A 43-year-old female was admitted to our hospital complaining of numbness in the left limb for one week. Past medical history was notable for the diagnosis of NMO and intracranial hemorrhage. The patient was diagnosed with NMO ten years ago due to repeated episodes of blurred vision and numbness and weakness in the limbs. Brain and spinal magnetic resonance imaging (MRI) at that time indicated lesions in the brain white matter as well as spinal cord involving cervical and thoracic regions. AQP4 antibody test was not performed. Considering the potential diagnosis of demyelinating disease, steroid pulse therapy was initiated and the patient improved after the treatment. After discharge, corticosteroid was gradually tapered and the patient was maintained at a low-dose corticosteroid and azathioprine in the long term. The patient was also diagnosed with left basal ganglia hemorrhage three years ago, presenting as right-sided hemiplegia and confusion. Brain angiography was not performed at that time, and the patient recovered after symptomatic treatment. Family members exhibited no sign of the case pathology. Upon examination, the patient appeared lethargic and sluggish, with normal vital signs. Visual acuity was impaired in the right eye with a score of 20/200 on testing. Pupils were 3 mm bilaterally, round and reactive. Regarding motor function, muscle strength was decreased in the left extremities (Medical Research Council strength score, grade 3). Hypoesthesia of the left side was also observed. Babinski sign was present bilaterally. Further investigations revealed a positive AQP4 antibody in the serum, with an elevated titer of 1:32. An initial diagnosis of NMOSD was made considering her medical history and radiological findings. Other tests including complete blood count, basic metabolic panel, serum glucose, and anti-nuclear antibodies were all normal. Brain MRI after admission indicated lesions with restricted diffusion in the right thalamus and hemosiderin deposition in the left basal ganglia (Figure ). Unexpectedly, brain magnetic resonance angiography revealed severe stenosis of bilateral anterior and middle cerebral arteries, as well as stenosis of the right posterior artery and the intracranial segment of the right internal carotid artery. Radiological findings, as a result, strongly suggested the diagnosis of MMD. Digital subtraction angiography further confirmed this diagnosis with findings of bilateral occlusion of distal internal carotid arteries and rich collaterals near the skull base (Figure ). After antiplatelet and other symptomatic therapies, the patient improved. She refused further treatment with vascular reconstruction surgery and received physical therapy at a local rehabilitation center.


A 54-year old man presenting with progressive cognitive impairment was admitted to the memory clinic at the Department of Psychiatry and Psychotherapy. His Mini-Mental State Examination score showed a cognitive impairment (24 out of 30 points). Furthermore, he had mild orofacial dyskinesia, which was suggested to be a side-effect of his medication with melperone. The patient received this treatment because of a sleep disorder and restlessness. After clinical examination he was referred to the Department of Nuclear Medicine with the suspected diagnosis of Alzheimer’s disease for an 18F-FDG PET/CT study. Family history was empty showing no neurodegenerative or psychiatric diseases in first degree relatives. The patient’s father had suffered from a stroke with persisting disability and died at the age of 66 years.
While CT and MRI showed no pathologic findings, the 18F-FDG PET/CT (Philips Gemini TF16, Best, Netherlands) of the brain revealed a severe bilaterally decreased uptake in the striatum (Fig. ). Additionally, we performed two different voxel-based intersubject statistical analyses to a reference database. First, using NEUROSTAT [] we performed 3D standard surface projections (3D-SSP) from patient’s 18F-FDG-PET and compared them to an age-matched 3D-SSP database in order to detect dementia-related hypometabolism in the cortical areas (Fig. ). In a second step, focusing on subcortical regions, we used SPM 12 (Wellcome Trust Centre for Neuroimaging at UCL, London) implemented in Matlab 9.0 (MathWork, Sherborn, Mass.) and performed a voxel-by-voxel single subject analysis of the whole brain. We then compared our patient to an age-matched healthy group used in NEUROSTAT []. Concordant to the visual findings we found a significant reduced bilateral uptake in the striatum (Fig. ).
Following imaging Huntington’s disease (HD) was being favored as underlying cause for the patient’s cognitive impairment. Subsequently, a molecular genetic testing was initiated, which confirmed the diagnosis of HD. One allele showed an abnormal CAG repeat of the Huntingtin gene (HTT) in chromosome 4p16.3 of 41 ± 1, while the other allele was normal (CAG repeat of 20 ± 1).


A seven-year-old boy presented to an outside facility after sustaining a hip injury while playing organized football. He reported that he was struggling at the bottom of a pile when he developed severe hip pain. At the outside hospital, he was diagnosed with a posterolateral hip dislocation. No attempt at reduction was made at the referring hospital. After consultation with a local orthopedist, the patient was transferred to our tertiary care facility via helicopter, and he arrived approximately 5.5 hours after initial injury. Prior to his arrival, preparations were made by ED staff for a rapid, comprehensive trauma evaluation and emergent sedation and reduction measures.
The patient complained of right leg pain and tingling upon arrival, with no reported pain elsewhere. Physical exam revealed that he was moderately distressed from pain and slightly tachycardic. The right lower extremity was internally rotated with flexion at the knee. He had normal distal pulses, good capillary refill, and was able to move his toes. Pelvic radiograph confirmed posterolateral right femoral head dislocation without evidence of fracture, as seen in . Point-of-care focused assessment with sonography for trauma exam and chest radiograph were also completed and both were negative.
A complete trauma evaluation confirmed an isolated right hip dislocation with no contraindications to procedural sedation to facilitate dislocation reduction. Given his stable hemodynamics, he was sedated with intravenous propofol. Once sedated, the pelvis was stabilized by providing posteriorly directed countertraction to the pelvic girdle preparing for reduction via Allis technique. The emergency physician (EP) stood on the bed, flexed the hip and knee to 90 degrees, placing the patient’s right leg into a simulated seated position, and provided steady anterior traction by pulling from behind the knee and slightly internally rotating. The right hip was easily reduced without complication and the patient remained hemodynamically stable. Post-reduction, radiographs were performed showing complete reduction of the femoral head, as seen in . The patient’s pain was improved and his paresthesias were resolved.
Pediatric orthopedics was subsequently consulted, recommending a pelvic computed tomography (CT), which was negative for fracture. The patient was placed in a knee immobilizer and admitted for observation. He was discharged the next day with a walker, restricted to toe-touch weight-bearing of the right lower extremity with no hip flexion past 90 degrees or adduction past midline. He did well in follow-up, returning to full weight-bearing activity and exercise two months post-injury.


Eleven years ago, when our patient was a 33-year-old unmarried nulligravida, she developed CCC of the ovary for the first time. At that time, her menstrual cycle was regular and 30 days long, with dysmenorrhea, manifesting as lower abdominal and lumbar pain, persisting for 5–7 days. There was no family or medical history of note. She had visited a local clinic with the chief complaint of lumbar pain, where a right ovarian tumor 8 cm in size that included solid internal components, was identified, and she was referred to the University of Tsukuba Hospital. Transvaginal ultrasound had revealed a right adnexal mass with solid components, 68 mm × 53 mm in size, and an intramural uterine fibroid 23 mm × 27 mm, with no hypertrophy of the endometrium, which measured 2.1 mm. Blood counts and blood biochemistry test results revealed no abnormalities. Her serum CA19-9 level was 45.9 U/ml, CA125 was 22 U/ml, and CEA level was 1.3 ng/ml. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an 80-mm unilocular cystic mass in the right ovary with a papillary protrusion of longest diameter 45 mm. The left ovary was not enlarged, and there was no obvious peritoneal dissemination or enlarged lymph nodes. Surgery, comprising right adnexectomy, left ovarian biopsy, partial omentectomy and uterine fibroid removal, was performed. The right ovary was enlarged to 8 cm in size, and it was removed without intraoperative rupture and with its capsule intact. The left ovary was not enlarged, but was seen to have a small endometrial cyst, which was resected. The absence of peritoneal dissemination and enlarged lymph nodes was confirmed during surgery. The pathological diagnosis was CCC localized to the right ovary and endometriosis was observed in the left ovary, with ascites cytology Class III. The cytology was composed of clusters that include atypical cells having somewhat nuclear enlargement, and it makes a diagnosis difficult to distinguish mesothelial cells from malignant cells. The patient expressed a strong desire to preserve her fertility. Hence, pelvic and para-aortic lymph node dissections were performed via staged laparotomy, which revealed no metastases in any of the 91 pelvic or para-aortic lymph nodes that were removed, leading to a diagnosis of Stage IA CCC. Four courses of postoperative combination paclitaxel (175 mg/m2) and carboplatin (AUC6) chemotherapy (TC therapy) were administered to complete the initial treatment.
Nine years after the initial therapy, MRI during regular 6-monthly monitoring revealed the appearance of a 95-mm polycystic mass with a mural nodule of longest diameter 53 mm in the left adnexal region. Those findings were never seen at the previous MRI. At this time, her serum CA19-9 level was 12.9 U/ml, CA125 was 18.3 U/ml, and CEA level was 0.5 ng/ml, all of which were within normal limits. Disease recurrence in the contralateral ovary was diagnosed, and total abdominal hysterectomy, left adnexectomy and omental biopsy were performed. At the time of surgery, the left ovary was enlarged to 95 mm in size, and it was removed intact without intraoperative rupture of its capsule. The internal lumen of the tumor contained several milky-white mural nodules extending around 15 mm into the cavity (Fig. ). The histological diagnosis was CCC, but in addition to the possibility of recurrence, it was also considered that the tumor might have developed de novo, and the fact that clear cell adenofibroma (CCAF) was also present (Fig. ) suggested that this might have provided the genesis for its development. In addition, there were no endometriotic lesions in the non-solid cyst wall, and it only consists of fibrous membrane. The tumor was localized to the left ovary, and since ascites cytology was negative, it was diagnosed as Stage IA disease. The treatment was completed with four courses of postoperative TC therapy.
Two years after the completion of treatment, the patient is continuing outpatient monitoring with no sign of recurrence to date.


