vitals included a heart rate of 115 beats per minute, 20 breaths per minute and blood pressure of 190/100 mmHg. Laboratory studies in the ED were significant for a leukocytosis (14.7 × 109/L), and a lactate level of 5.4 mmol/L. The remainder of laboratory studies were normal. Computed tomography (CT) images were obtained ( and ). |
pmc-6075494-1 | A previously healthy 35-month-old boy (weight, 12.5 kg) was brought to the emergency department (ED) immediately after he was found with partially chewed rivaroxaban tablets in his mouth. His mother reported missing 10 20-mg tablets (200 mg total; approximately 16 mg/kg). The patient had no known family history of bleeding or hypercoagulable disorders.
He was examined within 15 minutes of ingestion by a physician who did not find evidence of bleeding, bruising, or altered mental status. The regional poison control center was then quickly contacted. Activated charcoal (AC) (2 g/kg) was orally administered within 45 minutes of ingestion and was tolerated well by the patient. During the ED stay, a plasma anti-FXa level was obtained approximately four hours after ingestion. The result (>4.00 international units/mL) exceeded the upper limit of the reference range and markedly surpassed the therapeutic window for unfractionated heparin (0.30–0.70 international units/mL).
The patient was admitted and observed overnight. At 13.5 hours after ingestion (a time chosen to correspond with the pediatric hospital service’s morning rounds the following day), the anti-FXa level was rechecked and found to be 1.51 international units/mL. No other laboratory testing was performed by the ED or inpatient teams. The patient was discharged later that day, less than 24 hours after ingestion, without any complications. He did not receive blood products, reversal agents, or additional doses of AC during his stay.
We performed a literature search to identify case reports of rivaroxaban ingestion. All reports of pediatric ingestion are limited to pediatric subsets of two case series drawn from reports to poison control centers with limited details for individual cases. No reports of quantitative monitoring with anti-FXa levels or utility of AC in pediatric patients were identified.
In one case series, two “1.5-year-old” children accidently ingested an unknown quantity of rivaroxaban but did not have further evaluation by a healthcare provider. Both patients were lost to follow-up without any treatment or adverse effects reported. The other case series identified 18 reports of one-time exposure in pediatric patients (age <12 years) who did not have adverse effects. An unspecified minority of patients had results of coagulation studies (international normalized ratio [INR], prothrombin time [PT], or partial thromboplastin time) that were all within the reference ranges.
The other case reports, which involved adults, are summarized in the .– AC or prothrombin complex concentrate or both were given empirically in some cases with no report of serious morbidity. |
pmc-6075495-1 | A 35-year-old immunocompetent female with a history of intracranial fungal abscess with surgical resection 11 years prior presented with headache for four months. Her headache was located along frontal sinuses. Vital signs were normal. Head examination was significant for minimal left maxillary swelling with mild tenderness to palpation (). A fibrotic scar located on the right forehead was present from previous craniectomy. Nasal turbinates were normal appearing. Neurologic examination was normal.
Complete blood count and electrolytes were within normal limits. Computed tomography of the face showed ethmoid and maxillary sinus bone destructions with extension into the right frontal lobe and surrounding facial structures, consistent with severe fungal disease (). Inpatient nasal endoscopy with biopsy showed fungal elements consistent with Aspergillus species. |
pmc-6075496-1 | A 53-year-old male with a history of migraine headaches and sleep apnea was brought in by emergency medical services with the chief complaint of headache. He stated the headache had woken him from sleep approximately two hours prior to arrival, was in the occipital area, and was described as persistent, throbbing, sharp, and severe. He reported nausea, dizziness, trouble walking, and tingling of his extremities. He did not lose consciousness but described near syncope. The pain also was exacerbated by movement. He had a history of migraines; however, he stated this headache was different.
The review of systems was unremarkable. Physical exam revealed a blood pressure 134/87 millimeters of mercury, heart rate of 75 beats per minute, respiratory rate of 16 breaths per minute, oral temperature of 98.2º Fahrenheit, and oxygen saturation of 100%. He appeared mildly anxious and described an occipital headache, which was without meningismus and visual or neurological abnormalities. The remainder of the exam was unremarkable. The headache markedly improved with treatment. A noncontrast CT of the patient’s head was performed and interpreted as negative for masses or bleeds. A LP was performed with difficulty and revealed a large number of red blood cells (TNTC) but an absence of xanthochromia. Given the time frame, the difficulty with the procedure and the lack of xanthochromia, the providers interpreted this to be a traumatic LP. The EP prescribed metaclopromide, acetaminophen, decadron, promethazine and hydoromorphone with complete resolution of his symptoms. The patient was instructed to see his primary care physician for follow-up care.
The patient was seen in follow-up four days later in an outpatient setting. His labs were reviewed, and it was arranged for him to follow up with a neurologist. He was found dead at home the next day with a SAH secondary to a saccular aneurysm involving the anterior cerebral artery. In retrospect, the family stated that he had developed a headache the evening before his ED visit while weightlifting. |
pmc-6075497-1 | A five-year-old male with reported history of poor weight gain and mild intermittent “asthma” presented to the pediatric ED in respiratory distress. He was tachypneic and tachycardic, with an oxygen saturation of 86% on room air. According to the patient’s mother, he had been seen by a pediatric pulmonologist approximately two months prior and found to have normal pulmonary function tests that did not change with albuterol administration. He was diagnosed with asthma and given prescriptions for budesonide/formoterol and albuterol nebulizer.
The patient had further presented to his primary pediatrician approximately one month before his ED visit for complaints of fever. At that time he was diagnosed with acute otitis media and started on azithromycin, but returned four days later with increasing wheezing, upper respiratory symptoms, and exercise intolerance. His antibiotic was changed to cefdinir with a five-day course of prednisolone; the mother reported that he improved with this regimen. He had otherwise been in “normal” health since that time, though his mother did endorse continued issues of poor weight gain and intermittent wheezing.
On the day of presentation, the mother reported that the patient was unable to tolerate a single flight of stairs without fatigue and wheezing. He had used the budesonide/formoterol inhaler earlier that morning and had received multiple albuterol nebulizer treatments prior to arrival without improvement. The patient’s respiratory status had been worsening for the previous two days, with increased dyspnea and wheezing on exertion the day prior to arrival such that he could not play for more than 10 minutes outside without becoming severely dyspneic and fatigued.
On initial exam, the patient was notably tachypneic and tachycardic as well as hypoxic on room air. An expiratory wheeze was appreciated, but no obvious murmur was heard on cardiac auscultation. Splenomegaly was noted. Given the reported history, nebulized albuterol with ipratropium was ordered. Following the breathing treatment, auscultation demonstrated improvement of wheezes, though bilateral coarse breath sounds were appreciated at that time. He remained tachypneic and tachycardic but improved to the point that he was able to speak in full sentences. Oxygen saturation initially improved to 95% but quickly declined to 85% when the nebulizer treatment was completed. Work of breathing increased drastically with worsening hypoxia.
The patient was started on continuous albuterol and given magnesium, solumedrol, and ceftriaxone without significant improvement. Chest radiography demonstrated severe pulmonary edema (). At this time, the patient’s respiratory and mental status statuses rapidly declined and intubation was indicated. He was successfully intubated, but confirmatory chest radiograph demonstrated worsening edema consistent with acute respiratory distress syndrome (). At this time the patient was admitted and care was transferred to the pediatric intensive care unit (PICU).
After transfer to the PICU, the patient’s oxygen saturation gradually improved to 95% on 100% fraction of inspired oxygen (FiO2) with a high positive end-expiratory pressure. The pediatric cardiology team was consulted and performed a bedside echocardiogram that revealed cor triatriatum with severe supravalvar mitral stenosis and significant pulmonary hypertension. The patient was transferred for surgical correction of the malformation as pediatric cardiac surgery was not available at the admitting institution. |
pmc-6075498-1 | A 67-year-old male with past medical history only of hypertension was brought to the emergency department (ED) after a suspected self-inflicted gunshot wound to the head approximately 30 minutes prior to arrival. The patient was found supine and unresponsive by emergency medical services (EMS) with stridorous breath sounds. Paramedics attempted intubation once, but after recognizing esophageal intubation through auscultation they removed the endotracheal tube and placed a King laryngeal tube (LT) supraglottic airway (Ambu®). The second attempt was confirmed by auscultation of bilateral breath sounds and digital end-tidal carbon dioxide monitoring. The airway was suctioned through the King LT and 200 mL of blood was removed. Initial vital signs at the scene were pulse 77 beats per minute (bpm), blood pressure (BP) 134/63 millimeters of mercury (mmHg), room air oxygen saturation (SaO2) 70%.
