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pmc-6092536-1 | A 68-year old lady was referred by her general practitioner to the orthopaedic clinic with complaints of right heel pain for one year. The presenting complaints started about a year back as insidious onset of heel pain which was constant aching in nature and aggravated by periods of prolonged walking and standing. There was no history of trauma. She was a known seropositive rheumatoid arthritis patient on Hydroxychloroquine, Sulphasalazine and Methotrexate for 20 years. She was under the care of a rheumatologist and had steroid injections in the right heel for plantar fasciitis in the past. On examination there was diffuse tenderness around the heel with full range of ankle movements but painful limitation of subtalar joint movements. There was no hind foot malalignment evident on weight-bearing radiographs of foot and ankle (). But that of the ankle revealed a sclerotic line with areas of osteolysis suspicious of a fracture of the calcaneus (). An MRI scan of the ankle with T2 weighted images showed linear high signal intensity in the body of the calcaneus suggestive of an insufficiency fracture of the calcaneus (). The patient was treated with moon walker boot and commenced on oral Alendronic acid 10mg on alternate days for eight weeks with Calcichew and Vitamin D tablets. The patient was advised to use the moon boot while weight bearing and remove at bed time. At the eight weeks follow-up she was completely pain free and able to fully weight bear. The radiographic examination showed the fracture had healed ().
The patient was referred back to our orthopaedic clinic after two years by her general practitioner with complaints of recurrence of right heel pain with no history of trauma. On clinical examination there was tenderness around the talus and painful restriction of ankle and subtalar movements. Radiographic examination revealed a fracture of the talus (). An MRI scan of the foot and ankle showed insufficiency fracture of the head of the talus (). She was treated in a moon walker boot and 5mg of intravenous Zolendronic acid as a bolus dose. She was asked to continue with oral Alendronic acid 10mg on alternate days for 12 weeks. The patient was reviewed at 12 weeks. There was no tenderness around the talus or calcaneus. A repeat radiograph showed that the fracture of the talus had healed (). She has been on yearly review since. |
pmc-6092541-1 | A 54-year old female presented with complaints of painful swelling with restricted movements of right shoulder for past five years which had worsened over the last one year. She was a known case of rheumatoid arthritis diagnosed ten years ago. Five years back she had noticed painful fullness around her right shoulder. Size of the swelling had increased over the period of five years. She had felt her shoulder becoming stiffer with increase in the size of the swelling. On examination there was a well demarcated, firm with smooth surface, non-fluctuant and immobile swelling located at the right sub-deltoid space, with purplish discoloration of the overlying skin. Right shoulder movements were painfully restricted. Sub-acromial impingement signs were present.
Her ESR was 104, Rheumatoid factor 121.2 IU/ml and Uric acid 4.9 mg/dl. Plain radiograph of shoulder showed normal glenohumeral articulation with sub-deltoid homogenous soft tissue shadow without calcification (). Ultrasound suggested diffusely enechoic soft tissue mass surrounding the shoulder joint. MRI suggested marked distension of the sub-acromial/sub-deltoid bursa but more of sub-deltoid bursa, approximately 3cm deep all around. The bursal lumen was filled with multiple loose bodies ranging from 1 to 7mm in size. Loose bodies show iso-intense signal on T1 weighted images and hypo-intense on T2 weighted images. Rotator cuff and glenohumeral joint were normal. This MRI picture was suggestive of synovial origin lesions of arthritis ().
The patient was scheduled for arthroscopic loose body excision and sub-acromial bursectomy. She was positioned in beach chair position under general anaesthesia. Standard posterior, anterior and lateral portals were used for arthroscopy. Diagnostic arthroscopy revealed normal glenohumeral articulation without communication of sub-acromial sub-deltoid bursa with the joint. Multiple shiny white rice bodies of different sizes were observed occupying the sub-acromial space and extending into the anterior, lateral and posterior sub-deltoid space. Rotator cuff muscles were normal. Synovial fluid was submitted for fluid evaluation, Gram stain, Ziehl-Neelson stain, Tuberculosis Polymerase Chain Reaction (TB-PCR) and bacterial culture. Tissue sample from the bursa and rice bodies were sent for histopathological evaluation. All rice bodies were removed through 8mm arthroscopic cannula, placed in different portals sequentially, and attached to a suction device. Residual rice bodies were removed manually with an arthroscopic grasper. Sub-acromial bursa was excised and acromioplasty was performed.
She was started on range of motion exercises of shoulder from first post-operative day. TB-PCR of synovial fluid was negative for tuberculosis. Culture of synovial fluid did not grow any organism. On histopathological examination the bursal tissue showed hyperplastic synovial lining with marked lymphoplasmacytic inflammatory infiltrates, few neutrophils with vascular proliferation of stroma without granulomatous reaction. The rice bodies were composed of dense fibrin deposition with fibroblast and mononuclear cells (). She was started on disease-modifying antirheumatic drugs after suture removal at 12th post-operative day. The pre-operative painful swelling with restriction of movements markedly improved after surgery. At one year post-operative follow-up, there was no recurrence of shoulder swelling, with excellent range of motion. |
pmc-6092544-1 | An 11-year old boy had sustained a closed comminuted fracture of the right femur after a motor vehicle accident. He had undergone open reduction and plating of the right femur two weeks after injury. He developed osteomyelitis () two weeks after surgery and was referred to our hospital for further management. Multiple debridements were required to treat the infection. The plate was not removed as it was not loose. Cultures grew Methicillin-Resistant Staphylococcus Aureus (MRSA), which was treated with rifampicin and fusidic acid orally for 6 weeks. His latest follow-up 10 months after injury showed healing of the fracture and resolution of the infection () |
pmc-6092544-2 | An 8-year old girl had sustained closed fractures of the left femur and ipsilateral clavicle following a motor-vehicle accident. She had undergone open reduction and plating of the left femur, while the clavicle fracture had been treated non-operatively. She was referred to our hospital five months after surgery with fever, pain and swelling over the surgical site (). The plain radiograph showed osteomyelitis of the left femur and plate loosening (). She was treated by debridement () and plate removal as the femur had united (). The culture grew MRSA and she was treated with syrup trimethoprim/sulfamethoxazole for 6 weeks. The latest follow-up one year after injury showed the fracture had united and the infection resolved (). |
pmc-6092668-1 | A 24 year old male presented to us with urinary diversion by bilateral percutaneous nephrostomies (PCN), performed six months ago. He had undergone laparoscopic surgery for removal of prostatic utricle cyst elsewhere. Postoperatively he developed anuria. A sonogram revealed bilateral hydro-ureteronephrosis. Bladder was not commented upon. This acute crisis was treated by bilateral PCN. Nephrostomogram revealed complete cut-off of both lower ureters ().
He had history of lower abdominal pain with burning micturition on and off since two years. Investigations had revealed a prostatic utricle cyst with infection. Following conservative management, he was asymptomatic for about 18 months. Recurrence of symptoms was associated with increase in cyst size (). Surgical treatment was advised at this time. Laparoscopic cyst excision was undertaken which resulted in anuria leading to emergency bilateral PCN. Patient presented to us six months later.
Systemic examination was normal. Abdominal examination revealed port site scars, bilateral nephrostomies and coronal hypospadias. Investigations revealed normal hemogram and creatinine. Bilateral lower ureteric injury was the suspected diagnosis initially. Ascending and micturating cysto-urethrogram (MCU) showed smooth walled bladder with mildly reduced capacity and normal urethra ().
With evidence of bilateral ureteric cut-off and normal lower urinary tract, bilateral ureteric re-implantation was planned. Urethrocystoscopy showed normal anterior urethra. There was an opening on verumontanum, which accommodated 17 French cystoscope sheath easily. This lead to a smooth walled cavity containing about 200 mL of turbid fluid. The epithelium was not like normal urothelium. Ureteric orifices were not seen. Then we realized that this cavity was indeed the cyst which was falsely mistaken as bladder on MCU. The proximal urethra was completely cut off below the level of bladder neck, ending blindly. A situation of accidental urinary bladder cystectomy and not prostatic utricular cystectomy was realized. Further surgery was abandoned.
Patient was explained about absence of urinary bladder. MRI pelvis confirmed the same (). Surgical options were discussed and he opted for orthotopic neo-bladder. Ureters were dissected, prostatic utricle cyst was marsupialized, it's opening into urethra closed and Studer's orthotopic ileal neobladder was constructed.
Postoperative MCU showed good capacity neobladder and no extravasation (). Nephrostomies were clamped and removed.
At follow-up, he was voiding well with minimal residue and no incontinence. His outcomes in terms of ejaculation are yet not known. |
pmc-6092671-1 | A 63-year-old man presented with rising PSA that was 6.13ng/mL on last visit. He had a negative prostate biopsy 1 year ago, and is currently being treated with intravesical Bacillus Calmette-Guérin (BCG) instillations for pT1G3 bladder carcinoma. Multiparametric magnetic resonance (mpMRI) was carried out using a 1.5T system (Signa Excite, GE Healthcare) with a PI-RADS v2 score of 4 for diffusion-weighted imaging (DWI) in the right posteromedial peripheral zone at the midgland level (). Thus, a systematic 42-core, sector-guided transperineal prostate biopsy, with additional cognitive targeted biopsy of the suspicious lesion was performed (). Histological findings showed typical features of granulomatous prostatitis (GP) with epithelioid cells, multinucleated giant cells and infiltration lymphocytes ().
Patients with mycobacterial GP are mostly asymptomatic, with elevated PSA levels and indurated prostate at digital rectal examination, but because of its relative rarity, the MRI characteristics of infective GP caused by Mycobacterium tuberculosis or after intravesical BCG instillations have not been described extensively and only a few cases have been reported (, ). GP is found in approximately 75% of patients after intravesical administration of BCG for superficial bladder cancer (). Despite the consistent ability of mpMRI to identify lesions suspicious for prostate cancer (PCa), there are other entities which can cause a false-positive result as GP, bacterial prostatitis or malacoplakia. GP chronic pattern is common, with low mean ADC value <1000, decreased signal on the ADC map images and isointense or decreased signal on high-b-value imaging (b>1200) () that could be differentiated by the intralesional ADC values, significantly lower in PCa, as suggested by Rais-Bahrami (). Recent studies also demonstrated an acute pattern (less than six months prior to the mpMRI) of GP lesions, with lower signal intensity on T2-weighted imaging (T2WI) (), decreased signal on the ADC map images () and increased signal on high-b-value imaging (), that is indistinguishable from aggressive prostate cancer. |
pmc-6092780-1 | The patient was a 26-year-old Chinese male with a chief complaint of impaired vision in both eyes for more than a year. An ocular examination revealed that the vision in his right eye was FC/20 cm and left eye was 0.02, intraocular pressure was 18 mmHg in both eyes, ptosis of both upper eyelids, lateral eyelashes touched the cornea. Corneas were transparent in both eyes, central corneal thickness was 547 μm in right eye, and left corneal thickness was 540 μm. The central anterior chamber depth of the right eye was 3.25 mm, and the central anterior chamber depth of the left eye was 3.03 mm. The pupils were round, about 3 mm in diameter. The lenses were milky and opaque in both eyes (Fig. ). The thickness of the right eye lens was 3.30 mm and the lens of left eye was 3.32 mm. The fundus of both eyes was not clear due to the occlusion of cloudy lens. The right eye axial length was 22.38 mm, and the left eye was 22.17 mm. No obvious vitreoretinal abnormalities were found on ultrosonography. Family history showed that his parents were consanguineous (first cousions). The patient’s father died in a traffic accident at 40 years old, and his mother, and sister, uncle, cousin, and niece were in good health. The patient denied any family history of genetic diseases. Developmental retardation occurred when he was 8 years old and Achilles tendon elongation was performed due to Achilles tendon contracture. Physical examination on admission revealed the patient had a spare figure, weighed 40 kg and was 150 cm tall (Fig. ). Vital signs testing demonstrated his temperature was 36.7 °C, pulse was 98 b/min, respiratory rate 19/min, and the blood pressure was 108/65 mmHg. Heart and lung auscultation found no obvious abnormalities. A complete blood cell count, thyroid hormone levels, hepatic function, and renal function were evaluated, and no abnormalities were found. Figure depicts the patient with the symptoms of short stature, slightly built, gray hair, bird-like face appearance, skin depigmentation, skin drying and atrophy, scleroderma-like skin changes, beak-like nose, and teeth abnormalities.
According to the ocular symptoms and systemic signs, including low body weight, a short stature, a bird-like face, atrophic and scleroderma-like skin, and juvenile cataracts, the clinical diagnosis of Werner’s syndrome was made. Next-generation sequencing identified a homozygous WRN mutation in this patient. Five bases (c.3460_3461 insTTGTG) were inserted between the 3460 and 3461 nucleotides of WRN gene in this patient, resulting in a frame shift mutation of amino acids (p. Y 1157 Cfs * 7) (Fig. ). After searching the literature, this mutation has not been reported, and does not belong to the polymorphic site, incidence is very low in the population and not reported in the Human Gene Mutation Database (HGMD professional). The WRN mutation was the likely pathogenic variant. So the definitive Werner’s syndrome diagnosis was established. Besides, the same heterozygous WRN mutation was identified in his mother, his father’s brother, and sister. The pedigree chart has been constructed in Fig. .
The patient underwent phacoemulsification combined with intraocular lens implantation in both eyes. The right eye was implanted with a + 23.0 diopter intraocular lens and the left eye was implanted with a + 24.0 diopter intraocular lens. Post-operative appearance showed the clear IOL in place (Fig. ). The post-operative best-corrected visual acuity was 0.6 in both eyes. No vitreoretinal abnormalities were observed in both eyes. |
pmc-6092822-1 | A 60-year-old Persian man presented to the clinic with a chief complaint of headache for the last 2 months ago. He also suffered from progressive bitemporal hemianopia. His past medical history was significant for a non-functional pituitary macroadenoma which culminated in a transsphenoidal surgery (TSS) and complete resolution of symptoms, 11 years ago; however, microscopic examination of the tumor is not available, currently. Moreover, he received a total thyroidectomy because of MTC, 3 years ago. Also, he had mild hypertension controlled by anti-hypertensive drugs, with no history of hypertension crisis, and an asymptomatic kidney stone for the last 3 years. His familial history and habitual history were not remarkable. A physical examination was not significant, except for lymphadenopathy in left cervical chain.
With the impression of PA, the patient underwent brain magnetic resonance imaging (MRI). It demonstrated an isointense and high intense heterogeneous 34 × 27 mm solid mass, in T1 and T2 sequences, respectively, which was enhanced after contrast media administration. The lesion consisted of cystic and hemorrhagic centers with involvement of sella turcica and suprasellar cistern, and suprasellar extension. Moreover, it caused a mild mass effect on adjacent optic chiasm and bilateral involvement of cavernous sinuses. All of these findings suggested pituitary macroadenoma as the most probable diagnosis. Laboratory measurements failed to detect pituitary hormones in plasma; however, they had not been coupled with stimulation tests. Furthermore, level of serum prolactin was normal even after a dilution study.
The adenoma was resected through a non-complicated TSS. Post-operation MRI showed a non-enhancing center rimmed by a solid enhancing tissue consistent with tumor remnant in the sella area. Histopathologic and immunohistochemical (IHC) findings of the lesion were in favor of gonadotroph cell adenoma with a Ki-67 index of 4%; however, staining of the specimen was negative for luteinizing hormone and follicle-stimulating hormone, which confirmed the non-functional nature of the adenoma. Our patient’s symptoms, including headache and impaired visual field, were resolved remarkably after the surgery.
Further assessments were performed in order to evaluate the possible coexistence of MEN syndromes. Metabolites of cathecholamines including metanephrine, normetanephrine, and vanillylmandelic acid in 24-hour urine collections were in normal range, excluding pheochromocytoma. Furthermore, genetic testing for mutation of exons 10, 11, 13, 14, 15, and 16 of RET proto-oncogene was negative. Plasma calcium and parathyroid hormone levels were normal with no signs or symptoms of pancreatic adenoma (PA).
A neck ultrasonography was done due to the detected lymphadenopathy in the physical examination, which revealed a 15 × 7 mm lymph node with a bizarre shape and hilum in the left cervical chain suggestive of a metastatic lymph node. Furthermore, a 6 mm hypoechoic nodule in the left thyroid bed was detected that might be attributed to the thyroid gland remnant or local recurrence of MTC. Therefore, our patient underwent cervical lymph node dissection and surgical removal of the nodule. Consequently, histopathologic examinations delineated the nature of the lymph node and nodule as MTC metastatic lymph node and recurrence of MTC, respectively. |
pmc-6092826-1 | A 42-year-old Caucasian male presented with rapidly progressive gait disturbance, distal weakness of the lower extremities, ascending hypoesthesia, impaired fine motor skills, and beginning cranial nerve palsy showing dysarthrophonia, facial paralysis, and eye movement abnormalities within several months. Tendon reflexes of the upper extremities were reduced and absent in the lower extremities. Nerve conduction studies showed a proximal demyelinating sensorimotor polyneuropathy with active denervation, prolonged motor distal latency, and a reduction in the motor conduction velocity in N. medianus and N. ulnaris (Fig. ). The cerebrospinal fluid (CSF) revealed albuminocytologic dissociation with an elevated protein level of 22,300 g/L (reference value [RF] < 0.4 g/L). Ganglioside antibodies (GD1a, GM1, GM2, GQ1b, and GT1b) were negative. Nerve conduction studies showed proximal demyelinating sensorimotor polyneuropathy with active denervation. With progressing symptoms showing no response to intravenous methylprednisolone, the patient was transferred to our intensive care unit (ICU). Treatment with intravenous immunoglobulin (IVIg, 30 g/day for 5 days) was initiated and the patient rapidly improved. Due to the clinical course of the disease and according to the EFNS/PNS criteria, the patient was diagnosed with typical CIDP.
Three months after discharge, the patient developed dysphagia, facial nerve palsy, dyspnea, and paralysis of the lower extremities. Under combined treatment with IVIg and methylprednisolone, the patient improved and was discharged to rehabilitation care. There, he complained about increasing physical exhaustion, reduction of his walking distance, worsening of the residual dysphagia, and dysarthria with an inability to swallow. His AChR antibodies (17.0 nmol/L, RF < 0.4) and titin antibodies were positive and repetitive nerve stimulation showed an abnormal decrement (Fig. ) matching the criteria of MG.
The patient’s symptoms improved after the administration of pyridostigmine. Computer tomography of the upper chest revealed an inhomogeneous mass in the anterior mediastinum. Biopsy confirmed a thymoma, which was subsequently managed by a thymectomy.
Follow-up visits displayed consistent albuminocytologic dissociation in the CSF and the AChR antibodies decreased (2.1 nmol/L). Under long-term immunosuppression with azathioprine 150 mg and prednisone 15 mg daily and another IVIg application, dysphagia, dysarthria, and gait unsteadiness consistently improved.
However, almost 2 years later, the patient developed severe acute-on-chronic renal failure with high-grade proteinuria resulting in generalized edema followed by secondary hyperparathyroidism and dialysis-dependent renal failure. Renal biopsy confirmed beginning anti-phospholipase A2 receptor antibody-positive membranous glomerulonephritis (MGN), a common cause of nephrotic syndrome (Fig. ). One year of critical illness complicated by sepsis led to myasthenic crisis, but the patient recovered under repeated IVIg therapy and finally regained the partial ability to live autonomously. |
pmc-6092862-1 | A 26 year-old man attended our ophthalmic ward in April 2017 with intermittent bleeding of the right eye, from which there was also strong odor. The patient was a heavy smoker but had no other underlying conditions. He had no history of drug-use. From his medical history it was noted that the patient had undergone a right ophthalmectomy 24 years previously due to retinoblastoma, and implantation of an artificial right eyeball in 2014 (timeline shown in Additional file ).
On admission, his pulse rate was between 80 and 100 beats/min. His body temperature and respiratory rate were both normal. Physical examination showed narrow conjunctival sac in right eye and the exposure of ocular prosthesis, which was discharging a yellow-green secretion along with a strong odor. The visual acuity of left eye was 0.3, and the intraocular pressure was 15 mmHg. All other characteristics of the left eye were normal. A auscultation did not show any abnormality in the lungs, and no signs of carotid murmur were found. Interestingly, laboratory investigations did not reveal abnormal inflammatory markers such as leukocytosis or any increase in neutrophils or C-reaction protein. According to clinical and laboratory investigations, infectious endocarditis was not suspected. The patient had no history of other immunosuppressive conditions, except smoking and a retinoblastoma 24 years previously. The patient did not report any direct contact with animals; however, he did work in a clothing factory so would have been contact with wool and cowhide for one month of the year. Three months had elapsed between the patient last coming into contact with wool and cowhide and the appearance of clinical symptoms. Considering the results of these investigations, partial artificial eye infection, especially anaerobic organism infection, was suspected.
Imaging workups were completed, which included chest x-ray, transthoracic echocardiography and eye magnetic resonance imaging. As shown in Fig. , eye magnetic resonance imaging revealed that the tissue surrounding the right eye prosthesis as well as the soft tissue of the lacrimal gland area were swollen, whereas the left eye appeared normal. Inflammatory disease in the right eye was therefore suspected. According to chest x-ray and transthoracic echocardiography, no obvious abnormalities in the lungs or heart were observed.
Before surgery, a few specimens of the right eye secretions were collected to be cultured, but no bacteria were isolated, possibly because most of the secretions had been absorbed by the artifical eye making it yellow-green in appearance. After removal of the right artificial eye with debridement (5 days after admission), both the artificial eye and specimens of the eye secretions were sent for bacterial culture under aerobic and anaerobic conditions. No bacterial growth was detected from the ophthalmic secretions, but cultures were obtained from the artificial eye. Sparse growth of β-hemolytic cocci and heavy growth of small, non-hemolytic, translucent colonies were observed on Columbia agar plates supplemented with 5% sheep blood (BioMérieux, Marcy l’Etoile, France) under aerobic conditions after 48 h. And the latter colonies only grow close to the hemolysis zone of the former one. Under anaerobic conditions, only the small, translucent colonies were detected from the artificial eye (as shown in Fig. ). Of the two colony types, the β-hemolytic cocci were confirmed as Staphylococcus aureus, whereas the small, translucent colonies stained positive in a Gram stain and occurred singly, in pairs, or in short chains (Fig. ). Catalase and oxidase reactions of the unknown colonies were negative and phenotypic characterization using the Vitek2 GP system (BioMérieux) was inconclusive. However, Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry revealed a match with Helcococcus ovis DSM 21504 T DSM (log score: 1.637) according to the Brucker Maldi-Biotyper database. Identification of this organism was confirmed by 16S rRNA gene sequencing. BLAST analysis of the partial 16S rRNA gene sequence derived from our isolate (1492 nucleotides, deposited in the GeneBank database under accession number MG188744) showed 98.9% identity (15 nucleotide differences) with the 16S rRNA gene sequence of H. ovis s840–96-2 deposited in the GenBank database under accession number NR027228 by Collins and coworkers [] in 1999 when this species was first described.
Antimicrobial susceptibility testing (AST) of both strains was performed. The disk diffusion method was carried out and with the exception of penicillin, erythromycin and clindamycin, S. aureus isolated from this case was susceptible to all other drugs including cephalosporins and fluoroquinolones. AST for Helcococcus was performed using the CLSI broth microdilution method on Mueller-Hinton II broth (BD Diagnostics, Heidelberg, Germany) supplemented with 3% (vol/vol) lysed horse blood (Oxoid, Wesel, Germany) and 0.001% (wt/vol) pyridoxal HCl (Sigma–Aldrich, Munich, Germany) incubated at 37 °C in 5% CO2 for 24 h [, ]. Streptococcus pneumoniae ATCC 49619 served as a quality control. Then, we changed the method and performed an E-test on blood agar, with S. aureus ATCC 29213 as the quality control (for reference only). The MICs (μg/L) of the drugs for this strain are reported in Table . Since no antimicrobial testing guidelines are currently available from the Clinical and Laboratory Standards Institute (CLSI) for Helcococcus, the MICs were determined in reference to the CLSI guidelines for S. aureus []. According to the CLSI [, ], this strain was susceptible to penicillin, ampicillin, teicoplanin, ceftriaxone, vancomycin, and linezolid.
After admission, the patient received levofloxacin eye drops 4 times per day until being discharged from hospital. After surgery, the patient was initially treated with intra-venous cefotaxime (2.25 g/250 ml NaCl, 1/day) and ornidazole (500 mg/day) for 1 week. Two weeks after admission, the patient recovered and was discharged from hospital. Six months later, the patient returned to the hospital to finish implantation of the artificial right eyeball and no signs of infection were detected. With the patient’s consent, we collected samples from the skin around both eyes for aerobic and anaerobic culture, but only normal skin flora were detected, such as coagulase-negative Staphylococcus. After surgery, the patient was in good health and was discharged from the hospital. |
pmc-6092866-1 | The 55-year-old female patient arrived in our emergency room with epigastric for two days.
The patients’ prior events are sown on Table .
Twenty two years before, in 1995, a vertical banded gastroplasty by Mason (Fig. , left) was performed (Starting weight 185 kg). After an adequate weight loss of 95 kg in the next years, a rapid weight regain of 87 kg occurred in 2013 due to a gastrogastric fistula. Therefore, the gastroplasty was converted into a biliopancreatic diversion by Scopinaro (Fig. , middle). The procedure was started minimal invasively, but had to be converted to open surgery, due to a short jejunal loop. The remnant stomach was not resected. Following the last surgery, an adequate weight loss of 107 kg took place. Starting in early 2017 the patient was regularly admitted to our hospital with tarry stools and iron deficiency anemia despite substitution. Esophagogastroduodenoscopies repeatedly showed a gastrojejunal anastomotic ulcer. At this point, the ulcer appeared to be the cause of the anemia. After interdisciplinary discussion the decision was made to convert the BPD to a Roux-en-Y gastric bypass with resection of the problematical gastrojejunostomy.
On arrival in our emergency room, the blood work showed normal leucocyte counts and a normal CRP value, but elevated transaminases and hyperbilirubinemia. An ultrasound in the emergency room showed a hyperechoic mass in the liver hilum and intrahepatic cholestasis. With the epigastric pain continuing, we decided to perform a CT-scan with oral contrastation (Fig. ), in which evidence was seen of an intussusception reaching the ligament of Treitz with consecutive intrahepatic cholestasis. A complete antegrade intussusception of the remnant stomach into the duodenum reaching up to the ligament of Treitz (Fig. ) was found during surgery. The intussusception was reduced (Fig. ) and the remnant stomach was resected (Fig. , right). The gastrojejunal anastomosis ulcer was resected as a short segment. A new anastomosis was fashioned using a linear stapler. The biliary as well as the common channel remained unchanged with 250 cm and 100 cm respectively. The alimentary channel was shortened to 80 cm.
Following the procedure, no further blood transfusion was needed, and the patient was discharged on the sixth day after surgery. The pathological examination showed a tumor free specimen with chronic antrum gastritis and no indication of malignancy. |
pmc-6092867-1 | A 46 year old male who presented in 2006 with a 3.7 mm BT (Breslow thickness), BRAF wild-type melanoma on his left forearm. He had 1 positive lymph node at SNB (Sentinel Node Biopsy) with no further nodal involvement at left axillary dissection. He had over the years multiple subcutaneous loco-regional recurrences treated with surgical resections initially and then with topical imiquimod and intra-tumour IL-2, as per Green et al. []. Further recurrences led to him being enrolled on the IMM-101-001 study, which resulted in a reduction in the rate of new disease. Following the development of lung metastases he stopped IMM-101 and received 6 weeks thereafter ipilimumab on a clinical trial. On ipilimumab he experienced a rapid very good response (partial response [PR] > 50% as per RECIST 1.1 criteria) with most of the lesions resolving and a couple of visceral lesions remaining stable now over 5 years (Fig. ). |
pmc-6092867-2 | A 50 year-old female who presented in 2011 with an axillary mass, which on removal was shown to be a BRAF wild-type metastatic melanoma. No primary tumour was identified. She developed mediastinal, lung, gastric and peritoneal deposits within a couple of months from initial diagnosis. She had a partial gastrectomy to remove the cancer which was bleeding, and cyberknife treatment for the metastatic lung lesion. She also received systemic treatment with dacarbazine followed by IMM-101 on the IMM-101-001 study, which resulted in a minor response. She remained however stable for about a year until 2013 when she presented with a small bowel obstruction from new disease. She stopped IMM-101 and started ipilimumab and experienced a rapid complete response as per RECIST 1.1 criteria, which continued for 2 years until she had a further recurrence following trauma and stress in 2015. She is still disease free at the moment after further surgery. |
pmc-6092867-3 | A 79 year-old male presented in 2014 with a melanoma on his left cheek (BT 2.4 mm, not ulcerated, BRAF wild-type) with a positive SNB leading to left neck dissection at time of diagnosis (no further positive nodes). Within months he developed paracardiac nodes, adrenal, lung and multiple large subcutaneous metastatic deposits. In view of his age and performance status he was commenced on IMM-101 on a named-patient program with initial stabilisation of disease. Upon progression of the subcutaneous disease he stopped IMM-101 and started with pembrolizumab, which showed a very rapid benefit as the subcutaneous lesions started to shrink within 4 days of the first infusion (Fig. ). All visceral disease had also responded as seen on a restaging CT scan performed 6 weeks later with a PR > 50% as per RECIST1.1 criteria initially followed by a CR a few months afterwards (Fig. ) upon continuation of pembrolizumab which lasted for 18 months and is still ongoing. |
pmc-6092867-4 | A 63-year old male who presented in July 2016 with a 4.2 mm BT ulcerated BRAF wild-type nodular melanoma on his right upper back. He underwent wide local excision and SNB of his right axilla in September 2016 (N + 3/5) followed by completion of the lymphadenectomy in October 2016 (N + total 3/15). In May 2017 he developed subcutaneous metastases on the right lower leg, right forearm and anterior scalp. At the same time a re-staging CT scan showed new pulmonary disease (at least 3 metastatic nodules, the bigger measuring 1.6 cm in the larger diameter). He was then enrolled in the IMM-101-011 study aiming to evaluate the safety and efficacy of IMM-101 in combination with standard of care in patients with metastatic cancer. On the 1st of June 2016 he started treatment with nivolumab in combination with IMM-101. The combination treatment has been well tolerated with no major toxicities apart from transient hyperthyroidism. A minor response to treatment (SD as per RECIST 1.1 criteria) was observed at first re-assessment in August 2016 with a complete response achieved in December 2017. IMM-101 has been administered regularly every 4 weeks on the named-patient program after trial closure till December 2017 when he developed a grade 3 skin reaction at the site of the latest injection of IMM-101. Since then the treatment with IMM-101 has been postponed and rescheduled every 3 months. |
pmc-6092972-1 | The patient was a 72-year-old male who presented to the emergency department (ED) with complaints of headache and seizure-like activity with shaking of his bilateral upper extremities. His past medical history was significant for CLL with 13q deletion diagnosed 6 years prior to presentation. He was treated at that time with fludarabine and rituximab for 4 cycles; however, he was not able to complete a 5th cycle due to prolonged cytopenia. Two years later due to progression of disease, he was started on ibrutinib 420 mg daily and continued for 2 years. He developed severe neutropenia while on ibrutinib, and treatment was held for two months until resolution. He presented to the ED one month after resuming ibrutinib.
At presentation, the patient was alert with the only examination finding of episodic shaking movements. He was afebrile and had a leukocytosis of 15,200/µL with 66% lymphocytes. Initial workup included computed tomography (CT) of the head without contrast which showed no findings to explain presenting symptoms. Continuous electroencephalography (EEG) evaluation was negative for epileptiform activity. With persistent symptoms he was started on anticonvulsants with levetiracetam and phenytoin. A magnetic resonance imaging (MRI) of the brain with contrast was obtained, and it showed a nonspecific focal area of increased signal involving the right frontal cortex (). He was transferred to our institution for further workup and management.