A 28-year-old male, deaf and dumb since birth, presented to the medical department (MD) of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) in November 2018 for the evaluation of generalized upper and lower limb weakness along with progressive facial puffiness (Figure ) for the past nine years. There was also a history of lower limb swelling for the past seven years.
On examination (O/E), his pulse was 82 beats/min, blood pressure (BP) was 110/70, respiratory rate (RR) was 16 breaths/min, and he was afebrile. There was no thyroid enlargement. Lower limbs showed nonpitting edema up to the ankles. Upon neurological examination, bulk showed diffuse bilateral pseudohypertrophy of the calf muscles (Figure ) and the deltoids, tone was normal, power was 4/5, reflexes were 2+, and Gowers’ sign (GS) was positive. The skin was coarse and dry with dermopathy. Systemic examination was normal.
Laboratory investigations revealed hemoglobin (Hb) of 11.7 gm/dl, raised serum cholesterol of 310 mg/dl, raised TSH of 35.2 μIU/ml [Normal (N) = 0.4-4.0], decreased levels of thyroxine (T4) of 0.14 μg/dl (N = 4.5-12.5), low plasma triido thyronine (T3) of 26.2 ng/dl (N = 84-172), anti-thyroid peroxidase antibody (anti-TPO Ab) <10 (N = <35), elevated creatine phosphokinase (CPK) of 1108 U/L (N= 85-170), creatine kinase-muscle and brain (CK-MB) of 126 U/L, elevated lactate dehydrogenase (LDH) of 930 U/L (N = 225-450), and raised serum aldolase of 9.3 U/L (N = 0-7). Blood glucose, liver function tests, blood urea, and serum creatinine were not remarkable. Abdominal X-ray revealed bilateral renal cortical cysts; however, no calculus or hydronephrosis was seen in both kidneys. Evaluation of cardiovascular and respiratory systems did not show any significant abnormality. Electromyography (EMG) and nerve conduction study (NCS) were normal. A biopsy was taken from his right deltoid muscle which showed mild changes in fiber size and local fibrosis. The findings were suggestive of myopathy. Immunohistochemistry was not done due to financial constraints.
A diagnosis of HS was made based on clinical manifestations, laboratory investigations, and confirmatory muscle biopsy report. We further suspected PS as the cause of hypothyroidism in this patient based on his symptoms of congenital deafness and thyroid dysfunction. A tone audiometry was carried out which showed bilateral sensorineural hearing loss. A diagnosis of PS was finally established by performing a perchlorate discharge test which showed an abnormally rapid loss of radioactive iodine from the thyroid gland after the administration of perchlorate.
The patient was initially treated with 100 μg levothyroxine daily which was gradually increased to 150 μg after two weeks. The patient was assessed after four weeks. His swelling resolved and TSH levels went down to 13 μIU/ml . The patient is under regular follow up with improvements in his symptoms.


A 90-year-old woman was diagnosed with type 2 diabetes mellitus more than 10 years ago. Her body weight was 41.7 kg (BMI: 20.1 kg/m2). There was no problem with liver function, AST: 24 (10-40) IU/mL, and renal function, creatinine: 0.68 (0.45-0.82) mg/dL. Diabetic complications were not observed. Initially, hemoglobin A1c (HbA1c) level was controlled at 6% by glimepiride (3 mg) and metformin (250 mg); however, she visited our clinic before the scheduled date claiming that “the medicine is gone.” Due to cognitive decline, an overdose of glimepiride and metformin was suspected, and the drugs were discontinued.
The patient was prescribed teneligliptin (20 mg), a dipeptidyl peptidase 4 (DPP-4) inhibitor with low hypoglycemia risk, but HbA1c levels increased to 10.2% within 6 months. Although resuming glimepiride treatment was considered, we opted to administer 2 mg exenatide-LAR once weekly to minimize the risk of hypoglycemia caused by overdosing. Despite declining cognitive function, she visited our clinic weekly for exenatide-LAR injections. HbA1c level rapidly decreased; after 4 months, it reached 7.1% (Figure ). Moreover, good blood glucose control was achieved.
To reduce the dose frequency, we extended the dose interval to 2 weeks and subsequently to 1 month. HbA1c level was in the 6% range when exenatide-LAR was administered every 2 weeks. It was in the 7% range for more than 2 years when administered once monthly. Fasting glucose just before the next injection did not rise. Once-a-month administration allowed the patient to easily receive effective outpatient treatment despite cognitive loss. However, outpatient treatment became difficult after the patient sustained a spinal compression fracture; hence, the drug was administered by a home care provider without issues. During the period of observation, liver and renal functions were not changed. The patient's body weight did not appreciably change, and no adverse events, such as loss of appetite or hypoglycemia, were observed with exenatide-LAR.


An 85-year-old woman was diagnosed with type 2 diabetes mellitus several years ago. Her body weight was 61.0 kg (BMI: 31.1 kg/m2). There was no problem with liver function, AST: 24 (10-40) IU/mL, and renal function, creatinine: 0.54 (0.45-0.82) mg/dL. Diabetic complications were not observed. She was treated with teneligliptin (20 mg), but blood glucose control gradually worsened and HbA1c level increased to 9.7%. Her family informed us that she often forgot to take her multiple medications, which we assumed accounted for the poor blood glucose control.
As the patient did not wish to receive at-home injections, weekly injections of 2 mg exenatide-LAR were administered at our clinic. After switching from teneligliptin to exenatide-LAR, HbA1c level rapidly decreased and was maintained in the 6% range (Figure ). The administration interval was extended to every 2 weeks and subsequently to 1 month. The blood glucose level was well controlled after both extensions. It remained steady for more than 1 year after shifting to monthly administration even though the patient underwent chemotherapy for breast cancer during this time. Only exenatide-LAR was required for blood glucose control. During the period of observation, liver and renal functions were not changed. The patient's body weight did not appreciably change, and no adverse events, such as loss of appetite or hypoglycemia, were observed.


A 58-year-old obese male presented to our Emergency Department with 2-day history of progressively worsening left lower quadrant abdominal pain, urinary urgency, and 3/10 groin pain. The patient also reported dysuria. Comorbidities included hypertension and Class 1 obesity with body mass index of 32. He denied experiencing similar symptoms in the past and reported no other past medical history, no smoking history, or relevant family history.
Physical exam was significant for obvious 7 cm left inguinal hernia bulge with tenderness to palpation. On attempt to reduce the hernia, the patient reported urinary urgency. Laboratory studies and urinalysis were within normal limits. A computed tomography (CT) scan revealed left inguinal hernia containing a portion of the urinary bladder (A–C).
The patient was taken to the Operating Room the same day for planned open left inguinal hernia repair with mesh. Intra-operatively, a portion of the urinary bladder was found to be inside the inguinal hernia. The inguinal hernia sac was initially difficult to differentiate from the bladder due to its thickness (A, B). The bladder was subsequently distended with Normal Saline via the Foley catheter and a large bulge was observed in the inguinal canal, confirming the bladder herniation. The bladder was then reduced into the abdomen and the inguinal hernia and defect were fixed with a polypropylene mesh.
The patient had no intra-operative complications. On post-operative day (POD) 1, the patient appeared well with minimal groin pain. Incision was clean, dry, and with no drainage or signs of infection. Patient was able to ambulate and tolerate diet. His Foley catheter was removed and the patient was able to urinate without pain or difficulty. Patient was discharged to home on POD 2 with controlled pain, regular diet, and normalized white blood cell count. He was seen in clinic 2 weeks post-operatively free of pain and with no urinary voiding symptoms. Incision was clean, dry, and healed.


A 29-week-old pregnant woman, 36 years old, resident of Itaboraí, metropolitan region of RJ, started a febrile illness with vomiting, arthralgia, headache, and epigastria on 03/16/2013. She was admitted to a hospital in RJ on 03/17/2013, presenting a leukocyte count of 13,000/mm³, hematocrit of 33.7%, platelet count of 276,000/mm³, and a positive result for a DENV non-structural protein 1 (NS1) antigen. She was dismissed and requested to return within 48 h for a new evaluation. On 03/22/13, the patient returned to the health unit with pain in the lower limbs, vaginal bleeding, a leukocyte count of 14,000/mm³, a hematocrit of 34.3%, and a platelet count of 112,000 mm³. She was hospitalized in the intensive care unit (ICU). The following day, she had intense bleeding, blood pressure of 13 × 10, vomiting with blood, a leukocyte count of 445,000/mm³, a hematocrit of 26.5%, and a platelet count of 56,000/mm³. The ultrasound revealed a stillborn; vaginal delivery was performed. The fetus was detached from the placenta and an autopsy was performed. Fragments of liver, spleen, brain, lung, and placenta were collected and sent to the Flavivirus Laboratory, FIOCRUZ on 03/27/2013 for case investigation. After vaginal delivery, she remained in the ICU, but died 11 days later, on 04/02/13. No autopsy was performed at that time. The case was classified as Dengue with Complications (DCC), according the criteria established by the Brazilian Ministry of Health in 2000. DCC was established to define severe dengue cases that did not meet the 1997 WHO criteria for dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).


A 23-year-old woman was urgently hospitalized due to the acute onset of headaches, nausea, and vomiting lasting over 5 days, with left-side extremity paraesthesia. Two weeks prior to the hospitalisation, the patient underwent a C-section in her 31st week due to foetal hypoxia. The baby was safely delivered. Prior to that, the patient was monitored by ultrasound due to the absence of detectable vascularization in several limited regions within the placental tissue, with the diameters of 35, 19 and 11 mm. She was administered antibiotics (amoxicillin + clavulanic acid) postpartum due to a mild temperature, but her temperature was not high enough to indicate infection. Two days prior to hospitalisation she was urgently screened neurologically because of a 3-day long headache. At that moment, she was without neurological deficits. The occipital headache was transiently lower in intensity after she received analgesic therapy. On the day of the admission, the patient had an intermittent short-term numbness in the left hand, left leg, and she reported she once felt numbness on the left side of her face.
Neurological examination indicated mild palsy of the left hand. A confrontation visual field test detected inferior homonymous quadrantanopia. Her gait was normal, not paretic. The patient was afebrile. Meningeal signs were negative. Blood pressure was 120/85 mmHg. Laboratory values upon admission are presented in .
During the last period of the pregnancy, reduced levels of free protein S (fPS) antigen (0.43) (1), and protein C path (or protein C global or activated protein C resistance) (0.77 normalized ratios (reference range >0.80)) were detected. There was no mutation in the genetic markers for thrombophilia (Factor V Leiden, Prothrombin MTHFR and PAI-1). Pathohistological tests of the placenta conducted after birth indicated placental infarction.
The acute thrombosis of the right transverse sinus, the right sigmoid sinus, and the sagittal sinus (A) were detected by urgent computed tomography (CT) of the head. The CT did not detect brain oedema or any signs of focal lesion. Immediate magnetic resonance imaging (MRI) of the brain was performed and the results were normal. Magnetic resonance venography (MRV) confirmed the absence of flow in the right transverse and right sigmoid and sagittal sinuses as a consequence of thrombosis (B).
Immediately following neuroimaging detection of a CVST, low-molecular-weight heparin therapy was administered (dalteparin subcutaneously twice daily at 7500 IU), followed by analgesics and folic acid substitution therapy. As recommended by the infectious diseases specialist, antibiotic therapy (ceftriaxone and vancomycin) was administered for a total of 12 days. Fundoscopic examination detected initial bilateral optic disc oedema, without visible peripapillary or retinal bleeding. The otorhinolaryngologic examination excluded any infectious diseases in the respective area. From the second day of the hospitalisation onward, the patient did not report paraesthesia or sight deficit. Electroencephalogram during the interictal period detected generalized cerebral dysrhythmia without lateralization. The symptomatology of increased ICP and papilloedema continued, which lead to introducing acetazolamide on the eighth day of the hospitalisation at an overall daily dose of 500 mg, and for a few days, mannitol 10% was given intravenously. Eight days after the initial examination, fundoscopy findings and optical coherence tomography (OCT) indicated worsening of bilateral papilloedema. Voluminous veins and flame-shaped haemorrhages were noticed at the edges of the right optic nerve papilla as well as one larger flame-shaped haemorrhage on the left temporal side.
At the beginning of the second week of the hospitalisation, the patient reported horizontal diplopia when looking left, with visible left lateral rectus muscle insufficiency (A). Five days later, we noticed a deficit in the function of the right lateral rectus muscle (B). At that point, the patient reported double vision in both horizontal directions. The Hess–Lancaster test confirmed weakness of both lateral rectus muscles (C). Visual field examination performed according to Goldmann demonstrated normal findings.
In the third week, there was a significant reduction and then a complete cessation of headaches. A follow-up MRV was performed 18 days after the initial one, and revealed partial recanalization of the dural venous sinus thrombosis (A,B).
In the fourth week of treatment, the recovery of the function of the left lateral rectus muscle was noticed at the same time as the intensity of the left-sided horizontal diplopia receded and ceased. Ten days later, the recovery of the right rectus muscle function was noticed and the horizontal diplopia completely ceased. The results of the follow-up Hess–Lancaster test were normal. Outpatient anticoagulant therapy was continued with warfarin.
Two months after the beginning of the treatment, fundoscopy results and OCT recorded complete withdrawal of the papilloedema. At the follow-up neurological examination three months after the onset of the disease, the patient was without neurological symptoms and without a bulb motility disorder. The follow-up MRV, three and a half months after the initial one, indicated further significant regression of the CVST. Along with the clear findings of the sagittal sinus, there was minimal marginal contour irregularity in the right transverse sinus and minor residual strip defects in the right sigmoid sinus (). Six months after CVST, warfarin therapy continued and the fPS antigen level was persistently low at 0.36 (1).
The study protocol was approved by the institutional review board, with the ethical code number R2-1281/2019.