Upon arrival to the ED, the patient had a pulse of 74 bpm, respiratory rate 23 breaths per minute, a BP of 122/65 mmHg, SaO2 83%. During the primary survey, the King LT was removed and the patient was re-intubated with an endotracheal tube on the first attempt using direct laryngoscopy. He was pre-oxygenated with saturations maximizing in the mid-80s. Secondary survey findings were significant for a gunshot wound to the right temporal region. No additional injuries were found. Pupils were three millimeters bilaterally and fixed, weak corneal reflex, absent cough and gag reflex, and decerebrate posturing in all extremities. Head computed tomography revealed a right parietal entry wound with fragments scattered through the bullet tract and to the left of midline, a large subdural hematoma with rightward shift, diffuse cerebral edema, and a comminuted skull fracture. A chest radiograph (CXR) revealed widening of the superior right mediastinum with loss of definition of airspace in the right upper lobe and absence of the minor fissure, most consistent with complete collapse of right upper lobe (). Upon reexamination, no additional injuries or entry sites were found to correlate with the radiograph findings.
The patient was given 100 grams of mannitol for bradycardia and signs of herniation and one grams of levetiracetam prior to transfer to the intensive care unit (ICU) for expectant management of his head injury while waiting for family to arrive. At admission to ICU, his blood pressure was 80/50 mmHg with heart rate in the seventies. His neurologic exam remained poor. Bronchoscopy was performed in the ICU due to persistent hypoxia and revealed blood obstructing the right mainstem bronchus, which was suctioned and evacuated from the right lung. A right-sided chest tube was placed for pneumothorax identified after bronchoscopy with blood evacuated from the chest cavity. Due to the poor prognosis of the patient, care was transitioned to comfort measures and he was compassionately extubated.
Autopsy was performed approximately 12 hours after death. In addition to significant intracranial hemorrhage and edema, the patient was noted to have a transection of the gastroesophageal junction and a large disruption of the greater curvature of the stomach. Blood was noted in the mediastinum and within the pleural and peritoneal cavities. No inflammation or ischemic changes were noted on histologic specimens of the stomach, but specimens from the esophagus and gastroesophageal junction were suggestive of ischemia. |
pmc-6075499-1 | A 49-year-old female presented to the ED with diffuse abdominal pain, fevers, myalgia and nausea. The patient had an unsuccessful cervical dilation and endometrial biopsy six days prior to presentation. She was seen in gynecology clinic on post-procedure day two and was started on oral metronidazole for suspected bacterial vaginosis due to a foul-smelling discharge, which subsequently resolved. Pertinent surgical history included an endometrial ablation and bilateral tubal ligation.
On arrival, the patient was mildly tachycardic but otherwise hemodynamically stable and afebrile. She was ill-appearing. On physical exam, severe diffuse abdominal tenderness and guarding was noted. A pelvic exam noted uterine tenderness and scant dark blood in the vaginal vault, but without appreciable discharge. Laboratory results were significant for mild leukocytosis with white blood cell count of 12 × 10^3/μL (ref 3.98–10.04) but otherwise unremarkable. Her contrasted abdominal and pelvis computed tomography demonstrated a 2.8 cm × 4.8 cm intrauterine fluid collection (). Ampicillin, clindamycin and gentamycin were started. Gynecology was consulted and patient was taken to the operating room for emergent dilation and curettage. The procedure was unsuccessful due to complete cervical stenosis and severe uterine tissue inflammation and edema. Repeated ultrasound-guided attempts failed, and a non-perforating iatrogenic false lumen was created in the posterior myometrium. The following day, the patient was taken back to the operating room for a total abdominal hysterectomy. The surgeon reported a tense, fluid-filled uterus that ruptured when bi-valved, consistent with a pyometra (). |
pmc-6075500-1 | A 65-year-old female was transported to the emergency department (ED) at approximately 2:00 AM following a witnessed cardiac arrest. According to the patient’s husband, she had been asleep in bed when she awoke suddenly, sat upright, and reached for her albuterol inhaler before “collapsing.” He found her to be pulseless and initiated cardiopulmonary resuscitation (CPR) while placing a call to emergency medical services (EMS). On EMS arrival, the patient was unresponsive and continued to receive CPR. She was intubated in the field using a size 7.0 endotracheal tube. Her initial rhythm was pulseless electrical activity (PEA), but she converted to normal sinus rhythm after receiving 1mg of epinephrine intravenously and 15 total minutes of CPR. No further history was available.
Per her husband, her past medical history was notable for “thyroid problems.” Her only medications were an albuterol inhaler, recently prescribed by her primary physician, and a multivitamin. She had no known drug allergies. On social history, the patient was not known to drink alcohol, smoke cigarettes, or use other substances. A family medical history and review of systems could not be obtained due to the acuity of her condition.
On examination, the patient was an obese female, intubated, and unresponsive. Her temperature was 37.1 degrees Celsius, blood pressure was 97/65 millimeters Hg, heart rate was 75 beats per minute (bpm). Her body mass index was estimated at 32. She was initially receiving assisted ventilation by EMS, but on examination in the ED she was found to have a spontaneous respiratory rate of 12 breaths per minute with an oxygen saturation of 98% on 40% fraction of inspired oxygen. Her head was atraumatic and normocephalic. Her pupillary exam showed mid-dilated symmetric pupils with sluggish reactivity to light. There was no hemotympanium or Battle’s sign. She had no apparent facial droop. An oral endotracheal tube was in place, confirmed with radiography and audible bilateral breath sounds. She had a full, supple neck without palpable masses, but additional exam was limited by body habitus. On cardiopulmonary exam, her lungs were clear to auscultation bilaterally and her heart had a regular rate and rhythm with no murmurs, gallops, or rubs. The patient’s abdomen was soft and nondistended with normal bowel sounds. On neurologic exam, her Glascow Coma Scale was 3T. She had diffusely decreased muscle tone, and 1+ patellar and brachioradialis deep tendon reflexes. Her musculoskeletal exam was unremarkable for deformity, erythema, or edema. Skin exam did not show any rashes, wounds or other lesions.
Initial electrocardiogram (ECG) () showed normal sinus rhythm at a rate of 70 bpm, normal axis, normal intervals and no pathologic t-wave inversions or ST-segment changes. A complete blood count and complete metabolic panel were done (). Additional laboratory tests, including thyroid studies, were unremarkable except for an elevated lactic acid of 6.9 millimoles/liter (L) (). A point-of-care echocardiogram was performed, which demonstrated grossly normal heart chamber sizes and systolic function with no pericardial effusion (). A point-of-care ultrasound of the abdomen and thorax was negative for any intra-abdominal free fluid. There was bilateral lung sliding present and no B lines. An anterior to posterior chest radiograph (CXR) is shown in .
The etiology of the patient’s cardiac arrest was unknown until a further diagnostic test was performed that revealed the diagnosis. |
pmc-6075501-1 | A 94-year-old woman with chronic obstructive pulmonary disease, hypertension, and breast cancer presented to the ED in respiratory distress. She reported dyspnea starting the night prior to presentation with no history of trauma. She was normothermic, had a normal heart rate and blood pressure, but was tachypneic and hypoxic to 88% on room air. Physical exam revealed significant accessory muscle use, no stridor, no jugular venous distention, normal heart sounds and diminished breath sounds in the left hemithorax.
While the nurse gathered a 14-gauge needle and a chest tube tray for needle decompression followed by tube thoracostomy, a bedside ultrasound was performed. The ultrasound showed bilateral pleural sliding without significant B-lines or effusion. Portable chest radiograph revealed that a large amount of intra-abdominal contents had entered the thoracic cavity resulting in a shift of the mediastinum (). A nasogastric tube was not inserted to decompress the bowel, as the patient declined to have this performed.
We consulted the general surgery service, which recommended obtaining a computed tomography (CT) scan to further characterize the defect in the diaphragm (). The patient and her family members declined surgical intervention. She was admitted to the hospital to arrange home hospice care and was discharged within 24 hours. She died at home with her family three days after presenting to the ED. |
pmc-6075502-1 | A 24-year-old woman presented to the emergency department by emergency medical services with severe respiratory distress and hypoxia. The patient complained of exertional chest pain and nonproductive cough. Her room air saturation was 65% with improvement to 95% with oxygen supplementation. Her vital signs were a pulse of 110 beats per minute, blood pressure of 140/100 mmHg and a temperature of 36.5 degrees Celsius. Lungs were clear to auscultation, heart was without murmur, and extremities had no edema. Electrocardiogram demonstrated sinus tachycardia with rSR’ pattern, prominent p-waves, and an elevated R:S wave ratio in V1 and V2. Troponin was 0.08 ng/mL, d-dimer was 445 ng/mL, and hemoglobin was 16.4 g/dL. Portable chest radiograph was normal.