On arrival, the patient was evaluated for progression of CLL by the chest, abdomen, and pelvis CT which was negative for any evidence of disease with no lymphadenopathy or splenomegaly. MRI of the spine was performed and was negative for any disease other than degenerative changes. Ophthalmological evaluation was unrevealing for any intraocular pathology. He was worked up for autoimmune processes with ANA, CRP, and ESR, all of which were insignificant. Infectious workup with blood culture, urine culture, quantiferon-TB, histoplasma, blastomyces, influenza, RPR screen, and HIV were negative. He had a lumbar puncture which showed cerebrospinal fluid (CSF) with elevated WBC 97/µL, polysegmented neutrophils (PMN) 2%, lymphocytes 82%, red blood cells (RBC) 4/µL, elevated protein 93 mg/dL, and normal glucose of 44 mg/dL. FilmArray meningitis and encephalitis panel was negative for all the following tested agents: Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus group B, Streptococcus pneumoniae, Cytomegalovirus, Enterovirus, Herpes simplex virus 1 and 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, and Cryptococcus neoformans. Gram stain and culture also turned out to be negative. Cytologic analysis of CSF was negative for malignant cells or large cell transformation. CSF flow cytometry showed a minute population of 0.04% CD5+ B-CLL cells, which was not felt to be clinically significant and sufficient to explain the acute changes the patient was experiencing. Other CSF tests, which were negative, included angiotensin-1-converting enzyme, John Cunningham (JC) polyomavirus, cryptococcal antigen, fungal culture, and CSF toxoplasma serologies.
The patient became increasingly lethargic and started complaining of worsening headache. He also started having high fevers which persisted despite treatment with broad-spectrum antibiotics with vancomycin and piperacillin/tazobactam and antivirals with acyclovir. His neurological status continued to decline and repeat MRI brain showed new and increase in size of previously known scattered hyperintensities with associated rim enhancement (). At this time, infectious etiology was favored, given the acuity of changes seen on imaging and patient status. The infectious coverage was expanded and included IV vancomycin, cefepime, and ampicillin for bacterial meningitis; IV amphotericin B for atypical fungal meningitis; and IV acyclovir was continued for viral encephalitis. The patient continued to decompensate clinically, and a repeat CT of the head showed hydrocephalus. An external ventricular drain was placed which did not improve his status. A leptomeningeal biopsy was not performed considering the difficult location and size of the lesions. As all workup continued to be unrevealing, progressive multifocal leukoencephalopathy (PML) was thought to be the most likely diagnosis to fit the patient's medical history and imaging and laboratory results; however, JC polyomavirus was tested negative on two separate CSF analyses, making this diagnosis unlikely. The patient ultimately expired within two weeks after he presented with the neurologic symptoms after support was withdrawn per family request, and an autopsy was performed.
Autopsy of the brain showed diffuse cerebral edema with right-sided predominance on gross findings. There were multiple areas of hemorrhagic necrosis including the bilateral frontal lobe, right parasagittal posterior frontal lobe, left temporal lobe, bilateral medial occipital lobe, and paraventricular areas. Microscopic findings revealed parenchymal necrosis with mixed inflammation, amebic trophozoites, and occasional cysts (Figures and ). This mixed infiltrate was seen involving the meninges. The amebas were prominent around vessels, and occasional multinucleated giant cells were seen (Figures and ). The autopsy brain was sent to the Centers for Disease Control and Prevention (CDC) and immunohistochemical stains were performed, which identified Acanthamoeba species with no evidence of Naegleria fowleri. His final diagnosis based on autopsy was necrotizing meningoencephalitis with morphologic and immunohistochemical evidence of Acanthamoeba species. |
pmc-6092986-1 | The proband is a 14-year-old previously healthy female born to nonconsanguineous healthy parents who was admitted for having fever, fatigue, lower quadrant abdominal pain, and vomiting. Abdominal computerized tomography (CT) revealed significant hydronephrosis consistent with a right ureteropelvic junction (UPJ) obstruction, for which she underwent ureteral stent placement on hospital day 2. Her postoperative course was complicated by continued abdominal pain and fever, as well as an episode of rectal prolapse. Of note, she also endorsed an episode of rectal prolapse months prior to presentation which was manually reduced at home. On hospital day 6, due to continued fevers, abdominal and pelvic MRI was obtained. This study revealed a pelvic fluid collection concerning abscess; CT guided transgluteal drainage performed by Interventional Radiology resulted in 150ml cloudy yellow fluid. The etiology was believed to be an infected urinoma caused by instrumentation during stent placement and she was treated with ceftriaxone and metronidazole. The patient's fevers and pain continued, prompting an abdominal and pelvic CT on hospital day 10. The imaging was notable for diffuse ascites, bowel wall thickening, and organizing fluid collections within the pelvis. She ultimately went for exploratory laparotomy and washout with intraoperative findings of multiple pockets of turbid fluid. The entire bowel was evaluated and there was no evidence of perforations, fistulas, or other causes of gastrointestinal leakage. Peritoneal fluid cultures grew polymicrobial organisms, however, suggestive of gut flora. She was transitioned to meropenem and fevers eventually resolved prior to discharge.
Two months following discharge the patient underwent outpatient elective appendectomy, right pyeloplasty, and ureterotomy with stent placement due to persistent hydronephrosis. Pathology revealed normal appendix tissue. Ureter pathology was significant only for acute and chronic inflammation, with no evidence of malignancy. Routine screening abdominal ultrasound 2 months later revealed stable hydronephrosis; however, an incidental 3cm soft tissue mass presumed to be near the sigmoid colon was noted. Follow-up MRI showed nearly circumferential thickening of the sigmoid colon which was subsequently evaluated by esophagogastroduodenoscopy and colonoscopy. Findings were significant for 9-10 sessile polyps in transverse, descending, and sigmoid colon with large cluster of irregular appearing polyps in the sigmoid (). Histologic evaluation of the sigmoid polyp revealed invasive moderately differentiated adenocarcinoma with extensive lymphovascular invasion. Immunohistochemical staining demonstrated the carcinoma to be positive for CDX-2, villin, and CK7 and negative for CK20 and WT-1 (). The lack of CK20 suggested a possible primary upper gastrointestinal or hepatobiliary primary tumor; however this was not found on endoscopy or suggested on previous imaging. Further immunohistochemical staining revealed no loss of expression of MLH1, MSH2, and MSH6. There was complete loss of expression of PMS2; this testing was deemed indeterminate due to lack of staining in both tumor tissues and normal tissue.
The patient underwent repeat colonoscopy approximately 3 weeks after her first procedure with an adult interventional gastroenterologist. Findings were significant for two tubular adenomas in the colon at 25cm and 30cm from the anus, moderately differentiated adenocarcinoma at 24cm, a moderately differentiated adenocarcinoma in the rectum (10-15cm), and an anorectal mass with moderately differentiated adenocarcinoma arising in the background of tubulovillous adenoma with extensive high-grade dysplasia. Both tubular adenomas were removed by snare polypectomy, while the remaining masses were biopsied. Immunohistochemical staining was positive for CDX2, CK7, CK20, and villin. There was no loss of expression of MLH1, MSH2, and MSH6, suggesting intact proteins. There was again loss of expression of PMS2 in both tumor and nontumoral cells () consistent with complete protein loss. Genetic testing revealed biallelic pathogenic PMS2 variants: NM 000535: c.137 G>T; NP 0005261: pS46I and c.1831dupA (frameshift). Familial testing concluded that one variant was inherited from each parent, with her asymptomatic brother also carrying the father's PMS2 variant.
Due to the findings of invasive disease as well as previous pelvic fluid suggestive of a microperforation, the diagnosis of Stage 4 adenocarcinoma was established. Chemotherapy was initiated with Capecitabine (pyrimidine analog) followed by two cycles of FOLFOX6 (Oxaliplatin, Leucovorin, and 5-FU), as well as 6 weeks of radiation. She finally underwent total colectomy along with total abdominal hysterectomy with bilateral salpingectomy, and pathology revealed no evidence of residual adenocarcinoma in the colon. |
pmc-6093030-1 | A 60-year-old African American female was following up for her chronically elevated alkaline phosphatase levels. She had a history of hypertension, hyperlipidemia, type 2 diabetes mellitus, allergic rhinitis, and chronic lower back pain. Patient has a family history of arthritis, cardiovascular disease, and diabetes mellitus; she denies ever using alcohol or tobacco.
With the onset of elevated alkaline phosphatase level and vague abdominal pain in 2013, an abdominal ultrasound performed in December showed hepatic steatosis. Viral serologies for hepatitis during 2013 were negative, as a gastrointestinal consult was required to determine the need for a liver biopsy. A liver biopsy was subsequently performed, which showed focal mixed micro and macrovesicular steatosis. Portal tracts showed minimal focal chronic inflammation, no significant fibrosis, and no iron deposition.
The vague abdominal pain that she was experiencing waxed and waned for two years. Additionally, the patient experienced some vague chest pain and dyspnea that prompted an echocardiogram in February of 2015, which demonstrated a left ventricle ejection fraction of 44%. Consequently, a left heart catheterization in the following month showed no significant coronary disease with a dilated left ventricle with an ejection fraction of 50%. A 2-year follow-up in July of 2015 showed suspicious cirrhosis by Computed Tomography (CT) scan (), possibly due to granulomatous changes and chronic inflammation. A CT scan was determined to be necessary for our patient because of rising alkaline phosphatase without other explainable etiologies, in addition to the patient's appetite suppression and vague abdominal pains. Patient's weight during this time was 207 lbs (93.89 kg) and was advised to diet and exercise. After 4 months of continuous symptoms, especially with abdominal pain, a laparoscopic cholecystectomy was performed with a liver biopsy that showed subsequent granulomatous changes in September of 2015. The liver biopsy showed coalescing periportal nonnecrotizing epithelioid granulomas with associated multinucleated giant cells and chronic inflammation. The chronic and patchy inflammation is representative of the granulomatous hepatitis, despite not having elevated transaminases. The granulomatous changes suggested possible sarcoidosis (). The liver biopsy was not histologically suggestive of nonalcoholic steatohepatitis, with no steatosis noted. Chest X-ray at that time showed no significant findings.
Inflammatory bowel disease (IBD) was not explored in the patient because she never had clinical signs on past or present examinations, denying any symptoms of IBD including alternating bowel habits, predominant constipation, or diarrhea. Laboratory studies 2 years and 6 months since the onset, at the end of 2015 showed negative antinuclear antibodies (ANA), negative rheumatoid arthritis factor, negative cyclic citrullinated peptide (CCP) antibodies (IgG/IgA), elevated C-reactive protein of 8.9 mg/L, normal complement C3/C4, elevated B-type natriuretic peptide 688.6 pg/mL, and negative mitochondrial (M2) antibody. Subsequent office visits and additional laboratory results are shown in .
Additionally, patient experienced peak weight loss with a weight of 154 lbs. (69.85 kg) in 2016. During this time period, an echocardiogram showed a decreased ejection fraction of 26%. This result and a history of having ventricular tachycardia resulted in the patient having an automated implantable cardioverter-defibrillator (ICD) placed.
Urinalysis in June 2017 showed RBC 0-5/hpf, WBC 0-5/hpf, bacteria 2+, and moderate calcium oxalate crystals. Additionally, patient's weight increased in 2017 to 190 lbs. (86.18 kg). |
pmc-6093066-1 | A 33-year-old Caucasian male presented to our surgical unit after 3 days of progressively worsening abdominal pain. The patient also reported the onset of constipation for some days, but he denied any associated nausea or vomiting.
His past medical history included a right-sided Wilms' tumor treated with unilateral nephrectomy when he was 2 years old. Moreover, during the follow-up for this pediatric tumor, some progressively growing intra-abdominal cystic formations, localized at the level of the mesentery, have been incidentally identified.
Physical examination revealed a hypogastric mass and diffuse abdominal tenderness without abdominal distension.
The patient underwent an abdominal CT scan () which showed the presence of 3 contiguous and communicating cystic formations located at the level of the mesentery that altogether had a major axis equal to 115 mm. Among these, the mass with larger dimensions (major axis equal to 87 mm) was the most ventral one and it was localized in contiguity with the abdominal wall, in the subumbilical region. Moreover, further intra-abdominal lesions similar to the previous ones, but significantly smaller in size, were described.
Due to worsening symptoms, an exploratory laparotomy was performed and a voluminous cystic mass, composed of 3 confluent formations, with a major axis equal to about 10 cm, and incorporated in the mesentery of the last ileal loops, was observed (). Some other similar but significantly smaller lesions were found, in particular in the pelvic cavity and in correspondence of the cecal appendix. Thus, an en bloc resection of the voluminous mesenteric formation together with the corresponding intestinal loops with ileoileal anastomosis, an appendicectomy, and some peritoneal biopsies were performed. The whole procedure was hampered by the presence of scar adhesions due to the previous nephrectomy.
The postoperative period was complicated, on the 8th postoperative day, by a circumscribed peritonitis due to dehiscence of the ileoileal anastomosis. The patient was therefore submitted to another operation. On this occasion, a resection of the previous anastomosis and an ileocecal resection with ileo ascending colon anastomosis were performed.
Moreover, the postoperative period was complicated by a delayed return of normal bowel function which was resolved through prokinetic therapy with levosulpiride and neostigmine methylsulfate. The patient was finally discharged 33 days after the first operation in good condition.
Through histological examination a benign multicystic peritoneal mesothelioma was diagnosed.
At 8 months of follow-up, the patient is free of symptoms. |
pmc-6093270-1 | A 58-year-old female with a history of stage IV NSCLC of her right lung presented to the emergency department with complaints of shortness of breath for four days.
Her lung cancer was discovered 3.5 years earlier as a 4 x 5.3 cm right upper lung cavitary mass on routine lung computed tomography (CT) screening (T3N2M0, stage IIIA at diagnosis). She did have a long-standing history of tobacco use.
She underwent seven months of treatment with radiation and remained disease free until about two years later, when a sample from a pleural effusion confirmed lung adenocarcinoma. Molecular studies were negative for anaplastic lymphoma kinase (ALK), ROS-1, and programmed death ligand 1 (PD-L1) but positive for EGFR. She underwent one cycle of carboplatin and paclitaxel prior to finding this mutation. She was then switched to erlotinib. Six months later, CT showed the progression of the disease, so she was switched to afatinib at a dose of 40 mg daily.
She presented to the emergency department one month after starting afatinib. Initial evaluation was significant for a new two-liter oxygen requirement. Her blood work was unrevealing other than a mild non-gap metabolic acidosis secondary to chronic diarrhea. She was admitted and started on empiric broad-spectrum antibiotics. Afatinib was held at admission. CT chest with contrast was obtained that showed no pulmonary embolism but did demonstrate significantly increased ground glass opacities in the left lung, a right perihilar mass unchanged from prior scans, a right pleural effusion, and enlarged main pulmonary arteries (Figure ). Two days after admission, she developed profound hypoxemia requiring escalation to a non-rebreather to maintain oxygenation. A bronchoscopy revealed no endobronchial lesions, and the sample obtained showed scant white blood cells (70% monocytes, 10% polys) with no organisms. Despite completing a seven-day course of broad-spectrum antibiotics, a thorough infectious workup (including bacterial cultures, respiratory viral panel and procalcitonin) was unrevealing. The patient was started on a daily dose of 500 mg methylprednisolone on hospital day three due to a suspicion for afatinib-induced pneumonitis. After one week, the patient’s oxygen requirement gradually improved allowing for a decrease in steroid dosing. Unfortunately, she then suffered a bowel perforation (presumed to be unrelated to her pulmonary presentation) requiring sub-total colectomy with end ileostomy. She was discharged to a skilled nursing facility subsequently. At her one month post-discharge follow-up, she was off steroids and saturating well on two liters of supplemental oxygen. A follow-up CT scan obtained four months later showed marked improvement of the pneumonitis, although the primary lung cancer had increased in size (Figure ). |
pmc-6093271-1 | A 21-year-old male presented with a history of increased appetite, heat intolerance, fatigue, and sweating. On physical examination, he appeared to be anxious, He had a sinus rhythm with a heart rate of 96/min. His blood pressure was 126/85 mmHg. He also had mild exophthalmos with lid lag and a fine tremor on outstretching of the hands. Thyroid stimulating hormone (TSH) was suppressed 0.02 m IU/ml (0.04-4.50) while free thyroxine (free T4) was 2 ng/ml (0.8- 1.8) was elevated. The suppressed TSH and elevated free T 4 was consistent with hyperthyroidism. Anti-TG and anti-TPO were 517 IU/ml (<20 IU) and > 1,000 IU/ml (<35 IU/ml), respectively. He also had mildly elevated thyroid stimulating immunoglobulin (TSI): 164.9 (<125), but his radioactive iodine uptake scan was 9.6 (normal 9 5% to 30%). Based on the clinical presentation and biochemical tests, a diagnosis of hyperthyroidism was made. Because of the severity of symptoms, methimazole and atenolol were initiated to treat hyperthyroidism. The TSH level gradually increased to a high normal level over 16 months, after which the dose of methimazole was gradually decreased. Methimazole was finally discontinued after two years. On a subsequent follow-up visit, the TSH level increased to 4.15 mIU/ml, suggesting subclinical hypothyroidism. Eventually, after seven months, he presented with fatigue and weight gain and was found to have high TSH of 13 mIU/ml and low free T4 of 0.9 ng/ml, suggesting hypothyroid, with Hashimoto's thyroiditis as the most likely diagnosis. He was started on levothyroxine replacement therapy and remained euthyroid on levothyroxine since that day. The initial presentation mimics Grave’s disease, but his normal radioiodine uptake, despite the high TSI level, led us to treat him medically and not with radioactive iodine (RAI) therapy. |
pmc-6093272-1 | A 27-year-old woman presented with a progressive painless visual loss in both eyes for one week prior to consultation. It was associated with preceding headache, nausea, and vomiting of two months duration. There was no history of prolonged fever, chronic cough, reduced weight, or loss of appetite. However, her father was treated for pulmonary tuberculosis two years ago and he had completed his anti-tuberculosis therapy.
Her best corrected visual acuity was 3/60 (OD) and 4/60 (OS). The optic nerve function tests were impaired bilaterally and included light brightness, contrast sensitivity, and color vision; however, the right sight was more affected than the left. There was a relative afferent pupillary defect presence on her right eye. The confrontation test revealed generalized haziness with dense central scotoma on her bilateral vision. The anterior segment examination and intraocular pressure were essentially normal. The fundoscopy examination revealed bilateral papilledema. The optic discs were swollen and elevated with peripapillary flame-shaped hemorrhages as well as the presence of macular exudates (Figure ). However, no sign of vitritis or panuveitis was observed.
On presentation, she was alert and orientated to time, place, and person. Her vital signs were stable. She was also afebrile. There were no signs of meningism or localizing signs. A respiratory examination revealed crepitation in the right lung. The other cranial nerves examinations were normal. The rest of the systemic examinations were unremarkable.
Her baseline blood investigations were unremarkable except for an increased erythrocyte sedimentation rate (79 mm/h) and C-reactive protein (23 mg/l). The human immunodeficiency virus antibody test was negative. The Mantoux test was positive (16 mm area of induration). The sputum microscopic examination detected the presence of acid-fast bacilli. The chest radiograph showed cavitations at the right lower zone (Figure ).
The computed tomography (CT) scan of the brain and orbit revealed the presence of multiple ring-enhancing hyperdense lesions with central hypodensity and perilesional edema. The lesions were located at the anterior horn of the right lateral ventricle (Figure -). There were also multiple small lesions at the cerebrum and cerebellum (Figure ).
However, there was no traction over the septum pellucidum. The lateral and third ventricles were dilated on both sides. She declined further diagnostic tests, including lumbar puncture and magnetic imaging resonance (MRI) of the brain and orbit. A presumptive diagnosis of bilateral papilledema secondary to intraventricular tuberculoma with hydrocephalus was considered. However, the patient refused the ventriculoperitoneal shunt procedure.
Anti-tuberculosis therapy was commenced immediately with oral isoniazid 300 mg, oral rifampicin 600 mg, oral pyrazinamide 1500 mg, intramuscular streptomycin 1000 mg, and intravenous dexamethasone 4 mg. Her symptoms of headache, nausea, and vomiting subsided.
However, visual acuity of both eyes deteriorated progressively to non-perception of light after four weeks of treatment. She had no new emerging neurological symptoms or signs associated with the visual loss. A repeat funduscopy examination showed atrophy of the optic discs in both eyes (Figure ).
We planned to extend her oral dexamethasone while continuing the same anti-tuberculosis regime. Unfortunately, the patient defaulted follow-up after one month of treatment. |
pmc-6093274-1 | Our patient is a 44-year-old Caucasian female who presented to her primary care physician with a chief complaint of incredible thirst and increased frequent urination. The patient stated she returned two days ago from a vacation to Aruba where she spent the past week. On the last day of the trip, she began feeling these symptoms. Aside from the extreme polydipsia, she further admits to nausea, headaches, and malaise. She denied any fever, chills, weight loss, rash, and abdominal or joint pain. No other family member was sick. However, she admits to eating out in many restaurants off the resort, where there may have been seafood served. She has no other pertinent medical, surgical, or family history. She is not taking any medications, but is allergic to sulfa drugs. She denies the use of drugs, alcohol, or tobacco. She states she is sexually active, as she is in a monogamous relationship with her husband. She traveled alone and no other contacts were reported to be ill. On physical exam, she was afebrile and her vital signs were within normal limits. She appeared well-nourished, alert, and oriented, and her mucous membranes were moist. Her cardiovascular, pulmonary, abdominal, and genitourinary system exam findings were benign.
Laboratory studies undertaken by her primary care physician (PCP) revealed a serum alkaline phosphatase of 577 U/L (normal 39-117 U/L), aspartate aminotransferase (AST) of 376 U/L (normal 0-40 U/L), alanine aminotransferase (ALT) of 474 U/L (normal 0-32 U/L), and a total bilirubin of 2.9 mg/dl (normal 0.0-1.2 mg/dl). Upon receiving these laboratory results (of highly elevated LFTs), the patient was advised by her PCP to present to the emergency department (ED) for further workup. Upon admission to the hospital, she admitted to a history of eating a good amount of seafood—including shrimp and grouper—during her vacation to Aruba. At this time, she complained of epigastric abdominal pain and a continuation of her symptomatology. On physical exam, she was afebrile, had a BP of 122/91, a heart rate (HR) of 91, and a respiratory rate (RR) of 19, with a peripheral capillary oxygen saturation (SpO2) of 98%. She appeared well-nourished and was in no acute distress. On abdominal exam, she was tender to palpation in her epigastric region with a soft, non-distended abdomen and mild to moderate splenomegaly. Cardiovascular, pulmonary, and genitourinary system exam findings were benign.
Upon admission, laboratory studies revealed a white blood cell (WBC) of 11.3 (normal 4.0-11.0 x10(3)/mcl), serum alkaline phosphatase of 583 U/L (normal 39-117 U/L), aspartate aminotransferase (AST) of 356 U/L (normal 0-40 U/L), alanine aminotransferase (ALT) of 490 U/L (normal 0-32 U/L), and a total bilirubin of 3.1 mg/dl (normal 0.0-1.2 mg/dl). The urine pregnancy test came back negative. Right upper quadrant ultrasound (RUQ U/S) showed no dilatation of the common bile duct (CBD), the absence of a sonographic Murphy sign, mild pericholecystic fluid, with a 9 mm thickening of the gallbladder wall, suspicious for acute cholecystitis. A hepatobiliary iminodiacetic acid (HIDA) scan and computed tomography (CT) abdomen/pelvis showed benign findings, hence ruling out pathological biliary or gallbladder involvement.
Influenza A and B came back negative. Antinuclear antibody (ANA) and human immunodeficiency virus (HIV) antigene-antibody (Ag/Ab) were negative and nonreactive, respectively. The hepatitis panel drawn was negative for Hep A immunoglobulin M (IgM) (0.38, normal 0.00-0.79 s/c), HBS AG (0.14, normal 0.00-0.99 s/c), Hep B Core IgM (0.07, normal 0.00-0.99 s/c), and Hep C AB (0.06, normal 0.00-0.99 s/c). The patient was given fluids and her liver function tests (LFTs) began to trend downward over the next 24 hours, whereupon she was discharged with a diagnosis of “elevated LFTs.” She then presented to her primary-care physician (PCP) for post-discharge follow-up, whereupon a more aggressive workup was done. A heterophil antibody test was negative and, thus, EBV antibody titers were drawn. They were consistent with acute primary EBV Infection.
EBV viral capsid antigen (VCA) IgM was >160 (negative <35.9 U/mL and unequivocal 36.0-43.9), EBV EA IgG was 51.1 (negative <0.9 and unequivocal 9.0-10.9), EBV VCA IgG was 37.7 (negative <18.0 and unequivocal 18.0-21.9), EBV NA IgG was <18.0 (negative <18.0). In addition, smooth muscle antibody—actin Ab was 20 units (negative 0-19, weak positive 20-30, moderate to strong positive >30). Thus, hinting toward a hepatitis co-infection, as smooth muscle antibodies are found in 52%-85% of hepatitis patients. At this time, nearly 6 weeks from the beginning of her vacation, a hepatitis A panel was redrawn, as it was still high on the differential regardless of the initial negative results. Sure enough, this time around, the total hep A antibody was positive. The patient was encouraged to increase fluid intake with adequate electrolytes. Additionally, the patient was educated further on refraining from participating in contact sports until her physical exam returned to normal and there was no splenomegaly present. At her next PCP visit two weeks later, her LFTs were practically back to normal and her symptomatology had significantly decreased. |
pmc-6093594-1 | Case 1: A 46- year old Nigerian male cleric presented to the Endoscopy suite of the University of Ilorin Teaching Hospital having been referred on account of an 8- month history of dyspepsia, progressive weight loss, diarrhea alternating with constipation, occasional haematochezia and painful peri-umbilical swellings. He had no fever, cough or drenching night sweats. No history of cigarette smoking or alcohol ingestion. He had a history of surgical removal of a mass lesion from his scalp 5 years earlier with a histological diagnosis of inclusion cyst. He had no known family history of either cancer or polyposis syndromes. He had a twin brother who died of an unknown cause in childhood. His other siblings were in good health. At presentation he was pale, had discrete non-tender right inguinal lymphadenopathy and Sister Mary Joseph (SMJ) nodules. Rectal examination revealed melaena. Gastroscopy revealed multiple sessile polyps in the antrum and a solitary polyp in the duodenal bulb. Histology of the gastric polyps revealed features of dysplasia. Colonoscopy performed using an Olympus CF-180 Evis Exera II forward-viewing colonoscope revealed hundreds of polyps of varying sizes extending from the rectum to the ascending colon. Two large polyps were seen at approximately 15cm and 90cm from the anal verge. Biopsies were taken from these, and one of the pedunculated polyps seen at 45 cm from the anal verge was snared (). The histology of the large polyps was tubulovillous adenoma with low grade dysplasia whereas that of the snared polyp was tubular adenoma with low grade dysplasia. The histological diagnosis of the biopsies of the SMJ nodules was metastatic adenocarcinoma. He was commenced on chemotherapy. |
pmc-6093594-2 | Case 2: A 49- year old native Nigerian male artisan (upholstery maker), was referred for colonoscopy on account of a 2-month history of colicky left lower abdominal pain, hematochezia and progressive generalized body weakness. He had no history of weight loss, passage of pellet like stool, spurious diarrhoea nor abdominal swelling. He had laparotomy done 24 years earlier on account of an acute abdominal condition. The details of the surgical findings were not known. He was neither hypertensive nor diabetic. He neither smoked cigarette nor drank alcohol. On examination he was pale and dehydrated. Pulse rate was 120 beats per minute and blood pressure was 120/70mmHg supine. No postural hypotension. Abdominal examination revealed hypertrophied right paramedian scar. His packed cell volume (PCV) was 20%, and he was transfused with two pints of fresh whole blood prior to colonoscopy with an Olympus CF-180 Evis Exera II forward-viewing colonoscope. Numerous sessile and pedunculated polyps of varying sizes were seen in the rectum and colon (). Surgical intervention was delayed for about 3 months due to financial constraint and fitness concerns. The surgical findings were numerous polyps in the colon and rectum with a sigmoid mass lesion. Resection of the sigmoid mass along with some segments of the colon harbouring polyps was carried out. The histological diagnosis of the tumour was an adenocarcinoma. Post-operatively, he was commenced on chemotherapy. |
pmc-6093753-1 | During routine dissection of a male cadaver aged 59-year-old at death, an unusual muscle was identified on the back. The muscle was deep to the rhomboids, superficial to the erector spinae and was more or less vertically arranged. The origin of the muscle was from the spinous processes of the lower cervical vertebrae and the insertion was onto the second through sixth ribs (Figure ). The innervation and blood supply were via the intercostal nerve and artery, respectively.
Although the fiber direction and number of rib attachments were not consistent with the SPS, the position of the muscle between the rhomboids and erector spinae indicated that this muscle most likely represented an unusual variation of the SPS (Figure ). No other anatomical variations were found on the back and no pathology such as scoliosis was identified. |
pmc-6093754-1 | A 75-year-old Caucasian male presented to the hospital after a fall and was diagnosed with a left hip intertrochanteric femur fracture secondary to trauma. He was not on any prescription medication including oral anticoagulants. His prior surgical history included an uncomplicated tonsillectomy in childhood. He did not endorse a past history of prolonged bleeding or thrombotic episodes. He had no documented history of liver disease, significant alcohol use, dyspnea, or painful swollen extremities. On exam, he was breathing comfortably at rest, had a normal heart rate, and had no peripheral extremity edema. The left hip was externally rotated, sensation was intact in the extremity, and the foot was well perfused. Plain radiographs of the left hip revealed an intertrochanteric fracture of the left proximal femur. Operative repair of hip fracture was planned.
Routine preoperative laboratory testing revealed a hemoglobin of 9.7g/dL (normal range 14.0 - 18.0 g/dL) and hematocrit of 27.9% (normal range 37.0% - 52.0%), prolonged aPTT at 61 seconds (normal range 22-29 seconds). Prothrombin time (PT) was normal at 10.8 seconds (normal range 9.7-11.9 seconds). Mild transaminitis was noted after fall with alanine aminotransferase (ALT) 62 U/L (normal range <40 U/L) and aspartate aminotransferase (AST) 121 U/L (normal <35 U/L). Gamma-glutamyl transpeptidase (GGTP) was within normal limits at 10 U/L (normal range <60 U/L), ruling out acute ethanol consumption. Total bilirubin was normal at 1.1 mg/dL (normal range <1.2 mg/dL), alkaline phosphatase was normal at 35 U/L (normal range 35-130 U/L). Ethanol and acetaminophen blood levels were undetectable and an ultrasound examination of the liver did not demonstrate any liver disease. Serology for viral hepatitis A, B, and C was normal. Transaminitis improved and was subsequently normal. However, aPTT was persistently elevated on multiple measurements. Disseminated intravascular coagulation was ruled out with negative testing for fibrin monomer, normal PT and no evidence of low fibrinogen level. Fibrinogen at 568 mg/dL (normal range 185-408 mg/dL) and mildly elevated D dimer at 6.92 mg/L FEU (normal range <0.53 mg/L FEU) reflected their nature as acute phase reactants. Reptilase time was normal at 17 seconds (normal range 14-23 seconds), ruling out spurious heparin contamination in the intravenous line. Thrombin time was 14 seconds and on the lower end of normal reference range of 15-23 seconds. This was of no known hemostatic consequence. Normal dilute Russell viper venom time (dRWT) with ratio 1.1 (normal reference range 0.0-1.1) suggested no evidence of lupus anticoagulant. Mixing study of prolonged aPTT demonstrated no inhibition and, therefore, no evidence of lupus anticoagulant. Antiphospholipid antibody immunoglobulin G (IgG) and immunoglobulin M (IgM) as well as beta-2 glycoprotein antibody IgG and IgM were normal (<9.4 MPL with normal reference range <15MPL, <9.4MPL with reference range <15MPL, <6.4CU with normal reference range <20CU, <1.1 CU with normal reference range <20CU, respectively).
