In February 2019, A 56-year old male presented to our hospital with a 2-month history of dull upper abdominal pain without abdominal distention, nausea or vomiting, and an absence of an inciting event prior to onset. Work-up with computed tomography (CT) in local hospital suggested an infectious hepatic lesion in the hepatic V segment. The pain was not alleviated following antibiotic therapy and the patient then presented to our hospital for further treatment. The patient was admitted to the inpatient ward with a space-occupying lesion of the liver. The patient has a medical history of Hepatitis B for 1 year, treated with Lamivudine, 1 tablet a day. The patient does not have a family history of SHC or HCC. Upon physical examination, abdominal tenderness was noted. The exam was negative for rebound tenderness, muscular tension, nausea, vomiting, or fever. There was no history of weight loss, cough, jaundice, pruritus, or any clinical feature of cholangitis. Laboratory studies showed a white blood cell (WBC) 10.1∗103/μl with 74% neutrophils, ALT 61 U/L, AST 63 U/L, ALP 176 U/L, and a serum total bilirubin 18.2 μmol/L. Tumor markers were within normal limits with the exception of an SCCA of 1.8ng/mL. Urinary routine and microscopy examination were normal. Blood cultures were sterile. HBsAg and HBeAb were positive.
Ultrasound (US) in our hospital revealed a hypoechoic lesion of 5.1 by 4.0 cm in the hepatic V segment with a thick, irregular and shaggy margin. There was no evidence of intrahepatic biliary radical dilatation and the common bile duct appeared normal. Contrast-enhanced ultrasound (CEUS) detected an irregular, thick circular hyper-enhancement with no enhancement in the inner lesion during the arterial phase. Washout of the surrounding tissue around the lesion in early portal phase was observed with showed hypo-enhancement in the venous phase (Fig. ). The CEUS pattern revealed rapid wash in and wash out consistent with the diagnosis of a hepatic abscess. However, a diagnosis of atypical ICC was not excluded. Enhanced magnetic resonance imaging (MRI) showed a significant enhancement of the irregular margin with no enhancement of the central cystic necrosis. The portal venous phase revealed decreased enhancement consistent with a hepatic abscess, but not excluded atypical ICC (Fig. ).
Therefore, the first diagnostic, US-guided biopsy was performed (2019.2.22) and revealed hepatic coagulative necrosis and pseudolobuli formation with lobular fibrous tissue hyperplasia and ductular proliferation. Lab values were as follows: WBC 12.3∗103/μl with 79% neutrophils and a total serum bilirubin 23.2 μmol/L. The patient received Sulperazone 2 g twice a day in our hospital. In order to avoid a false negative result on the first biopsy, the second diagnostic biopsy was performed alongside a liver abscess drainage (2019.2.26). CEUS-guided biopsy from the enhanced wall of the lesion and drainage from the abscess cavity revealed a thick, purulent material. A culture of the abscess was sterile and cytology revealed abundant pus only. Pathology studies showed fibrous tissue proliferation with focal acute, and chronic inflammatory invasion with small ductular proliferation and a section of atypical tissue. Immunohistochemistry (IHC) expressed Vimentin with a population of fibroblasts. Based on these diagnostic findings, the patient was treated as a case of a hepatic abscess. After biopsy, the patient reported intermittent fever and was treated with Sulperazone for approximately 10 days. His temperature was normal with a WBC of 11.2∗103/μl after antibiotic and symptomatic therapy. He was discharged from the hospital (2019.3.1) and continued on oral moxifloxacin for about 20 days.
However, 20 days later, he presented to our hospital because of fevers up to 39.4 °C and severe abdominal pain (2019.3.20). Follow-up abdominal US and CEUS found a lesion of 6.7 by 4.7 cm in the hepatic V segment which was larger than on previous investigation. Enhancement was observed in the right portal vein without intra or extra-hepatic biliary extension (Fig. ). Due to these findings, an etiology of ICC was considered and contrast-enhanced CT (Fig. ) showed a solid, cystic mass of variable density, and no central enhancement due to necrosis. However, parenchymal tissue showed significant enhancement consistent with previous MRI. At this point, a third US-guided diagnostic biopsy was suggested (2019.3.28) and the following pathological diagnosis showed a poorly differentiated carcinoma with an IHC positive for cytokeratin (AE1/AE3) and vimentin (2019.4.17). With these findings, the diagnosis of SHC was finally confirmed (Figs. and ).
The patient was not a candidate for surgical resection due to the presence of metastasis. Therefore, treatment with chemotherapy was initiated. The chemotherapy regimen consisting of Albumin paclitaxel (105 mg/m2, 200 mg i.v. for 30 minutes) and gemcitabine (850 mg/m2, 1600 mg i.v. for 30 minutes). After 4 courses of this regimen, tumor progression was found on enhanced MRI (2019.6.14). Therefore, the patient received immunotherapy and targeted therapy that consisting of PD-1 (130 mg/m2, 240 mg i.v. for 30 minutes) on day 1 and Anlotinib (10 mg po) on day 1 to day 14. The patient dead 3 months later due to tumor progression (September 2019). The flowchart of the patient's treatment process is as followed (Fig. ).


A 70-year-old woman with a 45-year smoking history, who had undergone colectomy for CRC (pT3N0M0, p-stage II, well-differentiated tubular adenocarcinoma [tub1, pT3/SS, ly0, v0, pH0]). 2 years prior, presented with a CT nodule shadow in her right lower pulmonary lobe that had grown from 0.2 cm at her right hemicolectomy (Fig. a) to 0.3 cm at 12 months, and to 0.5 cm at 14 months postoperatively (Fig. b). The serum levels of tumor markers were within their normal ranges; CEA, 2.9 ng/mL; CA19-9, 6.8 U/mL; CA125, 4.0 U/mL. Because this growing cavitary lesion with a slightly irregular wall thickness suggested CRC metastasis, a thoracoscopic resection was performed.
As the lesion was barely palpable, preoperative marking was required. Although the dye material was radiolucent, the tip of the catheter used for dye marking was radiopaque. After confirming the positional relationship between the tumor and the tip of the catheter by using cone-beam CT in the hybrid operating room, dye marking with indigo-carmine dye (0.3 mL) by bronchoscopy was performed at a point around 5 mm cranial to the tumor. Preoperative marking took 6 min with two CT inspections (Fig. a, b). Intraoperatively, the tumor had no gross pleural changes, but because it was slightly palpable at 5 mm caudal from the dyed site, we performed a wedge resection (Fig. c). Intraoperative frozen sections revealed fibrotic tissues with no apparent malignant cells, which did not match the CRC tissue. Permanent sections showed proliferating papillary cells with cilia adjacent to the bronchi and mucous glands around the cystic wall; the alveolar structure was intact and was composed of normal epithelial cells, with no atypical cells (Fig. a, b). Immunohistochemically, the lesion was positive for cytokeratin-7 (CK7), focal positive for thyroid transcription factor-1 (TTF-1), and negative for cytokeratin-20 (CK20) and caudal type homeobox-2 (CDX2), which ruled out CRC metastasis (Fig. c, d). We therefore diagnosed the tumor as CMPT. The patient has remained recurrence-free for 7 months.


A 76-year-old woman with a past medical history of type-II diabetes mellitus, chronic obstructive pulmonary disease (COPD) on nocturnal 3 L/min home oxygen, obstructive sleep apnea on BiPAP (bilevel positive airway pressure) at home, hypertension, and dyslipidemia was diagnosed with COVID-19 infection eight days prior to her admission. She presented to the emergency department (ED) with a sudden onset of right-sided weakness and aphasia. The patient received thrombolysis therapy with tissue plasminogen activator (tPA) for ischemic stroke after a CT scan of the head was negative for hemorrhage. The patient was then transferred to our hospital for a higher level of care and evaluation for possible thrombectomy. In our ED, the patient had blood pressure (BP) and heart rate (HR) of 148/58 mmHg and 79 beats/min, respectively, with 95% SpO2 on 4 L of oxygen through a nasal cannula. She was awake, alert, and following commands. A critical neurologic examination revealed severe global aphasia, dense right hemiparesis, and a left gaze preference, with an NIH stroke score (NIHSS) of 13. Her initial laboratory reports did not show any derangements. The patient underwent a CT angiogram of head and neck and CT perfusion scan of the brain, both of which did not reveal any major vessel occlusion or a perfusion defect. She was then admitted to the COVID ICU and was subsequently started on aspirin and statin, and intravenous medications to maintain systolic BP < 180/105. She was also started on remdesivir for COVID-19 related illness. MRI of the brain was performed the next day that showed an acute/sub-acute infarct involving the left caudate nucleus and putamen (Figure ).
On day 3 of admission, she was observed to have worsening somnolence (NIHSS of 19), for which another head CT scan was performed that did not reveal any new findings. Over the course of the next three days, the patient continued to deteriorate with worsening lethargy and a progressive decline in her mental status. The patient was intubated for airway protection. Despite appropriate treatment and mechanical ventilatory support, the patient’s clinical condition continued to deteriorate. The patient’s family was updated regarding her clinical prognosis, and after an adjudicated discussion, the patient’s family decided that they no longer wish to subject her to further aggressive interventions, which were also in concordance with the patient’s wishes. The following day she was compassionately extubated receiving comfort measures only. Our patient expired six days into her hospital admission.