An apparently healthy 65-year-old man without a tendency to bleed was referred to our center because of abnormal coagulation assay results (
) that were detected prior to surgery for thyroid nodule. He had never received any anticoagulants. Hereditary deficit was excluded, due to normal coagulation assays tested a year ago. Patient never showed thrombotic or hemorrhagic diseases. Thyroid nodule was removed without any bleeding problems during or after the procedure. At present, the patient is healthy and asymptomatic.


A 74-year-old man underwent TAPP for a left indirect inguinal hernia (M2, according to EHS classification) with a Parietex (Medtronic plc. Dublin, Ireland) mesh measuring 13 × 9 cm. Recurrence was confirmed 5 years postoperatively. To diagnose the type of recurrence and clarify the location of the defect, the orifice was inspected using laparoscopy and a 2-cm indirect hernia was detected inferior to the lower edge of the mesh (a and b). Next, the skin was incised for the anterior open approach. The inguinal canal was opened in a standard manner, and the hernia sac was identified under increased pneumoperitoneum. After isolating the tissues surrounding the hernia sac, adequate space was secured in the preperitoneal cavity to insert a plug. Then, the plug was inserted into the defect following sac invagination under reduced pneumoperitoneum. An XL-sized PerFix (BD, Franklin Lakes, NJ, USA) plug (height 3.8 cm, diameter 5.1 cm) was fixed to the transverse fascia and the previous mesh with six interrupted stitches using absorbable sutures. Finally, the overlap was confirmed to sufficiently cover the myopectineal orifice, and the plug was inverted under the peritoneal membrane using laparoscopy with increased pneumoperitoneum (). The entire operation time was 1 h and 58 min. No complication was reported in the postoperative course nor was re-recurrence at 3 months postoperatively.


A 72-year-old man presented with a 5-year history of paroxysmal, severe and electrical right facial pain in V2 and V3 trigeminal distributions, and complained of typical tic douloureux. Episodes of pain were triggered by washing face and brushing teeth with cold water. It was not relieved by over-the-counter medications. In the third year of the disease, magnetic resonance angiogram (MRA) showed vertebrobasilar dolichoectasia for this patient, and he underwent microvascular decompression (MVD) surgery. His facial pain completely resolved immediately postoperatively but had recurred at 5 months after surgery. Then he accepted the treatment of carbamazepine (600 mg per day) and gabapentin (900 mg per day), without complete pain relief, and the pain resumed every time when the treatment was reduced. The patient reported no alalia and visual changes, no numbness, or paralysis.
He was a patient with arterial hypertension (treated with indapamide), but without diabetes and any history of trauma, tumor or multiple sclerosis–related TN. He was a former smoker and drinker (40 pack-years). Physical examination revealed a well-developed, anxious male. The neurological examination revealed hypoesthesia and hypoalgesia in right V2 and V3 trigeminal distributions, and the right eye fissure was smaller than the left. The other vital signs and physical examination were normal.
Laboratory tests documented mild anemia (red blood cell count 4.22 × 10∧12/L, hemoglobin 124 g/L), hypokalemia (serum potassium level 3.44 mmol/L) with normal renal function. A slight reduction in above indicators may be associated with the patient's anxiety and poor diet due to the facial pain.
Magnetic resonance imaging (MRI) and MRA demonstrated a VBD compressing the right ventrolateral region of brainstem and the trigeminal nerve root entry zone (REZ) (). The contrast-enhanced MRI revealed a significant expansion of the basilar artery () and the widest part of the basilar artery was about 12-mm-diameter. Lacunar cerebral infarction was found in bilateral basal ganglia, left thalamus and right periventricular area, and hemosiderin deposition was found in right cerebellar hemisphere. The remainder of the brainstem, brain parenchyma, and cranial nerves appeared normal. Subsequent digital subtraction angiography (DSA) examination identified a basilar artery dissection indicating the delayed image of distal basilar artery and the stratification and retention of contrast agent (). The patient underwent partial basilar dissecting aneurysm embolization based on above evidences.
Immediately after surgery, pain attacks had adequate initial relief (barrow neurological institute, BNI Grades IIIa). The patient was discharged on postoperative day 7 without occurrence of other adverse events and continuous to take carbamazepine, which were stopped progressively eventually. The pain disappeared completely and did not need any more medications 6 months later. Three years after surgery, he had experienced no recurrence of the right facial pain. Physical examination including a neurological exam was normal. The final clinical diagnosis was VBD and basilar artery dissection.


A 48- year-old Chinese woman, gravida 4, para 2, was admitted to our hospital due to abdominal pain for 1 month. The clinical features of the patient at baseline were summarized in Table . The patient had a history of tubal ligation and denied asbestos exposure.
Fifteen years ago, the patient was diagnosed with a uterine myoma, which was about 8 cm in diameter. Instead of undergoing surgery, she opted for regular check-ups. One month ago, she developed abdominal pain and ultrasonography showed a 12 × 11.4 × 9.8 cm heterogeneous mass behind the uterus, with a cystic dark area of 3.4 × 2.3 cm (Fig. ). Ultrasound suspected as degeneration of uterine myoma. A further CT examination also considered it as a myoma fatty degeneration (Fig. ). Therefore, the patient underwent exploratory laparotomy.
Intraoperative observations were described as below: There was a small amount of viscous fluid in the pelvic cavity. The uterus was enlarged to the size of 2 months gestation. There was a mass about 12 cm in diameter behind the uterus with a pedicle attached to the uterus. The mass was multilocular cystic with myxoid fluid. The surface of the left ovary was dotted with minute neoplasms. No obvious metastatic lesions were observed elsewhere.
The mass was removed and a quick-freezing examination was performed. The results indicated that it was a mesenchymal tumor and adenomatoid tumor was possible. We treated her with a total hysterectomy and bilateral adnexectomy. The final pathology of paraffin confirmed it as localized well-differentiated benign mesothelioma (Fig. A). The results of immunohistochemistry showed that the 3 molecules Calretinin, D2–40, CK were positive, while p53, EMA were negative (Table ). The tiny neoplasm on the surface of the ovary was also thought to be mesothelioma involvement. In addition, a small nodule with a diameter of about 2 cm was found in the myometrium, and the pathological result suggested adenomatoid tumor (Fig. B).
The patient is now in stable condition, without any signs of recurrence during 1 year of follow-up.


A 49-year-old male patient sought treatment due to “repeated cough and sputum for one year and aggravation with chest tightness for one week.” Chest computed tomography (CT) in a local hospital revealed encapsulated effusion in the right thoracic cavity. Chest-enhanced CT after admission revealed a space-occupying lesion in the right chest. The pathological diagnosis according to percutaneous lung biopsy was a solitary fibrous tumor. Preoperative three-dimensional reconstruction showed that the blood supply to the tumor originated from the arteries and veins of the right lower lobe (Fig. ). After complete preoperative preparation, the patient underwent resection of the tumor with single-operation-incision thoracoscopy. Incision selection is one cm for the endoscope port (at the midaxillary line of the seventh intercostal space) and two cm for the operation port (at the preaxillary line of the fifth intercostal space). Intraoperative exploration revealed that the tumor had two tumor pedicles (Fig. ), and both were located in the right lower lobe. The tumor pedicles were intraoperatively separated using a linear stapling device. Because the specimen was large and the surface was smooth, bagging the specimen by the traditional method was difficult; therefore, the specimen was bagged by adjusting the operating table. The detailed procedure was as follows: First, the operating table was arranged with the head at a lower position, and the specimen bag was inserted into the thoracic cavity. Then, the operating table was adjusted such that the head was at a higher position to enable loading of the specimen into the specimen bag by gravity. Due to the large size of the specimen, extracting the specimen by the traditional method was difficult. Therefore, a special method named “pulling carrot” was applied to remove the specimen (Fig. ). The specific procedure was as follows. (1) The operation port was extended to five cm. (2) Several drawstrings were intermittently sewn at the smaller end of the longitudinal axis of the specimen. The area of suturing should be as large as possible, and if necessary, additional sewing should be carried out during the process of specimen extraction. (3) Two people synchronously pulled the drawstrings and the specimen bag, with up and down, left and right shaking. The size of the specimen was 18 × 12 × 6 cm (Fig. ). The surface of the specimen was smooth and the texture was soft and tough. Postoperative pathological examination revealed a solitary fibrous tumor immunohistochemistry: Vimentin (+), CD34 (+), bcl-2 (+), CD99 (+), SMA (−), S-100 (−), Desmin (−), P53 (−), CK (−), EMA (−), and Ki-67 positive rate of about 10%.