Point-of-care ultrasound (POCUS) demonstrated significant right ventricular dilatation () with hypertrophy of the right ventricular myocardium (). On further questioning, the patient clarified that she had been diagnosed with “pulmonary hypertension” but hadn’t seen a doctor in over a year and was not prescribed any treatment. Subsequent review of outside electronic medical records revealed an echocardiogram performed approximately one year prior to presentation that demonstrated concern for an atrial septal defect.
POCUS revealed significant right ventricular hypertrophy supporting a longstanding disease process. Computed tomography angiography did not reveal any abnormalities. The patient was admitted for hypoxia and pulmonary hypertension. On admission, formal echocardiogram demonstrated concern for atrial septal defect with left-to-right shunt. Two days later, repeat echocardiography with bubble study demonstrated right-to-left shunt across the interatrial septum. The patient rapidly decompensated during the admission, leading to intubation for respiratory distress and then pulseless electrical activity arrest and death despite resuscitation. |
pmc-6075503-1 | A 69-year-old woman with a history of osteopenia and left total hip arthroplasty three months prior presented from home to the emergency department with leg pain and inability to ambulate. She had fallen from standing onto a tile floor, making contact with her left hip. She was mildly hypertensive, with a blood pressure of 137/92 mmHg and tachycardic, with a heart rate of 105 beats per minute, but had otherwise unremarkable vitals. On examination, she had tenderness and developing ecchymosis over the greater trochanter of the left femur. Her left leg was slightly shortened and externally rotated but neurovascularly intact. A pelvic radiograph () showed medial displacement of the acetabulum and femoral head into the lesser pelvis. Angiography failed to reveal any vascular disruption. She remained hemodynamically stable and was taken to surgery for an urgent but successful internal pelvic fixation. |
pmc-6075504-1 | A 71-year-old, 86 kilogram male with a history of alcohol abuse, dementia, chronic kidney disease, and hypertension presented to the emergency department (ED) after the ingestion of approximately half of a retail lava lamp’s contents. On-scene vitals by emergency medical services (EMS) were notable for 90% oxygen saturation on room air. The patient was placed on two liters of oxygen by nasal cannula (NC), and the North Carolina Poison Control Center was called; they recommended supportive care, laboratory studies, and an electrocardiogram (ECG) with continuous cardiac monitoring. The risk of toxic ingestion was thought to be low because of the recent manufacture date, which theoretically minimized toxic contents previously found in similar products because of regulatory changes.
In the ED, EMS reported that the patient had consumed the lava lamp because he believed it to contain alcohol. The patient was unsure of the time of ingestion, though all history was limited by his chronic dementia. Initially, he remembered having nausea and vomiting at home, but was asymptomatic on evaluation. On physical exam, vital signs were notable for a blood pressure of 129/68mmHg, heart rate of 74 beats per minute (bpm), and oxygen saturation of 97% on two liters NC. Patient was tearful but in no distress. He had equal and reactive pupils, his heart rate was regular, breath sounds were clear, abdomen was soft, and he had a normal cranial nerve exam. Family in the room reported he was at his baseline mental status: delayed speech and baseline dementia. They seemed unconcerned about any new or significant mental status changes.
Routine laboratory results were normal except for the following: white blood cell count 14.4×109/liter, hemoglobin 10.0 g/dL, potassium 6.3 mmol/L, carbon dioxide 14mmol/L, blood urea nitrogen 37 mg/dL, calcium 12.1 mg/dL, creatinine 2.3 mg/dL, and anion gap 23 mmol/L. Serum drug screen was negative for ethanol, acetaminophen, and salicylate. A 12-lead ECG showed normal sinus rate, with concern for peaked T-waves in the apical leads. A chest radiograph was read as persistent low lung volumes with bronchovascular crowding and bibasilar opacities, likely reflective of atelectasis.
The patient was treated for hyperkalemia with calcium gluconate, insulin, dextrose, and sodium bicarbonate; the Poison Control Center was updated on the findings and initial treatments. Within three hours, the potassium had corrected to 5.5 mg/dL and creatinine increased to 2.8 mg/dL. His mental status was unchanged. He continued to saturate in the low 90s, originally managed with two liters NC, but later requiring slight increases in his NC needs. Initially, it was thought that his lower saturations were attributed to a possible aspiration event, especially with reports of vomiting earlier in the morning.
About six hours into his ED visit, while pending admission, the nursing staff called providers to the room for an acute change in mental status with concomitant aspiration event. The patient’s oxygen saturation acutely dropped to 85% on NC, and high-flow NC was initiated. The patient’s saturation remained 85% on the Masimo SET™ pulse oximeter despite oxygen supplementation, and he was responsive to only painful stimulation. On auscultation, his lungs were clear bilaterally without wheezes or rales; his skin, especially distal, appeared gray and mottled. His blood pressure was 101/52 mmHg, and he became tachycardic to 101 bpm. A non-rebreather oxygen mask was applied at 15 liters and albuterol was administered with no change in respiratory status. Repeat radiograph was unchanged and it was thought this could be due to aspiration pneumonitis or acute respiratory distress syndrome. However, with the acute change, a venous blood gas was then also sent with the following notable results: pH of 7.22, methemoglobin of 45.6% and a lactate of 2.7 mmol/L.
Given this finding and the fact that his oxygen saturation remained the same on supplementation, the patient was diagnosed with methemoglobinemia. Subsequently, he was administered two doses of methylene blue (50 mg intravenously) 20 minutes apart. Over the next half-hour, his color and oxygen saturation improved, followed by a return of his mental status to baseline at initial presentation. A follow-up arterial blood gas at 45 minutes showed pH of 7.28 and methemoglobin of 9%. The patient was admitted to the intensive care unit.
The Poison Control Center was later updated. After research and testing, it was discovered that the components of the lava lamp ingested included 76% calcium nitrate, 23% water, and 1% potassium enol. |
pmc-6075505-1 | An 18-year-old female who was 10 days post-vaginal delivery presented to the ED in status epilepticus for which she required endotracheal intubation. She had a blood pressure of 163/89 millimeters of mercury, a heart rate of 155 beats per minute, a temperature of 37.0°Celsius, a respiratory rate of 22 breaths per minute, and an oxygen saturation of 94% on 15L per minute of oxygen via a bag-valve mask. Physical examination confirmed the presence of left leg swelling with mild erythema below the knee; otherwise, no palpable cords or other abnormalities were seen in her lower extremities. Initially it was thought to be deep venous thrombosis, but there was no evidence via venous Doppler ultrasound. Cardiac examination did not reveal murmurs, rubs, gallops, or other abnormalities, and her lungs were clear to auscultation. Upon questioning her family, it was revealed that a few hours prior to presentation the patient had developed sudden onset of difficulty breathing and subsequent loss of consciousness. She was rushed to the ED.
Further workup revealed leukocytosis of 19.84×109 /L, elevated D-dimer of 19.9 milligrams per liter, fibrinogen of 457.9 milligrams per deciliter, and troponin of 2.42 micrograms per liter. An electrocardiogram (EKG) revealed an S1Q3T3 pattern. A urine dipstick revealed +2 protein and was otherwise normal.
A magnesium sulfate (MGSO4) bolus dose of 4g intravenous (IV) over 30 minutes followed by a drip of 2 grams per hour was initiated for presumed eclampsia. A brain computed tomography (CT) without contrast was ordered for the workup of a first-time seizure. This was unremarkable. At this point, the patient’s differential diagnosis was reconsidered and prompted the team to order a CT venogram (CTV) of the brain with a CT pulmonary angiogram. It demonstrated CVT involving the superior sagittal and right transverse sinuses (), while her CT pulmonary angiogram showed bilateral pulmonary thromboses involving the main, lobar, and multiple segmental arteries bilaterally ().