A 60-year-old Caucasian male with a past medical history of coronary artery disease with a two-vessel coronary artery bypass graft nine years ago, heart failure, hypertension, dyslipidemia, type 2 diabetes mellitus, methamphetamine abuse, and tobacco abuse was brought to the ED after being found down at a friend’s house. His last-known well time was the night prior to the presentation. The patient upon presentation was lethargic with severe aphasia with an HR of 123 beats/min, BP of 112/88 mmHg, temperature of 37.2°C, and oxygen saturation of 76% on room air. Upon examination, he was noted to have right-sided hemiparesis, right-sided facial droop, expressive aphasia, severe dysarthria, and left gaze preference. While in the ED, the patient became more obtunded, requiring intubation for airway protection.
The patient had a white blood cell count of 12,500/µL, lactic acidosis of 2.9 mmol/L, and an elevated procalcitonin of 0.82 ng/mL. His chest X-ray showed bilateral patchy opacities. A CT angiogram of the head and neck revealed a moderate-sized subacute left middle cerebral artery (MCA) branch infarct, which was primarily perisylvian with a corresponding perfusion defect (Figure ). There was no intracranial hemorrhage, mass effect, or any major vessel occlusion. The patient was not a candidate for thrombolysis and was started on aspirin and atorvastatin. His chest CT did not show pulmonary emboli but diffuse bilateral ground-glass consolidation (Figure ). A nasopharyngeal swab for COVID-19 PCR (polymerase chain reaction) was obtained, which came back negative. Due to the concern for COVID-19 pneumonia, a tracheal aspirate was sent for COVID-19 PCR that returned positive. The patient was initiated on remdesivir and dexamethasone for COVID-19 pneumonia. The pneumonia panel from tracheal aspirate showed methicillin-sensitive Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae for which he was initiated on appropriate antibiotics. His echocardiogram showed normal systolic function with an ejection fraction (EF) of 55%. MRI of the brain showed an evolving moderate size subacute left MCA branch infarct (Figure ). EKG did not reveal any cardiac arrhythmia. The patient improved from a respiratory standpoint and was extubated to high-flow nasal cannula on day 8 of his hospital stay. The patient was awake, alert, and oriented; however, he continued to have right-sided hemiparesis and expressive aphasia.


A 62-year-old Hispanic male with a past medical history of hypertension and tobacco abuse presented to the ED with a two-day history of progressively worsening dyspnea and cough. His vitals upon presentation were as follows: HR of 110/min, BP of 105/74 mmHg, temperature of 37.2°C, and SpO2 of 87% on room air. He had a leukocyte count of 19,000/µL, lactic acid level of 1.4 mmol/L, C-reactive protein of 33.2 mg/L, creatinine of 2.29 mg/dL, and an elevated procalcitonin of 6.48 ng/mL. CT scan of the chest showed bilateral nodular ground-glass opacities with a crazy-paving appearance. A nasopharyngeal swab for COVID-19 PCR was positive. The patient was also initiated on antibiotics for concomitant bacterial pneumonia with a positive Streptococcus pneumoniae urine antigen. His oxygen requirements gradually worsened requiring intubation on day 3 of hospitalization and vasopressor support for shock. A pneumonia panel from tracheal aspirate detected Streptococcus pneumoniae. He also developed worsening renal function requiring renal replacement therapy. The patient was noted to develop paraplegia on minimal sedation on day 10 of hospitalization prompting a CT scan of the head, which showed a 4.3-cm low-density area in the right occipital lobe consistent with a subacute ischemic stroke (Figure ). He was started on aspirin and atorvastatin. A transthoracic echocardiogram showed an EF of 65-70% with no wall motion abnormalities. His mental status continued to deteriorate until he became unresponsive with bilaterally dilated pupils. A repeat CT scan of his head showed a new large 6.0-cm right intraparenchymal hematoma with associated midline shift and transtentorial herniation with evidence of global hypoxic-ischemic injury and herniation-related infarction as well as scattered subarachnoid hemorrhage (Figure ). The patient was receiving subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis but no therapeutic anticoagulation was given. In the best interest of the patient and in accordance with the patient’s wishes, the family decided to transition his goals of care to comfort care only. The patient expired after a prolonged hospital stay of 27 days.


A 31-year-old female noticed a painless barely palpable right mid-front thigh subcutaneous swelling. There was no relevant medical history. No history of chronic debilitating disease. No family history of TB.
The clinical examination elicited subtle discoloration of the skin overlying the mid-thigh swelling. The patient was of average built. The vital signs were within normal range. There were no enlarged inguinal lymph nodes. The rest of the systemic examination was unremarkable.
Conventional X-ray examinations of the chest () and thoracolumbar spine () were normal.
Conventional X-ray examination of the pelvis () showed osteolytic areas involved the superolateral and the superomedial aspects of the right acetabulum and likely breached to the acetabular articular surface.
High-resolution ultrasonography of the right thigh () demonstrated a large oblong-shape subcutaneous and intermuscular cystic structure (about 195 × 60 × 24 mm) at the mid-thigh and extends upwards between the tensor fascia lata, rectus femoris and the vastus lateralis muscles. The right thigh cystic lesion seen continuous with another oblong-shape right iliopsoas () compartment cystic lesion (about 115 × 47 × 24 mm). Both right thigh and right iliopsoas cystic lesions have thick-walls and turbid tenacious fluid content.
Abdominal ultrasound examination showed no renal masses or perinephric collections. No defined intestinal masses or calcifications. Pelvic ultrasound examination showed no tubo-ovarian masses or abscesses.
Pre- and post-i.v.-contrast MR examination of the pelvis and right thigh examination performed and the images () elicited a large oblong-shape enhanced walls cystic lesion extending from the right iliac fossa to the lesser trochanter down to below the mid-right thigh. Moreover, the MR images showed distal right iliac bone and acetabulum roof cystic areas (about 26 × 26 × 15 mm) with enhanced margins. Those cystic areas likely penetrated the acetabular roof to the right hip synovial cavity.
Non-contrast CT () performed to clarify the bone involvement. The CT images showed cystic lesions at the lower right iliac bone with defect and fragmentation at the anterior aspect of the bone underneath the right iliacus muscle. No defined gross calcifications. No regional inguinal or iliac lymphadenopathy.
The haematologic laboratory work-up showed an elevated leukocytic count (mainly neutrophilia), C-reactive protein and erythrocyte sedimentation rate. Human immunodeficiency virus and viral hepatitis antigens/antibodies/DNA were not detectable in serum. Other blood investigations were within the reference range. The acid-fast bacilli smear of two sputum samples was negative under fluorescent microscopy.
Diagnostic aspiration from the right thigh abscess was performed under ultrasound guidance revealed a straw colored fluid. The bacterial culture and Gram staining were negative. Blood cultures were sterile. The fluid acid-fast staining came positive, and the culture developed mycobacterium TB.
The patient underwent ultrasound-guided percutaneous drainage of the thigh compartment and began combination antituberculous therapy.


A 60-year-old female presented with chronic mechanical cervicobrachial neuralgia and paresthesia of the three last fingers of her right hand. There was no trigger factor. The pain was intermittent and moderate, but it was worsening over time in the past few weeks. She had no known medical history and took no drug therapy. The physical examination was unremarkable, in particular, she had no motor deficit. MRI showed no disc herniation but a lesion of the T8 vertebra that was further characterized by a CT-scan. It was an osteolytic lesion of the vertebral body with right and left pedicle and lamina extensions, containing thickened vertical trabeculae (; A–B). There was some degree of expansion of the whole vertebra, assessed by the enlargement of the anteroposterior diameter (; B). The paravertebral soft tissue extension was mild (; C). There was no other vertebral lesion. Differential diagnoses considered at this moment were aggressive hemangioma, plasmacytoma and, to a lesser extent, Paget’s disease. Blood test showed no abnormality except an IgM κ monoclonal gammapathy. A biopsy was performed under CT-guidance and samples were addressed to the pathology department. A systematic CT-scan control immediately after the biopsy showed the formation of gas bubbles along the path of the biopsy, but also remotely inside the vertebral body (; E–H). Pathology analysis revealed thickened trabeculae and medullary spaces filled with blood and thin-walled capillary vessels (). There was no evidence of tumoral proliferation. The diagnosis of hemangioma was therefore retained.


A 43-year-old male presented with moderate mechanical lower back pain and right anterior thigh pain for 3 months, onset after a jog. There was no radiculalgia, pain, numbness nor weakness of the leg. He had no significant past medical history and took no drug therapy. The physical examination was unremarkable; there was no sensory or motor loss. Blood test was normal. CT-scan showed an expansile osteolytic lesion of the L4 vertebra, involving mostly the vertebral body with rupture of cortices in some places (; A–C). A MRI was then performed and showed a low signal on T1 weighted images (; D) and high signal on short tau inversion recovery (STIR)-weighted images (; E), with invasion of the surrounding soft tissue and posterior protrusion inside the spinal canal (; F). The lesion was strongly and homogeneously Gadolinium-enhanced (; G). Differential diagnoses considered at this moment were aggressive hemangioma and plasmacytoma. Due to these imaging features, a biopsy has been performed under CT-guidance. On control CT-scan, we also observed the formation of gas bubbles along the path of the biopsy, but also remotely inside the vertebral body (; I–K). Pathology analysis including an anti-CD31 staining concluded to a hemangioma ().