A twenty-year-old male has been followed up at the Clinic Hospital of Federal
University of Paraná due to medical history of epistaxis, ecchymosis, and
petechiae since infancy. At first, Bernard-Soulier syndrome was suspected due to
macrothrombocytopenia and tendency of bleeding. When he was 17 years old,
hearing loss and hypertension were detected along with mild renal failure,
microhematuria and nephrotic-range proteinuria. Renal biopsy could not be
performed due to risk of bleeding (platelets count: 7000/µL). Cataracts were
excluded by ophthalmological evaluation. Due to the clinical suspicion of
MYH9-RD, genotyping of the patient and of his parents was
performed. A de novo missense mutation in exon 1 of the
MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu] was
detected (). Actually, neither his
parents nor his brother and sister had clinical manifestation of
MYH9-RD. Enalapril (20 mg/day) was initiated for renal
protection. The patient did not adhere to treatment and was lost to follow-up.
Two years later, he returned to the outpatient clinic complaining of foamy
urine, peripheral edema, and hypertension (160/120 mmHg). Laboratory tests
detected worsening of renal function and persistent proteinuria. shows the evolution of laboratory
parameters during the follow-up.


A woman, 70 years old, with dyspnoea (New York Heart Association scale, NYHA class III), referred for severe aortic regurgitation. At the transthoracic echocardiography (TTE) aortic valve presented with an annulus diameter of 23 mm, a mean gradient of 7 mmHg and a severe AR with a pressure half time (PHT) inferior at 300 msec. The effective regurgitant orifice was 0,3 cm2 and the regurgitant volume was 65 ml. The AR was associated with a left ventricular dilatation with a left ventricle end diastolic volume (LVEDV) of 160 ml, left ventricle end diastolic (LVEDD) and systolic (LVESD) diameters of 57 mm and 41 mm, and a normal ejection fraction (60%). The patient was previously treated for a myocardial infarction with drug eluting stents in the right coronary artery (RCA) and in the circumflex artery, and with another drug eluting stent in RCA for late in-stent restenosis. She had a stenosis of 55% of the left internal carotid artery and severe peripheral vascular disease. Preoperative Chest X-ray () and computed tomography (CT) of the thorax () confirmed the presence of a PA. In particular, CT showed heavy and diffuse calcifications involving all the aortic annulus and the aortic root and numerous large spots of calcium from the sinotubular junction to the upper portion of the ascending aorta. These findings allowed for a diagnosis of type IB PA.
The patient’s expected operative risk, calculated according to the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE II), was 2,24%.
We evaluated the available options and decided for an aortic valve replacement (AVR) with a sutureless Perceval valve (LivaNova, Saluggia, Italy) implanted in full sternotomy.
The ascending aorta was cannulated in a restricted safe area, previously identified on CT images, by Seldinger technique (EOPAtm, Medtronic-Inc, Minneapolis-USA), then cardiopulmonary bypass was instituted, and the aorta was clamped in a non-calcified ascending aorta segment. Myocardial protection was obtained with a single dose of warm blood cardioplegia delivered selectively in the two coronary ostia. Aortic valve leaflets were removed, and a Perceval valve (M-size) was implanted without using the 3 guiding sutures, because of huge and totally diffusing calcifications involving the aortic annulus and the aortic root. To correctly position the valve in the native annulus, the surgeon found the solution of carefully measuring the distance between the nadir of each cusp and the aortotomy. Closure of the aortotomy was reinforced with two layers of autologous pericardium. The cardiac arrest time was 45 min, the cardio-pulmonary bypass (CPB) time was 59 min. Intraoperative transoesophageal echocardiographic assessment showed no paravalvular leakages (PVL). The patient was extubated 7 h later in the intensive care unit. The correct position of the valve was confirmed by the postoperative TTE.
In the postoperative period we noticed an atrial fibrillation with left bundle branch block and an asystole of 7 s; those findings lead us to decide to implant a bicameral pacemaker. The patient was discharged on the 7th postoperative day.
At 2 years follow-up the patient was in NYHA class I and TTE showed no PVL (), a mean gradient of 11 mmHg, LVEDV, LVESD and LVEDD of 85 ml, 32 mm and 43 mm, and left ventricular ejection fraction was 66%.


An eight-year-old male child presented to the pediatric department of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) in January 2019 with the complain of ulcer on his right foot, high-grade intermittent fever without chills, and rigors and swelling in the same foot for the past three years, one month, and one week, respectively. He also had a history of urine dribbling and physical delayed development. He was a known case of MMC that was reconstructed at one month of age. As a congenital abnormality, he was also born with CF deformity for which PM was started as a treatment at four years of age. After the removal of the first cast which was applied for six months, his mother noticed ulcer on the right foot which was spreading but went untreated.
On examination (O/E), the patient was found alert and active, lying comfortably in bed. His heart rate (HR) was 88 beats/min, blood pressure (BP) was 110/80, respiratory rate (RR) was 26 breaths/min, and he was febrile with 103°F body temperature. Upon evaluation of the right foot, we found local non-tender edema over the dorsum along with ulcer and sinuses discharging pus with palpable posterior tibial artery. A scar mark was present on his back which was due to MMC repair. Upon central nervous system (CNS) examination, motor system evaluation of lower limbs revealed increased tone, slightly exaggerated reflexes especially increased dorsiflexion with the knee flexed accompanied by clonus and a power of 5/5. All other systems were unremarkable.
Laboratory investigations revealed hemoglobin (Hb) of 7.7 gm/dl, mean corpuscular volume (MCV) of 67.9 fl (Normal [N] = 76-96), mean corpuscular hemoglobin concentration (MCHC) of 28.2 gm/dl (N = 32-36), total leukocyte count (TLC) of 19.2 x 103/μL (N = 4-11) and platelet count (PLT) of 468 x 103/μL (N = 150-400). The level of C-reactive protein (CRP) was found to be 269.1 mg/L (N = <5). The clotting profile showed an international normalized ratio (INR) of 1.09 and prothrombin time (PT) of 11.4 seconds. Blood glucose, liver function tests, blood urea, and serum creatinine were not remarkable.
Electrophysiology tests, nerve conduction velocity (NCV) and electromyography (EMG), concluded the involvement of multiple lumbosacral roots on the right side and L4-L5-S1 roots on the left side. Multiple abscesses extending into deep tissues were revealed by ultrasound (US) scan of the right foot. On further investigation via a Doppler scan of the same foot, right dorsalis pedis artery (DPA) showed monophasic flow with normal peak systolic velocities which was suggestive of mild arterial insufficiency secondary to surrounding abscesses. Based on these findings, magnetic resonance imaging (MRI) of the right foot was ordered which demonstrated lytic center with a ring of sclerosis in tarsal bones (Figure ). A triple-phase technetium 99 (Tc-99) based bone scan was done which showed increased uptake in all three phases, therefore, suggested OM involving tarsal bones of the right foot. Keeping in view the provided history, clinical presentation, lab results and the radiologic findings of this patient, a diagnosis of OM secondary to PM for the treatment of CF was made.
The patient was initially started with intravenous (IV) ceftriaxone 900 mg 12-hourly along with vancomycin 360 mg 8-hourly. IV administration of provasc and dexamethasone were also given to relieve pain. Pus drainage was also done. After two weeks, ceftriaxone was replaced by IV ciprofloxacin 180 mg 12-hourly with the same dose of vancomycin. After another two weeks, ciprofloxacin was replaced by IV meropenem 360 mg 8-hourly again with the same dose of vancomycin. This regimen was also given for two weeks. The patient clinically subsided foot swelling and fever. Locally, the ulcer also healed leaving scarred skin (Figure ). He ended up with the monotherapy of meropenem 360 mg 8-hourly as a prophylaxis to complete the antimicrobial course.


A 27-year-old nulliparous woman presented with an increasing vulval lump for 2-year duration without any significant associated symptoms. She has no history of pain, discharge, or any bleeding from the area. She denied any history of previous vulvar lesion or any other systemic symptoms. Her past history and family history revealed nothing significant.
The physical examination revealed a hard, mobile, nodular, subdermal, mass measuring 30 × 20 mm over the mons pubis and it was about 2 cm superior to the clitoris and 1 cm lateral to the midline. It was fixed to the overlying skin which had a normal appearance. The lesion was nontender and on palpation there was no sign of discharge or bleeding. There were no palpable lymph nodes. Preoperative ultrasound scan showed no increased vascularity around the lump. An excision biopsy of the lesion was performed under regional anaesthesia. Macroscopically, the specimen measured 30 × 20 mm. The overlying skin was unremarkable. On slicing, the cut surface was pale tan. Microscopy revealed a poorly circumscribed, unencapsulated tumor composed of nests and strands of polygonal cells having abundant eosinophilic granular cytoplasm and small, central hyperchromatic nuclei. Cell margins are indistinct. The margins appear infiltrative. However, there is no nuclear or cytological atypia. There are no mitoses and excision margins are free of tumour. Immunohistochemistry showed that the tumor cells are S-100 positive. These features were compatible with a GCT without features of malignancy. On the follow-up appointment at 4 months after the excision procedure, the patient was asymptomatic. Microscopic appearance with Haematoxylin and Eosin and immunohistochemical staining has been shown in .