The lack of painful or swollen extremities to suggest a venous or arterial thromboembolic event along with his laboratory results made a diagnosis of antiphospholipid syndrome unlikely. The data from mixing study reflected no inhibition and suggested a coagulation factor deficiency, as the patient had correction immediately and after incubation at 37 oC. Assays of factors II, V, VIII, IX, X, XI, and XII along with von Willebrand factor assay were performed. Factor VIII activity assay was elevated at 205%, along with elevated von Willebrand factor antigen (vWFAg) at 322% and elevated von Willebrand factor activity (vWFActivity) at 358% (normal reference range 55%-200%). Levels of factor VIII, vWFAg and vWF activity were concordant, reflecting their activity as acute phase reactants.
Factor II assay was normal at 86% (normal reference range 75%-145%). Factor V assay was normal at 94% (normal reference range 70%-165%). Factor X assay was normal at 104% (normal reference range 70%-150%). Factor XI assay was normal at 102% (normal reference range 55%-120%). Factor IX assay was 159.9% (normal reference range 65%-140%) and likely represented acute phase reactant. Since the patient’s plasma had normal or elevated coagulation factor activity, no inhibitor screen was performed for specific inhibitors to factor II, V, VIII, IX, X, XI. Factor XII assay was 2% and confirmed a coagulation factor deficiency with a marked reduction in factor XII activity, well below the reference range of 55%-180%. Therefore, the patient was diagnosed with factor XII or Hageman factor deficiency.
Since this deficiency is of no known hemostatic consequence, the patient proceeded with surgery. A left hip trochanteric fixation was performed without complications. At the time of his hospitalization and treatment, the literature regarding the increased risk of venous thromboembolism in this condition remained uncertain. Therefore, he received extended duration postoperative prophylaxis with 40 mg of subcutaneous enoxaparin daily for three weeks after surgery []. Low dose aspirin 81 mg oral daily was prescribed after discontinuation of enoxaparin for prevention of venous thromboembolism []. At his four-month post-surgical clinic follow up, the patient reported no bleeding or thromboembolic events. |
pmc-6093755-1 | A 67-year-old African-American male with a history of type 2 diabetes mellitus complicated by neuropathy, hypertension, gastroesophageal reflux disease, and obstructive sleep apnea presented to the emergency room (ER) with chest pain. His chest pain was substernal in location, sharp in quality, and non-radiating. He had no previous history of myocardial infarction or congestive heart failure. His chest pain came on with exertion and was not completely relieved by rest or nitroglycerin. He denied fever, chills, sweats, shortness of breath, foreign travel, abdominal pain, nausea, or vomiting. His home medications included aspirin, vitamin D, docusate (as needed), gabapentin, lisinopril, loratadine, metformin, omeprazole, oxybutynin, sildenafil, and terazosin. He reported drinking one to two eight-ounce glasses of whiskey per night and occasional marijuana use. The physical examination was notable for normal S1 and S2 heart sounds, vesicular breath sounds, and a protuberant abdomen without evidence of ascites, hepatosplenomegaly, or other stigmata of chronic liver disease. He was given nitroglycerin and intravenous hydromorphone for pain. The electrocardiogram (ECG) obtained showed no ST-T changes concerning for acute ischemia. Laboratory studies were significant for two negative troponins, elevated aspartate amino aspartate (AST) and alanine aminotransferase (ALT), normal bilirubin, internalized normalized ratio (INR), and alkaline phosphatase (ALP) levels. Alcohol level was undetectable on admission. A review of the patient’s record shows he had normal transaminase, total bilirubin, and alkaline phosphatase levels one week prior (Table ). On further questioning, the patient mentioned that he was started on gabapentin 300 milligrams twice a day exactly one week prior (05/19/2017) for diabetic neuropathy. He denied taking any new over-the-counter medications or herbs. Liver serologies on 05/19/2017 were obtained before gabapentin initiation.
The patient was admitted to the internal medicine service for his chest pain and acute liver injury. The patient’s chest pain resolved in the ER after one-time administration of intravenous hydromorphone. Given the temporal association of the hepatocellular injury with the recent administration of gabapentin, the patient’s gabapentin was discontinued while he was an inpatient. The patient had a human immunodeficiency virus (HIV) and had an acute hepatitis diagnostic profile for A/B/C ordered, both of which were negative. Computed tomography (CT) of the abdomen and pelvis showed no evidence of cirrhosis or biliary obstruction. Mild hepatic steatosis unchanged from the previous examination was appreciated. The right-upper quadrant ultrasound showed no evidence of cholecystitis, and magnetic resonance imaging (MRI) showed no evidence of a gallbladder mass. The results of additional serologic testing for acute liver injury are presented in Table to include thyroid stimulating hormone (TSH), creatine phosphokinase (CPK), total iron binding capacity (TIBC), and Epstein-Barr virus (EBV). The urine drug screen was positive for opiates (given in the ER) and marijuana. The transthoracic echocardiogram obtained showed no evidence of pericarditis, right ventricular systolic failure, or right atrial dilation.
Within 48 hours, the patient’s transaminase levels began to trend down. Serologic markers of hepatic synthetic function remained within normal limits. The patient was advised that his acute liver injury could be secondary to gabapentin, and he was instructed to discontinue taking gabapentin. At the outpatient follow-up with gastroenterology eight weeks later, the patient had a repeat testing of his transaminase levels, whose results were normal (Table ). He continues to remain off gabapentin without any sequelae of liver disease. |
pmc-6093822-1 | The patient was a 55-year-old Japanese woman with decompensated cirrhosis by primary sclerosing cholangitis. Her Child-Pugh score was 13 points, which was categorized as class C, and the model for end-stage liver disease (MELD) score was 23 points. She underwent ABO-incompatible LDLT by right-lobe graft with hepaticojejunostomy for the right anterior duct (RAD) and right posterior duct (RPD). We performed hepaticojejunostomy using the “open-up” anastomotic technique, as described previously []. In brief, both the anterior and posterior walls of the graft bile duct were opened using 6-0 absorbable monofilament sutures before anastomosis. The graft bile ducts were anastomosed to the recipient jejunum by interrupted sutures, and a biliary drainage tube was placed for each bile duct across the site of anastomosis and exteriorized by the Witzel procedure.
Eighteen days after LDLT, double-balloon endoscopy was performed for bleeding in the digestive tract. Nineteen days after LDLT, bilious and bloody discharge was detected from the abdominal drain, and we performed emergency surgery. In the operation, we found that the hepaticojejunostomy of both the RAD and RPD suffered complete dehiscence, and re-anastomosis was impossible. Thus, we decided to avoid re-anastomosis of the bile ducts in the operation. Biliary drainage tubes were inserted from the stumps of the RAD and PRD and were exteriorized through the abdominal free space and abdominal wall. We avoided inserting biliary drainage tubes transhepatically due to the possibility of injuring the graft liver. The jejunum was simply placed and fixed near the RAD and RPD for future anastomosis by MCA (Fig. ). After surgery, we added percutaneous transhepatic cholangiography drainage (PTCD) tubes for the RAD and RPD to reduce the frequency of cholangitis. Her general condition gradually improved, and she was discharged 6 months after LDLT.
We next decided to treat the complete dehiscence of bilioenteric anastomosis by MCA and consulted with Professor Yamanouchi about MCA in order to improve the quality of life (QOL) and control her cholangitis. One year after LDLT, we performed contrast radiography using double-balloon endoscopy and the PTCD tubes to measure the distance between the stumps of the RAD and RPD and bowel (Fig. ). The magnet was introduced into the bowel and placed near the RAD by double-balloon endoscopy. We replaced the 16 Fr silicon PTCD tube with a 14-Fr introducer sheath. The other magnet was inserted through the introducer sheath (Fig. ). At the end of this procedure, we replaced the introducer sheath with a 14-Fr silicon tube. The magnets that were used for MCA are not yet commercially available in Japan. The bilioenteric fistula was completed 21 days after MCA (Fig. ), and we removed the magnets by double-balloon endoscopy. The PTCD tube of the RAD was inserted into the bowel and left to maintain the fistula. Two months later, MCA for the RPD was also performed by the same procedure. Before the procedure, we confirmed the RPD’s structure by 3D reconstruction of CT image (Fig. ) to check that there were no obstacles, such as bilioenteric anastomosis of the RAD between the stump of the RPD and bowel. It took longer to establish the RPD’s bilioenteric fistula than that of the RAD because the angle of the RPD’s structure was sharp and the force between the magnets was weak (Fig. ). Therefore, we adjusted the position of magnet in the bile duct and its wire several times.
Forty-seven days after performing MCA of the RPD, we performed double-balloon endoscopy and pulled down the magnets. We confirmed that the fistula of the RPD had been established and retrieved the magnets. The PTCD tube of the RPD was also introduced into the bowel to maintain the fistula (Fig. ). One year after MCA of the RAD, we confirmed the complete establishment of bilioenteric anastomosis for the RAD and removed the PTCD tube in the RAD.
With the confirmation of the complete establishment of anastomosis without stricture, we removed the PTCD tube in the RPD 19 months after MCA of the RPD. The patient is still alive without any tubes, and no complications, such as stricture, have occurred. |
pmc-6093826-1 | A 67-year-old woman visited our hospital. She complained of severe pain in the maxillary left anterior buccal vestibule. She also reported that her upper lip has tightened after multiple dental implants were placed in her maxilla. Clinically and radiologically, painful traumatic trigeminal neuropathy was diagnosed. Two hundred milligrams of Tegretol® (Novartis, Basel, Switzerland) was administered twice a day for 2 weeks, and the symptoms were alleviated, but the tightened pain on the bilateral sides of the nose persisted. The dose was therefore increased for another 2 weeks. Most of the pain was alleviated, but the pain that occurred when she moved her mouth was still present. She therefore received the medication for two additional weeks. The frequency and severity of the pain was reduced, but side effects such as headache and dizziness occurred; therefore, 10 mg of amitriptyline (Myung-In, Seoul, Korea) was administered once a day before bedtime and capsaicin ointment (Dipental cream, Dalim BioTech, Seoul, Korea) was applied locally at the site of the pain. A stent was made in the maxilla and capsaicin ointment was applied to the stent for 20 min. This stent was to be worn three times a day. However, no improvement was observed and the pain worsened. Thus, 100 mg of Neurontin (Pfizer Ltd., Seoul, Korea) was administered three times daily. Electric acupuncture stimulation therapy (EAST, Pulse Generator (PG)-8® (ITO Co., Tokyo, Japan)) was performed four times at 2-week intervals, but the burning and throbbing pain on the upper lip and tenderness of the palatal area remained. The medication of the patient was changed to 300 mg of Trileptal (Novartis, Basel, Switzerland) which was administered twice daily. Although there was a slight improvement, she still complained of persistent pain. In the upper part of the mucosa, 250 U of Dysport (Ipsen Biopharm Ltd., Slough, UK) was injected. As a transient side effect, food was spilled due to the unnatural movement of the lips at meal time, but the pain was significantly reduced. Three months later, the second injection of Dysport 250 U was performed. Thereafter, the pain was alleviated and the treatment was terminated. |
pmc-6093826-2 | A 52-year-old woman was referred to an oral and maxillofacial surgeon because of intermittent severe pain in the left facial area after facial nerve reconstruction during plastic surgery. During examination, the patient complained of general stiff pain in the facial region including the left zygoma, masseter, and temporomandibular joint area. There were also symptoms of excessive salivation in the left cheek. The patient was diagnosed with painful traumatic trigeminal neuropathy. Taking Trileptal did not improve the pain; therefore, it was replaced with Neurontin. At the same time, 25 U of Innotox (Medytox Inc., Seoul, Korea) was injected into the left masseter and physical therapy was performed. Physical therapy was performed five times with Sellalux (Medical United, Seoul, Korea), a low-level laser treatment unit, every 1 to 2 months. Two weeks after the first injection, the pain was significantly reduced. However, it persisted in the lower left eye and around the zygoma. Six months later, the second injection was performed with the same dose. Even though almost all the pain was alleviated, she still complained of pain in the stylomastoid foramen area under her left ear. Three months later, a third injection of 25 U of Innotox was performed and the pain was markedly reduced to a tolerable level.
All seven patients involved in this study were women with ages from 52 to 71 years. Five of the seven patients complained of pain in the oral mucosa, vestibule, teeth, and around the lips. Two of the patients complained of facial pain in the zygoma, masseter, and temporal muscle. The primary drugs used were carbamazepine, oxcarbazepine, gabapentin, pregabalin, amitriptyline, and nortriptyline. Physical therapy with either soft laser or EAST was performed additionally in most cases. Two of the patients were treated with Tegretol (carbamazepine), six were treated with Trileptal (oxcarbazepine), six were treated with Neurontin (gabapentin), two were treated with Lyrica (Pregabalin), one was treated with amitriptyline, and three were treated with Sensival (nortriptyline). Laser therapy was performed on all seven patients, while EAST was performed on two patients. Of the seven patients, five patients complained of oral pain. They received injections at the affected site. The remaining two patients received injections outside the oral cavity, specifically in the masseter and temporal muscles. Three types of BTX-A were used: Meditoxin (Medytox Inc., Seoul, Korea), Innotox, and Dysport (Ipsen Biopharm Ltd., Slough, UK), and the number of injections ranged from at least once to a maximum of three times every 3 months. In five of the patients with painful traumatic trigeminal neuropathy, pain was significantly reduced after BTX-A injection. The neuropathic pain in all patients who received implant surgery or facial nerve reconstruction was improved. However, in two patients with atypical orofacial pain who complained of persistent pain without any causative factors, the pain did not disappear after the injection. These patients were referred to the anesthesiology department for stellate ganglion block (SGB), but this treatment was not effective either (Table ). After BTX-A injection, transient facial unbalance, unnatural movements, and facial asymmetry occurred. However, all these symptoms disappeared over time and there were no more complaints.
Traditionally, botulinum toxin has been used to treat strabismus and eyelid seizures. Since then, it has become widely used for the treatment of cervical dystonia and hyperhidrosis and for esthetic purposes []. Botulinum toxin is used to reduce masseter muscle volume for facial cosmetic purposes. Additionally, it is applied for the treatment of persistent myofascial pain and masticatory muscle disorders []. In addition, when unspecified temporomandibular joint pain and headache are reported, symptoms can be improved by injecting botulinum toxin into the masseter or temporal muscle. Botulinum toxins have been applied in many of these areas.
When unspecified facial pain persists, various treatments, ranging from conservative physical therapy and medication to surgical treatment, can be applied. Conservative treatments usually include medication, physical therapy, and splint therapy. Medication is primarily used to treat various facial pain such as unspecified temporomandibular joint disorders, neuropathic pain, atypical facial pain, and facial pain caused by rheumatoid arthritis. The drugs used include non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, antidepressants, sedatives, muscle relaxants, and steroids. It is most important to diagnose the type and cause of facial pain and select the appropriate medication [, ]. Physiotherapy includes thermotherapy, cooling therapy, laser therapy, and electrical stimulation therapy. Of these, low-level laser therapy (LLLT) is the easiest to apply and produces no pain or discomfort. The laser has various effects such as improvement of vasodilation and blood circulation due to increase of temperature, relief of pain, relaxation of muscles, waste removal, and calming of the sensory nerve [–]. If conservative treatment fails, surgical treatment can be used, but the burden associated with invasive surgery and the risk of complications increase. In such cases, botulinum toxin can be a very useful therapy and has already proven its effectiveness in many studies. Freund et al. first reported treating temporomandibular disorder (TMD) with botulinum toxin [, ]. Since it has already been proven that parafunctions such as clenching and bruxism cause TMD, treatment with botulinum toxin was tested, and the effect was positive. Injecting botulinum toxin into the masticatory muscles not only reduces parafunctions but also relieves masticatory pain. The botulinum toxin inhibits the release of acetylcholine from all parasympathetic and cholinergic postganglionic sympathetic neurons. Therefore, it can be applied to smooth muscles and gland tissues. The analgesic effect of botulinum toxin is also caused by the inhibition of acetylcholine release and is directly associated with nociceptors. Botulinum toxin can influence sensitizing mediators, alter afferents derived from muscle spindles, cause physiological changes in reflex and synergistic movements, produce autonomic effects, and cause neuroplastic changes in the processing of afferent somatosensory activity. Therefore, botulinum toxin can be used effectively to treat pain syndrome because it can relax muscles []. Glenn et al. conducted a study among patients treated with botulinum toxin for complaints of orofacial pain of unknown origin. The patients complained of various orofacial pain such as trigeminal neuralgia, temporomandibular joint disorder, chronic tensional headache, and neuropathic pain. Their pain was significantly reduced after injection of botulinum toxin []. Thomas et al. conducted a meta-analysis study of botulinum toxin injections in patients with trigeminal neuralgia and postherpetic neuralgia. They concluded that botulinum toxin injection can be an alternative if there are no definitive medical solutions for pain [].
In this study, the dose of BTX-A used varied from 20 to 200 U. These differences in injection dose are due to differences in the conversion ratio of BTX-A. An onabotulinum toxin-A (ONA) to abobotulinum toxin-A (ABO) conversion ratio is approximately 1:3 to 1:4. And a new botulinum toxin type A (NBoNT) to onabotulinum toxin-A (ONA) conversion ratio is approximately 1:1. Meditoxin and Innotox are included in new botulinum toxin type A (NBoNT). Dysport is included in abobotulinum toxin-A (ABO) [, ]. All patients who received BTX-A injection for non-odontogenic orofacial pain were females. They received various medications and physical therapy, but these did not improve their symptoms. They therefore received BTX-A injections. Among these patients, traumatic neuropathic pains resulting from postoperative complications such as implant surgery or facial nerve reconstruction tended to be reduced after BTX-A injection. However, atypical facial pain with unknown cause was not relieved. Although transient facial asymmetry or unbalance occurred as a complication after BTX-A injection, such complications were not a major problem because the patient was more interested in relieving the pain she was experiencing. |
pmc-6094454-1 | A 64-year-old woman presented to our hospital with the chief complaint of a progressively enlarged mass in the left abdomen accompanied with flank pain, fatigue and weight loss for the last few months. Physical examination revealed a well-defined mass on the left abdomen. Routine blood tests showed that hemoglobin was 111 g/L (normal range was 115 g/L to 150 g/L) and hematocrit was 34% (ranging 35 to 45%), indicating anemia. The remaining blood tests were normal. Abdominal computed tomography (CT) confirmed presence of a tumor measuring 18 cm × 11 cm on the left posterior perinephric capsule (Fig. ), with enhanced density after administration of contrast medium (Fig. ).
The mass was excised and a pathologic consultation was requested. On macroscopic examination, the specimen was composed of a giant nodular mass measuring 18 cm × 11 cm × 9 cm with a little attached portion of normal renal cortex. The outer surface of the mass was smooth and brownish in color. Sectioning revealed patchy areas of hemorrhage and necrosis. Microscopic examination was performed on paraffin-embedded sections stained with hematoxylin and eosin. Histopathological examination revealed that two components interspersed with each other within this tumor and there were transitional zones between the two (Fig. ). One component comprised of atypical cells arranged in multiple architectures. Some well-differentiated fields were composed of irregular interanastomosing vascular spaces or channels lined with discrete and large endothelial cells with variable degrees of cytological pleomorphism, nuclear atypia and multilayering (Fig. ). Many of these structures contained red blood cells, indicating a vascular lesion. Some poorly-differentiated fields were composed predominantly of atypical epithelioid cells arranged in solid areas (Fig. ). The epithelioid cells had irregular round or oval nuclei with prominent nucleoli, abundant cytoplasm and a high degree of nuclear atypia. Tumorous necrosis was obvious (Fig. ), and up to five mitotic figures per high-power field were observed (Fig. ). The other component (including the areas adjacent to the renal cortex) was primarily composed of adipose tissue, smooth muscle cells and abnormal thick-walled blood vessels (Fig. and ), indicating the feature of AML. But in multifocal areas of AML, atypical cells with the morphological and structural characteristics resembling those of the first component were observed (Fig. and ).
An immunohistochemical study was performed on formalin-fixed paraffin-embedded tissue block to define the histogenesis of the lesion. Several pre-diluted antibodies against ERG, CD31, CD34, Ki-67, S-100, HMB45, Melan A, SMA, Actin, Vimentin, CD10, EMA, PAX-8, RCC and pan-cytokeratin were used. The results showed that the atypical cells in the areas of the first component were reactive strongly and diffusely to ERG (Fig. ), CD31 (Fig. ), CD34 (Fig. ), and Vimentin, but negative to HMB45 (Fig. ), Melan-A (Fig. ), SMA, Actin and S-100. In addition, the cells were also negative to pan-cytokeratin, PAX-8, RCC, EMA and CD10. The cell proliferation marker Ki-67 (MIB-1) was positive in about 50% of the atypical cells (Fig. ). To sum up, the immunohistochemical results supported the diagnosis of angiosarcoma. On the contrary, the cells in the areas of AML were reactive strongly and diffusely to Melan-A (Fig. ) and SMA (Fig. ), focally to HMB45 (Fig. ) and Actin, confirming the diagnosis of AML. However, the atypical cells in the AML background were positive to ERG (Fig. ), CD31 (Fig. ), CD34 (Fig. ), but negative to HMB45 (Fig. ), Melan-A (Fig. ) and SMA (Fig. ). On the basis of clinical, histologic and immunohistochemical findings, a final diagnosis of renal angiosarcoma concomitant with an AML was made.
Three months after the surgery, the patient presented again with progressive abdominal distention for about one week. CT examination showed diffuse thickening and nodular deposits of omentum in the left lower abdomen and a lot of abdominal and pelvic effusion. Combined with the history and imaging examinations, extensive abdominal metastasis was highly suspicious. The patient received intraperitoneal cisplatin perfusion and symptomatic treatments such as paracentesis and analgesia. However, one month later, she died. |
pmc-6094884-1 | A 55-year-old Caucasian woman with a 5-month history of abdominal pain and vomiting was diagnosed as having a probable high-grade ovarian malignancy with a large volume of peritoneal disease. She had a prior ultrasound of her pelvis which demonstrated a 17 cm large irregular solid vascularized mass in her right ovary. Her comorbidities included obesity (body mass index of 33), asthma, and she had previously undergone a laparoscopic cholecystectomy. There was no significant family history. She did not smoke tobacco and she drank alcohol occasionally. She was scheduled for debulking surgery; however, she presented to our emergency department with worsening abdominal pain, vomiting, and diarrhea. A physical examination showed dry mucous membranes, capillary refill < 3 seconds, and jugular venous pressure of 4 cm. Her chest was clear on auscultation with dual heart sounds. Her abdomen was distended with generalized tenderness but no guarding or signs of peritonism. Bowel sounds were present. A computed tomography (CT) scan of her abdomen and pelvis was performed which demonstrated the large right ovarian tumor, peritoneal tumor deposits, and ascites. There was extrinsic compression of her sigmoid colon due to the tumor without radiological signs of large bowel obstruction. There were no other abnormalities of her bowel. She received intravenously administered fluids for rehydration, anti-emetics for nausea, and intravenously administered morphine for abdominal pain. She remained overnight in our emergency department for treatment. She was reassessed the following morning after resolution of her symptoms and was found to be hemodynamically stable and subsequently discharged home.
She re-presented 1 week later with similar symptoms and was admitted to hospital for further management. Following multidisciplinary discussion, she was recommended for neoadjuvant chemotherapy prior to surgical debulking. An urgent core biopsy of the mass confirmed the likely diagnosis of ovarian malignancy. This biopsy indicated a high-grade serous adenocarcinoma. The histology and CT findings were consistent with an International Federation of Gynaecology and Obstetrics (FIGO) stage III ovarian cancer. She was appropriately counselled as to the benefits and risks of chemotherapy prior to commencing treatment.
She was commenced on a first cycle of the commonly used platinum-based two-drug chemotherapy regime of paclitaxel and carboplatin []. The dose prescribed was a three weekly cycle of paclitaxel 100 mg/m2 and carboplatin 385 mg/body to achieve area under the curve (AUC) of 5 using the Calvert formula. The results of her pre-chemotherapy blood tests were within acceptable ranges. Specifically, her white cell count (WCC) was 10.1 × 109/L (normal 4–11 × 109/L) and neutrophils were 8.5 × 109/L (normal 1.5–8 × 109/L). She reported feeling better 1 day after chemotherapy. However, 3 days following the commencement of chemotherapy, persistent diarrhea developed. Stool cultures were negative for stool pathogens including Clostridium difficile. On the sixth day post-chemotherapy, she became febrile and acutely unwell with severe abdominal pain. Blood tests at the time revealed a WCC of 0.6 × 109/L and neutropenia of 0.1 × 109/L. A repeat CT of her abdomen and pelvis showed a thickened descending colon and rectal pneumatosis with perforation into the mesorectum (Figs. and ). Blood cultures were positive for Escherichia coli and meropenem was commenced. She was transferred to our intensive care unit for hemodynamic support due to septic shock. A surgical assessment was conducted but immediate surgical intervention was deemed inappropriate due to high predicted mortality. She was administered granulocyte colony-stimulating factor but her white blood cell counts did not improve and her respiratory function deteriorated. She died 9 days after the administration of the first dose of chemotherapy. An autopsy was not performed due to the wishes of our patient’s family. |
pmc-6094901-1 | A previously healthy 5-year-old boy had been receiving intravenous vancomycin (40 mg/kg/day four times per day) for 26 days due to right wrist and left elbow osteomyelitis. The patient had exhibited clinical and laboratory improvement. He then suddenly developed a generalized erythaematous maculopapular and pruritic rash involving the face, trunk, back and limbs followed by the appearance of a high-grade fever (up to 40 °C) and weakness. Bilateral cervical and inguinal enlarged lymph nodes were detected. Cardio-respiratory and abdominal examinations were normal. The child also developed facial, neck and scrotal oedema (Fig. ).
Laboratory investigations revealed progressive leukocytosis (26,280/μL, normal value: 4800 − 12,100/ μL) and eosinophilia (5010/ μL; normal value: 100–500/ μL) on day 30. Liver function tests showed minimal alterations. In addition, lactate dehydrogenase (LDH) levels increased to 805 U/L (normal value: 120–300 U/lL. C-reactive protein (CRP) levels were slightly increased (6.10 mg/dL, normal value: < 0.5 mg/dL). Coagulation tests also showed alterations and a prolonged international normalized ratio (INR: 1.28, normal value: 0.94–1.22) and an increased d-dimer (1815 ng/mL, normal value: < 230 ng/ml). Renal function and electrolytes were normal. Virological examinations (including polymerase chain reaction for Epstein-Barr virus, cytomegalovirus, herpes-simplex virus, hepatitis and parvovirus) and autoimmune screening (anti-nuclear, anti-DNA, anti-neutrophil cytoplasmic, anti-smooth muscle, extractable nuclear antigen and anti-mitochondrial antibodies) were all negative.
A bone marrow aspirate did not show abnormalities, while a skin biopsy confirmed the presence of eosinophilic infiltration. Based on the patient’s clinical history and laboratory findings, the RegiSCAR scoring system was applied, and the boy was diagnosed with DRESS syndrome (total score = 7) on day 30. Vancomycin administration was discontinued and switched to oral linezolid (10 mg/kg/dose three times per day), which was interrupted 3 days later as a result of a worsening of the skin rash and the patient’s general condition. Thus, pulse methylprednisolone (20 mg/kg/day for 3 days) was started, resulting in rapid defervescence and prompt remission of the rash and facial-neck and scrotal edema within a few days. Oral prednisone (1.5 mg/kg/day) was continued, and the patient achieved a complete resolution of all symptoms and normal laboratory tests within 10 days. Prednisone was gradually reduced and finally discontinued after 1 month. |
pmc-6094901-2 | A 4-year-old girl with cystic fibrosis, pancreatic insufficiency and chronic pulmonary colonization by Gram-positive bacteria was admitted to our hospital for pulmonary exacerbation. Based on the last available sputum culture, intravenous piperacillin-tazobactam (150 mg/kg/day in three doses) and tobramycin (10 mg/kg in one dose) were started and resulted in progressive clinical improvement. Daily treatment with physiotherapy, an inhaled long-acting beta-agonist and oral pancreatic enzymes was continued throughout the patient’s hospitalization. After 14 days of treatment, she presented a high-grade fever (up to 40 °C) and a diffuse maculopapular erythaematous rash involving the trunk and eventually the whole body. She also developed generalized polyadenomegaly as well as hepatomegaly. Laboratory investigations showed a rise in CRP levels (10.31 mg/dL, normal value: < 0.5 mg/dL) and a progressive increase in serum transaminase levels, with aspartate aminotransferase and alanine aminotransferase levels > 40 U/L and > 10 times the upper limit of normal, respectively. Coagulation tests showed very high d-dimer concentrations (68,340 ng/mL, normal value: < 230 ng/mL), a prolonged activated partial thromboplastin time ratio (1.94, normal value: 0.86–1.20) and an INR of 1.23 (normal value: 0.94–1.22). LDH concentrations increased to 10,880 U/L at 4 days after the onset of symptoms. Also in this case, autoimmune, infective and haematologic tests were negative.
A parallel progressive increase in the patient’s eosinophil count reached a maximum absolute value of 2940/mmc on the 18th day. A diagnosis of DRESS syndrome was established based on a RegiSCAR total score of 6. Antibiotic treatment was therefore stopped, and without any further therapy, a progressive resolution of the patient’s clinical features was observed within 7 days, while the normalization of laboratory abnormalities was achieved at 14 days following the onset of DRESS syndrome (the 28th hospitalization day overall). |
pmc-6094910-1 | During a periodic visit to a health surveillance program, a heart murmur was found in a 40-year-old white man. He was employed as metalworker; he did not refer cardiovascular risk factors, had no significant medical history, did not consume drugs, and was totally asymptomatic. A cardiovascular examination did not show signs of congestive heart failure. His blood pressure was 130/55 mmHg. A standard electrocardiogram was normal.
He was referred to our Cardiology Unit for transthoracic echocardiography. The transthoracic echocardiography showed: a left ventricle with normal dimension, wall thickness, and global and regional function; a severe aortic valvular regurgitation (Fig. ); and the suspicion of a dysmorphic valve that could not be better specified due to a poor acoustic window.
A transesophageal echocardiography was performed, which confirmed the presence of a severe aortic valvular regurgitation (Fig. ); the short axis view showed an aortic valve characterized by four cusps of almost equal size, with a regular profile and without degenerative modifications (Fig. ). The examination did not reveal any further anomalies.
He was admitted to hospital. A cardiovascular examination did not show signs of congestive heart failure. His blood pressure was 130/50 mmHg and his temperature was 36.5 °C. Pulsus bisferiens was detected by palpating his carotid pulse (less evident in brachial pulse). No other physical abnormal findings were detected. A neurological examination was reported as normal. Routine blood tests were done, which revealed good blood count and good renal and hepatic functions. A stress test was not done. Before the cardiac valve surgery, our patient underwent coronary angiography that showed normal coronary arteries.
He underwent an aortic valve repair by tricuspidization technique, which was preferred to valve replacement because we did not want to expose our 40-year-old patient to valve-related risks across his lifespan.