A 28-year-old female patient applied for an elective laparoscopic sleeve gastrectomy, she had a BMI of 40.8 kg/m2. (Weight: 98 kg, Height: 1.55 m). She is a known case of hypothyroidism on levothyroxine 50 mcg. She tried to lose weight using multiple diets, all of which have failed.
During the patients’ pre-operative assessment, full physical examination was performed. Upon palpating the abdomen, the stomach was felt on the right side instead of the usual left. This raised doubts about the presence of a type of heterotaxy.
Routine laboratory tests including complete blood count, renal and liver function test, coagulation profile, and thyroid function test were all performed, all were within normal ranges. Moreover, chest radiograph and electrocardiogram were both insignificant. She was also seen by the anesthesiologist and was cleared for surgery.
In regards to imaging, contrast study of the stomach and duodenum, using gastrograffin meal, was done which showed the stomach located on the right side of the abdomen, and jejunal loops on the left upper part of the abdomen, with no evidence gastro-esophageal reflux or hiatus hernia. After that, abdominal ultrasound was performed with limited visualization due to the patients obesity. A left sided enlarged liver with a normal gallbladder were the only findings. These findings has led to the need for a CT scan for proper visualization of the patients’ anatomy.
The CT abdomen with intravenous contrast was performed pre-operatively, where multiple significant findings were seen and diagnosis of Polysplenia Syndrome was confirmed. These findings include a right-sided stomach, a duodenum crossing anterior to mesenteric vessels, complete intestinal malrotation as the small bowels are on the left side and the large bowel on the right side, and the terminal ileum and cecum are midline. Other finding include, right sided splenules with a parent spleen, a midline liver, and infra-renal IVC with infra-hepatic interruption. The partially seen apex of the heart was at the left side. The gallbladder, adrenals, and urinary bladder showed no abnormality. The impression was that these features are suggestive of Polysplenia Syndrome/left isomerism (, ).
Laparoscopic sleeve gastrectomy was then performed by a bariatric surgeon under general anesthesia, with the patient in supine position. Starting with insufflation of the abdomen by a Veress needle at the right upper quadrant to create a pneumoperitoneum. Four ports were inserted under vision starting from the supraumbilical port; 11 mm, right and left midclavicular line; 5 and 15 mm respectively, and a 5 mm port at the epigastric area. The 15 mm port was inserted on the left to comply with the patients’ anatomy. The intraoperative findings include a large fatty midline liver, a right sided stomach, with a spleen posterior to it (). Dissection was started at the gastrocolic ligament at 6 cm from the incisura by using a 5 mm ultrasonic device (LigaSure). The dissection continued from the incisura to the angle of His, with sealing of the short gastric vessels. The posterior attachment with the stomach was then removed. Bougie size 38 was inserted up to the pylorus, then 2 blacks and 3 purples were inserted using a reinforced stapler device (Signia). The hemostasis was reinsured then methylene blue test was done, as it is regularly performed, showing no leak or twist. The resected stomach was removed from the 15 mm port. Closure of the 15 mm port fascia was done using Vicryl and Endoclose. The skin incisions were closed subcuticularly, using Monocryl.
The only difference in this approach from the one used in the situs solitus patients undergoing LSG is the location of the 15 mm port, as it was inserted on the left midclavicular line instead of the right.
Day one post-operatively, imaging was performed to rule out incision site leak using single water-soluble contrast study of the stomach and duodenum, using gastrograffin meal, during which, free flow of the oral contrast is noted through the esophagus into the neo-stomach with no evidence of contrast leakage. The stomach emptied well into the duodenum, showing no evidence of contrast leak post laparoscopic sleeve gastrectomy (, ). This imaging is not regularly done; however, it was advised due to the patients’ anatomy.
The patient was discharged on post-operative day two, after drinking approximately 800 mL of clear fluids. She was not complaining of any nausea or vomiting. Her pain was tolerated with paracetamol and was improving gradually. She also passed urine, flatus, and stool normally. She was seen by a dietitian and consulted regarding the proper diet after LSG. She was encouraged to have a clear fluid diet of one to two Liters a day until her next follow up. Mobility and exercise were also recommended.
Two and four weeks after the surgery, she was seen in the out-patient clinic for a follow up. The patient was doing well, tolerating clear fluid diet with no complaints of nausea or vomiting. She did not complain of gastro-esophageal reflux either. Histopathology results were checked, and showed chronic inactive gastritis. She has lost 10 kg and her BMI decreased to 36.6 kg/m2. She drinks around 600 mL per day. She has been encourage to exercise daily, and to be followed up again in one month.


A 35-year-old, primiparous woman in Wuhan city with a singleton pregnancy of 37 weeks and 6 days was admitted to our hospital (Maternal and Child Health Hospital of Hubei Province) due to regular uterine contractions at 17:50 on February 8, 2020, after undergoing chest CT scans. The chest CT images revealed spotted and slightly high-density shadows scattered on the lateral side of the right lower lobe (Fig. a). Except for lower abdominal pain, the pregnant woman had no signs or symptoms related to COVID-19 infection, and she reported normal fetal movement. None of her family members were diagnosed with COVID-19 or developed any respiratory symptoms. Since the woman developed cervical dilation of 0.5 cm and her CT result was abnormal, she was given a surgical mask instead of her original one. She was then transferred to a designated isolation delivery room by designated medical staff with specialized infection control preparation and strict infection protection equipment, including disposable work caps, medical protective masks, protective goggles, work clothes, disposable protective suit, disposable latex gloves, and disposable shoe covers.
The physical examination revealed a body temperature of 37 °C, pulse of 100 beats per minute, blood pressure of 135/86 mmHg, respiratory rate of 20 breaths per minute, and oxygen saturation of 99% while breathing ambient air. Considering that the pregnant woman and her family hoped that she would deliver vaginally and that there was no surgical indication for her, we decided to help her give birth naturally in the isolation delivery room. Fortunately, the labor went smoothly with no fever and no artificial intervention. The mother gave birth to a male infant with a birth weight of 3180 g at 04:58 on February 9, 2020. Apgar scores were 9 and 10 at 1 and 5 min, respectively. During her labor course, the laboratory tests (Table ) showed significantly decreased lymphocyte counts (0.65 × 109/L), which is a common finding in patients with COVID-19 []. Then maternal nasopharyngeal swab samples were collected and sent to the designed hospital for testing for SARS-CoV-2 with the recommended kit in accordance with the WHO guidelines for qRT-PCR [, ]. The results were reported 2–3 days later. Considering the abnormalities in her chest CT images and lymphopenia on hematological examination, the mother was suspected of being infected with COVID-19; we asked the new parents for their opinions on breastfeeding and neonatal isolation, and they decided to temporarily isolate with the newborn and suspend breastfeeding. Then, the infant was discharged home for further isolation, and the mother was transferred to the designated isolation ward after 2 h of observation. Low-flow nasal oxygen inhalation, antiviral therapy and antibiotics were implemented for her.
The woman received a positive result for SARS-CoV-2 on the 2nd day after sampling (on February 11). According to this test result, we transferred the mother to the designated hospital and followed up with her by telephone interviews. Luckily, by February 23, which was the 14th day after birth, neither the newborn nor his father and grandmother who took care of him developed any COVID-19-related symptoms. The mother received antiviral (arbidol hydrochloride tablets), antibiotic (azithromycin dispersible tablets) and traditional Chinese medicine (Lianhua-Qingwen capsule) treatments after she was transferred to the designated hospital. During her hospitalization, she did not show any COVID-19-related clinical symptoms. The woman was tested five times, all of which were negative for SARS-CoV-2, after referral (Fig. ). However, the immunoglobulin (Ig) G antibody for SARS-CoV-2 was detected in her serum sample on March 12, so she should be diagnosed as an asymptomatic carrier [].


A 33-year-old pregnant woman (gravida 1, para 0) in Wuhan city, with a gestational age of 38 weeks and 2 days, was admitted to our labor and delivery unit for 6 h of lower abdominal pain at 10:20 on February 26, 2020, with a week-long history of dry cough and runny nose. However, she had not sought any medical care. Her transverse chest CT images revealed ground-glass opacities of the left upper lobe (Fig. c), and routine maternal outpatient blood tests showed lymphopenia (lymphocyte count: 0.92 × 109/L, Table ). This pregnant woman was admitted for spontaneous labor with a cervical dilatation of 5 cm, even though she was highly suspected of being infected with COVID-19. Similar to case 1, the woman was transferred to the designated isolation delivery room and was given a surgical mask to avoid droplets.
The physical examination revealed a body temperature of 36.5 °C, pulse of 99 beats per minute, blood pressure of 108/63 mmHg, and respiratory rate of 20 breaths per minute. With designated medical staff in attendance, the labor process progressed smoothly and resulted in the birth of a healthy female infant with a body weight of 2950 g at 11:28 on February 26, 2020. Apgar scores were 9 and 10 at 1 and 5 min, respectively. After being evaluated by a neonatologist, the newborn was transferred to a designated neonatal isolation ward immediately, and the mother was also transferred to another designated isolation ward after 2 h of postpartum observation. The mother also decided to temporarily suspend breastfeeding. Both the mother’s and her infant’s nasopharyngeal swabs for SARS-CoV-2 were collected (2 h after birth). The maternal laboratory tests (Table ) showed elevated liver enzymes (AST: 107.9 U/L; ALT: 100.3 U/L) and decreased lymphocyte counts (0.60 × 109/L). Reduced glutathione for injection was used to improve liver function, and the other treatments were the same as in case 1.
On February 28, we were informed that the maternal nasopharyngeal swab for SARS-CoV-2 was positive, and the infant’s swab was negative. Then the mother was transferred to the designated hospital and followed up via telephone. After she was transferred, antiviral, traditional Chinese medicine, and medicine for improving liver function were provided for her. Her symptoms gradually improved while she was in the designated hospital. The infant and the patient’s husband did not show any signs or symptoms related to COVID-19. Although the nucleic acid test for SARS-CoV-2 of the second patient was negative on February 29, the result was positive on March 3, and both SARS-CoV-2 IgG and IgM were positive on March 8. The patient should be confirmed with COVID-19.
Delayed cord clamping and skin-to-skin contact between the mother and infant were not permitted in either case. Because the two patients tested positive for SARS-CoV-2, the healthcare workers involved were temporarily quarantined for 14 days and tested after delivery. Luckily, none of the staff were infected during the deliveries. Further information on the two patients’ follow-up is provided in Fig. . The newborns in both two cases were followed for more than 14 days, and neither developed any COVID-19-related symptoms.