A 17-year-old girl; a known case of a repaired high imperforate anus, repaired type-C tracheoesophageal malformation, and left renal agenesis; presented to King Abdullah University Hospital (KAUH) complaining of dysmenorrhea for 3 years duration. She was 14-year-old when she had her menarche. The menstrual cycle was irregular and associated with severe dysmenorrhea. She had the dysmenorrhea 4 days before the period, during the period and lasted 1 week after. The pain was slightly relieved by analgesics. The complaint was associated with vomiting, anorexia, and general fatigability. Prior medical and surgical history included two-steps primary anoplasty repair for imperforate anus which involved a temporary colostomy creation followed by posterior sagittal anorectoplasty. The tracheoesophageal fistula was repaired by resection of the fistula and anastomosis of the esophageal limbs. Examination revealed abdominal mass and tenderness.
Laboratory investigations were conducted and revealed elevated levels of cancer antigen 125 (CA 125) (241 U/ml) and CA 19–9 (67 U/ml). Other tests including complete blood count, kidney function test, CA 15.3, alpha-fetoprotein, lactate dehydrogenase, and human chorionic gonadotropin (hCG) were all within normal levels. Also, urinalysis and culture disclosed no abnormalities.
Abdominal and pelvic ultrasound was performed and showed a thick-wall left pelvic mass measuring 6 × 6 cm and another 7 × 8 cm left pelvic mass mostly endometrioma. Renal ultrasound confirmed the solitary right kidney with compensatory hypertrophy. Pelvic magnetic resonance imaging (MRI) revealed a normal uterus on the right side, a normal right ovary, a 7 × 8 cm left endometrioma, a tortuous dilated fluid-filled structure in the left hemipelvis mostly represented left-sided hematosalpinx, and a well-defined lesion with thick enhancing wall in the left hemipelvis measuring 6.7 × 5.7 × 5.6 cm with similar enhancement to the uterus in the right suggestive of MDA probably double uterus obstructed on the left side with large hematometra. (Figs. and ).
Initially the patient had diagnostic laparoscopy using the open technique, however, the patient had extensive adhesions and thus laparotomy with adhesiolysis was performed. At laparotomy, there was a right unicornuate uterus with a normal cervix and a non-communicating distended left rudimentary horn. Additionally, there was a left hematosalpinx of the left tube which was connected to the left horn, and a left endometrioma. The right ovary and tube looked normal. The single right ureter was also identified. The left non-communicating horn was resected. In addition, left salpingectomy and left ovarian cystectomy were performed. The right uterus and both ovaries were preserved. The diagnosis of class U4a uterine anomaly (unicornuate right uterus with rudimentary non-communicating cavitary left horn) was established (Fig. ). No intraoperative or immediate postoperative complications were detected. The patient was discharged on the fourth postoperative day. Histopathological examination of the specimen was reported as uterine rudimentary horn with unremarkable myometrium and secretory endometrium, and left endometriotic cyst. At 9 months follow up, the patient had regular menstrual cycles and the pain subsided completely.


A 49-year-old man presented in February 2017 with chest wall pain and weight loss, leading to the diagnosis of a ccRCC with metastases to the lungs and a rib (Fig. ). Based on his presentation with anemia, hypercalcemia, and the need for prompt initiation of systemic therapy, his International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring predicted a poor prognosis with a median survival of 7.8 months []. Initial management included a right radical cytoreductive nephrectomy, which required a partial hepatectomy. Pathological analyses showed a 9 cm ccRCC invading into the perirenal and renal sinus adipose tissue as well as the ipsilateral adrenal gland of ISUP grade 4 with extensive sarcomatoid differentiation. Eight out of eight lymph nodes were positive for metastatic disease. Staging was consistent with a pT4N1 tumor. IHC studies showed positivity for CK AE1/AE3, and CA-IX. CK7 was negative. PBRM1 and BAP1 were present suggestive of a wild-type state. PD-L1 was expressed in more than 30% of tumor cells. Given the age of the patient, germline testing was pursued using a CancerNext-Expanded genetic panel including genes such as VHL, BAP1, FLCN and PTEN, but did not reveal any mutations.
Within two hours of surgery, a sample of the patient’s tumor was implanted orthotopically into several NOD/SCID immunocompromised mice to generate a tumorgraft (or patient-derived xenograft, PDX) model (Fig. ). RCC tumorgrafts have shown promise as models in preclinical experimentation preserving the molecular genetics and biology of the corresponding patient tumor []. The patient’s tumor was particularly aggressive and a renal mass could be palpated as early as 18 days post-implantation, which is unusual []. After 83 days, the tumor had reached 1500 mm3 and was passaged to subsequent cohorts. Histological characterization of the tumorgraft revealed preservation of the morphology of the patient’s tumor, with extensive sarcomatoid differentiation and high levels of PD-L1 expression by IHC (Fig. a).
One month from initial staging scans, repeat computed tomography (CT) imaging revealed progression of lung and rib metastases. The patient enrolled in a clinical trial combining stereotactic ablative radiotherapy (SABR) and HD-IL2 []. He received SABR treatments to his left rib (25 Gy, one fraction) and a left lung metastasis (25 Gy, one fraction) followed by two courses of 600,000 international units/kg IV of HD-IL2 q 8 h. He received ten and nine doses of HD-IL2, two weeks apart. Subsequent imaging studies demonstrated improvement in the radiated lung and rib metastases (Fig. a). Otherwise, there was a mixed response with improvement in some non-radiated lung nodules, but also the development of new metastases in the lungs, lymph nodes, and right femur (Fig. b).
In June 2017, the patient was switched to pazopanib (800 mg PO qd). He also underwent a right total knee replacement followed by adjuvant radiation (20 Gy over 5 fractions). Repeat scans after three months demonstrated progression of existing lung and nodal metastases, and three new right shoulder metastases, which were painful (Fig. c).
One week later, the patient began nivolumab monotherapy (240 mg IV q 2 weeks). A few days after the initial infusion, the patient developed grade 2 dermatitis (by Common Terminology Criteria for Adverse Events, CTCAE) [] at the sites of prior rib and knee radiation, possibly related to radiation recall (Fig. d). Inflammation improved over the following month during which nivolumab was withheld. Upon resolution, the patient resumed treatment with nivolumab and received three additional doses without a dermatologic reaction.
Restaging CT scans three months after the initial nivolumab infusion showed a decrease in size of all lung metastases (Fig. e), stable disease at all other sites and no new lesions. The patient continued nivolumab for five additional infusions with interim development of grade 2 hypothyroidism managed with levothyroxine therapy, but then stopped infusions after the development of autoimmune colitis (confirmed by colonoscopy and biopsy; Fig. f).
CT and magnetic resonance (MR) scans at this time, eight months from initial nivolumab infusion, confirmed an iRECIST [] PR with an interval improvement in several sites including the shoulder metastases. Following resolution of the diarrhea, the patient received additional nivolumab but developed grade 3 autoimmune hepatitis requiring intravenous steroids and mycophenolate mofetil, and nivolumab was discontinued.
Seven months after the last infusion of nivolumab and 2 years since diagnosis, the patient remains off immunotherapy without progression and near complete resolution of shoulder metastases (Fig. e).
We radiolabeled atezolizumab, a monoclonal anti-PD-L1 antibody with a mutant Fc, with zirconium-89 [89Zr]. Zirconium-89 is a well-studied positron emitting radioisotope used to label antibodies with a half-life of 78 h, which is compatible with the slower pharmacokinetics of antibodies []. This allows imaging to be performed for several days after injection to improve tumor-to-background signal. Accumulation of the isotope in tumor sites over time and clearance from other sites improves contrast.
Methodologically, the antibody was conjugated to the chelator deferoxamine (DFO) at a molar ratio of 1:1.9 and radiolabeled with 89Zr (5 mCi per mg of DFO-atezolizumab conjugate) using previously published protocols [, ]. Briefly, the DFO-atezolizumab conjugate was incubated with neutralized 89Zr for 1 h, and the reaction was quenched with 50 mM diethylenetriamine pentaacetic acid. The radiolabeled antibody fraction was purified using the Zeba™ centrifugal spin columns (40 K MWCO) and eluted in 0.2 M sodium acetate buffer containing 5 mg/mL gentisic acid (pH 5.5–5.6). The conjugate had a specific radioactivity of 2–4 mCi/mg protein, with high radiochemical purity (≥ 99%). The immunoreactivity of the radiolabeled immunoconjugate was confirmed using an in vitro cell-based Lindmo assay [] and was 86.2 ± 4% (n = 6). In addition, the conjugate was tested for stability in plasma and was found to be quite stable (> 80% of 89Zr activity retained with atezolizumab in rat serum at 37 °C after 7 days).
Mice bearing the patient-derived tumorgrafts were injected intravenously (by tail-vein) with ~ 100 μCi of 89Zr-DFO-atezolizumab. A second tumorgraft line from a tumor expressing low levels of PD-L1 (< 1%) by IHC was chosen as a negative control (Fig. c). PD-L1 IHC procedures and interpretations were standardized (Biocare Medical, Clone ACI3171A,C; 1:300) and results were scored by a pathologist blinded to other results.
Mice were serially imaged on a Siemens Inveon PET/CT system. PET quantification was performed blinded. PET imaging at day 6 post-injection (d.p.i.) showed a statistically significant difference in 89Zr signal between the index patient tumorgrafts (4.2 ± 0.6% injected dose/g [%ID/g]; n = 3) and the controls (3.1 ± 0.5% ID/g; n = 3) (p = 0.028) (see Fig. ). Similar results were observed with a second independent cohort of tumorgrafts (5.2 ± 0.4% ID/g; n = 3) compared to the same control group (p = 0.002).
Differences in tumor uptake could not be accounted for by differences in tumorgraft volumes, which were not significantly different between the index and control groups (831.9 ± 473 mm3 versus 1010.3 ± 492.6 mm3; p = 0.62, respectively). Further, the tumor/muscle contrast in the index tumorgrafts was 4.4 ± 0.4, which is also significantly higher than controls (2.7 ± 0.6) (p < 0.05). (All statistical analyses were performed using GraphPad Prism 7 by un-paired t-tests without correction for multiple comparisons and an alpha value of 0.05.) Following the last PET scan, mice were sacrificed, and tumorgrafts and other vital organs were collected for IHC assays. IHC analyses of the tumorgrafts confirmed expected levels of PD-L1 expression.