He was treated with orally administered anticoagulant for 1 month after surgery. At 6-month follow-up visit he was asymptomatic and echocardiography detected only mild residual aortic regurgitation; he did not receive ongoing therapy. |
pmc-6094996-1 | The proband was a 34 year-old right-handed man. From the age of 26 years, involuntary movements of the bilateral lower limbs, associated with dysarthria, grinding teeth and drooling, appeared and gradually worsened. At 31, he suffered from epileptic seizures, which were considered to be generalized tonic-clonic seizure, but antiepileptic drugs had never been administered. One year later, involuntary movements spread to his upper limbs and orofacial automatisms including abnormal tic-like facial movements, tongue protrusion and biting his lips appeared. Then he was treated with haloperidol (2 mg three times a day) and baclofen (10 mg three times a day) for 2 years for his choreic and dystonic problems, but he responded poorly to drug treatments. At age of 34, his involuntary movements gradually spread to his whole body and epileptic seizures increased in frequency. Since the disease onset, the patient had never suffer from psychiatric problems. Neurological examination revealed poor muscle tone and absent deep tendon reflexes in all limbs. Additionally, right positive babinski sign was elicited. Laboratory data revealed elevated creatine kinase level in the peripheral blood. Acanthocytes were found in 4% of cells on the peripheral blood smear test. Doppler ultrasound examination revealed splenomegaly. Brain magnetic resonance imaging (MRI) showed progressive, symmetrical, mild atrophy of the caudate heads (Figure ). His 24-h continuous electroencephalography (EEG) showed generalized asynchronous theta and epileptiform activity, which mostly originated from the right temporal lobe. A nerve conduction study showed a polyneuropathy, which revealed the right peroneal nerve, right median nerve and bilateral ulnar nerves were partly damaged. His score of Mini Mental Status Examination (MMSE) was 27. The father of the proband did not show any neurological abnormalities and died from pneumonia at 65 years old (Figure ). The mother of the proband (II-3), a 65-year-old woman, showed mild involuntary movements in her limbs since the age of 45 years (Figure ). The proband's uncle (II-5), a 52-year-old man, showed mild cognitive impairment (MMSE 24), characterized by memory impairment and had seizures history of 31 years, which were simple partial seizures and treated with antiepileptic drugs (Figure ). His another uncle (II-1) and two sisters (III-1, III-2) had no neurological clinical symptoms. Brain MRI and peripheral blood smears of the proband's mother, his uncles and two sisters are normal. The clinical picture of the proband was suggestive for ChAc, but the inheritance mode of this family seems to be autosomal dominant.
All patients were of Han nationality from Hunan province, China. Blood specimens and genomic DNA were obtained from family members and 100 control subjects after informed consent. The 73 exons and flanking intronic splice consensus sequences of VPS13A were amplified by polymerase chain reaction (PCR) (, ). By sequencing, we identified a novel homozygous nonsense mutation c.8823C > G (p. Tyr2941*) in exon 65 of VPS13A in the proband (Figure ). Five members of the family including the proband's mother (II-3) and his uncle (II-5) were detected to be heterozygous for mutation c.8823C > G (Figures ). The homozygous nonsense mutation c.8823C > G (p. Tyr2941*) causes the loss of TPR10 domain of the vacuolar protein sorting 13A protein. This homozygous nonsense mutation c.8823C > G was not detected in 100 healthy controls, thus representing a novel etiology in an ChAc Chinese family. Besides, the mutations in genes responsible for Huntington's disease and McLeod disease were screened and the results were negative. |
pmc-6095048-1 | A 64-year-old man consulted the emergency department with intermittent abdominal pain during the past 10 days. Clinical examination demonstrated tenderness in the right iliac fossa towards the inguinal region. Blood testing showed no signs of inflammation.
Ultrasound (US) examination of the abdomen revealed a direct inguinal hernia protruding anteromedially and inferiorly to the inferior epigastric vessels. A small tubular structure compatible with the appendix was present within the hernia sac (Figure , arrow). The appendix diameter was at the upper normal range, and the surrounding fat was hyperechoic (asterisk). Consequently, the patient was preliminary diagnosed with Amyand’s hernia with signs of inflammation.
Complementary computed tomography (CT) of the abdomen confirmed Amyand’s hernia (arrows, Figure ). Whether the inflammation was caused by some degree of incarceration or as a result of acute appendicitis remained unclear. There were no signs of complications such as perforation or abscess. |
pmc-6095083-1 | A 41-year-old man was admitted to the emergency department (ED) after a high-velocity car accident. He was ejected out of his vehicle. He had a severe bleeding head wound, symmetric breathing, and normal abdominal findings. Blood pressure and saturation were normal. On arrival to the hospital the patient had worsening bradypnea and bilateral rhonchi. A chest X-ray (Figure ) shows multiple left sided rib fractures without pneumothorax and blurry consolidations in both lungs, probably lung contusions.
After stabilization of the patient, he immediately underwent a computed tomography (CT) of the head, followed by a total body CT from the circle of Willis up to the pelvis with a split bolus intravenous contrast injection. This study shows multiple intracranial subdural and subarachnoid bleedings with secondary edema of the left hemisphere and a skull base fracture.
Multiple rib fractures are seen on the left side, without a notion of a flail chest, with underlying lung laceration on the left side and contusion. There are no signs of a haemothorax or a hemopericardium, nor an intra-abdominal bleeding or a laceration of the visceral organs are observed on CT.
A 12-lead ECG (Figure ) demonstrates an acute myocardial infarction. An urgent angiography was performed (Figure ). The angiography shows a complete occlusion of the right coronary artery (RCA), probably due to a traumatic dissection. Multiple stents were placed to approve reflow of the myocardium. There was no reflow to the myocardial tissue established, and the patient, unfortunately passed away. On review of the trauma CT, the dissection of the RCA was visualized (Figure ). |
pmc-6095188-1 | A 60-year old woman with a right breast neoplasm is presented to the Radiology Department for a thoraco-abdominal CT scan. The only anomaly displayed on the axial images is a well-marginated, 3 cm in diameter, enhancing mass at the level of the left upper abdominal quadrant between the spleen and the diaphragm. Although the lesion resembles an accessory spleen based on similar enhancement characteristics of the main spleen, a metastatic nodule is not entirely excluded (Fig. ).
Since the patient underwent previous thoracic CT scans for recurrent pneumonia, we reviewed those displaying some upper abdominal axial images. The nodule was already visible but its location was different: it was then spotted anterior to the lower pole of the spleen, between the greater curvature of the stomach and the upper left colon (Fig. ).
An examination of the thin slices of the last oncological CT reveals that the small mass is fed by an 18 cm-long thin vascular pedicle that we submit to curved multiplanar and 3D reconstructions. The obvious link between the nodule and the splenic vessels, a complex that we call the “Jokari sign”, enables us to give a correct diagnosis of a WAS (Figs. ). |
pmc-6095652-1 | Case 1. A man aged 34 years with a 17-year history of soft contact lens use was evaluated for left eye redness and blurry vision. He reported sleeping in his contact lenses 3–4 nights per week and swimming with contact lenses. He was treated for bacterial and fungal microbial keratitis for 2 months without improvement. He was evaluated at an academic medical center, where confocal microscopy, a technique that provides serial images of sections through the cornea, revealed findings suggestive of Acanthamoeba keratitis. He was treated with topical polyhexamethylene biguanide and chlorhexidine hourly that was tapered over 6 months. The infection resolved with final spectacle-corrected visual acuity of 20/40, requiring rigid contact lenses for correction to 20/20. |
pmc-6095652-2 | Case 2. A man aged 59 years wore his soft contact lenses overnight during a 2-day hunting trip and developed eye pain on the third day. He used over-the-counter eye drops with minimal response. On initial evaluation, he was diagnosed with a corneal abrasion and treated with a bandage contact lens to promote healing, along with tobramycin/dexamethasone drops prescribed four times daily. With worsening symptoms, his treatment was changed to ofloxacin drops every 2 hours. While in the shower, he wiped his eyes with a towel, then heard a popping sound and felt a painful sensation in his left eye. He was referred to ophthalmology where a large perforated corneal ulcer was diagnosed. An urgent corneal transplant was performed to reestablish the integrity of the eye, and he was treated with broad-spectrum topical antibiotics postoperatively. He recovered useful vision, which improved to 20/25 after cataract surgery 1 year later. |
pmc-6095652-3 | Case 3. A woman aged 34 years was evaluated for 3 days of sharp right eye pain. She routinely slept in her soft contact lenses and used lenses for longer than the recommended monthly replacement schedule. She reported not seeing an eye care professional in years and refilling her contact lens prescription through an online contact lens retailer for at least 5 years. Examination of the right eye revealed a paracentral 1.5 mm infiltrate with surrounding edema and trace anterior chamber cells. Symptoms and signs were improved the day after treatment with topical moxifloxacin. She was instructed to continue moxifloxacin but failed to return for a 1-week follow-up appointment as instructed. |
pmc-6095652-4 | Case 4. A man aged 57 years was evaluated in the emergency department with bilateral reduced vision and eye pain. He reported wearing the same soft contact lenses continuously for approximately 2 weeks. He did not disinfect his lenses daily, slept in them on a regular basis, and did not replace them regularly. On examination, uncorrected visual acuity was light perception in the right eye and hand motion in the left eye. The right eye revealed a central corneal infiltrate and perforation of the cornea. The left eye revealed a central infiltrate with two infiltrates paracentrally and a hypopyon (leukocytes in the anterior chamber of the eye). He received a diagnosis of bilateral bacterial keratitis. Hourly fortified tobramycin and vancomycin drops were required for treatment. A corneal transplant was required to save the right eye. The left eye responded to topical therapy with visual acuity of 20/40 and a central stromal scar. |
pmc-6095652-5 | Case 5. An adolescent female aged 17 years who slept in a soft contact lens purchased without a prescription at a chain store developed a right corneal ulcer; a culture grew Pseudomonas aeruginosa. She was started on fortified tobramycin and vancomycin eye drops. Her vision was light perception in the right eye, and the cornea showed a central white dense ulcer, stromal infiltrates, and 0.5 mm hypopyon. On follow-up, her vision had improved to 20/100, pinhole to 20/60. She had a stromal scar with thinning. |
pmc-6095652-6 | Case 6. A man aged 18 years went to the emergency department with a 3-day history of pain, redness, light sensitivity, and tearing in his left eye. He had a 1-year history of wearing decorative soft contact lenses obtained at a local store without a prescription. He also reported sleeping in his lenses. He was given fluoroquinolone eye drops in the emergency department and subsequently was seen at a local eye clinic, at which time bacterial keratitis was suspected. His vision was 20/25 in the right eye and 20/50 in the left. His left eye showed moderate injection with a central ulcer, edema, and moderate inflammatory reaction. Cultures were obtained, and hourly fortified cephalosporin and aminoglycoside drops were prescribed. Follow-up cultures of the patient’s eye, his lenses, and lens case each yielded heavy growth of Klebsiella pneumoniae and Pseudomonas aeruginosa. Ten days later his symptoms were better; vision in the left eye had improved to 20/25, but a stromal scar remained. |
pmc-6095932-1 | A 54-year-old man was referred to our institution because of ultrasonography findings of a hypoechoic pancreatic head mass with a dilated main pancreatic duct (MPD). Blood tests showed elevated liver enzymes and normal tumor marker levels: glutamic oxaloacetic transaminase, 47 U/L (reference range at our institution, 13–33 U/L); glutamic pyruvate transaminase, 81 U/L (6–30 U/L); γ-glutamyl transpeptidase, 135 U/L (10–47 U/L); carcinoembryonic antigen, 1.0 ng/ml (0–3.2 ng/ml); and carbohydrate antigen 19–9, 10.1 U/ml (0–37.0 U/ml). Enhanced computed tomography (CT) revealed a dilated MPD with a 20-mm-diameter enhancing mass at the head of the pancreas (Fig. ). Magnetic resonance cholangiopancreatography showed a low-intensity area in the pancreatic head and dilation of the distal side of the MPD (5 mm in diameter) (Fig. , ). Duodenoscopy showed a normal appearance of the orifice of the major papilla, while endoscopic retrograde pancreatography revealed a complete obstruction of the MPD at the area of the pancreatic head. Although pancreatic juice cytology was negative for malignancy, the pancreatic head mass was still highly suspicious of cancer based on the imaging findings. The patient subsequently underwent pancreatoduodenectomy. On gross examination of the resected specimen, the tumor appeared as a solid nodule with a dilated MPD and no visible mucin (Fig. ). On microscopic examination, the tumor showed a tubulopapillary growth pattern with scanty cytoplasmic mucin (Fig. , ). The tumor was confined to the pancreatic duct; we observed no apparent invasive carcinoma component consisting of individual cells or small, angulated nonmucinous glands extending away from the periphery of the involved ducts into the surrounding desmoplastic stroma. The neoplastic cells showed a uniform high-grade atypia (Fig. ). Necrotic tissue was also seen (Fig. ). All surgical margins were negative. Immunohistochemical assessment of mucin core protein expression in the neoplastic cells showed focal staining of MUC1, positivity for MUC6, and negativity for MUC2 and MUC5AC. The neoplastic cells were immunohistochemically positive for cytokeratin 7 (CK7) and CK19 but negative for CDX2 and trypsin. The Ki-67 labeling index was 20%. The pathological diagnosis of the resected specimen at that time was an intraductal papillary and tubular tumor with severe atypia of the pancreatic head. Thereafter, clinical surveillance by blood testing was performed every 2 months for 6 years. During the follow-up, the carcinoembryonic antigen level steadily increased up to 7.0 ng/ml (reference range, 0–3.2 ng/ml); thus, additional surveillance was implemented using alternate CT and MRI examinations every 6 months.
Sixteen years after the operation, enhanced CT showed a low-density mass at the remnant pancreatic body (Fig. ). Endoscopic ultrasonography demonstrated a 7-mm-diameter isoechoic and hypovascular mass protruding into the MPD of the pancreatic body with a slight dilation of the MPD of the distal side of the mass. Additionally, the MPD wall adjacent to the mass was ill-defined (Fig. ). Endoscopic retrograde pancreatography exhibited a localized narrow segment with irregular tapering of 4 mm in length in the MPD of the remnant pancreatic body (Fig. ). Pancreatic juice cytology was positive for malignancy. The patient was diagnosed with remnant pancreatic cancer and subsequently underwent completion pancreatectomy. On gross examination of the resected specimen, two tumors were identified at the pancreatic body and tail (Fig. , ). The lesion at the pancreatic body was a 5-mm-diameter white solid mass with well-defined margins adjacent to the MPD (Figs. , , ). The other lesion, which had not been detected preoperatively by the imaging studies, was located at the pancreatic tail and also presented as a 5-mm-diameter white solid mass but had unclear margins and was apart from the MPD (Figs. , , ). Neither of these tumors exhibited luminal mucin secretion. On microscopic examination, the remnant tumors in the body (Fig. ) and tail (Fig. ) were morphologically very similar to the original pancreatic head lesion, while the presence of invasive carcinoma was confirmed in both the remnant tumors. The immunohistochemical results of the remnant tumors were identical to those of the original lesion.
Moreover, we investigated the KRAS/BRAF/GNAS/PIK3CA mutational status (mutational analysis for exon 2 of KRAS, exon 15 of BRAF, exons 9 and 20 of PIK3CA, and exons 8 and 9 of GNAS) of the original tumor (pancreatic head) and the recently resected tumors from the pancreatic body and tail. These analyses revealed no KRAS/BRAF/GNAS/PIK3CA mutations in all tumor samples. We also reexamined the previous pancreatic head tumor, and the findings were compatible with ITPN according to the current 2010 WHO criteria []. Based on the morphological and biological similarities between the original tumor in the head and the recent tumors from the body and tail, we diagnosed the two lesions as intrapancreatic recurrent ITPNs from the original pancreatic head tumor.
The patient underwent postoperative adjuvant chemotherapy using S-1 (tegafur-gimeracil-oteracil potassium). At the time of this writing, he was alive with no evidence of disease during a follow-up period of 9 months after remnant pancreatectomy.
ITPN was first designated by Yamaguchi et al. [] and was categorized as a new entity in the pancreatic intraductal neoplasm family in the 2010 WHO classification of tumors of the digestive system []. Characteristically, these pancreatic intraductal neoplasms show a tubulopapillary growth pattern with entirely high-grade atypical cells and have less cytoplasmic mucin and no obvious luminal mucin secretion. Histologically and biologically, ITPN can be distinguished from other pancreatic intraductal neoplasms such as conventional pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasms (PanIN), IPMN, and intraductal variant of acinar cell carcinoma (ACC).
One of the characteristics of ITPN is the appearance of a solid nodular tumor obstructing the dilated ducts on macroscopic examination []. In both the initial pancreas head lesion and the remnant pancreas body lesion, we observed a solid nodular tumor with a dilated MPD on macroscopic examination. The pancreatic tail lesion was located apart from the MPD, and we did not observe a solid nodular tumor obstructing dilated ducts on macroscopic examination. However, microscopic examination showed a tubulopapillary growth with entirely high-grade atypical cells, minimal cytoplasmic mucin, and no visible luminal mucin secretion, which was identical to the histological features of ITPN in both the primary tumor and the pancreatic body tumor. Additionally, all immunohistochemical and molecular results were identical to both the primary tumor and the pancreatic body tumor. Therefore, the pancreatic tail tumor was also thought to be ITPN.
Although the neoplastic cells in IPMN usually express MUC5AC in all its subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) [], MUC5AC expression is negative in ITPN [, –]. The expression of MUC2 and CDX2, which is a characteristic of the intestinal lineage [, ], is also absent in ITPN [, –]. However, MUC1 and MUC6 show positive expression in most cases of ITPN [, –]. CK7 and CK19 expression are measured to assess ductal differentiation, and CK7, CK19, or both are reportedly strongly positive in all patients with ITPN [, ]. Additionally, the finding of intraductal lesions with a tubulopapillary growth pattern and absence of KRAS mutations also suggests the possibility of an intraductal variant of ACC [, ], which would show positive immunohistochemical staining for trypsin.
We analyzed the three tumors using immunohistochemical staining in the present case. All three lesions in this case were negative for MUC2, MUC5AC, and CDX2 expression, and the neoplastic cells of the three lesions showed focal staining for MUC1 and positive staining for MUC6, CK7, and CK19 expression. The possibility of an intraductal variant of ACC was easily ruled out by the negative staining for trypsin, which was also compatible with all three lesions. Thus, the immunohistochemical findings are in accordance with our diagnosis that the original tumor was indeed ITPN and that the remnant pancreatic tumors were recurrences of the initial tumor.
More than 90% of PDACs harbor KRAS mutations, and some proportion of PDACs without KRAS mutations also harbors BRAF mutations [–]. KRAS mutations are also frequently seen in PanIN and IPMN [–]. About 40 to 60% of IPMNs reportedly harbor GNAS mutations alone, and the vast majority of IPMNs harbor KRAS and/or GNAS mutations [–]. Conversely, ITPN lacks KRAS/GNAS/BRAF mutations [, –]. The three lesions in this study were genetically consistent with these characteristics, whereas none of the lesions harbored any KRAS/GNAS/BRAF mutations. Some studies have shown that ITPN can also be linked to PIK3CA mutations [–], but this was not observed in the present case. However, PIK3CA mutations occur in less than 30% of cases; thus, ITPN is still highly probable despite its absence in our samples. These genetic findings also support the probable diagnosis of ITPN rather than IPMN or conventional PDAC.
The remnant pancreatic tumor was identified by enhanced CT 16 years after the initial operation. Enhanced CT 6 months before the confirmed diagnosis of ITPN showed no mass at the remnant pancreas. Considering that the ITPN tumor grew from undetectable to 7 mm within 6 months despite the lack of tumor development for 16 years after the initial surgery, the growth rate of ITPN might be relatively rapid once the tumor has become visible.
ITPN is a rare tumor, and data obtained from clinical surveillance are very limited [, –, ]. Although ITPN with an associated invasive carcinoma has a poorer prognosis than noninvasive ITPN, the clinical course of ITPN is relatively indolent compared with conventional PDAC, even with the presence of invasive carcinoma []. To date, six cases of local recurrence of ITPN have been reported in the English-language literature [, , ]; two recurrences were observed at 12 and 34 months postoperatively, while the other four cases lacked timeline information [, , ]. Additionally, some studies have shown that recurrence of ITPN can occur even if no identifiable invasive carcinoma was present in the initial lesion [, ]. Yamaguchi et al. reported a case of intrapancreatic recurrence 12 months after the initial operation. In their case, the original lesion was noninvasive ITPN, and the morphological and molecular features of the recurring neoplasm were identical to those of the original lesion []. In the present case, invasive carcinoma was not identified in the original ITPN of the pancreatic head. However, intrapancreatic recurrence as invasive carcinoma occurred on the remnant pancreas 16 years after the initial surgery. Due to the limited numbers of long-term studies on ITPN and its recurrence rates, further investigation is needed.
Studies of remnant pancreatic lesions after resection of IPMN have been reported [–]. Similar to IPMN, three possible mechanisms of development of remnant pancreatic lesions after resection of ITPN can be suggested: (1) the presence of residual microscopic neoplastic cells at the resected margin in the remnant pancreas, (2) intraductal or intrapancreatic lymphovascular spread to the remnant pancreas, and (3) metachronous, multicentric development. In our case, the surgical margin at the time of pancreatoduodenectomy was negative for neoplastic cells, and the remnant pancreatic tumors occurred apart from the surgical margin; thus, the first mechanism is highly unlikely. ITPN is an intraductal tumor, and intraductal proliferation reportedly appears to extend from the MPD into the smaller secondary ducts in many cases of ITPN []. If the remnant pancreatic tumor develops in a metachronous, multicentric fashion, the tumor is likely to be located mainly in the MPD; in the present case, however, the pancreatic tail lesion was located far from the MPD. In addition, the molecular alterations between the original and recurrent lesion are likely to differ from each other in a metachronous, multicentric manner; in the present case, however, all molecular features were identical. Therefore, it is reasonable to think that remnant pancreatic tumors originate from intraductal or intrapancreatic lymphovascular spread of the initial tumor rather than by metachronous, multicentric development. Although it is difficult to determine the true mechanism, we speculate that the remnant pancreatic tumors in the present case were most likely recurrences of the original lesion. |
pmc-6095933-1 | A 55-year-old woman regularly visited our hospital as an outpatient because of hepatitis B occult infection. A liver tumor was point out by CT. CT revealed a protruding liver tumor located at segment 8 3 cm in size, which include cystic lesion (Fig. ). US and MRI reveal the same feature (Fig. ). There was no distant metastasis. The patient had no past or family history including gynecological illness. 18F-FDG PET revealed the accumulation of 18F-FDG, and maximum standard uptake value was 2.3. Laboratory results included a white blood cell count of 3200/μL and platelet count of 189,000/μL. Prothrombin time international normalized ratio was 1.02. Total serum bilirubin was 0.9 mg/dL, direct bilirubin 0.03 mg/dL, albumin 4.5 g/dL, aspartate aminotransferase 22 U/L, alanine aminotransferase 17 U/L, alkaline phosphatase 187 U/L, and gamma-glutamyltranspeptidase 49 U/L. Tumor markers such as CEA, CA19-9, AFP, and DCP were normal. HBs-antigen and HBc-antibody were positive, and HBs-antibody and HCV-antibody were negative. The Child–Pugh score was 5, grade A. She was diagnosed as intrahepatic cystadenocarcinoma and received extended posterior segmentectomy including diaphragm. Macroscopic findings revealed the tumor buried to the liver with the intracystic hemorrhage (Fig. ). The protruded comportment was closely touched to the diaphragm. Microscopic findings revealed the tumor and hemorrhage within the cyst (Fig. ). Tumor was located between the liver and diaphragm.
Histopathological evaluation revealed intracystic clear cell adenocarcinoma. The tumor has ductal structure including mucin and atypical nuclear with clear cytoplasm (Fig. ). The tumor was separated from the liver and the diaphragm (Fig. ). There is no traffic with the bile duct and ovarian stroma. PAS staining was positive. There was lack of ovarian clear cell carcinoma’s features such as hobnail appearance. The expression of Pax8 (Fig. ) was positive, but the expression CK7 and HNF1β(Fig. ) was positive and that of CD10 and ER was negative, which indicate that the tumor has the feature of clear cell carcinoma of the ovary, not renal cell carcinoma nor cholangiocarcinoma. The patient was discharged 13 days after surgery with no complication. According to the microscopic findings, gynecological interview and examinations after hepatic resection were performed, but there were no sign of menstrual irregularity and genital bleeding, and no endometriosis. |
pmc-6095960-1 | The patient, a 46-year old woman, was found unconsciously in her home. Upon arrival of the emergency medical service personnel, a Glasgow Coma Scale of 5 was present, the patient was intubated immediately and transferred to our intensive care unit. We assumed ingestion of 56 g of valproate based on the emptied medication boxes found by emergency medical services. Laboratory testing confirmed very high levels of valproate acid at >10389.5 μmol/l (normal range (NR) of therapeutic levels: 346.5–693.0 μmol/l). Additionally, a blood alcohol concentration of 1.18%0 was detected. The concentration of ammonia was slightly elevated (197 μg/ml, NR: 31–123 g/dl). Apart from slightly elevated uric acid (7.8 mg/dl, NR: 2.6–6.0 mg/dl), which was deemed to be clinically insignificant, all other laboratory values were within the normal range.
We initiated intravenous therapy with L-Carnitine (L-Car) with a loading dose of 100 mg/kg, followed by 50 mg/kg eight and 16 h later. Simultaneously, we performed extracorporeal removal with HDF. Elimination was performed using a high-flux dialyzer (FX60 CorDiax, Fresenius Medical Care) with two HDF sessions of 12 h duration per treatment, interrupted by a 10-h break. Valproate elimination was monitored by measurements of drug concentrations every 6 h. After two treatments, a serum concentration of 255.4 μmol/l was obtained and serum ammonia levels normalized.
Therefore, we stopped HDF treatment and further measurements 12 and 24 h later confirmed decreasing drug concentrations (Figure ). The patient's mental status improved and she was extubated 12 h after admission to the ICU. She finally was transferred to a psychiatric facility due to continued suicidal ideation but without neurological sequelae. |
pmc-6095973-1 | Case 1: A Caucasian 9.4-years-old boy followed because of a severe neurodevelopmental delay and epilepsy. Pre- and perinatal history was normal. At the age of three months old he showed irritability and gastroesophageal reflux. A severe neurodevelopmental delay rose at the age of four months. The patient showed a severe partial refractory epilepsy and severe tetraplegic cerebral palsy. He did not develop any form of language, eye-to-eye contact, neither basic motor nor social milestones. Cytogenetic, metabolic panels, including studies for mucopolysaccharidosis, organic acids, amino acids, long chain polyunsaturated fatty acids, and muscle biopsy were normal. The EEG records showed immature rhythms for the age of the patient. No paroxysmal events were recorded in the last two years before enrolling follow-up. The serial MRI studies showed a static cortico-subcortical atrophic pattern with marked asymmetry.
The genetic study showed 909 bases deletion in EN2 genomic sequence, G3 marker (155464018–155464926 bases).
Genetic analysis of LIS, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes did not reveal alterations. |
pmc-6095973-2 | Case 2: A Maghrabian14-month-old girl, followed because of neurodevelopmental delay and epilepsy. The patient has antecedents of gestational diabetes and delivery by cesarean section at the gestational age of 40 weeks. She also showed developmental delay and infantile spasms. The high definition karyotype and the basic metabolic panel were normal. The EEG record showed slow waves, sharp waves, and spikes and waves discharges. The MRI showed a Blake cyst in posterior fossa, corpus callosum atrophy and hyperintense signal in the white matter of the semiovale centrum, which was related to the normal myelinisation process. The combination of valproic acid and vigabatrin induced the remission of the seizures and a mild neurodevelopmental delay was persistent.
The genetic study showed 207 bases deletion, due to transcription problems in the EN2 exon 2 (C9 marker) (bases 2976–3182) (C#9 in Figure ).
The patient also showed 504 bases deletion in LIS1 marker region of PAFAH1B1 (from 729 to 1232 bases) and a 206 bases deletion in HLIS1 marker of LIS1[PAFAH1B1] coding region 4240–4562 (from 4357 to 4562 bases). No alterations were found in genes PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2. |
pmc-6095973-3 | Case 3: A Caucasian 6.5 year-old boy was followed by neonatal hypotonia without pre and perinatal significant antecedents. The patient showed a severe developmental delay, severe mental retardation with choreoathetosis, tetraparesis, cerebral palsy, and reflex generalized epilepsy. The physic exam showed microcephaly, weight, and stature delay. The patient did not develop language, gait, or even steady sitting. He also showed incessant choreoathetosis, which sometimes reminded stereotypies, and eye-to-eye contact making some social liaison with close relatives and immediate people surrounding him. The EEG showed abnormal discharges of slow waves and spikes and waves. The background rhythm was slow and immature for the age. The MRI showed cortico-subcortical generalized atrophy and corpus callosum atrophy. The treatment with valproic acid improved the reflex epilepsy. He also needs intensive treatment with physiotherapy. Head control is the unique milestone acquired at the moment.
The genetic study showed transcription problems, 208 bases deletion in C4 marker (1493–1719 bases) and 182 bases deletion, in C1 marker (bases 253–475) of the EN2 gene (C#4 and C#1 in Figures ). The patient also showed a 746 bases deletion in the HLIS3 marker (codifying sequence: 911–1656, 268–1013) of the LIS1 gene. No alterations were found in genes PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2. |
pmc-6095973-4 | Case 4: A Maghrebian 8.2 year-old boy. Coming from difficult social background, so no perinatal antecedents were available. The patient was referred for evaluation because of mild mental retardation and hyperactive behavior. He also showed history of partial secondary generalized epilepsy with persistent atypical absences and psychogenic episodes. The physic and neurological exam were normal. The patient showed moderate mental retardation with language delay. The EEG showed abnormal discharges of slow waves and spikes and bi-temporally localized waves. The MRI study showed cortico-subcortical atrophy and corpus callosum hypoplasia. A high definition karyotype and metabolic panel were normal. The seizures and the hyperkinetic behavior improved after the administration of valproic acid.
The genetic study showed 116 bases deletion in genomic sequence of EN2 gene: 155462376–155462491 (G1 marker). The patient showed abnormalities in the transcription of the EN2 gene, that implies the deletion of 208 bases (between 1493 and 1719 bases of the complementary sequence, C4 marker). (C#4 in Figure ).
In LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes no alterations were found. |
pmc-6095973-5 | Case 5: A mixed Maghrebian/Caucasian ethnicity 12 years-old girl, without pre and perinatal antecedents, followed in the outpatient’s clinic because of severe mental retardation, nuclear autistic condition, macrocephaly, severe language delay, neurosensorial hypoacusia, and joint malformations with elbows internal rotation, hip dysplasia that conditioned duck gait, and tarsal malformation, which conditioned flat plants. Facial features were peculiar with flat philtrum, wide nasal wings, bilateral epicanthus, prominent forehead, and low implantation ears. The EEG showed a delayed rhythm pattern. High definition karyotype and metabolic panel as well as organic acids, blood and urine amino acids, mucopolysaccharides in urine, medium, and long chain fatty acids, and a TORCH study were normal. MRI showed hyperintense signals in both posterior and anterior semiovale centrum. These leukodystrophy lesions did not changed throughout the seven years MRI follow-up. As the patient breaks into adolescence, the autistic behavior worsened with self-aggressions and stereotypies, which slightly improved with a risperidone and carbamazepine combination.
The genetic study showed 116 bases deletion in genomic sequence of EN2 gene: 155462376–155462491 (G1 marker).
Genetic analysis of LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes no showed alteration. |
pmc-6095973-6 | Case 6: A Caucasian 2.2 year-old boy without pre and perinatal antecedents was admitted to the outpatients’ clinic because a specific learning disorder. Neurological history showed developmental delay and hypotonia, with clearly retarded motor and cognitive milestones. The somatometry values were normal. Maturational EEG was normal. MRI showed left temporal arachnoids’ cyst and cortico-subcortical asymmetric atrophy. General metabolic panel and high definition karyotype were normal. The physic and neurological exam were also normal. With the diagnosis of specific learning disorder the patient was included into a psycho pedagogical teaching program.
The genetic study showed 116 bases deletion in genomic sequence of EN2 gene: 155462376–155462491 (G1 marker).