A 23-year-old male was admitted to the department of hematology because of elevated hemoglobin during routine check-up. Physical examination revealed digital clubbing, cyanosis of oral mucosa and extremities. Remarkable signs of laboratory work up included decreased O2 saturation on room air of about 85% and elevated hemoglobin of about 23.0 g/dl. Chest roentgenogram suggested remote infectious lesion in the left upper lobe (Fig. a) and echocardiography showed no cardiac malformation. Additionally, the patient reported history of TB in his childhood and had been treated with standard anti-TB therapy for almost 1 year. Family members reported no history of repeated nosebleed, anemia or similar features mentioned above. The patient had been informed by his doctor that his clubbed fingers were sequela of chronic hypoxia caused by TB and the left pulmonary lesion was residual TB lesion after standard treatment. Bone marrow examination demonstrated non-specific erythroid hyperplasia. The initial diagnosis made by hematologist was polycythemia vera and hydroxyurea was applied. After several courses of treatment, the patient’s hemoglobin still kept high (22.5 g/dl) without obvious change and cardiothoracic consultation was scheduled. Considering the digital clubbing, cyanosis of oral mucosa and extremities, elevated hemoglobin, low O2 saturation and left pulmonary lesion, PAVMs were suspected. CT pulmonary angiography showed abnormal communications between the left upper pulmonary arteries and veins and PAVMs of left lingual lobe was confirmed (Fig. b). No extrapulmonary vascular malformations were detected.
Since PAVMs were diffuse but restricted to left upper lobe of lung, complete feeding arteries embolization was difficult and the patient finally received video assisted thoracoscopic left upper lobectomy. Intraoperatively, diffusely dilated and angiomatous vessels with hemorrhagic tendency were detected on the surface of left upper lobe (Fig. c, d). The left superior pulmonary vein, left upper lobe bronchus and left superior pulmonary artery were resected by endo-stapler, respectively. After left upper lobectomy, the O2 saturation immediately increased to 98%.
The histopathological examination confirmed the diagnosis of PAVMs. The patient was discharged home on the 5th postoperative day with hemoglobin level of 19.2 g/dl. Three months after surgery, the symptom of cyanosis relieved and hemoglobin was down to almost normal level of 14.9 g/dl. So far, the patient has been followed up for about 5 years without occurrence of cyanosis, dyspnea, decreased O2 saturation or increased hemoglobin level.


We report a case of a 75-year-old Sri Lankan male who presented to a general practitioner for routine health checkup. A high blood pressure of 220/120 mmHg was found. His past medical record was unremarkable. At the time of presentation to the general practitioner, he did not have any symptoms or signs of new end organ involvement in the form of heart failure, aortic dissection, renal involvement, hypertensive encephalopathy, or retinal involvement. Treatment was initiated with losartan potassium 50 mg twice a day, hydrochlorothiazide 25 mg morning, and prazocin 1 mg three times daily at the same time by the general practitioner.
The next day morning, the patient was admitted to the Accident and Emergency department following a generalized tonic-clonic seizure. On admission, his blood pressure had been 80/50 mmHg. His blood sugar was 120 mg/dL. Urgent electrolyte profile revealed normal serum sodium, potassium, calcium, and magnesium. He was treated with intravenous fluids and the blood pressure improved.
After regaining consciousness after the seizure, the patient complained about difficulty in raising the arms above the head. Family members who witnessed the event assured that he did not have any trauma to the shoulder girdle during the seizure. His distal arm and finger movements were well preserved. He could walk without support and could get up on his own from a squatting position.
On neurological examination, we found a man who was fully conscious, rational, and oriented. His cranial nerve examination was normal with normal bilateral fundi.
Upper limb examination revealed reduced muscle power proximally with bilateral shoulder abduction 3/5, shoulder extension 4/5, and shoulder flexion 4/5. Shoulder adduction was in full strength. His power at the elbow flexion and extension was normal and distal hand motor functions were normal. Tone in the proximal muscle group was reduced. Reflexes of the upper limbs were normal with normal sensory examination. Lower limb examination was neurologically normal with bilateral flexor plantar response (Videos and ).
Noncontrast CT of the brain performed 24 hours after symptom onset revealed new bilateral hypodense areas involving parietal regions, suggestive of watershed infarctions and an occipital infarct (Figures and ) in comparison to the CT performed on admission. Shoulder joint X-rays excluded fractures or dislocations in the shoulder girdle. X-ray of the cervical spine did not show any evidence of cervical spondylosis. Electromyogram and nerve conduction studies excluded a myopathic disorder or cervical root pathology. Carotid artery duplex sonography was performed in bilateral carotid arteries and excluded carotid artery stenosis. 2D echocardiogram showed left ventricular hypertrophy without evidence of intracardiac thrombi or valvular dysfunction. Patient's resting ECG with a long rhythm strip was showing left ventricular strain without evidence of any arrhythmia and 24-hour holter monitoring did not show any clinically significant rhythm abnormality.
Biochemical blood measurements revealed hemoglobin of 14.6 g/dL with a platelet count of 340 ∗ 106/L. Serum creatinine was 90 mmol/L with blood urea of 6.5 mmol/L. Electrolyte profile revealed sodium of 138 mmol/L and potassium of 4.5 mmol/L. His coagulation profile was normal. EEG did not show evidence of seizure activity.
He was started on antiplatelets and statin. Physiotherapy and occupational therapy were arranged and the patient was started on phenytoin sodium for seizures. The blood pressure was monitored and controlled very cautiously with low doses of losartan potassium. He made a slow recovery with mild residual weakness in the shoulder abduction.


The described case is of a 40-year-old female patient who presented with a 10-day history of headaches, night sweats, and cough. She was admitted to Shanghai Public Health Clinical Center in July 2017. The patient was previously healthy and had no other diseases.


Starting a month before admission, a 77-year-old man described feeling fatigued and experiencing double vision. His symptoms gradually worsened, leading him to consult an ophthalmologist who diagnosed him with right abducens nerve palsy. The patient was subsequently referred to our department and was hospitalized in order to perform detailed investigations.
Findings on admission: height 165 cm, body weight 56 kg, body temperature 36.2°C, blood pressure 135/85 mm Hg, and peripheral capillary oxygen saturation 98% (room air). His superficial lymph nodes were not palpable, and there was no rash or mucosal eruption. He was lucid and fully conscious, with no sign of disorientation. His corrected visual acuity was 1.0 and 1.2 in the right and left eyes, respectively, and no abnormalities were observed in his anterior segment or fundus. Both pupils were of equal size and round, and demonstrated rapid light reflexes. The patient showed right esotropia, and right abduction disorder was identified in his eye movements; however, the movement did not exceed the median. His other cranial nerves did not show any abnormal findings, and he had no muscle weakness or sensory disturbance.
Laboratory data revealed a white blood cell count of 9.700 cells/μL and a C-reactive protein concentration of 2.43 mg/dL, indicating a mild inflammatory response. There were no notable findings in the biochemistry and coagulation tests. The cerebrospinal fluid was clear, with a cell count of 48 cells/μL (68% mononuclear cells, 32% polymorphonuclear cells), glucose concentration of 84 mg/dL (124 mg/dL blood glucose), protein concentration of 182 mg/dL, and negative oligoclonal bands. Hormonal analysis revealed low levels of free triiodothyronine and free thyroxine, no elevation of thyroid stimulating hormone (TSH), total urinary free cortisol excretion below the level of detection, and low serum cortisol, growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels (Table ). Based on the hormone findings, panhypopituitarism was suspected. His serum immunoglobulin concentrations were 1940 mg/dL, 432 mg/dL, and 137 mg/dL, for IgG, IgA, and IgM, respectively; his soluble IL-2R was 484 U/mL, and angiotensin-converting enzymes was 2.8 IU/L. Antinuclear antibodies, myeloperoxidase antineutrophil cytoplasmic antibodies, proteinase 3 antineutrophil cytoplasmic antibodies, anti-double-stranded-DNA, anti-single-stranded-A, and anti-single-stranded-B antibodies were all negative. Viral antibody tests for herpes simplex virus, varicella zoster virus, cytomegalovirus, human T-cell leukemia virus-1, and human immunodeficiency virus were negative, indicating an absence of infection.
Contrast-enhanced magnetic resonance imaging (MRI) of the head revealed enlargement of the pituitary gland and pituitary stalk (Fig. ). Abdominal computed tomography (CT) also showed a mass surrounding the left ureter (Fig. ).
Load tests were conducted using four hypothalamic hormones: LH-releasing hormone (100 μg), GH-releasing hormone (100 μg), corticotropin-releasing hormone (CRH, 100 μg), and thyrotropin-releasing hormone (TRH, 250 μg) in order to confirm the diagnosis of panhypopituitarism. During the load tests, TSH and adrenocorticotropic hormone levels were maintained in response to stimulation with TRH and CRH, respectively. In contrast, the response to LH and FSH was low, and there was no increase in GH. The patient's free cortisol levels remained low and did not respond to CRH administration. Based on these findings, he was diagnosed with panhypopituitarism, which, based on the imaging findings of swelling spanning from the pituitary gland to the pituitary stalk, had occurred as a result of hypophysitis.
Additionally, since the abdominal CT revealed possible retroperitoneal fibrosis, the prospect of an IgG4-related disease was considered. Thus, a CT-guided needle biopsy was performed of the solid mass surrounding the left ureter. Histological examination revealed lymphocytic infiltration, which included lymphoplasmacytes. Further IgG4 immunostaining confirmed an abundant infiltration of IgG4-positive plasma cells. The IgG4/IgG ratio was 66.9% and the number of IgG4 positive cells was 175/high power field (Fig. ). Although serum IgG4 was 129 mg/dL, the patient was diagnosed with IgG4-related retroperitoneal fibrosis based on the pathological findings.
He was started on levothyroxine sodium (12.5 μg/d) for his hypothyroidism, and was given corticosteroid pulse therapy (methylprednisolone: 1 g × 3 days) because, as hypophysitis had developed, his abducens nerve palsy was also considered to be an IgG4-related disease. In addition, oral corticosteroids (prednisolone, 0.5 mg/kg/d) were administered post-therapy, beginning on Day 12 of his admission. He responded well and his right abducens palsy improved. He was discharged on Day 24. Follow-up imaging on Day 35 revealed shrinkage of the pituitary lesions and the retroperitoneal mass (Fig. ).