Enoxaparin sodium was initiated in the ED and the patient was admitted to the intensive care unit (ICU) for further management. During her ICU stay, brain MRI with a magnetic resonance angiogram showed diffuse ischemia with a 5 mm tonsillar herniation and the absence of signal flow void in both internal carotid arteries (). She was started on 1 g/kg IV of mannitol over 60 minutes. Additionally, a presumptive diagnosis of seronegative antiphospholipid syndrome was made and IV immunoglobulin and methylprednisolone were initiated, with the addition of plasmapheresis. Unfortunately, none of the treatment measures showed a favorable response. Her poor prognosis was discussed with her family and the consensus was to place a do-not-resuscitate order. The patient died in the ICU two weeks later because of tonsillar herniation. |
pmc-6075624-1 | We present the case of a 76-year-old male with history of hypertension and deep vein thrombosis. He initially presented to the oncology clinic in June 2016 with a low white blood cell (WBC) (2,700 cells/microliter) and platelet counts (58,000 cells/microliter), which was found during routine blood work. Initial bone marrow biopsy performed in June 2016 showed normocellular marrow with no evidence of blasts. Fluorescence in situ hybridization (FISH) did not show evidence of myelodysplastic syndrome (MDS). The patient was treated conservatively and was given a trial of steroids. He did not respond to these treatments, and blood tests performed in February of 2017 showed a platelet count of 39,000 cells/microliter, a hemoglobin level of 7.8 gm/dl, and a WBC count of 2,000 cells/microliter. In view of the persistent trilineage depressed blood counts, a second bone marrow biopsy was performed in March of 2017, which revealed 20.8% blasts with hypercellular bone marrow. Therefore, he was diagnosed with AML. He underwent additional cytogenetic testing, which showed that he did not have any of the favorable cytogenetics, including mutations of the CCAAT/enhancer-binding protein alpha (CEBPA) gene or nucleophosmin (NPM) 1 gene. Unfavorable FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was detected with a polymerase chain reaction (PCR) product of 327 base pairs (bp). In addition, another poor prognostic marker, trisomy of the 21st chromosome, was detected. We administered the standard first-line induction chemotherapy regimen to the patient, including cytarabine (100 mg/m2) and daunorubicin (60 mg/m2), in March 2017. Unfortunately, a bone marrow biopsy performed 14 days after chemotherapy initiation showed AML with 72% blasts (Figure ). At that time, the patient decided that he did not want to continue with re-induction attempts involving intensive chemotherapy. After detailed discussions with the patient and a literature review, we presented the option of salvage chemotherapy with the less-toxic AZA for the treatment of his refractory AML. He agreed to this treatment, and we administered AZA (75 mg/m2) for seven days in the second half of March 2017. A subsequent bone marrow biopsy performed in April 2017 showed a positive response with no morphologic or immunophenotypic evidence of increased blasts. Subsequently, he received nine more cycles of AZA, which he tolerated very well. A repeat bone marrow biopsy performed in January 2018 revealed no blasts (Figure ). The patient continues to be in complete remission with incomplete hematologic recovery (low platelet counts - 44000 cells/microliter) after 10 cycles of treatment with AZA. |
pmc-6075625-1 | A 21-year-old female presented to the Case Western Reserve University School of Dental Medicine Clinic in Cleveland, Ohio. Her chief complaint was a slowly growing painless swelling involving the right side of the mandible that had started one year previously. Her past medical history revealed no previous surgeries or diseases. Her vital signs were recorded as 120/80 mmHg blood pressure, a pulse of 103 beats per minute (bpm), 15 respirations per minute, height - 5.1 ft, weight - 165 lb, and a calculated body mass index (BMI) of 23.71. No other medical conditions were identified, and the patient did not report taking any medications. Clinical examination revealed an intraoral swelling involving the posterior part of the body of the mandible and extending to the ramus on the right side. On palpation, the lesion was hard in consistency, except for select areas which exhibited a softer texture.
The patient was referred to a private dental imaging center for a CBCT scan to evaluate the extent of the lesion. A board-certified oral and maxillofacial radiologist performed the radiographic interpretation of the CBCT scan. The scan revealed a well-defined radiolucent lesion ranging from the interdental bone in between the second and third right molars and extending to the ramus of the mandible posteriorly in the anteroposterior direction. The lesion extended from the alveolar crest to the inferior border of the mandible in the superior-inferior direction (Figure ).
Osteolytic changes of the alveolar crest margin distal to the third molar were noted and displaced the roots of the third molar more distally. The sagittal cut showed that the lesion had a multilocular appearance with an incomplete internal septal structure, demonstrating wispy-like septations. The inferior border of the mandible showed some resorption with undulating borders (Figure ). The lesion showed expansion of the alveolar crest. In axial cuts, the lesion involved the ramus of the mandible, and expansion and thinning of the inner cortical plate were noted.
Extending more medially, the borders of the lesion showed fine wispy-like septations with undulating borders (Figure ). Coronal slices demonstrated the resorption of the outer cortical boundary, a multilocular appearance, an expansible nature, and thinning and resorption of the inner cortical boundary. The presence of an intact (albeit thinning) border, wispy septations, and expansion led to a provisional diagnosis of an aggressive benign tumor. Central giant cell granuloma, ameloblastoma, and keratocystic odontogenic tumor (KOT) were considered in the differential. However, the presence of fine, wispy septations and undulating borders favored a CGCG diagnosis.
An incisional biopsy was performed, and the histopathological report for the lesion revealed a giant cell reparative granuloma formed of proliferating spindle cells, multinucleated giant cells, extravasated red blood cells (RBCs), and mononuclear cells. No specific inflammatory granuloma or significant nuclear anaplasia and mitosis or other evidence of malignancy were noticed. This information, along with clinical and radiological features, was suggestive for CGCG and hyperparathyroidism (because of similar histopathological features). Laboratory investigations showed that the parathyroid hormone, alkaline phosphates, and calcium levels were all within normal limits. This excluded hyperparathyroidism as a possible diagnosis. The patient underwent surgical resection of the lesion. The surgery and recovery were uneventful. |
pmc-6075628-1 | A previously healthy 27-year-old man presented with complaints of left calf pain and erythema of four days duration, which was preceded by a petechial rash of the bilateral lower extremities and left foot pain. He also reported low-grade fever (100.7 F) with associated chills. He was initially seen at a Level 1 trauma center where he underwent a Doppler investigation of the lower extremities with negative findings. Blood work at the time was reported normal. A worsening induration and swelling of the left lower extremity prompted him to seek further work-up. An inquiry into past medical and family history was non-contributory. He had a history of hernia repair and tonsillectomy. Social history was significant for recreational marijuana and cocaine use in the past. He was homosexual and reported being sexually active with one male partner and inconsistent contraception use. The patient denied weight loss, night sweats, recent travel, recent major illness or surgery, or steroid use. On admission, he was afebrile (98.8 F) and tachypneic (18 breaths per minute). A blood pressure of 132/75 mmHg, heart rate of 81 beats per minute, and oxygen saturation of 99% on room air were documented. The physical examination revealed a mildly enlarged spleen and confluent erythema of the bilateral lower extremities that were tender to touch. Blood work showed a normal white blood count of 7.33X109/L, hemoglobin of 15.6 mg/dl with marked thrombocytopenia, and platelet count of 51X109/L. An aspartate aminotransferase (AST) level of 289/L, alanine aminotransferase of 372/L, and direct bilirubin of 0.22 umol/L confirmed transaminitis. The D-Dimer level was 14,000 ng/ml. The venous duplex of the lower extremities showed extensive thrombosis in the left peroneal (Figure ) and thrombosis of the left popliteal (Figures -).
Computed tomography (CT) of the chest with contrast revealed borderline splenomegaly of size 13 cm. Extensive investigations eventually showed evidence of an active CMV infection with CMV-Immunoglobulin M (IgM) seropositivity (>240.0 AU/mL) and positive polymerase chain reaction (PCR). Serology was positive for the Epstein Barr virus (EBV) (368 U/mL). He received a platelet transfusion with symptomatic improvement. He was discharged home on Eliquis 5 mg twice daily; however, he returned to the hospital a week after with new symptoms. He reported right lower leg pressure-like pain that was exacerbated with walking. Doppler revealed right great saphenous vein superficial thrombophlebitis along with unchanged findings in the left leg. He was initially switched to Rivaroxaban 15 mg twice daily; and on clinical improvement, he was later discharged on Apixaban 5 mg twice daily. |
pmc-6075635-1 | A 76-year-old female with history of remote tobacco use, hypertension, transient ischemic attack, and osteoarthritis presented after a fall for the first time due to syncope. Her home medications included aspirin 81 mg once daily, losartan 25 mg once daily and multivitamins. On examination, there were no focal neurological deficits, no additional heart sounds or murmur were noted, and the remaining examination was unremarkable. The initial electrocardiogram (EKG) found a 2-mm ST elevation in the lateral leads I and aVL and a reciprocal 1-mm ST depression in the inferior leads II, III, and aVF. The patient’s initial troponin T level was 0.81 ng/dL (the reference range is <0.03 ng/dL). The patient immediately underwent coronary angiography due to the ST-segment elevation myocardial infarction (STEMI) alert but was found to have non-obstructive coronary artery disease (Figure ). A left ventriculogram revealed an ejection fraction (EF) of 30% with poor anteroapical and distal inferior wall hypokinesis suggestive of Takotsubo cardiomyopathy (Figure ).