The patient also showed a transcriptional error in LIS1: a 504 bases deletion in LIS1 marker region (from 729 to 1232 bases; 206 bases deletion in HLIS1 marker LIS1[PAFAH1B1] coding region (4240–4562) (from 4357 to 4562 bases) and a 202 bases deletion in HLIS5 marker of LIS1[PAFAH1B1] coding region (2732–2933). Genetic analysis of PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes no showed alteration. |
pmc-6095973-7 | Case 8: A 12-year-old Caucasian boy referred to us to be evaluated because of moderate mental retardation, microcephalus and gait impairment. Perinatal deleterious events were not mentioned in the patient historic reports. Developmental delay has been a constant feature during his follow-up as well as microcephalus. Over the age of fifteen a complex obsessive-compulsive behavior arose. On the other hand, MRI, apart for microcephaly, as well as metabolic and infectious tests was normal. A slight ataxic gait with little knee flexion has been recorded during the follow-up.
The patient was heterozygous for the EN2 markers showing anomalies in the transcription-codifying region, which cause 182 bases deletion in one of the alleles (between 2475 and 2657 bases of the complementary sequence, C7 marker). (C#7 in Figure ).
On the other hand, analysis of LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes no showed alterations. |
pmc-6095973-8 | Case 9: A 16-year-old Caucasian female in follow-up in the outpatient’s clinic with the diagnosis of cerebral palsy of unknown origin although complete metabolic and genetic workouts have been done. A severe MR and CP with slightly progressive motor dysfunction were registered. The family reported no epileptic episodes. The MRI studies showed a normally structured encephalon but microcephalus.
The patient was heterozygous for the EN2 markers showing anomalies in the transcription-codifying region, which cause deletion of 182 bases in one of the alleles (between 253 and 475 bases of the complementary sequence, C1 marker). (C#1 in Figures ).
She also showed heterozygous abnormalities in the D17S5 marker that is localized in the lissencephaly critical region (17p13.3), causing a four bases deletion (between 2096690 and 2096882 bases).
Genetic analysis of PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2 genes no showed alteration. |
pmc-6095973-9 | Case 10: A 3.5 year-old Caucasian girl was referred to us because of gait impairment and microcephalus. At the age of five, she presented an episode of disconnection of the environment during few seconds. The EEG records were normal at the moment of the episode, although records of isolated febrile convulsions and disruptive sleep disorders have been obtained. She recovered from the gate problems, but during the pre-school year she showed a developmental delay mainly motor. At the beginning of the school time, a notorious behavior problem arose resembling an ADHD that requires psycho-pedagogic intervention and treatment with methylphenidate, obtaining discrete results at school performance but a worsening in the sleeping problems, so a new EEG is pendant. The MRI showed a normally structured encephalon but also with microcephalus.
The genetic study showed 182 bases deletion, due to transcription problems in C7 marker (bases 2475–2657). (C#7 Figure ).
No alterations were found in genes LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2. |
pmc-6095973-10 | Case 11: A 6 year-old girl of Romany ethnical background was followed because developmental delay, poor school performance and gait impairments. The MRI showed a hyperintense signal, especially in the right semi-oval center, which has been steady during successive MRI studies. The gait impairment has solved, but certain degree of motor clumsiness remains. The learning problems worsened and now she needs curricular adaptation. The school reports suggest a borderline intelligence or a mild mental retardation.
The patient showed abnormalities in the transcription of the EN2 gene, that implies the deletion of 182 bases (between 1944 and 2125 of the complementary sequence, C5 marker). (C#5 in Figure ).
No alterations were found in genes LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2. |
pmc-6095973-11 | Case 12: A 2.3 year-old boy of South American ethnical background, under a public social institutions care, was referred to us presenting microcephalus, complex febrile seizures, and moderate developmental delay. There were records of prenatal exposure to ethanol. The MRI study showed hyperintense lesions in both “corona radiata” more evident in the right side. The spectroscopy study suggests lack of maturity of the frontal lobe, parietal areas, and basal nuclei. EEG studies reflect the presence of abnormal activity with generalized slow pattern and theta and delta bursts bilaterally in temporal regions, both in sleep and awake states. He was treated with valproic acid with an adequate response both physiologic and clinic.
This patient shows abnormalities in the transcription of EN2 gene with the deletion of 183 bases (2475–2657 bases, C7 marker). (C#7 in Figure ).
No alterations were found in genes LIS1, PTAFR, PAFAH1B2, PAFAH1B3, FGF8, and PAX2. |
pmc-6095987-1 | A 57-year-old man presented with a complaint of increasing abdominal pain in June of 2014. A colonoscopy performed in July of the same year showed a stenotic and ulcerated lesion with an infiltrative aspect in the sigmoid region; the stenosis prevented advancement of the colonoscopy beyond the lesion. Computed tomography (CT) revealed hepatic nodules with peripheral contrast enhancement in segments II, IV, I, VIII, V, and VI. The largest hepatic nodule measuring 2.5 cm, was found in segment II. Additionally, a hypodense nodular formation, measuring 2.8 cm, was found in the right adrenal gland and a focal wall thickening, with an area of 6.0 × 3.2 cm, was found in the descending colon measuring. A subsequent magnetic resonance imaging (MRI) examination conducted in August of 2014 revealed hepatic nodules larger than 4.4 cm in segment I. A thoracic CT performed on the same date showed pulmonary micronodules suggestive of secondary implants.
Due to the obstructive sigmoid lesion, a laparoscopic sigmoidectomy with primary colorectal anastomosis was considered the first treatment option, followed by palliative chemotherapy. The patient received FOLFOX (10 cycles) as a first-line treatment and FOLFIRI (3 cycles) as second-line regimen. Further evaluations of the hepatic lesions were made every 2–3 months by CT imaging. Carcinoembryonic antigen (CEA), a serum marker used to monitor carcinoma progression, was evaluated at the time of diagnosis (145 mg/dl) and before commencement of the second-line treatment (1,678 mg/dl).
Microscopic evaluation of the surgical specimen revealed a moderately differentiated sigmoid adenocarcinoma (5.6 × 3.4 cm) with mucinous pattern areas and a pathology stage of pT4apN2apM1. The lesion had an invasive front compromising the serous layer. Lymph-node metastases with capsular extravasation were detected in four of fourteen lymph-nodes dissected from adjacent adipose. Surgical margins were tumor-free. Biopsies of hepatic growths at the moment of the primary tumor surgery confirmed a diagnosis of metastatic colorectal adenocarcinoma. Immunohistochemistry showed positive labeling for the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2. An activating KRAS mutation was identified by routine molecular testing for metastatic colorectal cancer at our institution.
Targeted resequencing was performed in the Ion Proton platform with the Ion AmpliSeq™ Cancer Hotspot Panel v2 (Thermo Fisher Scientific, Waltham, MA), which covers approximately 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes. A detailed description of the sequencing methods are provided in a . Tumor-specific genomic DNA mutations were assessed for the primary tumor, and metastasis. cfDNA from six plasma samples (PS1–6) were also assessed: one before treatment and five after surgery and during palliative chemotherapy.
Sequencing analysis of the primary tumor identified five tumor-specific mutations, including an activating KRAS mutation (p.Gly12Val), confirming previous analysis, a loss-of-function mutation in TP53 (p.Arg175His), two somatic mutations of unknown clinical impact in RB1 (p.Ile680Thr) and ALK (p.Gly1184Glu), and a synonymous ERBB2 (p.Lys860Lys) alteration (Table ). Evaluation of hepatic metastatic lesions detected three of these somatic mutations (KRAS, TP53, and RB1) with a 1% threshold criterion. In the plasma sample collected before surgery (PS1), only the two mutations (KRAS and TP53) detected with high allele frequency in both primary and metastatic samples were detected in ctDNA.
The remaining five additional plasma samples, PS2–6, were collected monthly, starting 1 month after the beginning of chemotherapy (Figure ). Interestingly, the allele frequency of the two aforementioned tumor-specific mutations in KRAS and TP53 decreased significantly, dropping below the 1% detection cut-off of by PS2 (Figure ). ctDNA mutations remained undetectable by NGS in PS3. The noticeable decrease in allele frequency mutations after primary tumor resection and during palliative chemotherapy can be related to a response to treatment. By PS4, in February of 2015, 3 months of FOLFOX treatment, the allele frequencies of both mutations started to rise, TP53 6% and KRAS 4%, approaching PS1 frequencies in PS5 and PS6. Although the initial decrease in mutation frequencies was in accord with an initial treatment response; subsequent increases in mutation frequencies anticipated tumor progression, albeit CT imaging showed maintenance of the number and size of the patient's liver lesions throughout palliative chemotherapy treatment. The timeline of the patient's peripheral blood collection, palliative chemotherapy, and follow-up scheme, as well as the ctDNA identification through NGS, along with their frequencies, are shown in Figure . In April of 2015, the patient presented signs of disease progression and FOLFIRI was started. After 3 cycles of FOLFIRI, the patient's clinical condition deteriorated, and he died due to liver failure in May of 2015. It is important to highlight that ctDNA analysis was not performed concurrently with plasma collection, and all ctDNA analysis were performed at a later time, such that ctDNA results did not alter the clinical treatment protocol. |
pmc-6096534-1 | Patient 10 (Tables and ), a 76-year-old female, was referred to the department of neurology in July 2012 because of progressing cognitive decline over the last 12 months, loss of weight, nausea, gait disturbance and tremor. She was seen on May 2011 for the first time by a neurologist with a 3-month history of dull holocephalic headache who ordered a cranial magnetic resonance imaging (MRI) and diagnosed a tension-type headache and a depressive disorder. Treatment with an antidepressant (duloxetine) was started. The patient experienced no improvement and a second examination by another neurologist was undertaken 2 months later. Again no focal neurological signs could be detected. Due to the weight loss, an occult neoplasm was suspected but not detected during an extensive inpatient investigation at a medical department during February 2012; however, the MRI showed bilateral white matter lesions (WML) and an old lacunar lesion located at the left striatum, the latter was not seen in the previous MRI from May 2011. Since the patient also suffered from mild hypertension, vascular encephalopathy was thought to be the cause of the progressive cognitive decline. Extensive neurocognitive testing was carried out in a rehabilitation centre in May 2012 and disclosed a severe decline of attention, memory and executive functions corresponding to subcortical dementia (Fig. ). When the patient was seen for a further diagnostic work-up at the SMZ-Ost-Donauspital in July 2012, the weight was 47 kg and a weight loss of 20 kg was reported over the past year. The gait was insecure with postural instability and with a tendency to fall when turning around. Frontal signs were positive, the voice was quiet, the tonus was mildly elevated and showed a slight hesitancy (“Gegenhalten”), tendon reflexes were brisk, paresis and pyramidal signs missing. There were no signs of ataxia, but a mild bradykinesia. Action tremor was more distinct than a mild resting tremor. Again, neurocognitive testing and gait disturbances were consistent with subcortical dementia (Figs. and ). Regarding the mild signs of parkinsonism, dementia with Lewy bodies (DLB) was also suspected but excluded by a dopamine transporter (DAT) scan. Fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated hypometabolism in the left striatum and in the left frontotemporal cortex (Fig. ). Cerebrospinal fluid (CSF) showed signs of a chronic lymphocytic inflammation. The CSF markers for dementia, total tau protein and phosphor-tau were within the normal range, while beta-amyloid 1-42 and the Innotest-amyloid-tau index (IATI) were found to be below the reference values (beta-amyloid 1-42: 290 pg/ml, reference value > 500 pg/ml; IATI 0.6, reference values > 1). Finally, LNB was diagnosed when further CSF examinations disclosed a highly elevated Bb-specific-AI indicating local intrathecal Bb-specific antibody synthesis (Table ). The patient was treated with 2 g ceftriaxone daily for 3 weeks.
Neurological symptoms and impaired cognitive functions, although persistent for a year, recovered rapidly within a few weeks (Figs. , and ) and so did the pathological CSF findings (Table ). A follow-up FDG-PET examination showed the left frontotemporal hypometabolism in remission, while this was not the case for the cystic lacunar lesion in the left striatum. A new and clinically silent small right thalamic lesion was detected that was not present in the pretreatment MRI (Fig. ). The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery at the last follow-up in April 2014 scored within the age-dependent normal range with the exception of verbal learning and semantic verbal fluency (Fig. ). In a telephone call in February 2018 at the age of 82 years, the patient reported no gait problems or cognitive impairment and had just returned from a trip to Cuba. |
pmc-6096534-2 | Patient 8 (Table and ), an 80-year-old female, was admitted to hospital in Mai 2006 because of gait disturbances, cognitive decline and frequent falls. The cranial computed tomography (cCT) showed enlarged ventricles and NPH was initially suspected. During a spinal tap test (STT) for predicting response to shunting, the CSF unexpectedly showed signs of an aseptic meningitis and LNB was revealed. The symptoms resolved completely after antibiotic treatment with ceftriaxone 2 g daily for 4 weeks (Table ; Fig. b; for more details see reference []).
The patient had a follow-up visit in 2013 when living independently in a retirement home, was fully ambulatory, oriented and showed no signs of cognitive impairment in the Clock-drawing test (CDT) (Fig. a). |
pmc-6096534-3 | Patient 9 (Tables and ), a 71-year-old female, was admitted to the psychiatric department of our hospital in November 2010 with the initial diagnosis of rapidly progressing dementia or delirium. A history of mild forgetfulness which was noticed half a year prior to the beginning of rapid deterioration and a slight mesiotemporal atrophy in the MRI together with a pathological score in the Mini Mental State Examination (MMSE) test and in the Intercategorical Delayed Selective Reminding Test (IDSR) supported the initial diagnosis of primary dementia (Table ; Fig. ). Short periods of altered consciousness on admission were compatible with a delirious state. Later, the patient’s daughter reported a tick bite followed by a widespread rash. Thus, LNB was suspected and confirmed by CSF investigations (Table ). The patient’s cognitive impairment remitted within the 2 weeks of antibiotic treatment with 2 g ceftriaxone/day (Fig. ). When discharged from the hospital the patient was still on galantamine and mirtazapine (for more details see reference []).
At the first follow-up investigation after 1 month the patient scored 29/30 (z −0.375) in the MMSE and treatment with galantamine was stopped. At the second follow-up 1 year after treatment of LNB cognition was normal with MMSE 29/30, and mirtazapine could be stopped. At another follow-up 5 years and 5 months after treatment of LNB, cognition was stable, and testing of episodic memory by the IDSR 7 now showed a z-score of +0.734, i.e. above the mean for females of the same age, which strongly argued against any dementing process (Fig. b). |
pmc-6096768-1 | A 53-year-old Japanese man with a liver tumor was referred to our hospital for further investigation. A hypervascular mass had been detected in the left lobule of the liver by computer tomography (CT) for other disease. He had a history of hypertension, but no history of hereditary disease such as Von Hippel-Lindau disease nor family history of the patients. The results of a physical examination were unremarkable, and no notable symptoms were present. The biochemical tests revealed slightly elevated levels of alanine aminotransferase (49 U/L) and lactate dehydrogenase (250 U/L). The serum gastrin level (312 pg/ml) was increased. An abdominal contrast-enhanced CT examination confirmed a 4-cm vascular and cystic mass in the anterosuperior segment of the right hepatic lobe and a 0.5-cm vascular lesion in antero/posterosuperior segment of the right hepatic lobe (Fig. a). In addition, a 4-cm vascular and cystic mass in the head of the pancreas and a 2-cm vascular and cystic mass in the posterior portion of the body of the pancreas were found (Fig. b, c).
Endoscopic ultrasonography (EUS) showed a 4.1-cm well-demarcated hypoechoic mass in the pancreatic head (Fig. d) and a 1.9-cm well-demarcated hypoechoic mass in the pancreatic body. High blood flow was detected in the mass by color Doppler ultrasonography. At the previous hospital, a needle biopsy for liver tumors was performed, and it showed that atypical cells with hyperchromatic nuclei and eosinophilic cytoplasm were arranged in a nested fashion. Immunohistochemically, atypical cells were positive for CAM5.2, synaptophysin, chromogranin A, and glucagon and negative for CK7, CK20, AFP, vimentin, CD34, desmin, c-kit, insulin, gastrin, and somatostatin. These results were suggestive of a metastatic neuroendocrine tumor. We performed enucleation for the pancreatic tumor together with lymph node dissection and partial hepatectomy. The postoperative course was uneventful, and the patient was discharged 36 days after the operation. The patient is alive 4.5 years after surgery without evidence of recurrence or metastasis. |
pmc-6096881-1 | A 59-year-old male with a known pituitary adenoma for the past 1 year was referred to ophthalmological examination after an endocrinological consultation with diagnosis of a non-secreting pituitary adenoma.
In this case, macroadenoma located mostly on the right side of pituitary gland (size: 18 × 12, 9 × 13 mm) without compression of the optic chiasm or optic nerves was revealed by MRI (Fig. ).
There was no family history of ocular disease and systemic disease with known influence on the visual system. The results of routine ophthalmological examination in both eyes were as follows: the distance best corrected visual acuity (DBCVA 1.0; Snellen chart), normal anterior and posterior segment of the eye (slit lamp, Volk lens) and normal color perception (The Farnsworth-Munsell Dichotomous D-15 Test). Retinal sensitivity measured by standard static perimetry (SITA 24-2 white on white threshold, Humphrey Visual Field Analyzer) (Fig. ), as well as circumpapillary retinal nerve fibers layer (RNFL), and the GCC thickness estimated in optical coherence tomography (Cirrus HD-OCT 5000, Zeiss) (Fig. ) were within the normal range.
Due to the absence of ocular symptoms and without clinical evidence of the visual impairment in routine ophthalmological examination and additional testes (SAP, OCT), it was decided to perform the multi-channel PVEPs and PERG according to ISCEV standards (RetiPort system Roland Consult GmbH, RC, Germany) [, ]. Obtained results were compared to the age-matched normative data of the laboratory, and parameters of the tests were as follows:
The tests were performed in normal illumination conditions of the examination room. Patient’s pupils were not dilated, monocular stimulation was used, refraction correction was applied with respect to the eye–screen distance (1 m) and central fixation was applied; interruptions of the test were introduced when frequent blinking or fixation loss was observed (patient was monitored with a TV camera). Parameters of the pattern stimulation were as follows: 21″ CRT monitor with a frame rate equal to 70 fps (frames per second); aspect ratio between the width and height of the stimulus field (screen proportion H/V) equal to 4:3; black-and-white reversing checkerboard (170 field, center to edge in the vertical axis) presented to the patient, with a check size equal to 0°16′ (64 elements in the vertical axis) and 1°4′ (32 elements in the vertical axis); luminance for white elements equal to 120 cd/m2, mean luminance of the stimulus screen equal to 62 cd/m2, contrast equal to 97%; temporal frequency for the contrast reversals equal to 1875 rps (0.938 Hz); central fixation was used, with persistent monitoring. Unipolar recordings were performed; active gold disk electrodes (Grass, USA) were placed on the skin at locations O1 and O2, reference electrode (gold disk, Grass, USA) was placed at Fz and ground (gold disk) electrode was placed on the forehead (Fpz). After cleaning the patient’s skin at the electrodes location and placing them using electrode gel (Grass, USA), inter-electrode impedance was checked before the recordings were performed; values < 10 kΩ were accepted. Parameters of the recording system were as follows: filters: 1–100 Hz; notch filters: off; artifact reject threshold: 95% of the amplifiers range; sweep time: 300 ms; average 100 sweeps. Two consecutive waveforms were recorded, off-line averaged, and then analyzed. According to the standard, amplitudes of the obtained waveforms were analyzed and especially peak times/amplitude of P100-wave; manual correction was applied to the automatic cursors placement.
Monocular stimulation was used, with appropriate refractive error correction in relation to the eye–screen distance. Examination was interrupted when frequent blinking or fixation losses were observed (patient was monitored with a TV camera). The patient’s pupils were not dilated, and central fixation was used. Parameters of the PERG stimulation were as follows: 21″ CRT monitor with a frame rate equal to 75 fps; black-and-white reversing checkerboard (30° FOV) presented to the patient, with a check size equal to 1°2′; temporal frequency equal to 4.6 rps (2.3 Hz), Michelson contrast equal to 97%, and luminance for white elements equal to 120 cd/m2. Ground (gold disk) electrode was placed on the forehead (Fpz), thread DTL electrode was used as active electrode, gold disk was placed at the outer position, canthus ipsilateral used as reference. Parameters of the recording system were amplifiers sensitivity: 20 µV/div, filters: 1–100 Hz, artifact reject threshold: 95% (for the amplifiers range ± 100 µV). Notch filters were off. Average was 200 sweeps. Sweep time was 250 ms (time base: 25 ms/div). Two consecutive waveforms were recorded and then they were off-line averaged and analyzed.
According to the guidelines in the literature, for all measured parameters in PVEP and PERG, the intersession variability determined by calculating the coefficients of variation (CV) does not exceed 10% []. The CV for different check size and participants were 9–14% for PVEP amplitude, but only 1–2% for P100-wave latency []. The CV for PERG is 9 ± 1% []. The increase or decrease in PERG amplitude have diagnostic significance when they are above 20% [].
At the baseline, the results of both electrophysiological tests revealed no abnormalities in comparison to normal values from our laboratory. (Table ).
Six months after initial evaluation, the same examinations were performed. There were no significant changes in DBCVA, SAP or OCT results. Also, no abnormalities in PERG were observed. However, multi-channel PVEPs (1°4′ check size) revealed an increase in P100-wave peak time of the RE (O1 122.1/O2 122.8 ms) in reference to high limit of normative data of the laboratory (max. 116.6 ms). Additionally, the P100-wave peak time of the RE became delayed relative to initial values (O1 122.1 vs 108.6 ms and O2 122.8 vs 109.8 ms). The values of P100-wave peak time of the LE remain in normal range (O1 110.3–O2 111.5 ms). The multi-channel PVEPs (0°16′ check size) of the RE and LE revealed no changes. The results from the right eye at 6-month visit suggest dysfunction in the right pre-chiasmal optic nerve (delayed VEP from all channels in the VEP and normal PERG).
After 12 months of follow- up, the visual acuity, perimetry, or OCT results were still normal, but progression in the electrophysiological tests were observed. The multi-channel PVEPs revealed characteristic crossed asymmetry. The PVEPs (1°4′ check size) detected continuous increase in P100-wave peak time in RE from crossed and uncrossed fibers (O1 128.6–O2 126.2 ms). Additionally, in the LE, the abnormal P100-wave peak time from crossed fibers (O2 129.3 ms) was detected. However, the LE uncrossed fibers recordings remain within the normal range (O1 110.2 ms) (Fig. ). Furthermore, the similar changes in PVEP (0°16′ check size) were revealed. The P100-wave peak time delay in the RE from crossed and uncrossed fibers was in the range O1 129.3–O2 128.4 ms. Additionally, in the LE, the abnormal P100-wave peak time in crossed fibers (O2 130.1 ms) was presented. The uncrossed fibers from LE recordings fall within the normal range (O1 111.3 ms) (Fig. ). The PERG revealed significant (51.8%) decrease in N95-wave amplitude in RE (4.14 µV) compared to baseline (8.59 µV), as well as in relation to lower limit of normal value (min. 4.8 µV). Additionally, amplitude of P50-wave was also significant (26.6%) and decreased (3.47 vs 4.73 µV), but remained in normal range (min. 3.2 µV). The PERG results of LE were contained in lower limit of normal value (N95-wave amplitude 4.9 µV; P50-wave amplitude 3.3 µV). At 12 months, the results suggest extension of the dysfunction of the optic chiasm, with involvement of the decussating optic nerve fibers from the left eye and involvement of the ganglion cells in the right eye with a reduced PERG N95.
In one-year follow-up, the results of the electrophysiological tests suggested the progressive dysfunction in the bioelectrical function of the RGCs and optic nerve. That is why the patient was referred for endocrine and neurosurgical consultation. The dimension of the tumor as noted on control MRI slightly increased (17 × 18 × 16 mm), with no visible compressive effect in tumor growth in relation to optic chiasm. Based only on the electrophysiological tests results, the current treatment was modified, and surgical tumor removal was performed.
The ophthalmological examination 6 months after neurosurgery revealed no abnormalities in the routine ophthalmological tests (DBCVA, fundus of the both eyes, OCT and SAP). It is worth noting that the results of the PERG and multi-channel PVEP show improvement in the bioelectrical function of the RGCs and optic nerve relative to preoperative value (Figs. , , ). The multi-channel PVEPs detected shortening of the P100-wave peak time with no asymmetry in both eyes (1°4′ check size, RE O1 116.4 vs 128.6 ms–O2 115.9 vs 126.2 ms and LE O1 110.5 vs 110.2 ms–O2 109.3 vs 129.3 ms) (0°16′ check size, RE O1 115.2 vs 129.3 ms–O2 114.7 vs 128.4 ms and LE O1 109.3 vs 111.3 ms–O2 110.4 vs 130.1 ms), and it returned to the normal range in our laboratory (Figs. , ). In the PERG, significant (28.2%) improvement in RGCs function in RE (N95-wave amplitude 5.77 vs 4.14 µV) and in LE (N95-wave amplitude 5.81 vs 4.9 µV) was measured, but not significantly (15.7%). However, P50-wave amplitude after surgery substantially unchanged compared to preoperative value (RE 2.43 vs 3.47 µV and LE 3.07 vs 3.3 µV) (Fig. ). |
pmc-6096900-1 | A 27-year-old man who received second matched unrelated donor HSCT for relapsed acute lymphoblastic leukemia (ALL) (D + 210) was hospitalized for treatment of aggravated grade IV skin graft-versus-host disease (GVHD). The patient started high-dose steroid therapy (> 1 mg/kg per day of prednisolone) for GVHD and continued taking posaconazole (PCZ) tablets (300 mg q12 h for 2 doses and then 300 mg once daily) which had been administered for 77 days from the outpatient clinic for fungal prophylaxis in severe GVHD. During the high-dose steroid treatment, more than 10% of blasts were detected in peripheral blood cell counts, and ALL again relapsed after the second HSCT was confirmed.
On the 7th day of hospitalization (HD 7), the patient suddenly complained of fever (maximum body temperature 38.6 °C) and dyspnea, and then, his blood pressure dropped to 84/43 mmHg. Oxygen demand was gradually increased, and tracheal intubation was performed. At that time, it was the seasonal influenza epidemic, and rapid influenza antigen test resulted in influenza A positive and chest X-ray showed infiltrations in the right lung fields (Fig. ). Therefore, the first impression was influenza A pneumonia with septic shock. Considering the possibility of combined other nosocomial bacterial pneumonia or atypical pneumonia, not only peramivir (600 mg once), but also cefepime (2g q12 h), levofloxacin (750 mg once daily), and teicoplanin (400 mg q12 h for 3 doses and then 400 mg once daily) were administered. On the chest, low-dose computed tomography (LDCT) performed, and multifocal ground-glass opacities (GGOs) accompanied by peribronchial consolidations and ill-defined centrilobular nodules in both lungs were observed (Fig. ). On the 3rd day of fever onset (HD 10), bronchoscopy was performed. His condition recovered rapidly and intubation was removed on the 4th day. Blood and sputum cultures, Streptococcal pneumoniae and Legionella urinary antigen tests, Mycoplasma serum IgM/IgG tests, and serum galactomannan assay were all negative.
On the 4th day after bronchoscopy (HD 11), Aspergillus spp. was cultured from the bronchial washing fluid specimen. It was thought to be a true pathogen because chest LDCT revealed consolidations with surrounding GGO and nodules consistent with fungal pneumonia that developed during the course of long-term maintenance of high-dose steroid treatment. According to revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria [], the patient was diagnosed as a culture-positive invasive pulmonary aspergillosis (IPA) with probable category. At the time of diagnosis of IPA, the patient had been receiving PCZ for 87 days, maintaining a therapeutic range of PCZ serum concentrations (1048–2232 ng/mL). Therefore, this case was considered as PCZ breakthrough IA.
PCZ was changed to intravenous voriconazole (VCZ) (loading dose 6 mg/kg q12 h, then 4 mg/kg q12 h). Other antibiotics were also discontinued because there was no evidence of other bacterial pathogens. Eight days later, Aspergillus spp. was finally confirmed as A. fumigatus by internal transcribed spacer (ITS) sequencing and PCR of the β-tubulin gene as follows. Their entire ITS regions were amplified using the primers of ITS1-F_KYO2 (5′-TAGAGGAAGTAAAAGTCGTAA-3′) and ITS4 (5′-TCCTCCGCTTATTGATATGC-3′), as previously described []. β-tubulin PCR was performed by bt2a (5′-GGTAACCAAATCGGTGCTGCTTTC-3′) and bt2b (5′-ACCCTCAGTGTAGTGACCCTTGGC-3′) []. Amplicons of ITS and β-tubulin were sequenced and then identified using the BLASTN. Antifungal susceptibilities were determined using the broth dilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 (2008) []. Antifungal susceptibility testing of the A. fumigatus revealed high minimal inhibitory concentrations (MICs) to both itraconazole (ITZ) and PCZ (MICs were > 16 and 4 μg/mL), while VCZ MIC revealed a susceptible upper limit (1 μg/mL). Chest X-ray showed steady improvement, and intravenous VCZ was changed to VCZ tablets (200 mg q12 h) and maintained. Therapeutic drug monitoring of VCZ was performed every week, and it was maintained within therapeutic range between 1.2 and 4.2 μg/mL. Thereafter, the patient’s absolute neutrophil counts were declined, and he experienced repeated neutropenic fever. On the 69th day of hospitalization (HD 69), the patient died due to KPC-producing carbapenem-resistant Klebsiella pneumoniae bacteremia which was thought to be associated with concurrent gut GVHD. Previous lesions of IPA were decreased in size (from 5.4 to 1.3 cm) at that time. Subsequently, the A. fumigatus isolate was analyzed for any known azole-resistant mutations in CYP51A gene. The amplification and sequencing of CYP51A promoter were performed using AFTR-F (5′-TAATCGCAGCACCACTTCAG-3′) and AFTR-R (5′-GCCTAGGACAAGGACGAATG-3′) []. Their CYP51A and promoter sequences were compared to that of an azole-susceptible A. fumigatus strain (GenBank accession no. AF338659). Including TR34/L98H, multiple mutations including S297T in the CYP51A gene were identified as shown in Table . |
pmc-6096929-1 | In April 2017, a 72-year-old homeless male patient was admitted to the emergency department at the Ramos Mejia Hospital, Ciudad Autónoma de Buenos Aires, Argentina. The patient was in very poor hygienic condition, malnourished and dehydrated. He presented a deep necrotic ulcer in the anterior aspect of his left tibia of 9-months’ evolution, with exposure of both tibia and fibula, complete loss of muscle mass, severe ischaemia, foul discharge and heavy burden myiasis. Unfortunately, maggots had been rapidly discarded, allowing neither bacterial analysis nor entomological identification.
The patient had a history of alcohol abuse and pulmonar tuberculosis in 1980 which resolved after complete treatment.
On physical examination, his blood pressure was 100/60 mmHg, his heart rate 97 and his respiratory rate 20 breaths min−1. His body temperature was 36 °C. Haematological and biochemical exams on admission showed: leucocytes 24750 K µl−1, with 92.5 % neutrophils; glucose level of 237 mg dl−1, haematocrit 40 %, haemoglobin 13.3 g dl−1, uraemia 126 mg dl−1, creatinine 2017 mg dl−1; sodium 127 mmol l−1; potassium 5.5 mmol l−1; chloride 87 mmol l−1.
Two blood culture sets were taken at the time of admission, at two different times. Gram-negative rods were obtained in pure culture. With this preliminary report, the case was described as sepsis caused by skin and soft tissue infection. Intravenous therapy with ciprofloxacin 400 mg/12 h and clindamicin 600 mg/12 h was initiated.
Conventional phenotypic test and MALDI-TOF-MS (Bruker Daltonics) failed to identify the bacteria isolated.
In order to confirm genus and species identification, PCR amplification of the 16S rRNA was performed. The nearly complete sequence of the 16S rRNA gene was amplified by PCR with the conserved primers 8F (5′-AGAGTTTGATYMTGGCTCAG-3′) and 1942R (5′-ACCTTGTTACGACTT-3′), as described previously []. The sequence obtained showed a 100 % identity with the sequence corresponding to the 16S RNA ribosomal gene of I. indica, type strain FFA1 (GenBank accession number. EU008088.2). The 16S rRNA sequence obtained was deposited in GenBank under number MF062521.