A 57-year-old previously healthy Caucasian male presented to a community hospital
with a 3-day onset of epigastric abdominal pain, nausea, vomiting, and new-onset
ascites. Initial workup revealed normal liver function studies. His lipase was
elevated. Diagnostic paracentesis was consistent with hemorrhagic fluid with red
blood cell count of 640 504/mm3 and white blood cell count of
1440/mm3. Computed tomography scan of the abdomen was concerning for
a 15 mm lesion in the pancreatic head, peripancreatic stranding, and large-volume
ascites. He was transferred to this tertiary care hospital for further workup of
acute hemorrhagic pancreatitis and possible endoscopic ultrasound/endoscopic
retrograde cholangiopancreatography for further workup of the pancreatic head
lesion.
He had been in good health prior to this presentation. Past medical history was
pertinent for hypertension and chronic obstructive pulmonary disease. He had no
history of pancreatitis, gallstones, or other hepatobiliary disease. Social history
revealed that he was active, independent, and lived by himself. He had 1 rum drink
daily and smoked 2 cigarettes per day. Review of systems was pertinent for
blistering of the hands, with subsequent scabbing and pigmentation changes, with
onset a few days prior to the abdominal pain. He was not sure if there was a
relationship to sun exposure. Associated with the blisters, the patient described
unrelenting pruritis of his hands bilaterally. This was the first time in his life
he was experiencing cutaneous symptoms as he had never had skin problems before.
On admission to our institution, vital signs demonstrated temperature 37.0°C, blood
pressure 146/95 mm Hg, heart rate 112 beats per minute, respiratory rate 20 breaths
per minute, and oxygen saturation 96% on room air. On examination, he was in mild
distress from abdominal pain and nausea. Abdomen was distended and mildly tender in
the epigastric region. A fluid wave was appreciated. There was no
hepatosplenomegaly. Dermatology examination revealed vesicles and bullae with
erythematous bases, in different stages of healing seen over the dorsal aspects of
the both hands with scaling, scarring, and hypopigmentation and hyperpigmentation of
the skin (). They
were pruritic but not painful. There was no hypertrichosis appreciated. There were
no stigmata of chronic liver disease and no scleral icterus.
Complete blood count demonstrated hemoglobin of 8.5 gm/dL (mean corpuscular volume 95
fL), white blood cell count of 10 500/mm3 (76% polymorphonuclear cells),
and platelets 328 000/mm3. Renal function tests were normal. Liver
function tests demonstrated total bilirubin 0.3 mg/dL, aspartate aminotransferase 16
U/L, alanine aminotransferase 7 U/L, alkaline phosphatase 88 U/L, and albumin 1.6
g/dL. The international normalized ratio was 1.35. Lipase was elevated to 352 U/L.
Repeat diagnostic paracentesis again demonstrated grossly bloody fluid with an
amylase of 2866 U/L.
Further workup for acute hemorrhagic pancreatitis included a computed tomography
angiogram, which did not show active bleeding. The nature of the pancreatic head
lesion was still indeterminate so an endoscopic ultrasound was performed, which did
not show any focal lesion concerning for malignancy. Endoscopic retrograde
cholangiopancreatography done showed a large proximal pancreatic duct disruption,
which was treated with a plastic stent. He was managed supportively with intravenous
fluids and pain relief for acute hemorrhagic pancreatitis.
Further workup of his skin lesions was initiated due to the concern for porphyria
cutanea tarda (PCT). Skin biopsy showed blistering dermatosis, subepithelial with
evidence of re-epithelialization. Periodic acid–Schiff stain (PAS) with diastase
highlighted increased PAS+ deposition around vessel walls and focal PAS+ deposits
within the epidermis (). Direct immunofluorescence demonstrated homogenously thickened dermal
blood vessels highlighted by immunoglobulin (Ig)G, IgA, C1q, fibrin, kappa, and
lambda. The specimen was negative for deposition of IgM and C3. Findings were
consistent with PCT. Serum porphyrin levels came back strongly positive with levels
of 8 µg% (upper limit of normal <0.9 µg%). Fractionation revealed high
heptacarboxyl, hexacarboxyl, and pentacarboxyl porphyrins as expected with the
heptacarboxyl highest at 2.6 µg% and the other 2 at 1.4 µg% each. After confirmation
of the diagnosis, hepatitis C, hepatitis B, and HIV were ordered and returned
negative.
Unfortunately, our patient developed secondary bacterial peritonitis and quickly
deteriorated. His repeat ascitic fluid grew Candida and
Enterococcus. His respiratory status declined as he developed
acute respiratory distress syndrome and needed mechanical ventilation. He then
progressed to multiorgan failure a few days later and eventually died.


In April 2018, a 14-year-old Caucasian boy with acute onset of affective FEP was referred to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari. Since the age of 12 he presented with debilitating intestinal symptoms as mucohemorragic diarrhea (discharge frequency, > 10/day), tenesmus, and abdominal pain, resulting in severe disability impairing his general and social well-being. He was diagnosed as having UC on the basis of clinical, laboratory, instrumental, and histologic criteria. In accordance with the “Guidelines for Management of Pediatric Ulcerative Colitis” [], he was treated with conventional therapies (mesalazine, prednisone, metronidazole, azathioprine, and biological agents such as infliximab and adalimumab) with no clinical response. Before elective surgery, a medical treatment with thalidomide was started, as an off-label option for patients with primary refractory IBD, and a clinical response was gradually observed. Two months later, he showed an acute onset of irritable mood, decreased need for sleeping, abnormally increased activity, disorganized behavior and speech, and thought alterations including inflated self-esteem and flight of insight-lacking ideas. These symptoms prompted the discontinuation of thalidomide and a mesalazine-based treatment was restarted. After admission at our Child Neuropsychiatry Unit, he was found to have no history of obstetric complications, neurological or psychiatric diseases, or substance abuse and no psychopathological symptoms prior to this acute episode. His parents reported a normal achievement of early childhood neurodevelopmental milestones and a normal intelligence quotient (IQ) was assessed. General and neurological examination, laboratory tests, and a brain magnetic resonance imaging resulted in normal ranges. An electroencephalogram showed slow waves including isolated spikes in the right temporal and parietal regions. After a mild improvement of symptoms, he developed a grossly disorganized behavior, with conceptual disorganization, auditory and visual hallucinations, delusion and suspiciousness, hostility, social and emotional withdrawal, somatic concerns, anxiety, and tension. Psychopathological assessment was performed by the use of Positive and Negative Syndrome Scale (PANSS). His PANSS total score was 115, while PANSS subscale scores were 29 for positive, 26 for negative, and 60 for general psychopathological symptoms. After proper informed consent, a treatment with antipsychotics and mood stabilizers (risperidone 6 mg/day, levosulpiride 72 mg/day, valproic acid 1000 mg/day) was started, leading to progressive improvement of psychopathological symptoms. During this phase his GI symptomatology remained silent, with 2–3 regular bowel movements/day and no blood or mucus emissions.
After a 6-month follow-up, a psychopharmacological maintenance with risperidone (4 mg/day) and valproic acid (1000 mg/day) ensured a partial remission of symptomatology. His PANSS total score was 71, with subscale scores of 11 for positive symptoms, 21 for negative symptoms and 39 for general psychopathological symptoms. On the other hand, only mesalazine efficiently controlled GI symptoms (2–3 regular bowel movements/day and no abdominal pain, diarrhea or rectal bleeding). Therefore, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated.


We report the case of a 64-year-old man with previous history of multiple left sided childhood ear infections requiring multiple grommets. He also had a history of mixed hearing loss since 2015, which had been managed conservatively.
On 21st February 2017, whilst on holiday, the patient suffered right sided otitis media (OM). The OM was complicated by pneumococcal sepsis, requiring ICU admission for observation and treatment. The patient was eventually discharged on a course of oral antibiotics. A computerised tomography (CT) scan of his head carried out during his admission was reported as normal. He was left with reduced hearing in the right ear due to right sided otitis media with effusion that resolved spontaneously on follow-up 6 months later.
The patient became unwell again while on holiday on 20th April 2018. He presented to his local emergency department with confusion, photophobia, and agitation on the background of a 2-day history of right sided otalgia.
The CT head scan showed signs of right temporal lobe encephalitis and right middle ear opacification.
The patient underwent surgical management of the OM, with myringotomy, washout, and right sided grommet insertion on 20/04/2018. He was then treated with intravenous ceftriaxone and rifampicin but had to undergo sedation due to the severity of agitation.
He eventually settled on antibiotics and was discharged home from ICU for ENT follow-up at his local hospital.


A 50-year-old Caucasian female with a history of difficult-to-control asthma since 1994 and chronic rhinitis presented to the hospital with severe jaw and ear pain in late February of 2009. She had been suffering from intermittent pain for a few months and underwent bilateral myringotomy tube placement about a month prior for recurrent otitis media with some benefit. The pain was distributed over the rami of the mandible bilaterally with radiation to her ears. She denied any fever, night sweats, weight loss, purulent nasal discharge, odynophagia, dysphagia, or shortness of breath. No significant history of travel or sick contact including contact to TB patients. The patient was a past smoker with 15 pack year history of smoking.
Vital signs on admission showed a BP of 101/63 mm·Hg, pulse of 105 beats/minute, temperature of 97.9 F, respiratory rate of 18 breaths/min, and SPO2 of 96% on room air. Physical examination revealed a patient in moderate distress. Bilateral tenderness was elicited while palpating the mandibular rami. The myringotomy tubes were intact without and significant drainage. The nasal mucosa appeared normal without any evidence of erythema, epistaxis, or discharge. The rest of the physical examination was unremarkable. The laboratory data are shown in .
Urinalysis showed trace proteinuria and no RBC cast. Electrocardiogram and a chest X-ray were normal. She underwent a CT scan of her neck with contrast which was unremarkable except left maxillary sinus thickening. However, the apical part of the lungs showed multiple nodules bilaterally. A dedicated high-resolution CT scan of the chest revealed multiple bilateral nodules, 5–11 mm in diameter. The largest nodule was noted in the lingula that measured 11 × 9 mm. There was also evidence of pericarditis and small pericardial effusion. Given her long standing history of uncontrolled asthma, upper airway symptoms, eosinophilia, and multiple pulmonary nodules, a clinical diagnosis of EGPA was made and the patient underwent an extensive rheumatologic workup which is shown in .
The patient underwent an open lung biopsy of the lingular nodule as well as a pericardial biopsy. The histopathology was consistent with necrotizing granulomatous vasculitis with extravascular eosinophilic infiltrate. The histopathology slides are shown in Figures and . The diagnosis of EGPA was confirmed.
The patient was started on high-dose prednisone and azathioprine in March 2009. She initially did well, but in August 2009 the patient was admitted to the hospital with pulmonary edema secondary to heart failure with reduced ejection fraction (HFrEF). The echocardiogram showed an EF of 25–30% with biventricular dilatation and global hypokinesis. No wall motion abnormality was identified. Cardiac catheterization was negative for coronary artery disease. No endomyocardial biopsy was performed. Given the high incidence of cardiac involvement in EGPA and a negative coronary angiogram, the myocardial dysfunction was thought to be secondary to EGPA and she was started on IV cyclophosphamide. Over the course of next 6 months, the patient completed 6 cycles of IV cyclophosphamide and started on mycophenolate. Steroid taper was continued. Her EF recovered completely, but she suffered from multiple vertebral body compression fractures and developed cushingoid appearance secondary to chronic steroid therapy. Between September 2009 and July 2011, she suffered from 2 episodes of sinusitis which was treated with short course of antibiotic. Her disease remained well controlled with normal inflammatory markers.
During an office visit in July 2011, the patient was noted to have depressed nasal ridge (). Physical examination showed nasal mucosal erythema. The patient underwent reconstruction of her nasal bridge in July 2013. Since 2011, the patient has been managed with mycophenolate without any incidence of exacerbation and is doing well currently.