Her second set of bloodwork showed troponin levels of 0.50 ng/dL, total creatine kinase (CK) of 329 units/L (the reference range is 24 to 200 units/L) and creatine kinase-muscle/brain (CK-MB) of 27 ng/mL (the reference range is 0.1 to 6.7 ng/mL). Her lipid panel showed a total cholesterol of 140 mg/dL, low-density lipoprotein (LDL) of 60 mg/dL and high-density lipoprotein (HDL) of 73 mg/dL. A subsequent transthoracic echocardiogram confirmed the presence of apical ballooning and akinesis typical of TCM. The function of the basilar septum and the lateral basilar walls were well-preserved with an EF of less than 20% (Figure ). In addition, she also had moderate aortic, mitral, and tricuspid regurgitation along with moderate pulmonary hypertension. A review of outside records included an echocardiogram from four months ago with an EF of 60% to 65% without any regional wall motion abnormalities, a concurrent nuclear stress test with no evidence of reversible ischemia or infarction, as well as an EKG without any pre-existing ST/T wave abnormalities.
A day later, the patient experienced a symptomatic 17-second sinus pause that was noted on telemetry (Figure ). The carvedilol 3.125 mg started after the angiography was performed, was discontinued. Despite this, 24 hours later the patient became unresponsive because of a 29-second sinus pause but was resuscitated by cardiopulmonary resuscitation (CPR). An emergent transvenous pacemaker was inserted due to this; it kept her hemodynamically stable after that. During the next day, the patient’s heart was paced twice by the device for eight and 14 seconds, respectively, but the patient remained asymptomatic.
As the patient required beta-blocker therapy long term to improve her cardiac function, the following day a dual-chamber permanent pacemaker was inserted, and the patient was restarted on carvedilol 3.125 mg twice daily in addition to losartan 50 mg once daily and aspirin 81 mg once daily. Two weeks after discharge on outpatient follow-up, the patient had no further recurrences of syncope. Her pacemaker was functioning normally with <1% pacing noted. |
pmc-6075637-1 | A 62-year-old Caucasian male with a history of type 2 diabetes mellitus and hypertension presented to the emergency room with acute onset blurry vision and headache. The patient was in his usual state of health until a few hours prior to his presentation. He was working on a presentation in a poorly lit room when symptoms started. His headache was frontal, sharp in quality, with no radiation, and was accompanied with blurry vision. There was no associated fever, chills, sinus congestion, focal weakness or numbness, head trauma, neck pain, jaw claudication, recent sick contact or travel. The patient described his vision blurriness as “glazed vision”. His last dilated eye examination was performed a month prior to his presentation and was found to be normal. Upon arrival to the emergency room, he started to complain of photophobia.
His primary care physician, a week prior to his presentation, started the patient on a daily 5 milligrams of extended-release oxybutynin. His other home medications included metoprolol, levothyroxine, metformin, and aspirin.
On physical examination, the pupils were mid-dilated, fixed and non-reactive to light or accommodation, 3.5 mm oculus dexter (OD) and 4.0 mm oculus sinister (OS). Upon visual acuity assessment, the patient was able to count fingers at four feet in the right eye and two feet in the left eye.
Computed tomography (CT) of the head was negative for acute intracranial hemorrhage or any other acute changes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were within normal laboratory limits. Ophthalmology consultation was obtained.
Slit lamp examination showed grade 2 epithelial and stromal corneal edema oculus uterque (OU) with some epithelial bullae OD. The examination also showed bilateral grade 2 to 3 perilimbal conjunctival injection, the irises were within normal limits, and the lens showed grade 1 nuclear sclerosis. Goldman intra-ocular pressure (IOP) was 55 OD and 56 OS while Tonopen was 63 OD and 65 OS. The posterior pole was poorly visualized due to corneal edema but the optic nerves looked perfused with no evidence of hemorrhage. The diagnosis of AACG was made and the patient was immediately treated with topical prednisolone 1%, pilocarpine 1%, bimatoprost 0.01%, and brimonidine-timolol 0.2%-0.5% ophthalmic solutions.
After 45 minutes and several cycles of eye drops use, IOP using Tonopen decreased to 55 OD and 56 OS. The patient started to notice improvement in visual changes as well. Visual acuity was 20/400 to counting fingers OU. Subsequently, the patient required urgent bilateral laser peripheral iridotomies.
Due to the recent normal eye examination and the timeline of the events, oxybutynin was believed to be the trigger of the event and it was discontinued. A follow-up with the patient a week later revealed normal visual acuity and normalization of IOP. |
pmc-6075640-1 | A 16-year-old male, prior to his presentation at our clinical setting, was diagnosed with an osteosarcoma in his left fibula. At the time of the diagnosis, he presented with a painful and progressively enlarging mass over the left ankle which restricted any weight bearing on the affected leg. A contrast-enhanced magnetic resonance imaging (MRI) scan of the lower extremities revealed a well-defined multicystic mass arising from the distal metaphyseal region of the left fibula (Figure ).
The mass was subjected to a core needle biopsy and subsequent histological evaluation of the biopsy specimen revealed a collection of hypercellular, spindle polygonal cells with an abundance of osteoclastic giant cells; which provided the tissue diagnosis of an osteosarcoma. Following this diagnosis, the patient presented to our clinical setting for further management. He underwent surgical excision of the tumor followed by the placement of a vascularized fibular bone graft. Following the surgery, the patient was provided with a total of 32 cycles of adjuvant chemotherapy with cisplatin, methotrexate, and leucovorin. He subsequently went into remission. After six months, he presented again with complaints of resurfaced pain in his left leg. A bone scan was performed due to the suspicion of tumor recurrence, which revealed an intense and irregular uptake in the distal segment of the left leg; confirming the reemergence of his primary pathology. The bone scan also showed areas of bony metastasis (evidenced by multiple areas of moderate tracer uptake) in the left maxilla, left parietal bone of the skull and greater trochanter of the left femur (figure ).
Further assessment with a contrast-enhanced high-resolution computed tomography (HRCT) scan of the lungs revealed multiple soft tissue nodules of differing sizes in both lungs. Some of these nodules were pleural-based and some showed internal cavitations (with the largest in the right upper lobe measuring 1.8 cm in diameter), which were suggestive of a metastatic disease process (Figure , Figure ).
The patient was subsequently started on a second-line chemotherapeutic regimen, which comprised of etoposide, ifosfamide, and mesna. One week (and two cycles) into his chemotherapy, the patient presented with complaints of shortness of breath (SOB) that particularly worsened on exertion. His predicament was accompanied by pleuritic chest pain and an intermittent, dry cough. The initial assessment revealed a blood pressure (BP) of 140/100 mmHg, heart rate (HR) of 115/minute, respiratory rate (RR) of 25/minute and temperature of 37.2 ˚C (98.96 ˚F). He was alert and well-oriented with a Glasgow Coma Scale (GCS) score of 15/15. Examination of the chest showed a hyper-resonant percussion note, and auscultation revealed bilaterally decreased breath sounds. Further evaluation with a chest X-ray revealed bilateral pneumothoraces with medial displacement of the lung parenchyma on both sides (Figure ).
An electrocardiogram (ECG) showed sinus tachycardia and an echocardiogram revealed an ejection fraction of 60%. Chest tubes (with an underwater air seal) were inserted bilaterally. During the course of this admission, the patient received multiple chest X-rays to follow the status of his pneumothoraces. These X-rays showed a marked reduction in the volume of the left pneumothorax but only minimal improvement of the right pneumothorax. A computed tomography (CT) scan of the chest without contrast showed bilateral pneumothoraces with a right-sided prominence as well as numerous cystic lesions in both lung fields; with the largest in the right upper lobe (1.8 cm in diameter) (Figure ).
A lack of improvement following a bilateral chest tube insertion incited a subsequent chemical (talc) pleurodesis, which yielded significant clinical and radiological improvement. He was later discharged with a right pigtail insertion. A follow-up chest X-ray revealed the resolution of the bilateral pneumothoraces (Figure ) and his chemotherapy was resumed.
The patient was readmitted to our clinical setting after one month following the resolution of his bilateral pneumothoraces; this time with a recurrent right-sided pneumothorax (Figure ).