Due to the severity of the lesions, a supracondylar amputation had to be performed in order to allow for adequate and prompt infection source control, and antibiotic treatment for 14 days was completed, which led to resolution of sepsis and normalization of laboratory parameters. The patient had a favourable outcome, with no surgical complications.
Members of the genus Ignatzschineria are difficult to identify using traditional methods, including classical biochemical tests and commercial bacterial identification systems. Even MALDI-TOF MS analysis has been unsuccessful. 16S ARNr gene sequencing has proved to be useful for identification, and is currently the most accurate method for clinical diagnostic laboratories. |
pmc-6096942-1 | A 49-year-old man presented to our hospital with severe, continuous epigastric pain. Initial laboratory tests showed increased amylase (AMY; 823 IU/L) and lipase (465 U/L) levels, as well as an increased white blood cell count (WBC; 11,160/μL) and C-reactive protein levels (CRP; 8.21 mg/dL). He was admitted with the diagnosis of mild pancreatitis based on the laboratory results and computed tomography (CT) findings of pancreatic head swelling and slight peripancreatic fluid effusion (Fig. a). There were no stones observed both in the bile duct or the gallbladder. The bedside index for severity in acute pancreatitis (BISAP) score was calculated to be 0. The patient was treated conservatively with fasting and fluid hydration.
The patient was diagnosed with SLE at 34 years of age and was being treated with an oral immunosuppressant (tacrolimus; 3 mg/day) in addition to a steroid (predonine; 10 mg/day) for the past 15 months. His history also included a laparoscopic ileostomy performed 2 months before admission due to an intractable rectal ulcer.
The enhanced CT scan showed an all-round wall thickening of the descending portion of the duodenum. The ill-defined mass lesion had invaded the pancreatic head (Fig. b). An upper gastrointestinal endoscopy showed the all-round ulcerative lesion over a large region from the superior duodenal angle (SDA) to the descending portion of the duodenum. This well-demarcated lesion consisted of an ulcer with a regular elevated margin that had an auricle-like shape (Fig. ). Histological examination of the biopsy specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL); immunochemical staining was positive for CD20 and CD79a (Fig. a–c). He was negative for Epstein–Barr virus (EBV). His abdominal pain continued to persist on the day 8 after admission, although his inflammatory reaction and pancreatic enzyme levels were improving with fasting and infusion therapy (WBC = 6300/μL, CRP = 4.09 mg/dL, and AMY = 350 IU/L). Tacrolimus therapy was stopped on day 9 in view of the possibility of “immunodeficiency-related lymphoproliferative disease.” In spite of tacrolimus withdrawal, the lesion continued to increase and his abdominal pain remained. Consequently, he started rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy from day 16 after admission. After six courses of R-CHOP therapy, a 95.3% lesion reduction rate was confirmed on CT, which was judged as a partial response (Fig. ). The symptoms had improved and the laboratory data showed a good clinical course (Fig. ).
One month after the completion of chemotherapy, nausea and vomiting after meals appeared. An upper gastrointestinal endoscopy revealed the scarring of the duodenal ulcerative lesion and the high-grade duodenal stenosis (Fig. ); therefore, gastrojejunal anastomosis was performed. He has been well without recurrence for 4 years following the end of chemotherapy. |
pmc-6097216-1 | A 54-year-old male patient presented with post-operative pain for 1 month. He underwent right inguinal hernioplasty 1 month ago at a different hospital. The patient complained about pain, of score 9 (on a scale of 1–10; 1 being normal 10 being most severe), around the right medial thigh and the pain intensified when he stands or walks for a long time and complains about abnormal walking posture. This situation was accompanied by lateral hip joint pain: the hip joint was unable to adduct and sometimes the pain can be felt at the knee joint if severe enough. It was also accompanied by pain during micturition which however, was relieved after rest. The CT scan showed bilateral hip joint degenerative changes, oedema at the region of the right inguinal hernioplasty and encapsulated effusion at the right pelvic cavity (Fig. ). He was diagnosed with neuralgia after right inguinal hernioplasty. When he was admitted to our hospital, local anaesthetics were used at two points: one just above the right pubic tubercle and the other 2 fingers above the right inguinal ligament and medial to the right anterior superior iliac spine. The pain was alleviated temporarily for just 2 hours. Conservative regimen which included pain killer Tramadol failed. He underwent partial neurectomy under general anaesthesia based on his right to autonomy. During the surgery, the spermatic cord was freed, and the mesh was visible. Modified Kugel mesh procedure was carried out in the previous surgery during which 4 sutures over the transversalis fascia were stitched. The mesh had adhesion with the surrounding tissues, with unclear boundaries. The mesh was exposed and right iliohypogastric nerve was observed on the superficial surface of the mesh. The right iliohypogastric injury was due to entrapment from 3 sutures and the ‘Kugel’ mesh (Fig. ). The genitofemoral nerve was explored for any abnormality. The nerves were identified based on their courses. The 4 non-absorbable sutures were all removed since the mesh has been integrated to the surrounding tissues. Tailored neurectomy of the iliohypogastric nerve was carried out whereby 3.5 cm of nerve length was resected. The proximal ends were cauterized. On POD 1 the patient stated that the pain was relieved and restored to ambulation and he had no pain during micturition either. He was discharged on POD 3. There has been no further complaints or abnormalities from this patient during follow-ups. |
pmc-6097227-1 | A 59-year-old Caucasian female presented with the acute, painless constant appearance of 3 spots in her vision. She described the spots as “tadpoles” that were constantly present in her vision. She noted the first spot while driving home immediately following a chiropractor neck adjustment, and became more aware that there were 2 additional spots the following day. She received cervical spinal manipulation using the high-velocity, low-amplitude (HVLA) technique on the posterior neck. She also received twisting of the neck that day where it was twisted both to the left and to the right. She had a history of headaches, psoriasis, and restless leg syndrome for which she takes Topamax (topiramate), Stelara (ustekinumab), and Flexeril (cyclobenzaprine), respectively, but denied any further medical history. She denied recent trauma or surgeries.
Visual acuity was 20/20 OU with minimal refractive error, full extraocular movements, and no ptosis. Neurologic examination was unremarkable. Blood pressure was 123/79, and work-up was negative for diabetes or blood dyscrasia. Slit lamp examination of the right eye demonstrated multiple unilateral preretinal hemorrhages with 3 present inferiorly along with a hemorrhage over the optic nerve (A) and a shallow, incomplete posterior vitreous detachment. Optical Coherence Tomography (OCT) demonstrated the pre-retinal location of the hemorrhage (B). Dilated fundus examination was otherwise unremarkable with normal vasculature including no plaques noted in the vessels, no nonperfusion, and no neovascularization. Scleral depression demonstrated no retinal tears, breaks, or detachments. The left eye was unremarkable (C). The patient's symptoms improved rapidly over 2 weeks. When seen for follow-up 2 months later, the hemorrhages were self-limited and there was resolution of the preretinal hemorrhages with no interval retinal tears (). |
pmc-6097278-1 | A 45-year-old Japanese woman with a swelling and bone exposure of the left buccal region was referred to our hospital. She had previously undergone excisional biopsy two times, which led to the same diagnosis of osteoma. She had no special medical and family history. On clinical examination, maxillary bone exposure without pain was observed around her upper left second molar. Other physical status was normal. Computed tomography (CT) showed a diffuse radiopaque lesion around the alveolar cortical bone surface of her maxilla spanning from the first molar to the second molar (Fig. ). A biopsy demonstrated features of necrotic bone without atypia. The exposed region in her maxilla recovered with healthy oral mucosa naturally after the biopsy without any additional treatment. However, she noticed bone exposure again in the same region after a year and swelling that tended to enlarge over time. As she did not want to undergo radical surgery requiring tooth extraction, we performed debulking surgery including biopsy twice in 2 years. However, these biopsies did not demonstrate features of malignancy. The lesion enlarged gradually during the observation period and CT showed a diffuse bone mass accompanied by radiolucent areas, which arose from the surface of maxillary alveolar bone and invaded into the pterygopalatine fossa (Fig. ). T1-weighted fat-suppressed magnetic resonance imaging (MRI) after injection of intravenously administered contrast medium showed heterogeneous contrast-enhanced masses and hypointense areas corresponding to mineralized areas on CT (Fig. ). Histopathological assessment showed stromal component consisting of dense atypical spindle cell proliferation and focal cartilage formation with mild atypia (Fig. ). Immunohistochemical staining showed diffuse expression of β-catenin and α-smooth muscle actin (α-SMA) in atypical spindle cells. These cells were also stained by runt-related gene 2 (RUNX-2), special AT-rich sequence-binding protein 2 (SATB2), or sex-determining region Y-box 9 (SOX9), indicating that these cells were derived from cells that had the ability to differentiate into osteoblastic cells and cartilage cells (Fig. ). Moreover, co-expression of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) along with a dedifferentiated subtype of high-grade sarcoma was seen []. We excluded a diagnosis of chondrosarcoma and high-grade osteosarcoma because these histopathological features are usually negative in these conditions. Together with these findings, we arrived at a diagnosis of DPOS derived from c-POS. Indication of distant metastasis was not documented. Finally, we diagnosed this patient as stage IIB DPOS based on Enneking staging system [].
The condition was treated by wide resection and chemotherapy. Since evidence-based chemotherapy for DPOS has not yet been established, we performed neoadjuvant chemotherapy (NAC) consisting of pirarubicin (THP-ADM) and ifosfamide (IFO) based on clinical trials carried out by the Japan Clinical Oncology Group (JCOG) 0304 []. THP-ADM (30 mg/m2, days 1 and 2) and IFO (2 g/m2, days 1–5) were administered and mesna (400 mg/m2) was added at 4 and 8 hours after infusion of IFO. This regimen was repeated for three cycles every 3 weeks. The administration dose was decreased by 40% for the second and third cycles, because grade 4 neutropenia and grade 3 febrile neutropenia were observed in the initial cycle. Although slight shrinking of the tumor was observed in radiological examination after three cycles of chemotherapy, the majority of the tumor did not demonstrate any other changes.
Subsequently, we performed subtotal maxillectomy using combined transcranial approach with orbitozygomatic osteotomy and transcervical approach with mandibulectomy. This approach was selected to avoid permanent surgical scar on our patient’s visible mid-face. Subtotal maxillectomy from her oral cavity was followed by a skull base surgery. Following resection of the lateral wall of the orbit, orbitozygomatic osteotomy was performed, which was contiguous to osteotomy from the oral cavity. The tumor invaded toward the foramen ovale and close to her optic nerve. We separated the tumor carefully from these anatomical structures on the upper levels of pterygopalatine fossa. Eventually, radical resection with an adequate margin was achieved followed by reconstruction surgery. After reconstruction of the lateral wall of the orbit with a titanium mesh, raw surface muscular flap reconstruction was also carried out immediately, as described previously []. Since morphological reconstruction mimicking natural morphology of the palate can be achieved by using this method, it was easier to apply the dental prosthesis for our patient. Finally, the temporal bone was restored and removed zygomatic bone was restored using an absorbent plate (Fig. ).
The surgical specimen was examined histopathologically. Although a decrease in cell density and tumor degeneration due to NAC were observed in the high-grade component, the number of tumor cells in the low-grade component remained viable. Therefore, the chemotherapy effect was considered to be grade 1 based on the Huvos grading system (grade 1, 0–49% necrosis) []. Based on the recommendation of adjuvant chemotherapy in DPOS treatment [], we decided to administer additional chemotherapy using cisplatin (CDDP) + THP-ADM. Adjuvant chemotherapy consisted of CDDP (120 mg/m2, day 1) and THP-ADM (30 mg/m2, days 1 and 2), and was repeated for two cycles every 3 weeks. The administration dose was decreased by 40% for all cycles due to experiences of adverse effects of NAC. The post-treatment progress was good, and no severe functional morbidity, such as eating dysfunction or dysphonia, was observed. As for our patient’s quality of life (QOL), her General Oral Health Assessment Indices (GOHAI) [] were 59 and 53 points before operation and a year after surgery, respectively (generalized mean, 53.1; Table ). She has shown no indication of recurrence after 15 months. |
pmc-6097298-1 | A 62-year-old Sri Lankan Sinhalese man from the North Central Province of Sri Lanka presented with generalized malaise and body weakness. He had type 2 diabetes and had been on Mixtard (human insulin) for 10 years. He had been hypertensive for 5 years and was on losartan potassium. His anti-hypertensive drugs were withheld 2 months previously because he had low-normal blood pressure. He described proximal muscle weakness of the body of 1 month’s duration with difficulty in getting up from a squatting position and raising his hands above his head. He noticed polyuria and nocturia with recent worsening of glycemic control. There was no history of fever, vomiting, diarrhea, or any drug abuse prior to the onset of the symptoms. He denied a suggestive family history of diabetes mellitus, hypertension, or renal disease.
On examination, he was conscious and rational. His blood pressure was 110/64 mm Hg and his pulse was 76/minute. The rest of the cardiovascular system and respiratory system examination was normal. His abdomen was soft and non-tender. A neurological examination revealed normal higher functions and cranial nerves. A motor system examination showed hypotonia of all four limbs and a power of 4/5 in both lower limbs and 5/5 in both upper limbs. All reflexes were present, but diminished. His plantar reflex was bilaterally unresponsive. There was no sensory or autonomic involvement.
Initial blood investigations showed sodium ion (Na+) 146 mEq/L, potassium ion (K+) 1.95 mEq/L, urea 4.3 mmol/L, creatinine 0.7 mg/dl, and random blood glucose 300 mg/dl. His hemoglobin was 13.2 g/dL with white count of 5.7 × 106 and platelets 240 × 106. Transaminases were normal. His serum albumin was 34 g/L. Severe hypokalemia was confirmed in the repeat blood sample. Arterial blood gas revealed severe metabolic alkalosis with pH of 7.6, partial pressure of carbon dioxide (CO2) of 41 mmHg, and bicarbonate of 40.3 mmol/L.
Further investigations revealed the following (Table ). The results of an X-ray of his kidney-ureter-bladder and an ultrasound scan of his kidneys were normal with no evidence of nephrocalcinosis.
He was treated aggressively with intravenously administered potassium chloride, and calcium and magnesium supplements. But he was noted to have persistent hypokalemia with pottasium wasting in urine. Spironolactone was added to the treatment regime. On day 4 while receiving potassium chloride and spironolactone, his serum potassium was 2.6 mmol/L. In this clinical context BS was suspected in our patient. Unfortunately, he could not afford plasma rennin and serum aldosterone levels. He was started on indomethacin 50 mg thrice a day. On day 7 he was noted to have a marked improvement in proximal muscle weakness and his serum potassium reached 3 mmol/L; with the correction of potassium, our patient’s glycemic controlled improved. He was discharged with the advice of liberal salt intake, K+ and magnesium cation (Mg2+) supplements, spironolactone, and indomethacin. He is currently doing well with low normal potassium value with the above treatment. |
pmc-6097304-1 | A 74-year old man, hypertensive, diabetic for 30 years, with chronic smoking symptoms, was admitted to the cardiovascular surgery department of the Mohamed Vth military teaching Hospital of Rabat, for single bypass. Ten days after surgery, the patient had febrile peaks at 39 °C and purulent sternum discharge. Aerobic and anaerobic blood cultures were performed. The C-reactive protein was at 327 mg per liter and the leukocyte counts to 24*103 cells per microliter, predominantly neutrophils (92%). In immediate postoperative, the patient developed bronchitis with interstitial pictures on chest radiograph but without purulent secretions.
The scanner has objectified the presence of a hypodense mass in the anterior mediastinum.
Microbiological examination of deep pus drained during a revision surgery of surgical site showed the presence of two bacterial strains (Fig. ). The identification of bacterial colonies obtained on Chocolate-isovitalex agar, was on biochemical basis using NH API* strips and bacterial grow in presence of the X-factor and the V-factor on Muller-Hinton agar which allowed the isolation of Haemophilus influenzae and Aggregatibacter aphrophilus. Susceptibility analysis of the isolated strains was carried out with the disc diffusion methodology according to the CA-SFM*. It showed the same susceptibility profile for the 2 strains with a susceptibility to the aminopenicillins, cephalosporins third generation, tetracyclines, quinolones and fluoroquinolones, rifampicin and erythromycin, chloramphenicol and imipenem.
The minimum inhibitory concentration (MICs) of aminopenicillins obtained by E-test strip was 0.75 μg/ml and imipenem was 2 μg/ml (Fig. ).
Blood culture performed during the same episode objectified the presence of the same bacterial strains with the same susceptibility profile to antibiotics.
The patient was treated by empirical antibiotic therapy: ciprofloxacin (800 mg per day), cephalosporins third generation (2 g per day) and vancomycin (2 g per day). Treatment was adjusted to the result of susceptibility studies (Amoxicillin 2 g per day with fluoroquinolone for 3 weeks) with the installation of an irrigation-suction system using suction drains (VAC® therapy).
The evolution marked by the improvement of the patient on the clinical and biological way after 10 days of curative antibiotic therapy. |
pmc-6097314-1 | A 65 years old male with history of colitis ulcerosa, and advanced sarcoidosis diagnosed 10 years before, on oral steroids was admitted to our department due to exertional dyspnea and right ventricular (RV) heart failure progressing since last 12 months to functional class IV. Two years earlier, he experienced the first severe decompensation of right heart function. At that time PH was diagnosed on echocardiography. RV to left ventricle (LV) ratio exceeded one (RV:LV - 39/32 mm); peak systolic tricuspid regurgitation gradient (TRPG) was 75 mmHg, and decreased tricuspid annular plane systolic excursion (TAPSE) 15 mm indicated significant pressure overload and RV systolic dysfunction. Chest computed tomography (CT) revealed sarcoidosis progression, however no pulmonary thromboemboli were detected. After typical heart failure treatment with diuretics, ACE inhibitors, and steroid dose increase the patient improved and he was discharged home in a good clinical condition in WHO functional class II, with the diagnosis of PH due to sarcoidosis stage IV. One year later, due to acute dyspnea, worsening of RV function and unilateral leg swelling he underwent another chest CT, which this time showed fresh thrombi in the left segmental upper lobe pulmonary artery. Moreover, acute deep vein thrombosis was detected with lower limb compression ultrasound. Long term oral anticoagulation with rivaroxaban was started. Two years later the patient was referred to our center due to progressive functional deterioration. On admission he was in WHO functional class IV, saturation on room air was 85%, blood pressure 120/80 mmHg, heart rate 90 beats per minute. Mild peripheral edema was present. Distance covered in 6 min walk test (6MWT) was 100 m with desaturation to 77%. Plasma natriuretic peptide (NT-pro-BNP) concentration was elevated to 6239 pg/ml (normal range < 125 pg/ml). Echocardiography showed severe RV pressure overload with TRPG 95 mmHg, dilatation of both right atrium and ventricle. Preserved morphology and function of LV was observed. Chest CT scan showed signs of advanced interstitial lung fibrosis (Fig. ) and calcified mediastinal lymph nodes (Fig. ). However, organized thrombi in both pulmonary were also detected (Fig. ). At that time multifactorial etiology of PH was considered: sarcoidosis with secondary PH and local in situ thrombosis, or CTEPH in a patient with stage IV sarcoidosis, and with deep vein thrombosis in the past. Lung perfusion scan with SPECT/CT showed bilateral perfusion defects which strongly suggested thromboembolic component of PH. Right heart catheterization (RHC) followed by selective pulmonary angiography (PAG) showed mean pulmonary artery pressure (mPAP) of 54 mmHg. Pulmonary artery wedge pressure (PAWP) was 6 mmHg and pulmonary vascular resistance (PVR) was 13,5 Wood Units. Selective PAG confirmed chronic thromboembolic lesions suggestive of CTEPH – left upper lobe artery occlusion, intravascular webs in right pulmonary artery (Fig. ). After experienced cardiac surgeon consultation, the patient was deemed inoperable due to advanced, sarcoidosis - related lung changes and propable complications regarding the use of extracorporeal circulation. He was finaly qualified for balloon pulmonary angioplasty (BPA).
BPA procedures were performed according the previously published protocol []. Importantly, in order to confirm intraluminal localization of thromboembolic lesions intravascular imaging with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) were performed. It allowed to definitely confirm organized thrombi (Fig. – white arrow, 2C, 2D). With the use of pressure catheter we assessed hemodynamic significance of intrapulmonary lesions (Fig. ). Pulmonary pressure ratio (PPR, the ratio of the pressure distal to the lesion (Pd) divided by the pressure proximal to the lesion (Pp)) was assessed to optimize the BPA procedure and to minimize potential complications such as reperfusion pulmonary injury (RPI). PPR in arteries A9 and A10 was 0.19 and 0.22 – which suggested functional occlusion of both arteries. After simultaneous inflation of balloon catheters - “kissing balloon” technique (4.0x20mm and 4.0x27mm respectively), followed by proximal optimization with 7.0x30mm balloon catheter resulted in PPR 0.63 in A9 and 0.65 in A10 (Fig. , part A and D – green curve marking distal pressure). There were no periprocedural complications. Mean PAP after the first BPA procedure decreased from 52 mmHG to 40 mmHg. The second BPA session was performed 3 weeks later (left pulmonary artery), also without complications. Both procedures (3 segmental lesions in total) resulted in further hemodynamic and functional improvement, with mPAP drop to 27 mmHg at 12 months follow – up. Patient was still in functional class II WHO, echocardiography and 6MWT showed further improvement in clinical condition and RV function (Table ). |
pmc-6097329-1 | An 11-month-old boy was referred to a tertiary center for failure to thrive, poor muscle tone, short neck, kyphosis, and unusual spacing between teeth. He was diagnosed with infantile HPP after repeated low ALP activity test results and radiographic assessment of severe rickets-like skeletal changes and tongue-like lucencies projecting into the metaphyses. He was hospitalized multiple times for pneumonia likely related to musculoskeletal manifestation of HPP, which required treatment with intravenous antibiotics. At age 9 years, he developed persistent headaches; a magnetic resonance imaging (MRI) cranial scan confirmed craniosynostosis with Chiari malformation and cerebellar tonsillar herniation. He underwent craniovertebral decompression, with removal of the posterior arch of C1; a ventriculoperitoneal shunt was inserted to relieve intracranial pressure. He subsequently underwent 2 shunt revisions.
The patient experienced multiple fractures, starting at age 17 years, when he sustained bilateral femoral fractures when jumping off a wall; this required bilateral intramedullary rod insertion. At age 18 years, he sustained a right tibial fracture while jumping. Bone healing was delayed, but the fracture eventually healed satisfactorily. At age 20 years, he sustained bilateral femoral fractures when he rolled off his bed during a seizure and required rehabilitation for approximately 8 months.
Over the first 18 years of life, the patient was hospitalized 8 times for a total of 43 days (Table ). Of these hospitalizations, 5 separate admissions required a stay of ≥5 days; the stay for insertion of a ventriculoperitoneal shunt was 14 days.
Outpatient specialist visits represented a significant proportion of the healthcare resource utilization by this patient (Fig. ). Most of the outpatient specialist visits required consultation with providers in 12 specialties, including pediatric dentist (38 visits), pediatric endocrinologist (32 visits), neurosurgeon (27 visits), and general pediatrician (19 visits; Table ). Outpatient management consisted of diagnostic imaging procedures (Table ). The most frequent procedures were radiography of the limbs and spine, performed on 18 and 12 occasions, respectively; the patient also underwent 14 MRI cranial scans. Dental surgery and tooth extraction were performed as day case procedures for management of dental carries and malocclusion on 3 occasions. |
pmc-6097329-2 | A 3-year-old girl was referred to a tertiary metabolic bone disease unit for premature loss of primary teeth with roots intact and low serum ALP activity (123 IU/L; reference range: 230–700 IU/L) []. Routine genetic testing revealed compound heterozygosity (c.350A > G, p.Y117C, c.400_401AC > CA, p.T134H) for different TNSALP missense mutations in exon 5 of the ALPL gene, confirming the diagnosis of HPP. On presentation, radiologic assessment of the left hand and arm showed tongue-like lucencies projecting into the metaphyses consistent with childhood HPP. She did not have any clinical features of skeletal involvement of the lower limbs and no motor developmental delay except for a mild waddling gait as a younger child. The patient had a relatively asymptomatic clinical course until she presented at age 11 years with swelling and tenderness of the left ankle that was nonresponsive to paracetamol or ibuprofen. An MRI scan of the ankle suggested a diagnosis of chronic recurrent multifocal osteomyelitis, which was subsequently confirmed by biopsy. The symptoms of pain and swelling of the lower limb joints showed spontaneous transient improvement at age 13 years. Recurring at age 14 years, the symptoms fluctuated and caused significant pain and disability. These symptoms eventually stabilized when the patient was transitioned to adult care at age 17 years. At age 18 years, she successfully underwent radiofrequency ablation for Wolff-Parkinson-White Syndrome, a cardiac disorder unrelated to HPP. The patient is now 27 years of age and has experienced an episode of metatarsal stress fracture; she also suffers from generalized aches and pain.
Over 22 years, this patient was hospitalized 3 times for a total of 19 days (Table ). Only 1 hospitalization exceeded 3 days, when the patient was admitted for 14 days to receive intravenous antibiotics for suspected osteomyelitis (Table ).
Outpatient specialist visits, outpatient procedures, and day case procedures represent the majority of healthcare resources used by this patient (Fig. ). Seven specialists provided care for the patient; a pediatric dentist was seen on 40 occasions. Dental procedures, including restorative dentistry (performed on 3 occasions), were the most common of these. This patient was also seen by a pediatric rheumatologist and psychiatrist (Table ). |
pmc-6097412-1 | A 71-year-old Japanese woman was admitted to Toranomon hospital because of reduced consciousness. She had a history of a mastectomy for right breast cancer. Eight months before admission, she came to our hospital because of partial paralysis of her right hand. A chest computed tomography (CT) scan showed a mass in the left upper lobe, as well as mediastinal and left hilar lymphadenopathy. Brain magnetic resonance imaging (MRI) showed multiple brain metastases. The patient was diagnosed with EGFR mutation-positive adenocarcinoma using transbronchial lung biopsy. She received 4 cycles of carboplatin and paclitaxel chemotherapy, and gamma knife treatment followed by whole brain radiation for brain metastases. Although chemotherapy resulted in a partial response, her state of consciousness rapidly worsened in the 2 weeks before admission. Her level of consciousness on admission was a Glasgow Come Scale (GCS) score of 8. She could not speak or move her extremities. A lumbar puncture was performed and cytological examination of her cerebrospinal fluid revealed adenocarcinoma cells. EGFR mutation analysis of cerebrospinal fluid was positive for L858R, but negative for exon 20 T790 M. Erlotinib at 150 mg/day was dissolved in 15 mL of water, and was administered via a feeding tube because she could not swallow a tablet. At the same time, 8 mg/day dexamethasone and glycerin administration were started via drip infusion. The patient’s state of consciousness gradually improved to a GCS score of 13, and serum levels of CA19–9 decreased from 3031 U/mL to 292 U/mL. As a side effect of erlotinib, diarrhea of the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 2 developed. Three weeks after receiving erlotinib and steroids, the patient started to vomit and suffered from grade 3 diarrhea. At that time, her body temperature, blood pressure, and pulse rate were 36.8 °C, 105/55 mmHg and 92 b.p.m., respectively. There was no abdominal tenderness on her physical examinations. The laboratory test results showed a normal leukocyte count (4700/mL), and a slightly increased C-reactive protein level (2.4 mg/dL). Arterial blood gas analysis showed alkalemia (pH 7.50). An abdominal radiograph showed a dilated colon and the presence of intraluminal air along the wall of the colon (Fig. ). A CT scan of the abdomen demonstrated pneumatosis; there was a thickening of the colon with free air, pneumoretroperitoneum, and pneumomediastinum (Fig. ). There were no signs of bowel ischemia or portal venous air. Erlotinib and steroids were stopped, and the patient was managed conservatively with a combination of antibiotics and inhalation of oxygen. Two weeks later, the CT findings of PI were improved. Erlotinib was re-administered without steroids, and PI relapsed 4 weeks later with diarrhea. After improving PI by discontinuation of erlotinib and conservative therapies, gefitinib was administered safely without PI and diarrhea for 3 month. At that time, the EGFR-TKIs afatinib and osimertinib were available in the Japanese market. The number of cells in the cerebral fluid decreased from 132/μL to 37/μL with erlotinib and gefitinib, although the cytology was still positive for adenocarcinoma. The patient died of worsening brain metastases 8 months after the diagnosis of LM. |
pmc-6097746-1 | An 81-year-old woman diagnosed 20 months earlier with CLL (Rai 0, Binet A), who had been followed by a wait-and-see policy, was referred to our hospital due to progressive diplopia since 2 weeks. Initial evaluation by the ophthalmologist had not clarified the cause of her symptoms. On admission, the patient had a paralysis of the left oculomotor nerve and left hemianopsia, without any other signs or symptoms. The peripheral blood counts showed a haemoglobin of 7.2 mmol/L, with a leukocyte count of 33.4 × 109/L and platelets of 163 × 109/L. A few months earlier, she had had a leukocyte count of 39.9 × 109/L with a lymphocyte count of 35.6 × 109/L. On the cerebral computed tomography (CT) and magnetic resonance imaging (MRI), no relevant abnormalities were observed. Lumbar puncture (LP) results showed an elevated cerebrospinal fluid (CSF) protein (907 mg/L) and elevated leukocytes (67.0 × 106/L). Immunophenotyping showed a monoclonal B cell population in 5% of the leukocytes. As the cerebrospinal fluid sample did not contain any erythrocytes, contamination with peripheral blood was not considered likely. The diagnosis of leptomeningeal CLL was established (Table ).
Intrathecal methotrexate (IT-MTX) was started, and the patient was discharged. However, after three treatment courses, she was readmitted with malaise and pancytopenia, ascribed to CLL progression. Treatment with rituximab and chlorambucil (R-chlorambucil) was commenced. A rapid progression of her prior mild cognitive impairment was objectified. MRI and LP showed no signs of CLL progression or encephalitis. Hence, the decline was accounted to the IT-MTX [], although a causal effect of leptomeningeal CLL cannot be ruled out. Despite of her weak condition, treatment with IT-MTX and R-chlorambucil was completed. Finally, her general condition stabilised and her vision improved considerably. |
pmc-6097746-2 | A 77-year-old man who had been diagnosed 9 years earlier with CLL (Rai 2, Binet B) and was followed by watchful waiting policy after initial treatment with fludarabine and cyclophosphamide, was referred to our emergency department due to apathy. Since months, he had been easily fatigued. A few days before presentation, he had developed urinary incontinence and a non-productive cough. On examination, he was conscious but barely reacted to speech and was tachypneic. Laboratory results showed a haemoglobin of 8.5 mmol/L, a leukocyte count of 48.0 × 109/L, of which 44.5 × 109/L lymphocytes, and 104 × 109/L thrombocytes. C-reactive protein was slightly elevated to 34 mg/L.
For a suspected pneumonia causing a hypo-active delirium, treatment with meropenem was started. The day after admission, the patient was transferred to the intensive care unit due to a declining consciousness and impending respiratory failure. Neuroimaging showed a communicating hydrocephalus without leptomeningeal enhancement, signs of a herpes encephalitis or sinus thrombosis. Initial LP did not show an elevated pressure, and there were no cellular abnormalities by routine analysis, nor bacterial or viral pathogens.
After initial slight improvement, the apathy worsened. A second LP, repeated for immunological evaluation, showed an abnormal B cell population in 2% of the leukocytes confirming leptomeningeal CLL (Table ). No erythrocytes, granulocytes or monocytes were visible in the cerebrospinal fluid, making contamination with peripheral blood very unlikely.