A 35-year-old woman presented to the ear, nose, and throat outpatient department of the hospital with the swellings of right-sided neck, one in the region of the angle of the right jaw and the other below the right jaw (corresponding to submandibular region). She first noticed these swellings about 2-3 years ago when they were about the size of a bean. The swellings gradually progressed in size. There was no history of pain, fever, trauma, difficulty in mouth opening or facial nerve weakness. There were no comorbidities or history of addictions. On examination, she was found to have swellings present in relation to the right parotid and submandibular regions. The parotid swelling was about 2.5×2.5 cm in size, non-tender, firm, lobulated, mobile with normal overlying skin.
The swelling in the submandibular area was also about 2×2 cm in size, non-tender, firm, lobulated, mobile with normal overlying skin (). Facial nerve functions were within normal limits. Mouth opening was normal and there was no bulge in tonsillar fossa or the floor of the mouth.
Fine needle aspiration cytology (FNAC) from both the lesions showed a cellular smear with abundant chondromyxoid matrix associated with singly scattered and poorly cohesive myoepithelial cells with plasmacytoid appearance. There was no atypia. The features were suggestive of a pleomorphic adenoma.
A contrast-enhanced computed tomography (CT) scan of face and neck showed a well-defined, slightly lobulated mass lesion involving right parotid gland, suggestive of mild heterogeneous contrast enhancement. Another well-defined smooth marginated tumor with no significant contrast enhancement involved right submandibular gland. The radiographic appearance of tumors in both the locations was suggestive of a benign pathology ().
With the presumptive diagnosis of pleomorphic adenoma of right parotid and submandibular region, the patient was planned for right-sided superficial parotidectomy and right submandibular gland excision under general anesthesia. A modified Blair incision with cervical extension was performed to surround the submandibular area. The superficial parotidectomy and submandibular gland excision were performed after raising skin and subplatysmal flaps, which preserved the function of the facial nerve and its branches (). Intraoperatively, the tumors in both the locations were firm and lobulated. The treatment policy was the excision of entire tumors, superficial lobe of the parotid gland, and entire submandibular gland (). Postoperative period was uneventful and facial nerve functions were normal.
On gross pathological examination, the parotid and submandibular gland tumors were measured 34×25×22 mm and 45×25×20 mm, respectively. Serial slicing of the tumor showed grey white firm well-circumscribed lesion with pushing margins, with a surrounding rim of normal salivary gland tissue. Microscopic inspection showed both the tumors were surrounded by a capsule. The biphasic population of epithelium and mesenchymal cells were observed with epithelial cells in glands and myoepithelial cells embedded in the chondromyxoid stroma. The investigated regions had no necrosis or significant atypia. The final histopathological diagnosis of parotid and submandibular gland pleomorphic adenoma was performed postoperatively ().


A 21-year-old Kazakh man was referred to the National Research Center for Oncology and Transplantation in Astana, Kazakhstan, in October 2017 because of portosystemic shunts secondary to portal vein thrombosis. The past medical history did not reveal abdominal trauma, previous surgery, omphalitis, gastrointestinal bleeding, or hepatitis. The patient had been healthy until March 2017, when he developed lumbar pain, malaise, peripheral oedema, and nausea and began to lose weight. In May 2017, he felt right upper quadrant discomfort and developed abdominal distension; an abdominal ultrasound revealed splenomegaly and ascites. Liver cirrhosis was suspected. Alanine aminotransferase and aspartate aminotransferase levels were within the normal range; HBsAg, anti-HCV, and tumour markers (CEA, Ca19-9, and alpha- fetoprotein) were negative, total protein and albumin levels were reduced (49.2 g/L and 22.6 g/L, respectively), and total cholesterol increased (6.6 mmol/L; normal 3.1-5.2). Urea, creatinine, and electrolyte levels were normal. An EGDS showed superficial distal gastritis; oesophageal or gastric varices were not detected.
In June 2017, an abdominal CT scan confirmed the presence of splenomegaly and mild ascites and detected voluminous paraoesophageal varices, left splenorenal shunts, and hepatomegaly. A Doppler ultrasound of the liver showed no flow in the portal vein and its branches and enlarged splenic vein (diameter 1.7 cm) with laminar blood flow. The patient received a provisional diagnosis of portal vein thrombosis and was started on IV heparin, which was stopped four days later because of worsening thrombocytopenia. Further serologic tests revealed subclinical hypothyroidism and hypergammaglobulinemia (25.8%); ANA and AMA were negative. A urine test showed proteinuria (1.3 to 2.0 g/L) and microscopic haematuria (18-22 RBC/high power field). The patient was started on spironolactone 100 mg/day and torasemide 5 mg/day.
In October 2017, he was admitted to the National Research Center for Oncology and Transplantation and underwent mesentericoportography, which showed hepatic arterial buffer response, an indirect sign of reduced or absent blood flow in the portal vein. An abdominal ultrasound did not visualise the portal vein and showed an enlarged spleen. Lab tests revealed mild leukopenia (3.6 WBC/μL), normocytic normochromic anaemia (Hb 9.8 g/dL), thrombocytopenia (80,000 platelets/μL), proteinuria (2.1 g/L), and microscopic haematuria. Further tests revealed that the patient was heterozygous for both factor V Leiden (FV) and methylenetetrahydrofolate reductase (MTHFR) genes; methionine synthase (MTR) A2756G mutation was not detected. IgM and IgG anticardiolipin antibodies and antiphospholipid antibodies were negative, and homocysteine levels were normal.
A revision of the images of the CT scan performed in June 2017 revealed voluminous collaterals between the left renal and the splenic veins, paraoesophageal varices, dilatation of the superior mesenteric vein with lack of visualization of the intrahepatic portal branches, dilatation of the left renal vein with a possible filling defect, and enlarged left kidney ().
In May 2018, the patient was admitted to another hospital where an echocardiography showed global enlargement of the cardiac chambers and hypertrophy of the posterior wall of the left ventricle (1.3 cm) with normal ejection fraction, II degree mitral valve regurgitation, I degree aortic regurgitation, and no signs of pulmonary hypertension. Arterial blood pressure monitoring revealed Max BP – 173/86 mm Hg, Average BP - 145/73 mm Hg, max BP (night) 141/70 mm Hg, and average BP (night) – 122/57 mm Hg. Indices of average BP were elevated during night and day, being 92% and 58%, respectively. A kidney biopsy showed moderate to severe mesangial hyper cellularity, dilation of mesangial matrix with focal lymphocytic stasis in the capillary space, basal membrane thickening of capillary loops with well-defined fuchsinophilic granules and focal total glomerulosclerosis (16%), grade II epithelial renal tubular dysplasia, diffused moderate fibrosis of the interstitium, tubular atrophy, intimal fibrosis, and hypertrophy of the arterial muscle layer of middle calibre with narrowing of one artery to 1/3 (Figures and ). A diagnosis of membranoproliferative glomerulonephritis was made and the patient was started on methylprednisolone (64 mg/day, tapering down to 16 mg/day maintenance dose) and perindopril 10 mg/day. Unfortunately the response to treatment was not optimal, leakage of ascitic fluid from the umbilicus developed, and further deterioration of the renal function led to haemodialysis. No episodes of bleeding or clinically symptomatic thrombosis occurred after the diagnosis.


A 62-year-old otherwise healthy woman presented with three to four months of mechanical right groin pain radiating to the right buttock. She had a history of a benign soft-tissue mass in the right thigh that had been biopsied 10 years earlier, and the patient was told it was a myxoma. No other workup was done at the time, and no other lesions were clinically detectable. She had been very active and played tennis regularly. She was assessed with a hip ultrasound for her right groin pain and was prescribed physiotherapy. During physiotherapy, she felt a snap in her right groin and was no longer able to ambulate without a walker. Initial radiographs demonstrated a lucent intramedullary lesion within the subtrochanteric region—further characterized by a focally aggressive appearance with cortical destruction and lytic expansion of the lesser trochanter (Figures and ). A ground-glass appearance, typical of fibrous dysplasia, was also noted in the mid-femoral shaft ().
Further workup included a Computed Tomography (CT) scan of the chest, abdomen, and pelvis which showed multiple hepatic and renal cysts but no evidence of a primary carcinoma or lung metastases. Bloodwork including serum protein electrophoresis was normal. A Total Body Bone Scan (TBBS) revealed increased uptake in the right proximal femur and two areas of relatively mild uptake in the mid femur. Fat-suppressed T2 Magnetic Resonance Imaging (MRI) displayed an intermediate to high signal lesion within the medullary cavity of the proximal and mid right femoral shaft (). In line with the initial radiographs in which two benign sites of fibrous dysplasia were noted, in the third proximal lesion, there was cortical destruction with an extraosseous soft-tissue mass in the region of the lesser trochanter. Additionally, in keeping with the known myxoma, a soft-tissue T2 hyperintense mass within the medial distal thigh was also present (). On further review of the MRI images, five other myxomas were seen. The imaging features were consistent with Mazabraud's Syndrome, with sarcomatous transformation of benign fibrous dysplasia in the proximal femur.
Due to the high risk of fracture, the patient was immediately placed on bedrest and a biopsy was not performed—as a preventative measure to reduce fracture risk. She was taken to the operating room and underwent wide resection of the proximal right femur with endoprosthetic reconstruction via a lateral approach. Along with bony specimens, one of the soft-tissue masses was also excised and sent to pathology for investigation (Figures and ). Pathology later confirmed a high-grade osteosarcoma in the setting of fibrous dysplasia and a benign myxoma (Figures –). There were no complications during the procedure.
Postoperatively, the patient stayed in the hospital for one week, with physiotherapy beginning on postoperative day one. Her postoperative course followed the normal trajectory of recovery with no major complaints or issues at her two-week follow-up. The patient declined adjuvant chemotherapy. The standard management of osteosarcoma at our center would include wide surgical excision with neoadjuvant or adjuvant chemotherapy (methotrexate- and doxorubicin-based multidrug regimens). The patient is being followed to assess for complications and local or systemic relapse every three months with radiographs of the femur and chest. At one year postoperatively, there have been no complications or evidence of disease relapse.


A 21-year-old woman sought care to replace the resin restoration of her fractured anterior tooth. The existing restoration had a poor color match and excess material (). Considering the age of the patient, the possibility of reversibility of the procedure, the time, and the cost, a direct adhesive restorative system was planned to restore the tooth.
After prophylaxis, the dentin and enamel color were selected using the Essentia, GC, resin system. For enamel color selection, each of the two enamel colors (light enamel and dark enamel) were placed on the tooth and polymerized (). The light enamel replicated the patient's tooth best. The dentin color was selected by applying the three dentin colors (light dentin, medium dentin, and dark dentin) on the patient's tooth and polymerizing. Light dentin was selected ().
After making a silicone putty matrix, the existing restoration was removed with abrasive disks (Sof-Lex, dark red, 3M; thick granulation). A beveled margin was made with the same disk (). The operative field was isolated and the gingiva displaced with ligated rubber dam (). The adjacent teeth were protected with polyester tape. The enamel surface was conditioned with 37% phosphoric acid (), and the adhesive (G-BOND, GC) was then applied on the facial and lingual surfaces () and polymerized according to the manufacturer's instructions.
The silicone matrix was positioned lingually to provide a well-contoured restoration (). Resin matching the lingual enamel was applied with the matrix in position (LE). After polymerization of this increment with the matrix in position, the lingual and incisal contour was established (). Dentin resin was then applied to the middle third (LD), leaving room for the creation of a dentinal lobe in the incisal region (). The incisal halo was made by using the opalescent translucent resin of the OM system (), followed by a layer of white stain on that halo to simulate the opacity of this region (). The dentin mamelons were made with clear resin (), and opalescent resin was applied between the mamelons (). The enamel layer was applied to the facial surface and spread with the aid of a polyester strip and brush (Kota 4A) ().
Each increment was polymerized with an LED unit (Radii-cal, SDI) for the time recommended by the manufacturer. After removal of the rubber dam, any excess was removed, and the incisal edge adjusted.
In the following appointment, the restoration was finished and polished with sequential grit abrasive disks (Sof-Lex Pop-on, 3M). Rubber points and composite polishing paste applied with a felt disk were used to obtain the final gloss (). The final restoration can be seen in Figures and . The definitive appearance of the restored smile can be seen in .