A second chemical (talc) pleurodesis could not be performed owing to the patient’s refusal for the procedure, while a video-assisted thoracoscopic surgery (VATS) was not offered because of the widespread pulmonary metastatic lesions. In this admission he was managed conservatively via a chest drain, ultimately resulting in the resolution of the pneumothorax. |
pmc-6075642-1 | We present a 40-year-old male with a history of chronic back pain and a recent, acute progression of bilateral lower extremity paresthesias and weakness. Over a seven-day period prior to presentation, the patient experienced a sudden onset of bilateral leg numbness, with no history of trauma or another precipitating event. The right leg was affected more severely than the left, traveling primarily in a distribution down the lateral leg into the dorsum of the foot and great toe. He eventually began having a shooting pain in this same distribution. He also reported a progressive weakness with bilateral ankle and toe dorsiflexion and five days duration of perineal numbness and mild urinary retention. On exam, he was unable to dorsiflex his ankles or great toes against gravity and had reduced sensation in the lateral aspect of both lower legs and the dorsum of bilateral feet. The patient’s Achilles reflexes were also diminished bilaterally, though reflexes were present and brisk at the knee. It is also pertinent that no upper motor neuron signs were present.
Magnetic resonance imaging (MRI) of the lumbar spine revealed a somewhat heterogeneous, but predominately T2-weighted, hyperintense mass in the left lateral and dorsal epidural spaces (Figure ). There was significant lumbar stenosis present at the level of L4-5 secondary to the mass, with the rightward displacement of the thecal sac. There was no clear connection to the adjacent facet joint although the dorsal mass did seem to be contiguous with the dorsal aspect of the L4-5 disc (Figure ).
Due to the acute onset of symptoms, as well as the severity of neurologic involvement, the patient was taken to surgery for exploration and removal of the epidural mass. An L4-5 laminectomy was performed, which revealed a very large dorsally migrated disc fragment that erupted as soon as the ligamentum flavum was removed. The large mass, which was displacing the thecal sac to the right, was removed in several large pieces, tracking down to the L4-5 disc space until all neurologic elements were satisfactorily decompressed. At that time, the annular tear was visualized on the left-hand side; the fragment was sent to pathology and confirmed to be disc material. Confident that the extruded disc material was completely removed, the wound was irrigated and closed uneventfully.
Postoperatively, his leg pain and saddle anesthesia resolved immediately. By the six-week follow-up appointment, he had regained full strength in his ankles and reported no bowel, bladder, or sexual dysfunction. |
pmc-6075643-1 | A sixteen-year-old male was admitted with complaints of shortness of breath and hemoptysis for three days. The patient also had complaints of palpitations, fever, and weight loss for two months.
On physical examination; he was a malnourished and anemic male, with a blood pressure of 130/80 mm of Hg, a pulse of 103 beats per minute, and oxygen saturation on pulse-oximeter of 84%. On respiratory examination, markedly reduced air entry in the right upper zone was noticed with bilateral basal coarse crepitations. A 2-3/6 systolic ejection murmur was appreciated on cardiac examination. Other systemic examinations were unremarkable.
A chest X-ray (PA view) was done, which showed boot-shaped heart with cavitation and fibrosis in the right upper lobe, resulting in a collapsed right upper lobe (Figure ).
A trans-thoracic echocardiographic study revealed an enlarged and hypertrophied right ventricle, a right-to-left shunt across the large ventricular septal defect with a mild overriding of the aorta, pulmonary stenosis, valvular as well as infundibular, and a right pulmonary artery of only 8 mm. The findings were consistent with tetralogy of Fallot (TOF). Sputum examination for acid-fast bacilli (AFB smear) was positive in two of three-morning sputum samples. GeneXpert MTB/RIF was also positive. Hence, the diagnosis of multi-drug-resistant pulmonary tuberculosis was formed.
The patient was started with anti-tuberculous therapy (ATT) with second-line agents, including injectable amikacin, along with oral levofloxacin, cycloserine, ethionamide, and pyrazinamide. All drugs were to be continued for 12 months; except for amikacin, which was to be stopped after eight months. All daily doses were adjusted according to the patient’s weight.
However, the patient didn’t show any signs of improvements even after two weeks of ATT. A CT scan chest with contrast was then planned. It showed multiple fluffy alveolar infiltrates in both lung fields; some of which formed a tree-in-bud appearance representing an endobronchial spread. Patchy consolidation with cavitation in the right lung and middle right-sided pleural effusion with mediastinal lymphadenopathy were seen (Figure ).
Based on the findings of CT chest, it was suspected that either tuberculosis had resulted in the endobronchial spread or there was another co-existing pathology. A bronchoscopy with culture and cytology for bronchoalveolar lavage (BAL) were done. Galactomannan (GM) was found in BAL fluid cytology and the culture was positive for Aspergillus species. It confirmed the presence of pulmonary aspergilloma.
Due to the non-availability of first-line drugs for aspergilloma–voriconazole and itraconazole–in this part of the world, the patient was started with amphotericin B, 50 mg intravenous (IV) once daily for 10 days. The patient was discharged on ATT and oral fluconazole 150 mg once daily for 21 days. Upon outpatient follow-up, the patient was seen to be considerably improving by the end of one month. BAL could not be repeated for GM, as the patient didn't consent. He is still on ATT and has been referred to a tertiary cardiovascular center for surgical repairment of his congenital heart condition.
We report this undiagnosed case of TOF with pulmonary complications secondary to immunosuppression for physicians practicing in third-world countries where tuberculosis is still endemic. |
pmc-6075644-1 | A 70-year-old lady, belonging to a poor village in the province of Balochistan, presented to the cardiology clinics at Aga Khan University Hospital, Karachi, Pakistan with complaints of palpitations. She was married with six children, all born in her village via spontaneous vertex delivery with no complications. She had previously been diagnosed with hypertension by a local general practitioner and had been taking bisoprolol 5 mg once a day for elevated blood pressures. She had started experiencing palpitations for the past one month. She did not complain of any chest pain or syncope but mentioned having dyspnea on climbing two flights of stairs for the past 25 years. Her family history was significant for diabetes and hypertension only.
On physical examination, her heart rate was 72 beats per minute, blood pressure was 148/76 mmHg and oxygen saturation was 96% on room air. There was neither clubbing nor cyanosis. On cardiac auscultation, she was found to have grade 3/6 crescendo-decrescendo murmur at the pulmonic area radiating to the left suprascapular region and left lower sternal border. Chest auscultation revealed normal vesicular breathing and the abdomen was soft, non-tender with no visceromegaly.
An echocardiogram was done which showed that the visceroatrial situs was solitus with levocardia. The interatrial septum was thin and aneurysmal but had no defect. Pulmonary venous connections were normal. Single right-sided superior vena cava and inferior vena cava drained into the right atrium. The atrio-ventricular connection was discordant. Tricuspid valve was normal on the left side. There was moderate tricuspid regurgitation with maximum pressure gradient of 50 mmHg. Mitral valve was normal on the right side with no mitral regurgitation. Ventricular inversion was noted with the systemic ventricle (right ventricular morphology) being dilated with mild hypertrophy. Right ventricular (RV) systolic function was mildly reduced with a tricuspid annular plane systolic excursion (TAPSE) of 12 mm. There was no left ventricular (LV) hypertrophy and LV systolic function was normal. The inter-ventricular septum was intact as shown in Figure .
Ventriculo-arterial connection was discordant. Pulmonary artery arose from LV as shown in Figure . Aorta originated from the RV, anterior and to the left of the pulmonary artery. The aortic valve was normal with no stenosis or regurgitation. Pulmonary valve was thickened, domed and dysplastic with moderate pulmonary stenosis and a maximum pressure gradient of 50 mmHg as shown in Figures , .
There was no pulmonary regurgitation. Post-stenotic dilatation was identified. Pulmonary valve annulus was severely hypoplastic and measured 9.6 mm (z score -5.4) with main pulmonary artery size being 17 mm (z score -1.4), right pulmonary artery size 14 mm (z score +0.2) and left pulmonary artery size 12 mm (z score +0.2). Neither aortic coarctation nor patent ductus arteriosus was seen. A 24 hour Holter monitor revealed no significant abnormalities. She remained in normal sinus rhythm throughout the Holter monitoring even during periods where she complained of palpitations. Her electrocardiogram (ECG) is shown in Figure .