Considering the patient’s poor clinical condition, no viable therapeutic options were available. The patient died 4 days after the diagnosis of leptomeningeal CLL. |
pmc-6097975-1 | A 47-year-old man underwent distal gastrectomy with D2 lymph node resection for gastric cancer. Resected specimen disclosed a circumferential type 3 tumor at the pyloric antrum of the stomach (Fig. ). Pathological diagnosis based on the third English edition of the Japanese classification of gastric carcinoma was poorly differentiated adenocarcinoma, pT2, ly2, v1, pN1, pM0, and pStage IIA. Then, the patient underwent adjuvant chemotherapy of S-1. CT at 11 months after the operation revealed no recurrence. The patient presented with left dorsal tenderness 12 months after the operation, and CT revealed a solid mass, measuring 40 mm × 30 mm, in the left latissimus dorsi muscle (Fig. ). Contrast-enhanced magnetic resonance imaging (MRI) revealed extensive peritumoral enhancement (Fig. ). A positron emission tomography (PET) revealed elevated [18F]-fluorodeoxyglucose uptake in the tumor. CT, MRI, and PET did not reveal any other metastases. We then performed the ultrasound guided needle biopsy of the tumor. Pathological examination of the biopsy specimen revealed poorly differentiated adenocarcinoma similar to the previously resected gastric cancer (Fig. and ), and the tumor was diagnosed as metastasis of gastric cancer. Thereafter, the patient underwent two courses of a combination chemotherapy of S-1 and cisplatin, two courses of S-1 and docetaxel, and one course of S-1 and CPT-11. However, all of chemotherapeutic regimens were not effective, and the metastases were extended to the paraspinal muscle and quadriceps 6 months after the recurrence (Fig. and ). The patient died 7 months after the recurrence. Autopsy was not performed. The pain from muscle metastasis was under control with oral non-steroidal anti-inflammatory drugs, oral oxycodone and/or transdermal fentanyl.
The liver, peritoneum, and lymph nodes are common metastatic sites for gastric cancer. The muscle is well vascularized, and hematogenous metastasis is therefore expected to occur in muscular tissue; however, it has been reported that skeletal muscle metastasis rarely occurs in gastric cancer patients, with the incidence rate of 0.03–0.16% [–]. Although the reason for the rarity of skeletal muscle metastasis is unclear, the following reasons have been suggested: (1) the prevention of settlement of tumor cells by the inconstant blood flow and changing tissue pressure due to muscular contractions, (2) the inhibition of tumor cell proliferation by lactic acid, and (3) lower PH values in the muscle []. Skeletal muscle metastasis is generally associated with widespread metastatic disease, and often accompanied with synchronous metastasis to any other organs []. Skeletal muscle metastasis without any other organ metastases is therefore extremely rare. The present case had normal level of exercise, and the reason why muscle metastasis without any other organ metastases occurred in the present case remains uncertain.
It is sometimes difficult to distinguish muscle metastasis from primary soft tissue sarcoma accurately. Needle or open biopsy is usually performed to confirm a diagnosis. The imaging modalities, such as CT, MRI, ultrasonography, and gallium scintigraphy, have been employed to make a diagnosis. MRI has been reported to be the most useful not only for differential diagnosis but also for delineating the extent of the involved muscle, because of its high contrast to the surrounding muscle and its wider observational capability via multiple sections []. Muscle metastasis typically shows low- to iso-signal intensity on T1 weighted images and high-signal intensity on T2 weighted images compared with surrounding muscle. However, primary soft tissue sarcoma can show the similar findings. Contrast-enhanced MRI reveals extensive peritumoral enhancement and lobulation associated with central necrosis in muscle metastasis. These findings seem to be useful to distinguish between muscle metastasis and primary soft tissue sarcoma []. However, the histological examination should be performed to make the definitive diagnosis of muscle metastasis. In our case, the ring-enhanced peritumoral area on MRI suggested the skeletal muscle metastasis, and the definitive diagnosis was able to be achieved by the needle biopsy. Immunohistochemical examination is useful for the definitive diagnosis, although data on immunohistochemical staining is unavailable in our case. In general, gastric cancer cell shows positive staining for cytokeratin 7 [], and desmin and muscle specific actin are positive in primary soft tissue sarcoma [].
We reviewed the reported cases of skeletal muscle metastasis from gastric cancer. To search the literature, we used key words of “gastric cancer (or carcinoma)” and “muscle (or musclar) metastasis (or metastases)”, and found five cases that had metachronous skeletal muscle metastasis without any other organ metastases after curative gastrectomy (Table ) [, –]. In detail, all cases were male, and median age was 60.5 years (range 47–75 years). Median duration between gastrectomy and muscle metastasis was 14 months (range 7–60 months). Four cases had multiple muscle metastases, and the remaining two cases had solitary metastasis. The histologic type was described in four cases, and all of these four cases had undifferentiated adenocarcinoma. The stage of gastric cancer was described in four cases, including three cases of stage IIA and one case of stage IB. These findings suggest that skeletal muscle metastasis without any other organ metastases tend to occur in patients with relatively early stage disease and undifferentiated adenocarcinoma.
Among the six reported cases, surgical excision was performed in only one case with solitary muscle metastasis (Table ). Surgical excision was reported to relieve the pain due to the muscle metastasis []. Radiotherapy may also be effective in relieving pain and reduction in the size of metastatic lesions []. Chemotherapy is considered as the standard treatment for the muscle metastasis of gastric cancer. Four cases, including the present case, underwent chemotherapy. These included doxorubicin, a combination chemotherapy of 5-fluorouracil, leucovorin, and cisplatin, a combination chemotherapy of S-1 and cisplatin, chemotherapy plus trastuzumab. A phase III trial demonstrated that the overall survival was better in patients with advanced gastric cancer treated with S-1 and cisplatin than with S-1 alone []. Based on the results of this trial, the Japanese gastric cancer treatment guidelines recommend a combination of S-1 and cisplatin as the first-line chemotherapy for recurrent gastric cancer []. In the present case, the pain had been manageable with an oral analgesic. Therefore, we firstly performed a combination chemotherapy of S-1 and cisplatin, and the present case was the only case that underwent S-1-based chemotherapy among the reported cases.
The prognosis of patients with skeletal muscle metastasis was reported to be extremely poor. Among the reported cases, four cases had died, with a median survival time of 12.5 months (range 6–18 months). Only one case, which underwent chemoradiotherapy for multiple skeletal metastases, remained alive at 24 months after recurrence []. The metastasis to skeletal muscle seems to be a sign of systemic hematogenous metastasis and the terminal stage in the progress of gastric carcinoma []. Although the present case underwent a S-1-based chemotherapy, including S-1 and cisplatin, S-1 and docetaxcel, and S-1 and CPT-11, all of these regimens were not effective, and the patient died 7 months after the recurrence. More recently, some studies suggest that S-1-containing chemotherapy is ineffective in patients who showed S-1 adjuvant failure []. In addition, no benefit of adding S-1 beyond progression has been shown in a recent study. On the other hand, several molecularly targeted drugs such as trastuzumab, ramucirumab, and nivolumab have been developed, and the efficacy of such drugs has been shown in clinical trials [–]. Therefore, a change of the key drug and molecularly targeted drugs are expected to prolong survival time of patients with skeletal muscle metastasis of gastric cancer. |
pmc-6098574-1 | An 85-year-old (Swiss-German) Caucasian woman, born and raised in Switzerland, presented to her family doctor with left hip pain and limitation of hip joint movement but no fever, weight loss, or night sweats. Her medical history included hypertension, hypothyroidism, and asthma. Her daily medication was valsartan, levothyroxine, and ciclesonide oral Inhalation. Her family history was uneventful. The widowed patient lived on her own; she did not smoke tobacco or drink alcohol. An MRI scan showed advanced degeneration of her lumbar spine and destruction of the left iliac joint with surrounding edema and a small collection of fluid ventral to the iliosacral joint (see Fig. ). Arthritis of her left sacroiliac joint was diagnosed. Despite numerous sacroiliac joint infiltrations and thermocoagulation of sensory nerves there was no long-lasting improvement. Her exacerbated lumbar pain led to repeated CT and MRI scans 9 months after the onset of the lumbar pain. Imaging showed progressive destruction of the sacroiliac joint and a 10 × 8 × 7 cm fluid collection in her left iliopsoas muscle (Fig. ).
She was in good health except for her persevering hip pain. An examination revealed normal vital signs and no fever. Sensations were normal in both lower limbs. Muscle strength was grade M5 throughout (Medical Research Council scale of muscle strength), and deep tendon reflexes were normal. Laboratory testing showed low hemoglobin (100 g/l, reference range 118–158 g/l), peripheral monocytosis with a normal leukocyte count, and a C-reactive protein (CRP) level of 20 mg/l (reference < 5 mg/l). Her liver and kidney function were sufficient, the electrolytes were normal. No antibiotics were used before abscess drainage. After the abscess was drained surgically, her condition improved, and she remained afebrile. Blood cultures remained negative. A presumptive diagnosis of a pyogenic abscess secondary to a bacterial sacroiliitis after numerous infiltrations was made.
Seven biopsies from the pus-like fluid were collected and analyzed. Leukocytes were present in the Gram-stain smear; acid-fast bacilli could be visualized in auramine-rhodamine stain. The aerobic and anaerobic cultures showed no bacterial growth, neither did the enrichment cultures. A polymerase chain reaction (PCR) assay for TB was positive. Mycobacterium tuberculosis complex cultures were found to be positive. Drug susceptibility testing revealed a M. tuberculosis isolate fully susceptible to all first-line drugs. An X-ray film of her thorax was normal, and acid-fast bacteria staining of sputum was negative. Therefore, tuberculous sacroiliitis with secondary iliopsoas abscess was diagnosed and combination treatment with isoniazid (100 mg), rifampicin (240 mg), pyrazinamide (600 mg), and ethambutol (400 mg) was started. The potency of the therapy was increased over the following days (isoniazid (250 mg), rifampicin (600 mg), pyrazinamide (1500 mg), and ethambutol (1000 mg).
For further observation of the treatment and rehabilitation our patient was referred to a rehabilitation hospital where she developed a hypoactive delirium. After exclusion of all other causes the delirium had to be attributed to the antituberculous drugs. Laboratory testing showed persistent low hemoglobin (109 g/l) and a CRP level of 10 mg/l. Her liver enzymes were elevated: alanine aminotransferase (ALT) 183 U/l (reference range < 35 U/l) and aspartate aminotransferase (AST) 149 U/l (reference range < 35 U/l). Her kidney function and the electrolytes were normal. Despite discontinuation of pyrazinamide and ethambutol her hypoactive delirium did not resolve. Therefore her antituberculous treatment was discontinued and she started to improve. After a treatment interruption of 10 days an alternative treatment with rifampicin and moxifloxacin was started.
A control imaging 9 months after therapy initiation showed persistent destruction of her left iliac joint with regressed edema and fluid collections. Repeated laboratory tests showed normal leukocytes, CRP, and liver enzymes, only her erythrocyte sedimentation rate was still elevated (40 mm/hour, reference range < 12 mm/hour). Her condition showed continuous improvement; she now lives on her own with nursing assistance once a week. She has hardly any pain and she has no deficits in sensorimotor function. After a total of 12 months the antibacterial therapy with rifampicin and moxifloxacin was discontinued; a control MRI is planned. |
pmc-6098582-1 | A 32-year old female presented to us with progressively deteriorating vision in her right eye for 2 months.
When the patient presented to us, visual acuity (VA) in her right eye was counting fingers and in the left eye, it was 20/30. Anterior segment examination was within normal limits for both eyes and intraocular pressures were 14 mmHg. Right eye fundus examination was significant for vitritis, with vitreous clumps manifesting as classic ‘pearls on a string’ appearance. A full thickness, yellowish-white foveal lesion was also appreciated (Fig. ). Left eye examination was normal. Uveitis workup was unremarkable, except for an elevated erythrocyte sedimentation rate (ESR = 38). Mantoux test (0 mm), VDRL, FT-ABS, ANA, ASMA, AMA, and Toxoplasma IgG and IgM were all negative. Prior to consulting us, she had seen outside ophthalmologists where she was given intravitreal triamcinolone acetate in the affected eye. In addition, systemic prednisolone therapy had also been given. However, no improvement was observed with these treatments. A diagnosis of Toxoplasma retinochoroiditis was presumed and the patient was started on empiric Septran DS (sulfamethoxazole and trimethoprim).
On direct questioning, the patient revealed having undergone back-alley abortion 3 weeks prior to onset of her ocular symptoms, and that she was also suffering from vaginal discharge. She was referred to gynaecology, who felt, that the two problems were unrelated. Vaginal swabs were however taken, and Gram-positive rods were identified on Gram staining. A diagnosis of bacterial vaginosis was made, and she was commenced on Metronidazole.
Based on the patient’s history and clinical findings, we strongly suspected a fungal sub-retinal abscess. Retinal imaging, which included optical coherence tomography (OCT) and fundus fluorescein angiography (FFA), were ordered. OCT of the right eye showed a sub-foveal conical lesion extending from the choroid into the full thickness of retina (Fig. ). The apex of the lesion was directed towards the inner retina and formed a tiny protuberance (roof of the abscess). Blood cultures were requested but did not reveal any microbial growth. A vitreous tap was subsequently performed, and intravitreal amphotericin B 5 μg/0.5 ml was administered. Vitreous culture showed profuse Candida albicans growth. Because of limited response to intravitreal antibiotics, therapeutic 25 g pars plana vitrectomy, with gas tamponade and repeat intra-vitreal amphotericin B was performed. She was also commenced on oral voriconazole. The eye responded well to debulking surgery. Three weeks post-vitrectomy, inflammation resolved completely with macular scar formation (Fig. ). During the subsequent 4 years follow-up, the patient had no recurrences. |
pmc-6098616-1 | A 63-year-old woman, with 2 years’ history of dizziness and weakness probably related to an anaemic syndrome, presented to the emergency room with hematemesis, melena and hemodynamic instability. There was no history of chronic liver disease, dyspepsia, ulcer disease, nonsteroidal anti-inflammatory drugs or aspirin use.
On examination, she had conjunctival pallor with reduced general condition, blood pressure of 90/45 mmHg and a pulse between 110 and 120 beats per minute. On digital rectal examination, she had melena. There were no abdominal wall varices, no hepatomegaly, and no palpable mass or adenopathy.
Laboratory blood tests revealed a haemoglobin level at 38 g/l with haematocrit at 13.4%. The mean corpuscular volume was in the normal range.
The patient was admitted to the intensive care department. After initial resuscitation, transfusion and intravenous Omeprazole continuous infusion, her condition was stabilized. She underwent upper gastrointestinal endoscopy showing a tumour of the cardia, protruding in the lumen with mucosal ulceration and clots in the stomach (Fig. ). Biopsies were taken. Histological examination showed interlacing bundles of spindle cells, ill-defined cell borders, elongated hyperchromatic nuclei with marked pleomorphism and numerous mitoses. Immunohistochemistry showed positivity for Vimentine, a strong and diffuse immunoreactivity for SMA. Immunoreactivities for KIT and DOG1 were doubtful.
Computed tomography (CT) scan revealed a seven-cm tumour of the cardia, without adenopathy or liver metastasis (Fig. ).
After multidisciplinary meeting, we suspected the diagnosis of stromal tumour of the cardia with high risk of re-bleeding and we decided to perform a total gastrectomy.
The patient underwent laparotomy. There was a nine-cm tumour of the cardia and the fundus, and no sign of peritoneal seeding or liver metastasis. A total gastrectomy was performed without lymphadenectomy (Fig. ). Post-operative course was uneventful.
Histological examination of the tumour specimen found the same features as preoperative biopsies with negative margins (Fig. ). We solicited a second opinion of an expert in a reference centre for sarcomas in France. Immunohistochemistry showed the following: DOG1 staining was focally positive for some normal cells of Cajal. Otherwise, neoplastic cells were DOG1 -, c Kit - (Fig. ), CD34 -, smooth muscle actin + and h-caldesmon + (Fig. ). In conclusion, it was in favour of a high grade gastric leiomyosarcoma. |
pmc-6098631-1 | A 25-year-old man presented with a 14-year history of intellectual disability (since 11 years of age), clumsiness (12 years), spastic ataxia (16 years), slow and slurred speech (17 years), schizophrenic delusions (18 years), dysphagia (19 years), and frequent falls (21 years). He had prolonged neonatal jaundice, for which exploratory laparotomy and simultaneous cholecystectomy were performed at that time. He was also diagnosed with Crohn’s disease at the age of 16 years. Neurological examination at presentation revealed VSGP and involuntary movements including choreoathetosis, dystonia, and myoclonus. Ultrasonography revealed unpalpable mild splenomegaly. The NPC-SI was 98% with a risk prediction score (RPS) of 183 (high likelihood of NPC when the NPC-SI is more than 14% and the RPS is more than 40). Filipin staining of skin fibroblasts showed a variant pattern (Fig. ). Gene analysis of NPC1 using genomic DNA extracted from the patient’s blood via Sanger sequencing revealed compound heterozygous mutations, including the known c.1421C > T (p.P474L) mutation [] from the father and a novel c.3722 T > C (p.L1241S) mutation from the mother. We deposited the latter mutation to the Leiden Open Variation Database (LOVD); the individual number of this data entry is 00165102. Oral intake of miglustat for 12 months did not relieve his symptoms. The treatment had to be discontinued because the patient had succumbed to a vegetative state following massive pneumonia secondary to severe ileus due to Crohn’s disease. |
pmc-6098631-2 | The proband, a 28-year-old woman, presented with a 1-year history of orofacial and oromandibular dystonic movements. The woman had no neonatal jaundice; however, at the age of 1 year, marked hepatomegaly (2 cm) and splenomegaly (7 cm) were noted. Vacuolated lymphocytes were observed in her blood and cerebrospinal fluid, and many foam cells were observed in the bone marrow. The enzymatic activity of acid sphingomyelinase in skin fibroblasts had decreased to 17 nmol/mg/h (118 ± 53). As there was relatively conserved enzymatic activity (more than 10% of control), a diagnosis of infantile-onset NPC was considered. However, contrary to the expected severe prognosis of known infantile cases, she survived well with minimal neurological symptoms. The patient developed auditory hallucinations, nocturnal urination, and sleep paralysis at the ages of 3, 6, and 9 years, respectively. These symptoms gradually subsided by the age of 12 years. She had an eating disorder between the ages of 17–19 years, and excessive daytime sleepiness appeared at the age of 19 years. Orofacial and oromandibular dystonic movements with facial pain appeared at the age of 27 years. Modafinil 300 mg/day was not effective for sleepiness, and medications such as amitriptyline 10 mg/day, zonisamide 100 mg/day, trihexyphenidyl 2 mg/day, and L-dopa 50 mg/day were not effective for the painful dystonia. Only clonazepam 2 mg/day minimally relieved the symptoms. At the age of 28 years, when she was referred to our hospital, she was neurologically intact except for the dystonia. Ultrasonography detected mild unpalpable splenomegaly. The NPC-SI was 18% with an RPS of 47. Filipin staining of the skin fibroblasts was positive with a variant staining pattern (Fig. ). The urinary levels of bile acids [] were partially elevated (Table ). NPC1 gene analysis showed compound heterozygous mutations including the known c.3011C > T (p.S1004 L) mutation [] from the father and a new mutation of c.160_161insG (p.D54GfsX4) from the mother. Oral intake of miglustat for more than 12 months was not effective for the painful dystonia. |
pmc-6098632-1 | A 23-year-old Arabic single woman was brought to our emergency department (ED) by her family around 4 hours after intentional metformin ingestion. She was on metformin for weight reduction (her body mass index was 28), as she was found to have polycystic ovarian syndrome (PCOS). She ingested around 60 tablets of 500 mg metformin as a suicide attempt after she experienced a stressful social event. Four years prior, she had undergone a kidney donation to her brother, who had renal failure due to an unknown cause, and otherwise she was healthy. She was not known to have any psychiatric illness or previous suicidal ideation or attempt. There was no history of smoking or alcohol intake. She does not have any family history of diabetes mellitus or mental illnesses. On examination, she was alert and well-nourished but generally fatigued, with no pallor, jaundice, or cyanosis. Her vital signs were as follows: blood pressure 119/65 mmHg, heart rate 122 beat/min, respiratory rate 20 breaths/min, pulse oximetry oxygen saturation 100% on room air, and oral temperature 36.9 °C. She had dry and cool skin, and bilaterally mid-sized pupils, equal and reactive. The rest of her physical examination was unremarkable.
Her bedside point-of-care capillary blood glucose level was checked, and it was low. A peripheral intravenous cannula was inserted, and blood extracted followed by administration of 50 ml (25 g) of 50% dextrose (D50) solution. Her blood glucose level was 6.3 mg/dL in serum chemistry; however, it increased to 106 mg/dL after the D50. After that, 5% dextrose-water solution was initiated as a maintenance infusion. Her blood investigation results are summarized in Table . They were unremarkable except for a very low blood glucose level, leukocytosis, hypocalcemia, hyperphosphatemia, and mild creatinine elevation. An initial venous blood gases reading revealed pH: 7.18; PO2: 76.9 mmHg; PCO2: 40.3 mmHg; and bicarbonate of 14.3 mmol/L. Her first lactate level was elevated (8.4 mmol/L), and so a 1 L bolus of Ringer lactate solution was given. Her serial venous blood gases and lactate measurements are shown in Table . Results of analyses of her acetaminophen and aspirin levels were negative. In addition, urine analysis as well as urine pregnancy test results were negative.
Two hours later, her capillary blood glucose dropped to 38 mg/dL, and another 50 mL ampule of D50 was infused, which increased her glucose level to 319 mg/dL. During the hospital stay, her blood sugar was monitored frequently (Table ). As our patient had worsening lactic acidosis, a nephrologist was urgently consulted, and she was admitted to the intensive care unit (ICU). She had a drop in her blood pressure, and so norepinephrine infusion was initiated. After that, continuous renal replacement therapy (CRRT) was started. At around 3 hours later, her blood sugar dropped to 42 mg/dL, and another dextrose bolus was given. After 13 hours of CRRT initiation, the norepinephrine infusion was discontinued, and our patient was hemodynamically stable. The CRRT was continued for 24 hours. Our patient’s renal and liver function tests did not worsen and remained within normal limits till hospital discharge.
On day 3, she was transferred to the ward with normal mental status and vital signs. She was tolerating oral intake and did not develop any more hypoglycemic attacks. The psychiatrist was consulted for further assessment and treatment. On the fifth day of hospitalization, our patient was discharged home with a good health status. This patient was provided, as a part of our multidisciplinary discharge planning, with follow-up appointments within 1 month for internal medicine, nephrology, and psychiatry. As per our medical records, this patient did not show up for any of these outpatient follow-up appointments. |
pmc-6098643-1 | A 58-year-old Japanese man was referred to our hospital for surgical treatment of two hepatic tumors. He had a history of blood transfusion at the age of 6 years during surgical treatment for a traumatic left femoral fracture. He was diagnosed as hepatitis B and C viral infection positive at the age of 30 years, and he had a history of interferon therapy at the age of 33 years. He also had a history of diabetes, and hemodialysis was introduced for diabetic renal failure at the age of 49 years. He had no familial history. Medical check-ups included computed tomography (CT) scans at his previous hospital each year. A CT scan revealed two hepatic tumors, and he was referred to our hospital 1 month later. His abdomen was soft and flat without ascites; his liver and spleen were not palpable in the subcostal area on physical examination. Laboratory findings on admission to our hospital included: platelet and white blood cell counts of 4.0 × 104/μL and 2000/μL, respectively; hemoglobin, albumin, and total bilirubin levels of 12.0 g/dL, 3.8 g/dL, and 0.4 mg/dL, respectively; and aspartate and alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase concentrations of 27 U/L, 27 U/L, 199 U/L, and 29 U/L, respectively. He had a prothrombin time (percent) of 66.5%. His Child–Pugh grade was corresponding to A. His indocyanine green retention rate at 15 minutes was 4.9%. Hepatitis B virus antigen and hepatitis C antibody were positive. His serum alpha-fetoprotein was elevated (126.0 ng/mL). The protein level induced by the vitamin K antagonist (18.0 mAU/mL) was within normal reference limits.
Pre-contrast CT scans revealed two hypoattenuating hepatic lesions (each ≤1.0 cm in diameter) in segments 3 (S3) and 7 (S7). Contrast-enhanced CT scans revealed that the tumor in S3 was enhanced in the arterial phase and became isodense to liver parenchyma in the portal and venous phase. The tumor in S7 was not enhanced in any phase (Fig. ). Magnetic resonance imaging revealed similar findings of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images for both the S3 and S7 lesions (Fig. ). The preoperative diagnosis was multiple HCCs. However, CT findings were not typical of HCCs. Partial resections of S3 and S7 were performed. The resected specimens revealed that the tumors in S3 and S7 were well-defined lesions of 8.0 mm and 14.0 mm, respectively (Fig. , ). His preoperative platelet count was low, but a transfusion was not required. Pathological examination of tissue from the S3 tumor revealed small, regular, oval-shaped cells with mild atypia, which formed the luminal structure. Tumor cells proliferated in an anastomosing pattern of Hering’s canal-like small glands with an abundant fibrous stroma that replaced the non-cancerous tissue (Fig. , ). The pathological diagnosis was CoCC. The tumor in S7 was partially surrounded by a thin fibrous capsule and septum. Atypical tumor cells proliferated in a trabecular and pseudoglandular pattern corresponding to moderately differentiated HCC (Fig. ). The pathological findings of each cancer resulted in T1aN0M0 stage I according to Union for International Cancer Control the 8th edition. The pathological findings of the non-cancerous tissue included liver cirrhosis. On immunohistochemical analysis, S3 tumor cells stained positive for cytokeratin 7 and cytokeratin 19 (Fig. , ) and negative for hepatocyte paraffin 1 and Alcian blue. The membranous region of the lumen stained positive for epithelial membrane antigen (EMA; Fig. ).
His postoperative course was uneventful and he was discharged on postoperative day 13. He was alive without recurrence 36 months after surgery. |
pmc-6098650-1 | A 70-year-old female patient was admitted for confusion. One week before admission, the patient discovered, while bathing, that she had been bitten by a tick that had attached to her skin while she was planting lawn grass earlier, and removed the tick accordingly. She reported that the tick was approximately 3 mm in size, but that she disposed of the tick after removal. Subsequently, there were no specific symptoms and she continued in planting lawn grass. However, 3 days after the tick bite, she began to develop dizziness with a fever. On the day of admission, she was waving her hands, was non-communicative, and provided irrelevant responses to questions. She appeared relatively fine while lying down, but, when standing up, the symptoms became severe and she struggled to maintain her balance. Therefore, she was admitted to the emergency room for further evaluation.
At the time of admission, a lesion suspected of being a tick bite with a diameter of approximately 5 mm was found in the right buttocks area (Fig. ). Her blood pressure, pulse, respiratory rate, and body temperature at admission were 100/60 mmHg, 88 beats/min, 24 breaths/min, and 38 °C, respectively. Blood test results indicated a white blood cell (WBC) 920 /μL (neutrophil 86.8%), hemoglobin level of 14.1 g/dL, and platelet level of 22,000/μL, whereas the biochemistry test results indicated: aspartate aminotransferase 99.9 IU/L, alanine transaminase 54.7 IU/L, total bilirubin 1.3 mg/dL, blood urea nitrogen 20.1 mg/dL, creatinine 0.67 mg/dL, cholesterol 156 mg/dL, and triglyceride 81 mg/dL. Although the erythrocyte sedimentation rate was 7 mm/h, the C-reactive protein level was increased to 22 mg/dL, whereas lactate dehydrogenase and creatine phosphokinase levels were elevated to 1052 (normal: 200–450) U/L and 1394 (normal: 55–215) U/L, respectively. The blood coagulation test showed normal findings in prothrombin time (10.7 s), international normalized ratio (0.96), activated partial thromboplastin time (26 s), and fibrinogen (384 mg/dL), but elevated levels of fibrinogen degradation products (50.3 [normal: 0–5.0] μg/mL) and D-dimer (3199 [normal: 0–255] ng/mL). A lacunar infarction in the left basal ganglia was found during magnetic resonance imaging for determining the cause of the altered state of consciousness at the time of admission (Fig. ); however, no significant stenosis or occlusion was found on magnetic resonance angiography. A cerebrospinal fluid (CSF) tap was performed to rule out encephalitis and meningitis, although there was no neck stiffness, with the results showing CSF WBC 0 per mm3, CSF protein 34.7 mg/dL, and glucose 130.2 mg/dL (serum glucose 221.3 mg/dL). No microorganisms were found in cultured blood and CSF using the BACTEC culture system (Becton Dickinson, Towson, MD, USA), whereas cerebral fluid herpes virus, enterovirus, Orientia tsutsugamushi, and Leptospira interrogans polymerase chain reaction all tested negative.
Although cerebral infarction in the left basal ganglia was identified, the patient exhibited low levels of platelets. Therefore, she was not qualified to receive antiplatelet agents. Furthermore, based on clinical signs of fever and altered state of consciousness after a tick bite, doxycycline 100 mg twice daily was administered starting from post-admission day 2. The fever began to subside 1 day after doxycycline administration and resulted in the rapid resolution of symptoms. The patient showed a complete recovery of her consciousness by the 4th day of doxycycline administration.
A blood sample was tested using nested PCR with Anaplasma and Ehrlichia-specific primers targeting the GroEL heat-shock protein gene (groEL) and ankyrin-repeat protein AnkA gene (ankA), Additionally, a portion of the 16S ribosomal RNA gene (16S rRNA) was amplified using PCR [–]. The PCR amplicons were purified and directly sequenced using PCR primers. BLAST (Basic Local Alignment Search Tool) analysis of sequenced productsconfirmed A. phagocytophilum infection (Fig. ), although morulae were not detected in a stained peripheral blood smear.
Immunofluorescence assay (IFA) antibodies against A. phagocytophilum were also measured from the blood sample []. Upon admission, the immunoglobulin (Ig) M level was below 1:16 and the IgG level was below 1:80. At 7 days later, the IgM level was 1:64 and the IgG level was 1:320. The IFA examination using CSF showed an IgM level below 1:16 and an IgG level below 1:80.
Furthermore, other blood tests were negative for Hantavirus, severe fever thrombocytopenia syndrome virus, O. tsutsugamushi, and leptospirosis. Indirect IFA and reverse transcription-PCR were performed to diagnose hemorrhagic fever with renal syndrome and severe fever with thrombocytopenia syndrome in blood specimens, respectively [–]. Scrub Typhus RAPID kit (ImmuneMed, Republic of Korea) and 56-kDa nested PCR were used for the diagnosis of scrub typhus []. Leptospira RAPID kit manufactured by ImmuneMed (Republic of Korea) and hap1 nested PCR were used for the diagnosis of leptospirosis [].
The patient exhibited an improvement in symptoms after doxycycline treatment and was discharged on the 12th day with no specific sequela. |
pmc-6098651-1 | Patient A, a thirty year-old male patient diagnosed with severe dilated cardiomyopathy, received a heart from a brain-dead donor in Japan. After transplantation, he followed an uneventful postoperative course for 6 months.
Subsequently, Patient A was involved in a traffic accident. He suffered severe injuries, including trauma to his head, and was transported to an emergency hospital. Upon arrival, physicians determined that Patient A met clinical criteria for brain death. From his personal belongings, the medical team retrieved a signed donor card that expressed his intention to donate all organs in case of brain-death. The card was also signed by his family. Given the documented consent by his family toward his intent for organ donation, the clinical team considered the indication of his intention valid and contacted the Japan Organ Transplant Network (JOTN) []. |
pmc-6098828-1 | A 62-year-old female patient presented at our hospital with pain in the left lateral keen and an acute foot drop. She had had a traffic accident 12 days before and received neurotrophic drug treatment (Methylcobalamin 1500 μg, intramuscular, daily). The patient had no history of lumbar disc disease. Physical examination showed complete foot dorsiflexion in the left ankle. Neurologic examination revealed numbness on the contiguous side of the first and second toes. Tinel’s sign was positive at the level of the proximal fibular head. Ankle dorsiflexion and large toe extension showed severe weakness (Medical Research Council (MRC) rating scale grade 2). Ecchymoses were seen in the left lateral of knee and calf (Fig. ). She did not receive magnetic resonance imaging (MRI) because of her cardiac pacemaker and was not examined by ultrasound because no superficial mass was detected. Electromyography (EMG) showed a deep left peroneal nerve axonal neuropathy, decreased nerve conduction velocity, motor amplitude, and denervation potential in the extensor hallucis longus (EHL) and tibialis anterior muscle (TA) (Table ). X-ray and computed tomography (CT) revealed no fractures (Fig ). Laboratory studies revealed routine blood test results and tumor markers, and erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein was within the normal range.