A two-month-old, exclusively breastfed male infant presented to the Emergency Department after two episodes of vomit and five episodes of diarrhea without blood or mucus. In the previous week, the baby had some occasional episodes of loose stools and a mild, but persistent, abdominal distension. He was born at term (39 weeks of gestational age) from spontaneous vaginal birth after an uncomplicated pregnancy, with a birth weight of 3480 g. Before he came to our attention, the boy was always in good health and his weight was regularly increasing. On physical examination, the child appeared pale and irritable, with low-grade fever (37.8 C°), heart rate 178 beats per minute and a prolonged capillary refill time (3 s). An intravenous bolus of 0.9% saline at 20 ml/Kg was administered in 20 min, followed by continuous intravenous hydration. Blood tests were in range, except for an increased C-reactive protein (3.5 mg/dl) and hypoalbuminemia (2.7 g/dl). The arterial blood gas analysis (ABG) was normal, except for a significant increase in methemoglobin (13%, normal range between 0 and 1.5%). Two urinary dipsticks in two different samples showed no signs of infection, later confirmed by a negative urine culture. Six hours after the admission, the child became irritable and his skin was mottled. Blood cultures were obtained before starting an intravenous antibiotic therapy with ceftriaxone. Central nervous system, thoracic and abdominal ultrasounds were negative. Eventually, the blood cultures and stool analysis (for bacteria, viruses, fungi and parasites) tested negative as well. The day after, through fluid resuscitation and antibiotic therapy, the boy’s conditions generally improved, and his mother kept breastfeeding him. However, he continued to present numerous episodes of diarrhea, around 12–15 per day, with greenish liquid stools, that led to a mild weight loss (− 200 g in 48 h). Two days after the admission, despite intravenous support, the child developed a severe dehydration, with hypernatremia (152 mmol/L), hypokalemia and hyperchloremic metabolic acidosis (pH 7.26, bicarbonate 18 mmol/L, base excess − 7.7, acid lactate 2.39 mmol/l). Blood tests showed anemia (hemoglobin 9 g/dl), thrombocytosis (platelets 552.000/mL), worsened hypoalbuminemia (1.7 g/dL) which required an IV supplementation, stably elevated methemoglobin (13%) and raised levels of transaminases (peak values: ALT 396 U/L, AST 121 U/L). Due to the worsening clinical condition and to a very poor suction, a central venous line was placed and parenteral nutrition was started. Remarkably, when breastfeeding was suspended because of the baby’s hypotonic suction, diarrhea started to improve and halved to five-six episodes per day. Serologies and PCR for cytomegalovirus, Parvovirus B19, Epstein Barr virus, Adenovirus, hepatotropic viruses, and a nasal-pharyngeal swab for viruses and bacteria were negative. In the following days, the patient regained good general clinical conditions, and laboratory tests were normalized, except for the methemoglobin, which was still very high (8–10%). However, when breastfeeding was reintroduced, his diarrhea worsened once again to 10–15 episodes per day. A metabolic disease was suspected but it was unlikely, as demonstrated by the negative neonatal screening, the clinical presentation and the values of ammonium, glucose, lactate and ABG, all in range. Congenital causes of diarrhea were ruled out because they should have appeared earlier, in the first days of life. Thus, according to some similar clinical cases reported in the literature, the close relationship between breastfeeding and diarrhea and the high level of methemoglobin were emphasized and Food Protein-Induced Enterocolitis Syndrome (FPIES) caused by maternal milk was suspected. Since the mother was already on a milk exclusion diet, breastfeeding was definitely stopped and replaced with an amino acid-based formula. Over the next 72 h, diarrhea gradually improved and then stopped, so that the intravenous hydration was reduced and subsequently suspended, and the infant started to gain weight. Skin prick test resulted negative for cow’s milk proteins (lactalbumin, lactoglobulin, and casein) and soy. After the hospital discharge, an oral food challenge test (OFC) was proposed to the child’s parents but they refused it, in consideration of the severe clinical symptoms that the infant previously developed. The boy was weekly checked through the following months and he kept gaining weight without presenting any clinical symptom. Therefore, the amino acid-base formula was continued, which he’s still taking at the age of 6 months.
A three-month-old, exclusively breastfed female baby presented to the Emergency Department for a 3 days history of persistent vomit and diarrhea without fever. She was born at term (39 weeks of gestational age) from spontaneous vaginal birth after an uncomplicated pregnancy, with a birth weight of 3210 g. Her previous medical history was silent and her growth has always been regular. On physical examination, the baby was pale and hypotonic and a weight loss of 6% was noticed. Blood tests showed mild anemia (hemoglobin 10.9 g/dL), lymphomonocytic leukocytosis (white blood cells 14.050/mmc, lymphocytes 7.370/mmc, monocytes 2.680/mmc), thrombocytosis (platelets 927.000/mmc), electrolyte imbalance (sodium 131 mEq/L, potassium 3.27 mEq/L, chloride 109 mEq/L, calcium 8.33 mg/dL), hypoproteinemia (3.2 g/dL) with hypoalbuminemia (1.8 g/dL) and slightly altered coagulation values (INR 1.6, aPTTr 1.85). Arterial blood gas was normal, except for a raised level of methemoglobin (7%, normal range between 0 and 1.5%). A venous catheter was placed and continuous intravenous hydration with 0.9% saline was started. Stool analysis tested negative for viruses, bacteria and parasites. Suspecting a post-viral intestinal colonization, an antibiotic therapy with rifaximin was started, later substituted by oral gentamicin, both without clinical improvement. Due to the persistent diarrhea and the alteration of blood tests, we integrated the girl’s therapy with vitamins, trace elements (such as zinc) and albumin, and we performed a red cells and a plasma transfusion. Even if she continued to assume breast milk regularly, we added supportive parenteral nutrition. Laboratory tests were requested to rule out myocarditis, metabolic diseases, botulinum intoxication, cystic fibrosis and pancreatic insufficiency, and they were all normal. The patient also developed a severe hypotonia with hypoexcitability of deep tendon reflexes. A cerebral MRI and an electromyography showed no remarkable alterations, and vitamin B12 and folate were in range as well. Because of the persistence of the intestinal symptoms, an esophagogastroduodenoscopy was requested. The histopathology of the biopsies showed an eosinophilic infiltration of the duodenal mucosa, raising the suspicion of a non-IgE mediated food allergy to cow’s milk proteins, conveyed by maternal breast milk. Therefore, the baby’s mother started an exclusion diet and stopped the consumption of cow’s milk and dairy products. In the following 2 days, we noticed a slow but steady improvement of the general conditions of the patient, which was still mildly hypotonic but showed reduced episodes of diarrhea. Therefore, an amino acid-based formula was started, leading to a rapid and stable regularization of the bowel function, a gradual increase in weight and a complete recovery of the muscle tone. Blood tests confirmed the clinical improvement with an increase in hemoglobin and total proteins and the normalization of coagulation parameters and methemoglobin. RAST and skin prick test for cow’s milk proteins tested negative. An oral food challenge test (OFC) was proposed to the child’s parents after the hospital discharge, but they preferred to not perform it. Therefore, the girl was kept on amino acid-base formula and her mother continued the exclusion diet. We monthly checked the infant for the following 9 months and she kept gaining weight, without presenting any clinical symptom. Weaning was regularly started at 6 months, with the exclusion of cow’s and soy milk and dairy products, which we’ll try to introduce in the next months.


A 5-year-old girl presented to our department with high fever, headache, and vomiting for 2 days, and a high inflammatory response was found. She had commenced amoxicillin (40 mg/kg/day) a day before presentation. She never had a urinary tract infection (UTI) or a history of fever without a focus. Her general condition was good, and physical examination showed mild redness in the throat and no signs of Kawasaki disease. Laboratory tests revealed a high inflammatory response (white blood cell count [WBC], 21,080/μL [neutrophil, 85.8%]; C-reactive protein [CRP] level, 19.5 mg/dL), and a bacterial infection was suspected. Although no bacteria were identified in the urine on Gram staining, the urine test showed WBC > 100/high-power field, and we diagnosed her with a UTI. We administered both ampicillin (150 mg/kg/day) and cefotaxime (150 mg/kg/day) intravenously.
A day after admission, gram-negative rods were detected from blood cultures. Although she continued to have a high fever, her general condition was good, and recurrent blood tests showed that the CRP levels had reduced to 14.1 mg/dL. We could not detect any signs of hydronephrosis, acute focal bacterial nephritis, or renal abscesses on renal ultrasound. We thought that the antibiotics were effective and therefore continued with the same treatment. However, the fever was prolonged, continuing on the third day of admission when contrast-enhanced computed tomography (CT) was performed, and signs of renal abscess in the left kidney were observed (Fig. ). On the same day, blood cultures came back positive for ESBL-producing E. coli. We then changed the antibiotics to meropenem (120 mg/kg/day).
We did not perform drainage of the renal abscess because the mass was only 10 mm and too small to puncture. ESBL-producing E. coli were also detected in the urine cultures obtained on admission. Her fever resolved on day 5, and there was no recurrent fever. After 3 weeks of treatment with meropenem, improvements of the left kidney abscess were observed on repeat CT scanning (Fig. ). Although poor contrast enhancement remained in the area where the abscess was located, we did not perform another CT scan to check for further improvement to avoid exposing the patient to additional radiation. Technetium-99 m dimercaptosuccinic acid renal scanning conducted 4 months after the onset of symptoms revealed the presence of renal scarring in the upper and lower poles of the left kidney along the low-density areas in the initial CT scan (Fig. ). No signs of vesicoureteral reflux were found with a voiding cystourethrogram, and no decrease in renal function was found on laboratory examination. At the 1-year follow-up, she had no recurrence of the abscess or renal sequelae such as hypertension, proteinuria, or impaired kidney function.