It was decided to keep her on medical management. Perindopril was started and the previous beta-blocker was continued. On a two month follow-up, her symptoms had improved. It was planned to closely follow her in the outpatient clinics. |
pmc-6075646-1 | A 26-year-old pregnant patient was referred from the outpatient Gynecology department to the outpatient Cardiology department with shortness of breath and fever for four weeks. Her shortness of breath was gradual in onset and progressive in nature. The patient reported having shortness of breath after walking three blocks during the early course of the disease. However, she reported having shortness of breath at rest for the past four days. She experienced no associated symptoms such as chest pain, cough, runny nose, rash or any antecedent infection. Patient’s past medical, surgical and family history was unremarkable, and she had no modifiable or non-modifiable cardiovascular risk factors. She had no known allergic reaction to food or drugs. She never smoked cigarettes or used any illicit drugs.
Obstetric and Gynecological history revealed she was gravida 1, para 0, at 35 weeks age of gestation. She had no symptoms until four weeks ago when she suddenly developed fever and shortness of breath.
The patient's vital signs on examination were (1) Temperature: 100.4 F with no associated chills or rigors, (2) Blood Pressure: 110/72 mm Hg, (3) Respiratory Rate: 30 breaths/min, (4) Heart Rate: 102 beats/min. Cardiac examination revealed regular pulse with no radio-radial or radio-femoral delay. On auscultation, an end systolic murmur (3/6 grade) radiating to the carotids at the second and third intercostal spaces was heard. On abdominal examination, the spleen was palpable 1 cm below the subcostal margin. Examination of the soles revealed erythematous lesions near the third and the fourth digits. Rest of the systemic examination was unexceptional.
The patient was admitted to the ward for additional investigations. The initial electrocardiogram (EKG) on admission showed sinus tachycardia without specific ST and T-wave changes. Chest X-ray was insignificant with no signs of pulmonary congestion. Laboratory findings revealed erythrocyte sedimentation rate (ESR) = 102 mm/hr (normal range: 0-29 mm/hr for women), hemoglobin = 8.2 mg/dl (normal range: 12-15.5 mg/dl in women), white blood cells = 13,600/cumm (normal range: 4000-11,000/cumm), platelets = 324,200/cumm (normal range: 150,000-450,000/cumm), serum sodium = 135 mEq/L (normal range: 137-145 mEq/L), serum potassium = 3.6 mEq/L (normal range: 3.5-5.0 mEq/L ), d-Dimers = 390 ng/ml (normal range <500 ng/ml), creatinine = 0.7 mg/dl (normal range: 0.1-1.2 mg/dl). Urine dipstick was negative for proteins and blood. Viral markers for hepatitis B and C were non-reactive. Antinuclear antibody (ANA) titers were in normal range.
Transthoracic echocardiography (TTE) revealed thickened bicuspid aortic valves with restricted movements. Transesophageal echocardiography (TEE) confirmed the findings. The echocardiography showed large vegetations (9 x 11 mm in dimensions) attached to the aortic cusps. Ejection fraction was within the normal range. Two sets of blood cultures were positive for Staphylococcus Aureus and displayed sensitivity towards ampicillin, amoxicillin, gentamicin, and clindamycin. Based on clinical signs and symptoms, TTE and TEE findings, and positive blood cultures the patient was diagnosed with infective endocarditis secondary to severe aortic stenosis.
The patient was started on appropriate medications for infective endocarditis (ampicillin + sulbactam 12 gm). Follow-up visit revealed the patient’s condition to be deteriorating despite being compliant with the prescribed antibiotics. After consultation with the obstetrician and the cardiac surgeon, a decision was made to perform an urgent cesarean section followed by aortic valve replacement. Transvaginal ultrasound showed an appropriate for gestational age fetus in vertex presentation. A healthy baby was delivered via cesarean section with no maternal or fetal complications. The patient underwent successful aortic valve replacement three days after her delivery.
The patient was discharged after a five-day observation period. At the fourth-month follow-up visit both the patient and baby were in good clinical health. |
pmc-6076022-1 | A 9-year-old boy presented to a local hospital with vomiting and occasional headache with a blood pressure of 210/170 mm Hg. No obvious diseases were observed on digestive endoscopy and abdominal computed tomography (CT) scan, and no remarkable improvement by medicine treatment. CT scan of the chest revealed a 7 × 5-cm-sized soft tissue mass in the left paraspinal area from T3 to T7 with destruction of the adjacent thoracic vertebra and ribs (Fig. ). Biochemical reports revealed elevated levels of serum norepinephrine, urine norepinephrine, urine dopamine, and serum neuron specific enolase. Serum epinephrine, urine epinephrine, alpha fetoprotein, and carcinoembryonic antigen were within the normal range (Table ). The admitting diagnosis was tumor in the posterior mediastinum: paraganglioma? Before operation, the patient was prepared by orally administering captopril, propranolol hydrochloride, and phenoxybenzamine by mouth. The patient's blood pressure remained stable at approximately 110/80 mm Hg. In addition, body fluid volume was also prepared by vein and mouth in 3 days before surgery.
Thoracotomy was performed through the left fifth intercostal space. Intraoperatively, several membranous and fascicular adhesions existed in the thoracic cavity. The irregular ovoid mass measured 8 × 7 × 5 cm. The tumor originated from the nerve root and adhered to the surrounding tissue. It invaded the spine and chest wall. The mass was tough and rich in blood supply. There were intraoperative changes in the patient's blood pressure, which ranged from 85/50 mm Hg to 180/130 mm Hg. During the resection, the surgeon closely communicated with the anesthesiologist to decide the operative process. Histological studies demonstrated that the mass was a tumor (Fig. ). Immunohistochemical (IHC) studies demonstrated that tumor cells stained positive for synaptophysin (syn, +) and chromogranin A (cgA, +). The positive rate of Ki67 (MIB-1) staining was 2% to 5%. The S100 and PCK staining was negative (Fig. ). The immunohistochemical studies suggested that the tumor was a paraganglioma. Postoperatively, the patient's blood pressure was stable and within the normal range. On postoperative day 2, the concentration of serum epinephrine was 236 ng/L and serum norepinephrine was 4686 ng/L. On postoperative day 4, serum norepinephrine (321 ng/L) and epinephrine (76 ng/L) were normal. The patient was discharged on postoperative day 6. After operation, the patient did not exhibit hypertension and his blood pressure was normal without medicine. After 1 year, follow-up chest CT did not reveal tumor recurrence (Fig. ). |
pmc-6076098-1 | A 74-year-old woman was admitted to the Gastroenterology Department of our hospital for an asymptomatic gastric mass. She had a schistosomiasis cirrhosis splenectomy at the age of 29 years.
The patient was initially submitted to a computed tomography (CT) scan for pneumonia in other hospitals, which revealed pipe stem cirrhosis (Fig. A), a well-demarcated 4-cm solid mass confined to the gastric wall suggestive of a GIST (Fig. B), and a 1-cm low-density lesion with a clear outline in the mass (Fig. B; red arrow). Thereafter, she was submitted to an upper gastrointestinal endoscopy in our hospitals, which revealed a smooth and rounded mass in the gastric wall without mucosal infiltration (Fig. C) at the level of the greater curvature. Endoscopic ultrasonography revealed a 3.95 × 2.82-cm slightly low-level echoic homogeneous mass derived from the muscularis propria (Fig. D) and a 1 × 1-cm lower level echoic area with a clear boundary in the mass (Fig. D; red arrow); these findings confirmed the diagnosis of a gastric GIST. The laboratory test findings were normal, except for the following: platelet count of 369 × 109/L, glutamyl transpeptidase level of 53.4 U/L, total bilirubin level of 22.4 μmol/L, serum creatinine level of 44.0 μmol/L, potassium level of 3.5 mmol/L, and levels of other serum tumor markers (cancer antigen [CA], cytokeratin 19, alpha fetoprotein, carcinoembryonic antigen, CA125, and CA15-3). After discussion in a multidisciplinary conference, the patient was considered for a GIST resection under gastroscopy.