We explored the common fibular nerve surgically. The common fibular nerve was identified and was traced to its bifurcation. The deep peroneal nerve was swollen. A fusiform cystic mass was located within the epineurium (Fig. ). The cyst was found to track along the deep branches of the peroneal nerve (Fig. ). A longitudinal incision was made on the cystic wall, mucoid material was evacuated from the cystic mass (Fig. ), and part of the cystic wall and synovium were removed. The articular branch was not found. The surgical procedure was carried out with surgical loupes. Pathology showed a cystic wall structure with mucoid material, blood vessel scar fibrotic tissue, and neural tissue proliferation. From the operation and pathology report, the diagnosis was intraneural ganglion cyst with tissue hemorrhage and hydrosarca (Fig. ). The patient was kept non-weight bearing for one month postoperatively with physiotherapy. She reported the return of sensation to the first and second toes three months after surgery and achieved a significant recovery. EMG investigations showed that the nerve conduction velocity improved three months later, the motor amplitude and denervation potential in the extensor hallucis longus (EHL) and tibialis anterior muscles improved. The muscle strength was fully restored relative to the contralateral leg. The patient was asymptomatic and able to return to her normal activities at one-year follow-up.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Ethical approval was given by the medical ethics committee of the First Affiliated Hospital, College of Medicine, Zhejiang University. |
pmc-6098831-1 | A 51-year-old Thai man was referred because of a perforated left cornea. One year previously, he had a non-penetrating left eye injury from a tree branch, which caused a corneal scar and poor vision. The plant that caused the injury was Dendrocalamus membranaceus Munro, which is a type of bamboo with edible sprouts. His systemic medical problems were poorly controlled hypertension, dyslipidemia, and diabetes mellitus: fasting blood sugar (FBS) level, 94 mg/dl; glycated hemoglobin (HbA1c), 8.8%.
On the first visit, the best-corrected visual acuity (BCVA) of his left eye was 20/100. The cornea had a descemetocele with microleakage. Neither stromal infiltration nor pigmented endothelial plaques were observed. The anterior chamber showed 2+ cells. Iridocorneal touch was observed. The lens and posterior segment were obscured. The intraocular pressure was not recorded. Uneventful corneal gluing with a bandage contact lens was performed to restore globe integrity. However, investigation for microorganisms was not performed. He was discharged home with moxifloxacin and lubricant eye drops (EDs) to be administered every hour, atropine EDs to be administered twice daily, ciprofloxacin tablets 500 mg twice daily, and acetazolamide tablets 250 mg four times a day.
During the follow-up period, his BCVA was determined by counting the finger to hand motion range and prophylactic moxifloxacin EDs were prescribed. His clinical condition was stable for 11 months until he complained of visual loss. On ocular examination, his BCVA had decreased to light perception. Total iridocorneal touch with stromal and microcystic edema was observed. However, there were no signs of infection. He was readmitted for amniotic membrane transplantation (AMT) because of suspected microleakage. A preoperative laboratory examination showed that his FBS level was 108 mg/dl and HbA1c was 8.3%. Moxifloxacin and lubricant EDs four times a day were provided postoperatively. He was also sent to a diabetes clinic.
Unfortunately, AMT was unsuccessful and further corneal perforations were observed. The anterior chamber was totally flat and the amniotic membrane had disappeared (Fig. ). One week after AMT, a successful triple operation was performed using a 7.5-mm donor graft and 7.0-mm recipient bed, with 16 interrupted sutures of 10-0 nylon. His BCVA was improved in counting fingers on the discharge date. Surgical pathology unexpectedly showed fungal hyphae (Fig. ), while potassium hydroxide (KOH) preparation and fungal culture showed negative results. Therefore, our patient received prophylactic natamycin and levofloxacin EDs four times daily, methylprednisolone EDs every 2 hours, and lubricant EDs hourly as home medications.
Three months after the triple operation, his BCVA slightly diminished in hand motion. Pigmented endothelial plaques appeared at the inferior half of the corneal graft (Fig. ). Recurrent fungal infection was suspected. He was readmitted for anterior chamber irrigation and 0.1 ml intracameral amphotericin B injection. The treatment regimen was changed to amphotericin B and natamycin EDs hourly, moxifloxacin and lubricant EDs four times daily, itraconazole capsules 400 mg once daily, and orally administered prednisolone 0.5 mg/kg per day.
However, after two weekly doses of intracameral amphotericin B, the corneal graft became more edematous with pigmented endothelial plaques, which increased from the inferior half to two thirds. A second graft was performed by using the same recipient/donor size, together with copious intracameral amphotericin B irrigation. A corneal button showed moderate polymorphonuclear leukocytes on a Gram stain and septate hyphae on a KOH preparation. Aerobic and anaerobic bacterial cultures were negative. A fungal culture showed Phialophora species growing on Sabouraud’s dextrose agar, and this was later identified as P. verrucosa by polymerase chain reaction (PCR). Natamycin and amphotericin B EDs were tapered to every 2 hours.
Tiny, inferior, endothelial plaques were observed again on the second postoperative day, with a few pigmented keratic precipitates (Fig. ). These precipitates gradually increased and reached the superior limbus 1 month postoperatively. A small, central, epithelial defect was also observed and our patient’s BCVA was determined by counting fingers.
Intracameral antifungal injection was switched to voriconazole because of our patient’s worsening condition. After three biweekly doses of intracameral voriconazole, his condition greatly improved as shown by a decrease in pigmented keratic precipitates. Accordingly, medications were switched to voriconazole EDs hourly with a tapered dose and voriconazole tablets 200 mg twice daily.
Although his infection appeared to be under control, the epithelial defect was even larger, with a raised, rolled-up edge. Sutures began to loosen, especially at the 6 o’clock position where the corneal graft was also friable. Corneal graft perforation eventually occurred at the end of 1 month after the last dose of intracameral voriconazole. Gluing with a bandage contact lens was then performed (Fig. ). Temporary complete ptosis was induced by 5 units of botulinum toxin injection into the levator palpebrae superioris muscle to promote wound healing. Instead of regrafting, corneal cross-linking (0.1% isotonic riboflavin solution with 18 mW/cm2 of 365 nm ultraviolet A light) was performed to strengthen corneal integrity. Timeline of treatments in chronological order was shown (Fig. ).
At 6 months of follow-up, no further corneal melting was observed. The infection was under control without use of medication. His eye was saved from enucleation or evisceration with BCVA of hand motion. |
pmc-6098839-1 | A 62-year-old woman, who was negative for the BRCA1/2 germline mutation, presented to our institution with abdominal pain in October 2011. She was referred from another institution, where she had undergone a primary suboptimal cytoreduction. Pathologic analysis revealed a carcinosarcoma with a high-grade serous adenocarcinoma component associated with high-grade endometrial sarcoma in the right ovary and fallopian tube, with angiolymphatic embolization. There were also peritoneal implants in the upper abdomen and pelvis. The uterus, left fallopian tube and ovary, and lymph nodes had no evidence of disease; however, peritoneal cytologic analysis was positive for malignancy. Immunohistochemistry of the right ovary demonstrated that the tumor was positive for estrogen and progesterone receptor but HER2/neu-negative.
From April through June 2012, the patient received adjuvant carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks for four cycles. In July 2012, she underwent an interval cytoreduction (optimal) followed by treatment with intraperitoneal cisplatin (75 mg/m2) and intravenous (135 mg/m2) and intraperitoneal paclitaxel (60 mg/m2) for six additional cycles. After the end of chemotherapy, she received tamoxifen as maintenance treatment for 4 months. She was observed off treatment for 6 months. In May 2013, retroperitoneal adenopathy was discovered following a serial rise in CA125, which prompted radiographic assessment. She received carboplatin (AUC 5), pegylated liposomal doxorubicin (30 mg/m2), and bevacizumab (10 mg/kg) for four cycles and had a partial response. Paclitaxel was not used again owing to residual neuropathy. In light of localized recurrence and response, she underwent a tertiary debulking procedure with complete macroscopic gross resection. Unfortunately, 6 months later a positron emission tomography/computed tomography study (PET-CT) revealed disease progression in a right retropectoral lymph node, as well as in paraesophageal lymph nodes. She then received cisplatin (35 mg/m2), gemcitabine (800 mg/m2), and bevacizumab (10 mg/kg), but had disease progression.
From April 2014 through December 2015, the patient received various treatments for platinum-resistant disease: pemetrexed, nab-paclitaxel, megestrol, capecitabine, and vinorelbine. The metastatic sites were predominantly lymphatic and peritoneal. Despite the extensive pretreatment, she remained largely asymptomatic and had a good performance status. However, owing to disease progression, in January 2016 she initiated treatment with pembrolizumab (200 mg every 3 weeks). Unfortunately, there was not enough material to test the status of microsatellite instability, mutational load, or PD-L1 expression in the tumor. Also, the tumor was not analyzed for druggable mutations due to lack of insurance coverage. After the third cycle, she developed thyroiditis grade 1 but no other adverse events. After the fourth cycle, PET/CT showed objective partial response in the left external iliac lymph nodes (Fig. ), as well as in the right-posterior pectoral lymph node conglomerate (Fig. ). Another major site of metastatic disease was the right retropulmonary lymph nodes. With the goal of increasing local control and potentially causing an abscopal effect, she underwent radiotherapy (24 Gy in three fractions of 8 Gy). She then received an additional four cycles of pembrolizumab. Unfortunately, disease progression was discovered in the liver shortly thereafter. She received olaparib (400 mg twice per day) for 2 months but without response, and she died in October 2016. |
pmc-6098845-1 | A 68-year-old Japanese woman with no significant medical history had suffered from pain in her right lower quadrant. She was examined at the regional cancer center and diagnosed with appendiceal cancer. She underwent ileocecal resection with lymph node dissection at the aforementioned hospital, and the postoperative course was uneventful. The pathological evaluation revealed KRAS-mutant (codon 12) moderately to poorly differentiated adenocarcinoma, and the final TNM stage was T4b (small intestine) N1M0 (stage IIIc). Thereafter, she received adjuvant chemotherapy with oral tegafur/uracil and leucovorin for one year.
One year after the surgery, a positron emission tomography/computed tomography (PET/CT) scan showed sporadic foci of intense tracer uptake in the pelvic cavity, consistent with peritoneal dissemination and vaginal metastasis. The recurrent tumor deposits were considered resectable. She received three courses of mFOLFOX6 regimen (oxaliplatin, folinic acid, and fluorouracil) as neoadjuvant chemotherapy, followed by resection of the peritoneal dissemination and partial resection of the vagina. The pathological diagnosis confirmed negative resection margins. Then, she resumed the mFOLFOX6 regimen as adjuvant chemotherapy; however, the regimen was discontinued after two courses for an allergic response to oxaliplatin.
One year after the second surgery, a surveillance abdominal ultrasonography showed a 27 × 16 mm irregular and low-echoic tumor around the right external iliac artery (). A contrast-enhanced CT scan showed an irregularly enhanced tumor around the right external iliac artery and vein. In addition, the tumor appeared contiguous to the small intestine. These findings suggested tumor invasion to the right external iliac artery, the right external iliac vein, and the small intestine (). A PET/CT scan showed tracer uptake (standardized uptake value max: 17.5) at the tumor (). It also showed regional lymph node enlargement around the right iliac vessels and no findings of distant metastases. The patient was diagnosed with a locoregional recurrence after the first reoperative surgery for appendiceal cancer. She was then referred to our hospital for potential surgical resection.
We assumed that the tumor was resectable; however, the external iliac vessels also required resection during the surgery, which required a simultaneous procedure for vascular reconstruction. We proposed neoadjuvant chemotherapy and subsequent surgery for the patient because it was deemed important to control the tumor progression and increase tumor resectability.
We selected a FOLFIRI (irinotecan, folinic acid, and fluorouracil) plus bevacizumab regimen as neoadjuvant chemotherapy, considering the mutant KRAS status. We initially planned six courses of FOLFIRI plus bevacizumab therapy and assess the tumor progression and resectability every 3 months. We discussed with the patient, and she agreed with our proposed treatment strategy. Follow-up CT scans after three and six treatment courses showed no tumor progression. After six courses of the treatment, we recommended surgical resection for her as we planned, but she wanted to receive chemotherapy. FOLFIRI plus bevacizumab regimen was continued accordingly.
After eight courses, she developed edema in the right lower extremities. A contrast-enhanced CT showed a narrowing of the right external iliac vein without any thromboemboli in both lower extremities; however, she was incidentally found to have suspicious emboli in her pulmonary arteries. The neoadjuvant chemotherapy was terminated, and she was administered an anticoagulant therapy (edoxaban). After two months, a contrast-enhanced CT was taken again and showed no thromboemboli and no significant tumor progression. Although she had been asymptomatic for the suspicious pulmonary embolism, her lower extremities remained edematous. We, thus, indicated surgical resection of the tumor. The tumor was considered to be resectable, and we asked cardiovascular surgeons for vascular reconstruction at the time of surgery.
The surgery was performed in the following sequence. At first, vascular reconstruction was performed by cardiovascular surgeons. A femoro-femoral arterial bypass with synthetic vascular graft (Gelsoft™ 8 mm, Vascutek Ltd., Renfrewshire, Scotland, UK) was made to secure the blood supply to the right lower extremities. Subsequently, a laparotomy was performed by colorectal surgeons. A fixed and solid tumor was observed at the right inguinal fossa, involving the external iliac artery, external iliac vein, ileum, and right obturator lymph nodes. En bloc tumor resection was successfully performed including a partial resection of the external iliac artery, external iliac vein, and ileum (). The postoperative course was uneventful except for a prolonged ileus. She was discharged home 30 days after surgery. The leg edema was improved over time and did not recur during the follow-up.
The pathological evaluation revealed moderately and poorly differentiated adenocarcinoma consistent with rerecurrence of appendiceal cancer. Tumor invasion was extended to the external iliac vein with tumor embolus inside. The external iliac artery and ileum were free of tumor invasion but strongly attached to the tumor. The obturator lymph nodes and those in the resected mesentery of the ileum were positive for metastasis. Microscopically, cauterized cancer cells were present at the resection margin (R1 resection).
She received a FOLFIRI regimen as adjuvant chemotherapy. After six courses, a follow-up CT scan showed liver metastasis, para-aortic lymph node metastasis, and peritoneal dissemination. These recurrent lesions were considered unresectable. The chemotherapy regimen was altered to trifluridine/tipiracil. After seven courses, a follow-up CT scan showed a significant progression of the liver metastasis. Regorafenib was then administered for two weeks; however, it was discontinued because she denied further aggressive treatment. She had received palliative care and died one and half years after the last surgery. |
pmc-6098865-1 | A 26-year-old female presented to our hospital with a primary complaint of intermittent, progressive right upper quadrant abdominal pain of one week's duration, which coincided with the onset of darkened urine and yellowing of the eyes. There was mild nausea, but no emesis. The patient had no subjective fever or rashes. She perceived no significant swelling or unusual bleeding. She had no chest pain or myalgia. Her appetite was normal.
The past medical history was notable for a diagnosis of primary lung adenocarcinoma by bronchoscopic biopsy of a right lower lobe radiographic consolidation four months prior to this presentation. By immunohistochemistry, the adenocarcinoma expressed cytokeratin 7, thyroid transcription factor-1 (TTF-1), and napsin-A, but did not express cytokeratin 20, GATA-3, or PAX8, findings consistent with adenocarcinoma of lung origin. Fluorescence in situ hybridization (FISH) analysis of the primary tumor showed cytogenetic evidence of a ROS1 gene rearrangement. No actionable mutations were detected by exon-targeted sequencing. Staging positron emission tomography-computed tomography studies revealed a fludeoxyglucose- (FDG-) avid right lower lobe lung mass with additional consolidation/nodularity in the right middle lobe, left upper lobe, and lingula, and no evidence of mediastinal or hilar lymphadenopathy; however, endobronchial ultrasound-guided biopsy of a level ten lymph node showed involvement by metastatic disease. MRI of the brain showed no evidence of intracranial metastasis.
Given the presence of a ROS1 gene rearrangement, the patient was started on oral crizotinib therapy (250 mg twice daily) 10 weeks prior to her presentation. One week after the initiation of crizotinib therapy, the patient was admitted to another hospital with chest pain, subjective fever, and emesis. She was diagnosed with a bacterial pneumonia and discharged from the hospital with instructions to complete seven-day courses of levofloxacin and metronidazole and a ten-day course of fluconazole, while decreasing her crizotinib dose to 250 mg once daily. One week after discharge from this preceding hospitalization, the patient's liver chemistries were normal: total bilirubin 0.2 mg/dL, AST (SGOT) 15 U/L, ALT (SGPT) 25 U/L, and alkaline phosphatase 58 U/L. Five weeks and two days prior to the current presentation, after the resolution of the abovementioned symptoms, the patient was instructed to increase the crizotinib dose back to the original 250 mg twice per day. However, on admission to our hospital, the patient reported restarting crizotinib at one dose of 500 mg daily, as she found the side effects of gastrointestinal upset more tolerable with this self-imposed regimen. The patient denied other new medications, toxin exposures, or drug/alcohol use. There were no known sick contacts or significant travel.
On physical examination, the vital signs were normal with blood pressure 107/69, heart rate 75 beats per minute, temperature 36.8°C (oral), respiratory rate 12 per minute, and oxygen saturation 96% on room air. The patient was not in distress. The eyes showed mild scleral icterus and the oropharynx was without lesions. Both the rate and rhythm of the heart were regular; there were no heart murmurs. The lungs were bilaterally clear to auscultation: there were no wheezes or rales. The patient exhibited mild epigastric and right upper quadrant abdominal pain on examination, but there was no palpable mass or organomegaly. Examination of the extremities showed no cyanosis or edema. The skin itself was not jaundiced and did not display spider angiomata or palmar erythema. There was no asterixis.
Liver chemistries at the time of admission showed total bilirubin 4.5 mg/dL (3.5 mg/dL conjugated, 1.5 mg/dL unconjugated), AST 1736 U/L, ALT >3500 U/L, and alkaline phosphatase 144 U/L. The INR was above the threshold of normal at 2.2. The white blood cell count was 10.6 K/μL. The platelet count was 195 K/μL. PCR studies of the serum for hepatitis B virus, hepatitis C virus, herpes simplex viruses- (HSV-) 1 and 2, and Epstein-Barr virus (EBV) were negative. Serologic studies for anti-hepatitis A virus antibody (IgM), anti-hepatitis C virus antibody (IgG), anti-hepatitis B virus core antibody (IgM), and hepatitis B surface antigen were all negative. Anti-varicella zoster virus IgG antibody was present, while IgM antibody was not. Analysis of the serum for anti-nuclear antibody was negative (titer <1:80), as were studies for anti-liver-kidney-microsomal antibody and anti-smooth muscle antibody. Serum acetaminophen levels were below the limit of detection (<2.0 μg/mL). Ceruloplasmin was normal at 27.7 mg/dL.
Computed tomography imaging with the aid of intravenous contrast was notable for periportal edema with a small amount of perihepatic fluid and gallbladder mural edema. There were no intra- or extrahepatic mass lesions. Significant interval decrease in the radiographic burden of disease in the right lung was noted with minimal ongoing ground-glass opacities in the right upper and right middle lobes.
Given suspicion of crizotinib-associated hepatotoxicity, targeted therapy was discontinued on admission to our hospital. A continuous infusion of N-acetylcysteine was started (6.25 mg/kg/hr). The AST showed immediate improvement, peaking on the first day of admission (). The ALT remained at the maximum limit of detection until the third day of admission and then precipitously declined. Six days after admission, results of serologic studies showed mildly elevated anti-HSV IgM (1.35; normal <1.10); anti-HSV-1 IgG was also present, while anti-HSV-2 IgG was not. With this information, intravenous acyclovir (10 mg/kg every eight hours) was initiated.
On the seventh day of hospitalization, a transjugular liver biopsy was performed. Histologic sections of the liver biopsy were notable for a predominantly lymphohistiocytic panlobular inflammatory infiltrate accompanied by swaths of parenchymal dropout (Figures and ). The inflammatory infiltrate included abundant pigment-laden macrophages and the occasional plasma cell. Granulocytes, including the rare eosinophil, were also seen. The sampled portal tracts showed the appropriate constellation of artery, vein, and interlobular bile duct without evidence of ductopenia. The inflammation was not centered on the portal tracts and the bile ducts themselves showed no obvious intraepithelial infiltrate or reactive-type epithelial changes. Numerous degenerating and necrotic hepatocytes were seen. Those hepatocytes that remained showed reactive cytoplasmic vacuolization and mitotic activity suggestive of a regenerative response. Periodic acid-Schiff (PAS) stain with diastase pretreatment drew attention to the ceroid pigment-laden Kupffer cells indicative of the significant hepatocyte death that must have preceded this biopsy (). The PAS-positive intracytoplasmic aggregates of alpha-1-antitrypsin deficiency were not seen. Cholestasis was also prominent. Reticulin and trichrome stains highlighted areas of hepatocyte loss and parenchymal collapse (). There was no significant fibrosis by trichrome stain. Hepatic stores of copper and iron were not significantly increased on special stains for each element. The periportal copper deposition of chronic cholestasis was not present. No viral cytopathic effects were identified; immunohistochemical stains for HSV and adenovirus were both negative. Furthermore, analysis of biopsied tissue by PCR showed no evidence of varicella zoster virus, HSV-1/2, cytomegalovirus, or EBV. Nonspecific viral culture of the liver biopsy also showed no viral cytopathic effect.
Acyclovir was discontinued eight days after admission (two days following its initiation), at which time the total bilirubin also peaked. N-acetylcysteine was discontinued and the patient was discharged to home nine days after admission with continually downtrending liver chemistries. She developed edema and ascites post discharge and required furosemide 40 mg daily and spironolactone 100 mg daily for three weeks until these symptoms resolved. Despite this, the liver tests continued to normalize during the patient's subsequent outpatient treatment. She never developed hepatic encephalopathy. All liver chemistries had normalized at follow-up 79 days after admission (). Computed tomography studies at that time showed an interval increase in the right lower lobe ground-glass opacity, along with small nodules throughout the remainder of the bilateral lungs; the radiographic appearance of the liver was improved. Given evidence of residual cancer burden, a chemotherapeutic regimen of carboplatin and pemetrexed was initiated. |
pmc-6098868-1 | An 86-year-old male with a past medical history significant for IgG lambda light chain multiple myeloma, congestive heart failure, and atrial fibrillation on anticoagulation presented for evaluation of abdominal pain, increasing abdominal distention, and inability to pass flatus or bowel movements for two days. Prior to his ileus-like symptoms, he experienced anorexia, rigors, and severe watery diarrhea for several days in correlation with the completion of his second cycle of Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone induction chemotherapy for multiple myeloma.
On presentation, he was afebrile and hypotensive to 72/42. Physical exam demonstrated a pale man with dry oral mucosa and a mildly tender, tympanitic abdomen without peritoneal signs. On laboratory examination he was found to have a white blood cell count of 4.6 x10∧9/L, hemoglobin of 8.1 g/dl, platelets of 15 x10∧9/L, creatinine of 2.35 mg/dL (baseline of 0.9 mg/dL), and lactic acid of 2.3 meq/L. A noncontrast abdominal computerized tomography (CT) scan was performed, which demonstrated diffuse colonic distention with submucosal and intraluminal gas, distended fluid-filled distal small bowel loops, and innumerable small submucosal lesions covering the surface of the colon (Figures and ). The clinical picture and data were interpreted as concern for an infectious colitis, but extensive stool testing including clostridium difficile toxin polymerase chain reaction, giardia antigen, cryptosporidium antigen, and stool cultures were all negative.
Initially, the diagnosis of bortezomib-induced ileus was entertained; however, the patient's diarrhea quickly resumed once he had been fluid resuscitated. He continued to have watery stools requiring rectal tube placement without improvement on piperacillin-tazobactam and metronidazole. The gastroenterology service was consulted to determine the etiology of his diarrhea and abdominal pain, at which point the diagnosis of pneumatosis coli was considered. Repeat CT scan with IV contrast was requested and revealed bowel wall thickening of the transverse and proximal descending colon as well as multiple mildly thickened mid and distal small bowel loops. Based on the updated CT findings, concern for underlying typhlitis arose and the patient was maintained on empiric antibiotic therapy. Due to continued voluminous watery diarrhea, hypotension requiring constant fluid administration, severe hypokalemia, and little to no improvement on antibiotics, the patient was prepped for colonoscopy for direct visualization of the abnormal appearing bowel on imaging.
On colonoscopy, the colonic mucosa was normal appearing except for the presence of diffuse intramural gas consistent with pneumatosis coli (Figures –). Biopsies of the colonic lesions were obtained and sent for pathological evaluation. After confirming the diagnosis of pneumatosis coli on colonoscopy, the objective for patient care shifted to controlling stool output with antidiarrheal agents. Treatment was successful using a combination of diphenoxylate/atropine, cholestyramine, and loperamide. The surgical pathology of the colonic biopsies returned positive for apple green birefringence on Congo red stain consistent with gastrointestinal amyloidosis (). The patient received continued treatment directed towards his multiple myeloma, which was thought to have caused the amyloidosis. The patient had a dramatic response to chemotherapy with resolution of his gastrointestinal symptoms. |
pmc-6098876-1 | A 40-year-old female patient presented with pain and decreased range of motion in her both hips. She was unable to maintain her daily activities. Radiographies revealed bilateral osteoarthritis of the hip, secondary to developmental hip dysplasia, and the patient underwent bilateral total hip arthroplasty (). In her right hip, trochanteric osteotomy was needed to restore hip biomechanics and the fixation was made by a stainless steel cable system. After a 4-year pain-free period of time, she presented with pain and tenderness in her right inguinal area since last month. There was an immobile and painful prominence by palpation. The pain was not related to weight bearing, and hip examination did not reveal any pathology. In routine radiographies, it was discovered that the trochanteric cable was broken and approximately 5 cm part of the cable migrated medially (). The patient's medical records were investigated and it was found out that her last radiography was taken 2 years before, in which the cable was firm and one part. The patient had not returned for follow-up since that date. C-reactive protein, blood counts, and sedimentation rate were between reference values, and there was no clinical sign of infection. The broken part of the cable was extracted with a small incision from the medial, while the remaining part was extracted with a larger lateral incision under general anesthesia (). The tip of the broken cable part was buried in medial adductor muscles which lies posterior to the femoral neurovascular bundle and anterior to the sciatic nerve. The patient was comfortable and pain-free at her follow-ups after extraction. |
pmc-6098884-1 | A 26-year-old woman came to AG Dental Care Clinic, South Sulawesi, Indonesia, in October 2015 with a chief complaint that her gingiva often bled spontaneously and she felt pain on her gingiva and felt less comfortable and no self-confidence with her anterior and posterior gingival condition on the right maxilla region which is slightly larger than normal. She often felt that her gingiva could bleed spontaneously when she was talking or remains silent though. The patient is disturbed by the malodor she felt. At that moment, the patient sought for gingivectomy treatment. Three years afterward, the patient came back with the same complaint. Gingival crevicular fluid has been taken from the gingival sulcus before and after gingivectomy. Clinical and GCF follow-up examination was performed one week and three weeks after gingivectomy, and successful results on biological, functional, and aesthetic parameters were observed.
The expected results with the gingivectomy treatment are that patients should not perceive any more complaint such as spontaneously gingival bleeding, pain on the gingiva, and malodor. Besides, after the gingivectomy treatment, the patient already felt comfortable and had her self-confidence back with her anterior and posterior gingival condition on the right maxilla region not having the appearance that is slightly larger than normal. Besides, the expected results after gingivectomy and scaling and root planing treatment such as localized gingival enlargement on the anterior and posterior of the right maxilla region do not recur.
Gingival crevicular fluid (GCF) was taken from the gingival area with enlargement using a paper point. The paper point was inserted into the gingival sulcus to absorb the gingival fluid. Then, the paper point was inserted to medium fluid L6. GCF was then checked using real-time polymerase chain reaction (RT-PCR) to find TGF-β1 gene expression and examined using enzyme-linked immunosorbent assay (ELISA) to find TGF-β1 protein level (). On the other hand, smear plaque was taken from the tooth surface both supragingival and subgingival and then inserted to medium transport.
Furthermore, the transport medium containing plaque and calculus was taken to the microbiology laboratory for bacterial culture examination, and the bacterial culture was cultured using Brain-Heart Infusion Broth (BHIB) medium (). Then, the observation of swabs of dental plaque samples incubated for 1 × 24 hours in the incubator at a certain temperature was conducted. Identification of bacteria under a microscope was performed to determine bacterial species based on bacterial morphology before and after gingivectomy treatment (). On excised gingival tissue, biopsy was performed to find tissue morphology and tumour subtype and to grade gingival cells. |
pmc-6098894-1 | A 29-year-old female patient consults for pain and paresthesias in the 4th and 5th fingers with 2 years of evolution with several minor traumas in the past year. The patient had a history of supracondylar elbow fracture at the age of 5, treated nonsurgically. No symptoms were presented until she started with higher activity and physical demand such as bar exercises and push-ups. With the beginning of these symptoms, she was initially treated at another hospital for epicondylitis with physiotherapy, rest, and 2 corticoid injections without remission of symptoms.
Physical examination showed pain, an evident varus deformity, chair sign positive, and clear pivot shift. In anteroposterior radiograph, varus of 20 degrees and paresthesias in the ulnar nerve territory were observed. Electromyogram reported signs consistent with ulnar nerve entrapment. Her range of motion in flexion extension and supination was complete (grades: 0-145 flexion-extension, 50-50 pronosupination). The MEPI (Mayo Elbow Performance Index) was 60.
Valgus osteotomy was performed in the distal humerus through a lateral wedge and ligament reconstruction with tendon graft of the autologus palmaris longus, by tunneling the distal humerus and ulna crest. In rehabilitation, the range of motion was controlled with an articulated splint.
Postoperative complications were delayed union and radial neuropraxia with spontaneous remission after 3 months.
The osteotomy did not lead to valgus but to a correction of 5 degrees of the varus (previously 20 degrees). In the evaluation, after 4 years of follow-up, partial clinical deformity correction, remission of symptoms of ulnar nerve irritation, and complete range of motion were achieved. However, the patient cannot perform some exercises with high force demand or more than 2 hours of continuous activity. The MEPI was 80 and DASH (Disabilities of the Arm, Shoulder, and Hand) was 13.33 (Figures and ). |
pmc-6098894-2 | A 19-year-old female patient consults for lateral elbow pain and functional limitation with 3 months of evolution. She mentions a history of elbow fracture when she was 4 years old (apparently lateral condyle) treated nonsurgically. She did not have previous symptoms. These appeared with increased elbow overload because of physical activity when entering the Military Academy. Physical exam showed pain and sign of instability such as positive pivot shift, which had to be confirmed under fluoroscopy; clinical attitude in the elbow varus was less evident than in the first case. In the anteroposterior radiograph, 10-degree varus was observed. MRI informed signs of chondral injuries in the radial head and the lateral collateral ligament, too. The MEPI was 65.
A lateral ligament reconstruction with autologous graft of palmaris longus was performed with similar technique of the first case and also capsular plication. The repair was protected with a transarticular nail for 3 weeks. Then, she began with progressive rehabilitation.
A stable elbow, full flexion and extension range, and full pronosupination were achieved. After 2 years of follow-up, the MEPI is 100 and DASH 0. She was capable of performing all daily life activities (Figures –). |
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