A 56-year-old woman diagnosed with galactosialidosis (β-galactosidase-neuraminidase deficiency) presented with vomiting. At admission, her general condition was poor, with a pulse rate of 90 bpm, blood pressure 110/60 mmHg, and oxygen saturation 100% without oxygen flow. On a physical examination she showed muscular defense over the whole abdomen. The laboratory test results on admission were as follows: red blood cell count, 488 × 106 cells/μL; hemoglobin 13.5 g/dL; leukocyte count, 6400 cells/μL; platelet count, 15.6 × 104 cells/μL; aspartate aminotransferase, 20U/L; alanine aminotransferase, 7 U/L; and C-reactive protein, 12.1 mg/dL. Abdominal X-ray photograph revealed a large amount of gas over most of the abdomen. Peritonitis due to perforation of the intestine was diagnosed based on the free air and dilated loop of the small bowel found on contrast-enhanced computed tomography (Fig. ).
Laparotomy revealed perforation of the Meckel’s diverticulitis located 50 cm from the ileocecal valve. Partial resection of the ileum, including the diverticulum, and end-to-end anastomosis of the small intestine were performed (Fig. ).
Regarding the pathological findings, ectopic gastric mucosa was not observed in the diverticulum. The edge of the diverticulum wall consisted of a solid mass measuring 1.0 cm in size, and the tumor cells were spindle-shaped with 1 mitosis present per 50 high-power fields (Fig. a). The perforation site of the diverticulum was separated from the tumor nodule. The immunohistochemistry findings were as follows: the cytoplasm was stained positive for c-tyrosine kinase receptor (kit) (Fig. b) and α-smooth muscle actin (Fig. c) and stained negative for CD34 (Fig. d). The Ki–67 index was 1.6%. The diagnosis was established as GIST of Meckel's diverticulum.
As the patient had been diagnosed with galactosialidosis and was intolerant to imatinib and because the perforation of the diverticulum was not associated with the tumor nodule, imatinib was not administered. The postoperative period was uneventful. Follow-up at two years revealed no evidence of recurrence.


We present a case of a 41-years-old man living in a rural area with a history of treated duodenal ulcer and uncontrolled type II diabetes mellitus. Five days before the hospital admission, this patient had an epigastric pain associated with a high fever (up to 39.5 °C). Four hours before the hospitalization, his epigastric pain was seriously and dramatically increased. A physical examination on admission to the emergency department revealed high temperature of 39 °C and generalized rigidity of the abdominal wall, suggesting a peritonitis. His heart rate was 109 beats/min and his blood pressure were 120/80 mmHg. There was not a clear clinical anemia or jaundice. His white blood cell count was 19.1 × 109/L and the percentage of neutrophils was 85.3%. Other laboratory results were as follows: serum pro-calcitonin level, 17.73 ng/ml; serum glucose level, 14.7 mmol/L; serum bilirubin level, 37.6 mmol/L; serum aspartate aminotransferase level, 51 U/L and serum alanine aminotransferase level, 87 U/L.
Both of the chest and abdominal X-ray showed bilateral subdiaphragmatic air, indicating pneumoperitoneum (Fig. ). Consistently, ultrasound scan of the abdomen was conducted and detected free intraperitoneal air and fluid. It was hard to evaluate liver tissue due to the presence of intraperitoneal air and no hypoechoic foci was detected in the liver by this method. Unfortunately, computed tomography (CT) of the abdomen was not available by the time of the admission.
Patient was diagnosed peritonitis and pneumoperitoneum presumed to be secondary to perforation of a hollow viscus and treated for septic shock with intravenous fluid and broad-spectrum antibiotic. He was subjected to emergency laparotomy. Based on his previously reported duodenal ulcer history, we carefully checked and did not find any gastrointestinal perforation. Surprisingly, we detected a 4 cm × 4 cm pus-containing abscess in the left liver lobe of the liver. The abscess was ruptured. Pus was running into abdominal cavity through one hole. At the end of the operation, 80 ml of turbid pus was drained from the subphrenic and subhepatic spaces. We carefully checked and did not find any underlying disease of the biliary tract. We concluded that the pneumoperitoneum resulted from spontaneous rupture of the hepatic abscess in the left liver. We placed abdominal drains in the abscess cavity and the subhepatic area. K. pneumoniae was isolated from culture of the abscess. The histopathological examination of the abscess did not yield any evidence of malignancy. Blood glucose levels were controlled. Antibiotic therapy was used according to antibiogram (piperacilin and tazobactam). A reassessment chest X-ray showed no air-fluid level or subdiaphragmatic air by the hospital day 14. The patient eventually made a full recovery without any complication and was discharged home 23 days after the operation.


A 49-year-old perimenopausal female with a past medical history of hypertension, hypothyroidism, multiple fibroids, a body mass index (BMI) of 33.2, and a history of iron deficiency anemia presented with AUB and chronic lower abdominal pain with associated urinary urgency. The patient was referred from her primary care doctor due to a large, symptomatic fibroid uterus, and the patient elected to have an abdominal supracervical hysterectomy with bilateral salpingo-oophorectomy. The patient had been diagnosed with leiomyomas in her twenties but had refused surgery until now to maintain fertility. Preoperative transvaginal and pelvic ultrasounds revealed a uterine size of 22 x 20 x 17 cm and a 15.9 x 13 x 9 x 9.2 cm subserosal fibroid occupying the majority of the fundus and body of the uterus. The endometrial thickness on ultrasound was 1.4 cm but with limited visualization due to the fibroid. The ovaries were not visualized.
Under general anesthesia, a midline incision was performed from the pubic symphysis to and around the umbilicus. Once the abdominal cavity was entered, traction was performed bilaterally on the rectus muscles and peritoneum, extending the incision superiorly and inferiorly. The uterus was exposed and the bowel and omentum were packed with sterile gauze packing. The uterus was externalized and the left fallopian tube was clamped and cut using a sealing instrument. Cauterization and transection were done at the level of the infundibulopelvic ligament. Then, the left ovarian ligament and the left round ligament were clamped, cauterized, and transected. The broad ligament on the left side was then skeletonized. The uterine vessels were identified, clamped twice, cut with scissors, and tied with suture. A similar maneuver was performed on the right side excluding clamping and transection of the right fallopian tube, which was left attached to the uterus, and adequate hemostasis was noted. At this point, the uterocervical junction was identified. The bladder flap was developed and the bladder separated from the uterocervical junction. Using cauterization, the cervix was amputated from the uterus and the cervical stump was reapproximated with adequate hemostasis. Blood loss was approximated at 50 mL with no intraoperative complications. The patient was discharged on postoperative day three with a routine follow-up one week following surgery.
The uterus and adnexa were submitted for pathology, the results of which were read as a uterus with multiple leiomyomata as well as endometrial polyps with focal atypical endometrial hyperplasia and squamous metaplasia (Figures , ). The myometrial nodules ranged in size from 1.7 x 1.5 x 0.9 cm to 17.3 x 15.2 x 12 cm with mucoid-like and calcified areas of degeneration. The endometrial cavity contained two endometrial polyps, 0.9 cm and 1.4 cm in size, not previously visualized on ultrasound. Overall, the uterine corpus with one attached adnexa weighed 3433 g and was 25.8 x 20.3 x 15cm in size. The endocervix, bilateral fallopian tubes, and ovaries had demonstrated no pathological changes.


A 48-year-old female presented to us with neuropathic pain, restricted to the dorsum of the right hand, and numbness of the dorsum of the second web space and ulnar half of the index finger (Figure ). The patient had experienced blunt trauma to this region of her hand in May 2015.
The patient complained of electric pain and painful tingling when the site on the back of the hand was touched. The patient is a right-handed architect and due to the trauma could no longer shake hands for fear of pain. She was diagnosed with neuroma-in-continuity of the third digital nerve originating from the superficial branch of the radial nerve. She was first treated with a trigger point injection of Naropin; this proved to be ineffective. She was then referred to a hand therapist to start sensorimotor rehabilitation, which alleviated the painful neuroma. Rehabilitation of the hypoaesthetic territory of the dorsum of the index finger was also performed and was ultimately successful. Aesthesiography results are shown in Figure and Table .
Three years later, she presented with worsening neuropathic pain and numbness in the previously treated areas of her hand. The pain was restricted to the dorsal surface of MCP2/3 (the second and third metacarpophalangeal joints). In contrast, the recurrent numbness was restricted to the dorso-ulnar surface of the proximal phalanx of the right hand. The pain was not related to posture, nor did it radiate to another site, and it only occurred in response to touch. Her Tinel’s test was strongly positive. There was no loss of motor function. She was scheduled for AFT and the surgery was performed under general anaesthesia. The donor site (abdomen) was infiltrated with 0.9% NaCl and 0.001 mg/ml adrenaline and the adipose tissue was harvested. Only 2 cm3 of the lipoaspirate was then injected subcutaneously into the pre-operatively marked area of the hand (Figure ). After the operation, a pressure bandage was applied to her hand and the patient was advised to keep it held high. The patient also wore a corset around her abdomen to maintain pressure on the donor site for two weeks. The patient was monitored for 12 weeks after the operation. The neuroma pain completely disappeared and the patient could shake hands again. Also, the numbness on the dorso-ulnar surface of the proximal phalanx was cured. After one year she was still free of pain and numbness in her hand and therefore satisfied with the results.