Under the gastroscope, a large submucosal uplift was seen near the posterior wall of the gastric angle. The surface of the mucosa was hyperemic and edematous; the texture was hard; and the activity was poor. After dual-knife labeling, the mucosa and submucosa were opened, and the tumor was initially exposed. The tumor surface was covered with larger blood vessels (Fig. E). The IT-NanoKnife was used for detachment around the tumor capsule, and the muscular root penetrated the muscularis propria. In the process of peeling, the surface of the mucosal, submucosal, muscle layers, and the tumor surface were diffusely oozing. The effect of electrocoagulation and hemostasis was extremely poor (taking into account the low coagulation function of liver cirrhosis and the abundant blood supply to the tumor body); further, the procedure took too much time. The tumor roots were poorly exposed owing to persistent oozing. Forcibly removing the full thickness of the stomach wall might lead to difficulties in controlling intra-abdominal bleeding on the serosal side. Therefore, endoscopic surgery was arrested. After dealing with the patient's family, a combination of laparoscopic-gastroscope double-mirror surgery was decided in accordance with the principle of minimally invasive surgery to preserve the stomach. In the process of laparoscopic umbilical puncture point incision, the intestinal mucosa was perforated and was thus subsequently repaired. Owing to the patient's history of 2 abdominal surgeries, several adhesions were seen during laparoscopic surgery, which were then slowly separated. However, the tumor location was high and concealed (gastric angle near the posterior wall); even after following gastroscopy positioning instructions, the tumor still could not be found under laparoscopic direct vision. Therefore, we stopped the double-mirror combination surgery plan. Based on what was seen during the surgery, we communicated with the patient's family again. Considering the great possibility of a malignant GIST, we still decided to continue the traditional surgical resection. The tumor was then removed via surgery; its size was approximately 3.5 × 5 cm, and its blood supply was extremely rich. The abdominal drainage tube and gastrointestinal decompression tube were indwelling. The patient's vital signs were stable; she was then transferred to the intensive care unit and discharged on postoperative day 10.
On macroscopic examination, 3.9 × 2.8 × 2.4-cm dark red masses surrounded by a completely thin capsule were observed in the gastric fundus muscularis propria. On the cut surface, the mass appeared red to bluish with scattered white tiny nodules embedded in the muscularis propria. At the edge of the mass, an approximately 1 × 1-cm nodule appearing as a circumscribed, non-encapsulated, honeycomb-like, and red-purple nodule, which formed with dilated congested vascular space with bleeding, was also observed. On microscopic examination, a well-formed splenic tissue divided into 2 compartments—white pulp and red pulp—was separated by an ill-defined interphase known as the marginal zone (Fig. A). However, a nodule in the heterotopic spleen was mainly composed of larger thin-walled muscular vessels, which were variably dilated and occasionally displayed thrombosis. The widely dilated vessels showed attenuation of their walls, mimicking a cavernous hemangioma (Fig. B). Immuno-phenotypically, the endothelial lining cells of the vascular walls were immunoreactive for cluster of differentiation (CD) 31 (Fig. C), CD34 (Fig. D), and Factor VIII (Fig. E).
The final diagnosis was gastric fundus splenosis with an associated hemangioma. |
pmc-6076109-1 | A 60-year-old male was hospitalized with the primary complaint of diarrhea and abdominal pain for over 7 months. He mainly presented a pinching pain around the umbilicus and watery diarrhea. On physical examination, body mass index (BMI) was 20.1 kg/m2, and an approximately 3-cm-diameter, relatively hard, slightly movable mass was palpable in the left lower abdomen without obvious tenderness or superficial lymphadenopathy. Laboratory examination showed the following positive findings: C-reactive protein level (CRP) was 12.14 mg/L↑ (normal: 0.1–10.0 mg/L) and fecal occult blood (OB) was positive (+). The blood routine, erythrocyte sedimentation rate (ESR), set of tumor markers, antinuclear antibody spectrum (ANAs), and inflammatory bowel disease antibody spectrum showed no abnormalities. Computed tomography enterography (CTE) demonstrated that the regional 6th small intestine wall was enhanced with multiple air pockets inside the involved bowel. The lesion abutting the ileocecal junction and sigmoid colon had a distorted contour (Fig. A and B). The ileum internal fistula and ileac-sigmoid colon fistula were highly suggestive of malignancy. Transabdominal ultrasound (US) was then performed rather than an enteroscopy. Abdominal US revealed remarkably uneven thickening of the small intestinal wall in the pelvic area. The serosa layer of involved intestines remained intact and smooth. The most thickened part measured 1.9 cm. Colour Doppler flow imaging (CDFI) demonstrated that the inferior mesentery artery was thickened and was wrapped by the involved small intestine. The sigmoid colon was inseparable from the involved small intestine. Several enlarged mesenteric lymph nodes could be seen around the lesion (Fig. C). The US imaging features also indicated that the thickened intestinal wall and the fistula developed as a result of the tumors. Photon emission tomography/computed tomography (PET/CT) suggested that lymphoma was a very likely diagnosis. The patient underwent enteroscopy under local anesthesia. The enteroscope was passed smoothly into the terminal ileum by approximately 15 cm and but was unable to be further inserted as a result of extreme pain. The enteroscopy showed that the mucosa of the terminal ileum was congestive and edematous with sporadic erosion. A fistula appeared in the sigmoid colon approximately 28 cm from the anus, and the adjacent mucosa was edematous and disordered (Fig. D). A biopsy was performed on the lesions in the terminal ileum and sigmoid colon. Unfortunately, the biopsy sample showed chronic inflammation in pathology and thus failed to provide a clear diagnosis. The patient chose to have an operation. The part of the terminal ileum near the cecum and the sigmoid colon was found to form an adhesion, accreting in the superficial region of the inferior mesenteric vessels during the operation. Then, the surgeon performed accretion lysis, right hemicolectomy, sigmoidectomy, and ileostomy. The ileocecal valve and parts of the colon were removed. Histopathological examination demonstrated a gray 6 × 5 × 3.5-cm nodule that was found in the serosa of the intestine 7 cm from the ileocecal valve. The mass was adhered to another portion of the intestine where a fistula could be seen. Three other gray masses were also found 15, 20, and 31 cm from the ileocecal valve. They could not be separated from the surrounding tissue. Histopathological examination proved the diagnosis of primary non-Hodgkin's intestinal lymphoma (large diffuse B-cell lymphoma) (Fig. E). Postoperatively, the patient received 8-course chemotherapy with R-CHOP. For nearly 12 months, his general condition remained stable, and intestinal imaging reexaminations showed no abnormalities after stoma closure. |
pmc-6076109-2 | A 43-year-old male who presented with abdominal pain and diarrhea lasting 1 year was admitted to our hospital. He started presenting with hematochezia and lower fever 1 month before admission. On physical examination, his BMI was 17.58 kg/m2, and no mass could be distinctly palpated on his scaphoid abdomen. Laboratory examinations showed the following blood and biochemical findings: 95 g/L hemoglobin, OB (+) stool, and 20.24 mg/L CRP, negative for the entire set of tumor markers and negative for T-SPOT.TB (tuberculosis). The transabdominal US demonstrated that the intestinal wall of the sigmoid colon was irregularly thickened and had a loss of normal construction, presenting a hypoechoic mass as the rough serosa. Increased blood flow signal was also detected in the intestinal wall. The sigmoid colon was found adhered to the abutting pelvic small intestine. A fistulous communication was confirmed when intestinal content was moving between the sigmoid colon and the ileum during a real-time dynamic US scan (Fig. A). Multiple enlarged pelvic lymph nodes were nearby. Barium enema examination showed a tract between the small intestine and the sigmoid colon, where the wall was stiff, and the lumen was narrow. Contrast-enhanced CT and intestinal reconstruction demonstrated that the wall of the partial sigmoid colon was abnormally thickened and enhanced with an ileal-sigmoid fistula that strongly suggested the diagnosis of lymphoma (Fig. B and C). PET/CT showed an irregular hypermetabolic focus located between the rectum and the sigmoid (SUVmax: 16.0) that was suspected to be a malignant lesion. Enteroscopy revealed a large ulceration from the sigmoid-rectal junction to the segment 12 cm above the anus. One side of the ulceration formed a fistula, from which smooth intestinal mucosa could be seen. The sigmoid-ileum fistula was confirmed. The histopathologic result showed non-Hodgkin's large diffuse B-cell lymphoma (Fig. D). Because of the large lesion, severe adhesion and lack of surgical indication, the patient accepted chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine (R-CHO), and prednisone (R-CHOP) after the first chemotherapy treatment rather than the operation.
The patient had sudden central abdominal colic pain with discontinued exhaust and defecation after eating oatmeal when 2 courses of chemotherapy were completed. Emergency CT suggested mechanical ileus. The patient improved with nonsurgical therapy. In the following treatment course, the patient maintained a relatively stable condition by continuous consumption of a liquid or semi-liquid diet. PET/CT showed remarkable shrinkage of the rectosigmoid lesion size and decreased metabolic activity after 4 courses of chemotherapy. The patient finished 8 courses of chemotherapy. During the 12-month follow-up period, colonoscopy and CTE did not reveal obvious fistula, and his diet and defecation were good. |
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