A 16-year-old male presented to the emergency department following a high-speed front-end collision with another vehicle. He was restrained and occupied the front seat of the vehicle that was struck head-on. The speed at the time of the collision was estimated to be in excess of 79 miles per hour. On arrival, the patient was unconscious and not breathing independently. Attempted intubation at the scene was unsuccessful and the patient was pronounced dead soon after arrival to the hospital.
Radiographs at the time of the incident noted internal decapitation with AO assimilation specifically between the anterior arch of the atlas and the basiocciput (Figure ). No fractures were noted, including the odontoid process. There was no known past medical or surgical history and the AO assimilation was unknown to the family.


The female infant was born to healthy non-consanguineous parents (25-year-old father, and 22-year-old mother) after an uncomplicated first pregnancy and 40 weeks of gestation. A Cesarean section was performed due to a failed vaginal delivery, but the Apgar score until 15 min after birth and birth weight was normal (3,300 g). The patient was intubated after developing progressive tachypnea, moaning, and severe hypoglycemia (0.9 mmol/L). The patient developed hyperbilirubinemia that was unresponsive to phototherapy, but the parents took the baby home, for home care at the age of 9 days.
At the age of 1.4 months, the patient was admitted to a provincial hospital for jaundice, vomiting, afebrile seizures, and pneumonia. The lowest blood glucose level during the hospital stay was 1.4 mmol/L. The serum cortisol levels were extremely low (13.8–29.3 nmol/L, normal range 138–690 nmol/L) while adrenocorticotropic hormone levels were slightly lower or normal (6.0–18.5 pg/ml, normal range 6.4–40 pg/ml). A cortisol deficiency was diagnosed, but parents refused hormone replacement therapy. The patient was discharged after the pneumonia was resolved and blood glucose levels were stabilized.
At the age of 3.2 months, the patient was presented to our hospital for cholestasis without obvious symptoms of hypoglycemia, infection, alacrima, or achalasia. Repeated morning serum cortisol levels were extremely low (8.8–10.6 nmol/L, normal range 138–690 nmol/L), while ACTH was extremely elevated (1656.9–1911.8 pg/ml, normal range 6.4–40 pg/ml). Upon physical examination, significant jaundice, skin hyperpigmentation and slight hepatosplenomegaly (liver 2–2.5 cm below the right costal margin, and 2.5 cm below the xiphoid process; spleen 1.5–2.0 cm below the left costal margin) were observed. Slight dysmorphic features such as a transverse palmar crease in the right hand, a prominent forehead, hypertelorism (inner canthal distance greater than the palpebral fissure length) were noted. The palmar crease, and the changes in skin pigmentation are presented in . Written informed consent was obtained from the parents for the publication of this case report and related images. Changes in body weight/length, complete blood count, procalcitonin, serum biochemistry, blood coagulation, and endocrine profiles throughout the disease course are provided in .
Genetic screening for abnormalities related to congenital adrenal hyperplasia (list of 44 genes are provided in ), and multiplex ligation-dependent probe amplification (MLPA) analysis of the CYP21A2 gene were performed by a commercial genetic testing company (Customized target capture sequencing, ). The result showed compound heterozygous variants in the melanocortin 2 receptor (MC2R) gene, but the result of the CYP21A2 gene MLPA analysis was negative for hot-spot mutations and copy number variants (). We conducted protein modeling with SWISS-model () using the most similar structure (5jtb.1.A, Adenosine receptor A2a), and polar contacts of wild-type and mutated amino acid residues were compared with Pymol software (). The c.433C>T/p.R145C was reported in the dbSNP152 (), and gnomAD (), but not in the 1000 Genome Database () and Exome Variant Server (). The c.712C>T/p.H238Y variant was not reported in the dbSNP152, gnomAD, 1000 Genome Database, and Exome Variant Server. The c.433C>T/p.R145C variant of maternal origin caused the change of arginine (polar, basic) at the amino acid position of 145 to cysteine (non-polar, neutral). R145 is a relatively conserved amino acid residue, and five out of eight in-silico prediction tools () predicted this variant as pathogenic. This is a known disease-causing variant (HGMD CM116421, rs139218324), and reported to be associated with FGD1 in an adopted Chinese girl (). Protein modeling showed no effect of R145C residue change on polar contact with V149. The c.712C>T/p.H238Y variant of paternal origin caused the change of amino acid residue histidine (polar, basic) at the position of 238 to tyrosine (polar, neutral). H238 is a strictly conserved residue, and all eight in-silico prediction tools predicted this variant as pathogenic (). Protein modeling showed that the H238Y mutation changed polar contact of the amino acid residue in the position of 238 with adjacent residues, and polar contact with N261 in the transmembrane domain (TMD) 7 was lost. Confirmation with Sanger sequencing, conservation status of amino acid residue that have been affected, protein modeling results, and in-silico pathogenicity prediction results for both MC2R variants are provided in and .
Extensive etiologic evaluations from birth until the last follow-up (4.9 months) are provided in . After ruling out other causes of hypoglycemia, cholestasis, and adrenal deficiency, a diagnosis of FGD1 was made. Oral hydrocortisone was started at a dose of 30 mg/m2 body surface area (divided into three doses) at the age of 3.4 months. Cholestasis was resolved at 4.9 months, skin hyperpigmentation was improved, and no further episodes of hypoglycemia occurred. Morning serum cortisol levels 1 h after hydrocortisone intake was normal, while ACTH levels returned to near normal levels. However, parents decided to stop the medication at the age of 7.4-months, and serum cortisol/ACTH levels returned to extreme levels at the age of 8.1-months ().


A 77-year-old man with no history of smoking was admitted to our hospital due to worsening dry cough and dyspnea on exertion over the previous two months. The previous year, he was tentatively diagnosed with asymptomatic idiopathic interstitial pneumonia (IIP) at another hospital. Reticular infiltrates on computed tomography (CT) examination, performed at the time of his initial admission to our hospital, revealed the progression of IPF when compared with CT images obtained one year previously ().
Laboratory findings did not reveal any collagen disorders associated with interstitial pneumonia (IP). These investigations, however, did reveal elevated levels of fibrotic markers KL-6 (1448 U/mL), SP-A (66.4 ng/mL), and SP-D (353 ng/mL). The patient also had a familial history of IPF: his uncle had died from it and his niece had the disease. We diagnosed this case as probable usual interstitial pneumonia pattern with bronchiectasis in the lower lung field via the multidisciplinary-discussion approach, and prescribed a low dose of pirfenidone (600 mg/day) for a month and 1200 mg/day for the following month, after which his symptoms of dry cough and dyspnea during exercising improved. Although the history of cough occurrence/persistence was not investigated by the questionnaire, symptoms of dyspnea improved from 2 to 0, as measured by the modified British Medical Research Council (mMRC) questionnaire []). The reticular shadow in the lower field of his chest radiograph and his pulmonary function, including forced vital capacity (FVC), were improved three and six months later, respectively. Because he experienced appetite loss with pirfenidone at a dose of 1800 mg/day, he has been taking 1200–1400 mg/day with a proton pump inhibitor for approximately two years, and has experienced no marked side effects. Since he began pirfenidone treatment, the reticular shadow on his chest and his FVC appeared to have improved, and his condition has been stable for more than two years (; A). Although levels of fibrotic markers KL-6 and SP-D were temporarily elevated with no symptoms, 14 months after pirfenidone treatment, they normalized under continuous administration of pirfenidone (B). Interestingly, his serum periostin levels were not high at the time of his initial admission to our hospital and, in contrast with the decrease in levels of fibrotic markers, were not affected by pirfenidone treatment (C,D).
Written informed consent was obtained from the patient for publication of this article and accompanying images. This work was supervised by the Ethics Committee of Gunma University Hospital (No. 13-66) approved on 15 April 2014.


A previously healthy, 77-year-old female was referred to our hospital, with a lung adenocarcinoma measuring 28 mm in the right upper lobe. We therefore planned a UVATS to resect the tumor. The patient was placed in the left lateral decubitus position under general anesthesia. Then, we made a 4-cm skin incision for the main port in the sixth intercostal space at the anterior axillary line. A wound retractor (Alexis-xs; Applied Medical, Rancho Santa Margarita, CA) allowed the insertion of a flexible thoracoscope (10 mm in diameter, Olympus Optical Tokyo, Japan), endoscopic autosuturing device (GIA Universal; Covidien, Mansfield, MA or Echelon; Ethicon, Cincinnati, OH), and vessel-sealing device (Ligasure; Covidien) via the main port incision. It also allowed specimen extraction.
During operation, we found the incomplete interlobar fissure between the upper and the middle lobe and the abnormal lobulation of the upper lobe. (Fig. ). Therefore, we carried out the so-called modified marionette technique as follows. First, the Internal organ retractor (IOR; Aesculap, Tuttlingen, Germany) applied with a looped 1-0 nylon thread was inserted into the thoracic cavity by the clip applier (Aesculap). The clip applier also allowed the IOR to grasp the targeted lung parenchyma properly. Second, two sets of looped 1-0 nylon-threaded 18-gauge injection needles were prepared (Fig. a). These needles were optimally pierced through the thoracic wall separately (Fig. a and b). Third, the both ends of the 1-0 nylon thread attached to IOR were separately pulled out through the looped nylon extruded from the 18-gauge injection needles. Each thread was clamped by mosquito forceps (Fig. b). The looped nylon extruded from 18-gauge injection needles worked as a pivot, so that the vector of retraction of the IOR was converted into an ideal direction (Fig. ). This method gave the sufficient thoracoscopic views to perform surgery with safe and ease. The patient had an uneventful postoperative course and was discharged in 1 week after the operation without any wound complications.