A 30-year-old Japanese man was admitted to our hospital because of high-grade fever with transient consciousness disorder and double vision. He had no medical history throughout his childhood and adolescence but continued to have repeated fever and productive cough since the age of 25. He also presented with stomatitis and dental caries. His mother had a history of disseminated cryptococcosis and died from chronic hepatitis C virus infection. His younger brother had been clinically diagnosed with CMCD for having recurrent and refractory cutaneous candidiasis although no genetic analysis has been performed on his dissent.
Physical examination on the admission revealed that the majority of his teeth were corroded, and that he had white moss throughout his mouth. A nuchal stiffness was noted with right abductor paralysis. His chest computed tomography (CT) showed bronchiectasis and multiple granular shadows randomly distributed in the bilateral lower and middle lobes, thin-walled cysts predominantly in both upper lobes, and consolidation in the lower left lobe (). Cryptococcus neoformans was isolated from his blood and cerebrospinal fluid samples and was also detected in liver and lung biopsies. Accordingly, he was diagnosed with disseminated cryptococcosis with meningitis and oral and cutaneous candidiasis.
The patient was treated with a combination therapy of liposomal amphotericin B and flucytosine for 8 weeks. Consequently, his respiratory symptoms and neurological abnormalities resolved. The cryptococcal antigen titers in his cerebrospinal fluid decreased from 1,024 times to 32. His chest CT on day 44 of the treatment showed that the granular shadows and consolidation entirely improved, but the bronchiectases in his right middle lobe and left lingular segment remained. The antifungal treatment was then switched to oral fluconazole, and the disease did not recur for one year.
The patient was suspected of having primary immunodeficiency because of the present clinical course and his family history. We sequenced the patient’s CMCD-related genes and found a previously recognized heterozygous missense mutation in the coiled-coil domain of the STAT1 gene (c.820C>T, p.R274W) (, ). The same mutation was also detected in his younger brother. The monocytes of the patient showed hyper-phosphorylation of STAT1 after stimulation with interferon-γ (). Based on these results, the patient was diagnosed with STAT1 GOF.
Additionally, the patient presented with low serum IgG and IgA levels [IgG: 2.36 g/L, normal range (NR): 8.61–17.47 g/L; IgA: 0.05 g/L, NR: 0.93–3.93; IgM: 0.92 g/L, NR: 0.33–1.83]. Surface marker analyses revealed that 72.3% (NR: 54.3–81.9%) of his peripheral lymphocytes comprised CD3+ cells with a CD4/CD8 ratio of 32.8 (NR: 24.3–49.7%)/36.2 (NR: 18.4–49.0%), and that 0.1% (NR: 2.9–20.1%) comprised CD19+ cells (). Peripheral blood lymphocyte responsiveness to phytohemagglutinin was normal (Stimulation Index: 281, NR: 254–388). The level of T-cell receptor excision circles was 2.06 x 102 copies/μgDNA [NR: 3.4 ± 3.6 x 102 copies/μg DNA ()], whereas both those of the coding joint and signal joint kappa-deleting recombination excision circles were undetermined. We then investigated the cause of hypogammaglobulinemia and B-cell lymphopenia. The B-cell differentiation was blocked in the stages between VpreB+IgMlow (pre-B1b) cells and VpreB−IgMlow (pre-B2) cells in the bone marrow sample obtained three months after the onset of cryptococcosis (). Human immunodeficiency virus-RNA and Epstein-Barr virus- and cytomegalovirus-DNA were undetectable by polymerase chain reaction. No pathogenic variants in antibody deficiency-causing genes listed in the 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity were detected using the target panel sequence (). The reduction in the peripheral B-cell counts had persisted even after the patient’s recovery from cryptococcosis (). His prolonged respiratory symptoms did not recur upon regular subcutaneous immunoglobulin infusion to maintain a trough level of >7.0 g/L.


A 22-year-old female presented with history of haemoptysis for eight days. The condition started as a productive cough (green sputum containing streaks of blood). Over the course of the following days, her haemoptysis worsened as she was coughing copious amount of blood. She also had constitutional symptoms (fatigue, anorexia, intermittent fever, sweating, and shivering at night), sore throat, shortness of breath, nausea, non-projectile vomiting, dizziness, and dark coloured urine. The patient had no past medical and surgical history of note. She was not on any long-term medications.
On examination, she was conscious, oriented, looked toxic, dyspnoeic, and pale. Her vital signs were as follows: temperature 38.5°C, heart rate 118 b/min, blood pressure 120/80 mmHg, respiratory rate 26 cycle per minute, and peripheral capillary oxygen saturation (SpO2) 89% on room air. There were petechiae in the roof of the oral cavity. Auscultation of the chest revealed bilateral bronchial breath sounds at midzone. The abdominal and pelvic examination was unremarkable. She had no pedal oedema. There was no cervical, axillary, or inguinal lymphadenopathy.
The following investigations were performed and their results as shown in Table .
The patient was admitted to hospital. She was commenced on intravenous (i.v.) vancomycin as an empirical treatment for a possible chest infection given the clinical picture. During her stay, she developed right ankle joint pain and tenderness, and pitting oedema over both legs. On day 5, the temperature spiked to 40°C associated with rigors. The fever did not respond to parenteral paracetamol. As the patient was distressed due to high fever, we decided to administer dexamethasone. The following morning, a dramatic response was observed. Her fever subsided, haemoptysis improved, and the right ankle joint pain eased. The response to steroid and the failure of other treatments raised the possibility of a rheumatological disease causing this illness, like vasculitis. Therefore, we consulted one of the rheumatologist colleagues who shared the same suspicion around vasculitis. On the eighth day, she received two pints of whole blood, albumin infusion 100 mL (20 g)/day for three days, methylprednisolone vial 500 mg i.v. infusion/day for three days, omeprazole capsule 40 mg/day, and continued vancomycin injection.
On the 11th day, she continued to improve. At the point, she was fever free for six days and her dyspnoea as well as the joint pain subsided. She was coughing minute amount of blood.
On the 12th day, induction of remission regimen was planned through administrating high-dose steroid at 50 mg prednisolone/day and rituximab injection 375 mg/m2 every week for four weeks. At the end of the course, the haemoptysis resolved and she was well enough to be. She developed moon face and acne vulgaris, but she was well apart from that. According to those investigation results (Table ) and advice of the rheumatologist, the diagnosis of granulomatosis with polyangiitis was concluded. We advised her to have a follow-up every month for next three months and then bimonthly for one year (Figs. , ).


A 12-year-old, 23 kg, spayed female Golden Doodle; that was privately owned was presented for evaluation of a large cranial abdominal mass as well as a firm caudal abdominal mass. Historical clinical signs included polyuria and progressive weight loss for 1–2 months. Biochemistry performed through the primary care veterinarian revealed an elevated alkaline phosphatase (ALP) of 2181 U/L (reference range: 20 to 150 U/L), and an elevated alanine aminotransferase (ALT) of 303 U/L (reference range: 10 to 118 U/L). Radiographs and ultrasound indicated there was a large cranial abdominal mass suspected to be associated with the liver and a second caudal abdominal mass with an unknown origin that appeared to be compressing the urinary bladder.
On presentation, the dog was bright, alert, and responsive. Body condition score was 4/9. The patient was non-painful on abdominal palpation. Abdominal palpation revealed a cranial abdominal mass effect as well as a firm irregular caudal abdominal mass. The remainder of the physical examination was unremarkable. Hematology was unremarkable. The serum biochemistry revealed an elevated alkaline phosphatase (ALP) of 2102 U/L (reference range: 20 to 150 U/L), and an elevated alanine aminotransferase (ALT) of 299 U/L (reference range: 10 to 118 U/L). Urine analysis demonstrated 3 + protein, with a urine specific gravity of 1.050. A coagulation profile was performed, which was unremarkable. Three-view thoracic radiographs did not show any signs of metastasis or any other significant abnormalities.
An abdominal computed tomography (CT) scan showed a well-defined, irregularly marginated, multilobulated, hypoattenuating mass, measuring 4.7 cm x 6.8 cm x 8 cm, at the level of the left distal ureter and ureteral papilla, with secondary severe left proximal ureteral dilation, measuring 0.5–0.6 cm (Fig. ). The cranial abdomen revealed a well marginated, mildly heterogenous, contrasting soft tissue attenuating mass, measuring 6.3 cm x 12.5 cm x 10.9 cm, arising from the caudal aspect of the left lateral liver lobe (Fig. ).
An exploratory celiotomy was performed. The celiotomy identified a large mottled mass, measuring 18 cm x 10 cm x 4 cm associated with the left lateral liver lobe (Fig. ), along with a firm, nodular, multilobular mass, measuring 8 cm x 5 cm, associated with the distal left ureter attached to the left aspect of the urinary bladder (Fig. ) with proximal ureteral dilation. A left lateral liver lobectomy was performed with a TA-55 stapler and the Ligasure Precise vessel sealing device. The left ureter mass was dissected out and found to be adhered to the bladder serosa and found to enter the bladder lumen through the left ureteral papilla. A left sided ureteronephrectomy and partial cystectomy were performed to remove the mass en bloc. No other abnormalities were noted on final exploration. The patient underwent a successful and uneventful recovery and was discharged from the hospital three days postoperatively. Adjunctive therapy including chemotherapy was discussed but declined. At the initial postoperative evaluation (12 days), the owner reported no overt issues and improvement in appetite and energy, with no abnormalities noted on physical exam. At subsequent evaluations (30-days, 40-days and 120-days), the patient is reported to show consistent and progressive status improvement with no concerns.
Histopathology was performed by a board-certified pathologist and confirmed by a second pathologist. The ureteral mass was narrowly excised with 0.1 mm surgical margins. Histologic findings of the ureteral mass (Fig. ) revealed a densely cellular, poorly demarcated (Fig. ), unencapsulated, infiltrative, variably cystic, and hemorrhagic mass which variably borders foci of marked hemorrhage, fibrin, edema, and necrosis. The cells are plump and spindloid, with indistinct cellular borders and wispy eosinophilic cytoplasm (Fig. ). The nuclei are oval to elongate, with finely stippled to vesicular chromatin and one to three nucleoli. Anisocytosis and anisokaryosis are moderate, with a mitotic count of 6 in ten 400x fields. Immunohistochemistry was then performed revealing positive CD31 staining of the neoplastic spindle cells confirming ureteral hemangiosarcoma (Fig. ).
Histologic findings of the liver mass revealed a densely cellular, poorly demarcated, unencapsulated, infiltrative, variably hemorrhagic, and necrotic mass (Fig. ). The cells form coalescing broad hepatic cords and trabeculae, supported by a small amount of fibrovascular stroma (Fig. ). Portal areas and central veins are not discernible within the mass. The cells are polygonal, with distinct cellular borders and a moderate to abundant amount of granular eosinophilic cytoplasm, which variably contains ill-defined vacuolar regions of clearing. The nuclei are round to oval with finely stippled chromatin and one to four nucleoli. Anisocytosis and anisokaryosis are moderate, and 11 mitotic figures are observed in ten 400x fields. The findings observed were confirmed to be consistent with hepatocellular carcinoma.


A 17-year-old girl was admitted to the Psychiatric Clinic of Parma because of a refusal to eat manifested in the previous days and a report of suicidal ideations that emerged following stressful environmental and relational events. The patient was followed up by the local child neuropsychiatric service for 1 year for adaptation disorder with mixed anxiety and depressed mood. The patient had a positive history of self-injurious gestures for suicidal purposes and was in treatment with venlafaxine (75 mg/day), lamotrigine (25 mg/day), gabapentin (200 mg/day), and lorazepam (2.5 mg/day) with a poor response to therapy and a family history of depression. No history of neck irradiation as well as treatment with lithium preparations was reported. After 9 days of hospitalization, necessary to reach sufficient a psychopathological state within the limits of the basic personological framework, a transfer to the Pediatric Clinic of our Children's Hospital was requested for the incidental detection of hypercalcaemia. At admission, the subscore at the Hospital Anxiety and Depression Scale was 10.
Upon arrival, the initial laboratory work-up showed elevated calcium level (13.3 mg/dL; normal range: 8.8–10 mg/dL), increased ionized calcium concentration (6.7 mg/dL; normal range: 4.7–5.2 mg/dL) and reduced phosphorus level (2.6 mg/dL; normal range: 2.7–4.5 mg/dL), which is why intravenous fluids and serial ECG recordings were started. The parathyroid hormone levels was 193 pg/mL (normal range: 14–72 pg/ml), while the vitamin D levels was slightly reduced at 21 ng/mL (normal range: 20–79 pg/mL); no other abnormalities were detected in blood tests. Regarding urinary tests performed on 24-h urine collection, they pointed out hypercalciuria at 10.5 mg/kg/day (normal value <4 mg/kg/day), which strongly suggested PHPT excluding familial hypocalciuric hypercalcaemia.
The imaging work-up first involved thyroid/parathyroid ultrasonography, which revealed a thyroid of normal size with homogeneous echotexture and no lesions, while the parathyroids were not visible. The subsequent Sesta-MIBI parathyroid scan combined with SPECT-CT fusion study of the neck-mediastinum highlighted an anterior mediastinal parathyroid adenoma localized behind the manubrium body of the sternum ().
Therefore, further laboratory and instrumental tests were necessary to exclude the presence of lesions or associated alterations attributable to a MEN framework. For this purpose, neck-thorax-abdomen contrast-enhanced CT was performed, which confirmed the presence of a solid nodularity with a diameter of ~9 mm in the anterior mediastinal site and excluded the presence of further alterations of the studied organs (). Brain-pituitary gadolinium-enhanced MRI was also performed and showed a globular aspect in the adenohypophysis with normal pituitary functionality.
The results of blood and urinary tests executed to study calcium-phosphorus metabolism and the pituitary-adrenal, pituitary-thyroid, and pituitary-gonadal axes and to exclude the presence of neuroendocrine tumors (neuron specific enolase, chromogranin A, urinary metanephrines, vanillylmandelic acid, serotonin) or other PHPT possible complications were negative. In order to exclude a multiple endocrine neoplasia, mutation analysis of the MEN1 and RET genes was performed and resulted negative.
During hospitalization, the calcium level remained stable at 11 mg/dL initially with intravenous fluid therapy alone, after which 25 mg/dL furosemide was administered per os. In consideration of the new verbalization of suicidal ideations by the patient, two psychiatric consultations were performed with subsequent re-modulation of the pharmacological treatment (lamotrigine 50 mg/day, gabapentin 100 mg/day), which led to a slight improvement in the psychic framework. Mediastinal parathyroidectomy associated with complete thymectomy was finally performed with a robot-assisted approach (duration of intervention: 3 h) with no perioperative complications and in a few hours led to the normalization of PTH and calcium levels. Histological examination showed a parathyroid adenoma with an organoid pattern composed of medium-sized oval to polygonal cells, a moderate amount of eosinophilic cytoplasm, round to oval centrally placed nuclei, and, in many cells, prominent nucleoli. Although intraoperative PTH was not evaluated, subsequent blood laboratory tests did not highlight further alterations (). The patient was discharged after 3 days from the intervention. Regarding the neuropsychiatric sphere, during the following investigations, no other suicidal ideations were registered, while a modest improvement in mood, energy and health perception with a subscore of 5 at the Hospital Anxiety and Depression Scale was reported at the 3-month follow-up. Lamotrigine and gabapentin were stopped and no further need of neuropharmacologic treatment was requested at the 6-month follow-up.


A 51-year-old male patient who had been in good general condition over the last 2 years was admitted to our hospital with severe headaches, a feeling of weakness in his legs, noise sensitivity and nausea. An MRI revealed signs of chronic intracranial pressure with hydrocephalus (extended ventricles and diapedesis of CSF). The ophthalmologic examination revealed bilateral papilloedema. In his ventricular CSF, HSV2 was detected by PCR (3 × 104 copies/mL, ref. < 500; in CSF: protein 1130mg/L, ref. < 150; cell count 221MPt/L, ref. < 2) and a renewed HSV2 meningoencephalitis was diagnosed like 2 years ago. With external ventricular drainage and i.v. administration of aciclovir (1950 mg/day for 21 days) the patient improved. The intraventricular drain could be removed and the hydrocephalus did not recur.
The patient’s medical history reached back to early childhood. On day 4 after birth, he received a BCG vaccination under immunoglobulin substitution. At that time, physicians assumed that this substitution could provide protection, in case the patient had inherited a primary immunodeficiency. They suspected a primary immunodeficiency, because his older sister had suffered from generalized BCGitis after vaccination. Despite IVIG substitution, the boy developed BCGitis with lymphadenitis axillaris and fever, and a generalized exanthema a few days later. M. bovis (type BCG) was detected in granulomas from a lymph node biopsy and the boy was treated with INH and streptomycine. At the age of 4 months, the patient developed alleged hepatitis tuberculosa (multiple granulomas with caseating necrosis in a liver biopsy, no microbiological evidence of mycobacteria) and was therefore started on another anti-tuberculous medication. A few weeks later, after an episode of enteral salmonellosis, he developed high fever and right leg pain and was diagnosed with osteomyelitis of the right tibia caused by Salmonella typhimurium. At the age of 5 years, the patient developed VZV pneumonia during his first chickenpox infection. This episode is well documented because he was an inpatient for two weeks. At age 6, he was operated for presumed appendicitis. Retrospectively, pronounced lymphadenitis mesenterialis due to Yersinia pseudotuberculosis had mimicked appendicitis. At age 31, the patient suffered from severe chickenpox with a generalized pronounced vesicular rash and had another episode of VZV pneumonia requiring hospital admission at the same time as his son fell ill with chickenpox. During the following 15 years, the patient had repeated episodes of thoracic shingles (typical painful segmental vesicular rash, diagnosed by general practitioner, treated with oral and local aciclovir administration), which resolved without sequelae, but he was otherwise healthy. At age 49, he was admitted to our hospital with personality change and somnolence and was finally diagnosed with meningoencephalitis. HSV2 was detected in CSF by PCR (9 × 106 copies/mL, protein 3460 mg/L, cell count 1617 MPt/L in CSF). The MRI showed mild signs of inflammation. The meningoencephalitis was treated successfully with i.v.-aciclovir (2250 mg/day for 14 days). In the following 2 years, the patient reported repeated and sometimes severe headaches some of which he treated with aciclovir on his own without consulting a physician. This patient had been reported by Jouanguy et al. [] and Dorman et al. [] (Table 1 nr. 31C) before the onset of the remarkable viral infections.
The family history of the patient revealed that his mother had suffered from alleged tuberculosis of the urinary bladder early in life, which was cured by anti-tuberculous therapy. She died at age 30 from chronic progressive hepatitis that could not be further specified.
The patient’s sister developed generalized BCGitis after vaccination and was treated with anti-tuberculous therapy. A relapse could be controlled with tuberculostatic treatment, and no other infectious complications occurred during childhood. However, the sister died at age 27 from an intestinal mycobacterial infection, which had been misinterpreted as Crohn’s disease and therefore treated with steroids.
The patient described in this report has two sons with the same IFNγR1-deficiency. The older son remained clinically healthy. The younger son suffered from various infections such as VZV-pneumonia, VZV-meningoencephalitis, shingles, suspected HHV-6 hepatitis, lymphadenitis mesenterialis, and mycobacterial osteomyelitis []. The patient’s daughter and a nephew are not affected. Genetic testing of the patient and his sons revealed the common c.818–821del4 mutation in one allele of the IFNGR1-gene causing dominant partial IFNγR1 deficiency. Whole exome sequencing (WES) of the patient, his wife and the clinically affected son did not reveal any potential causative variation other than IFNɣR1 deficiency. Jouanguy et al. recently published inborn errors of human antiviral immunity to herpes viruses []. All genes listed by Jouanguy et al. (Table 1 []) were unaffected as determined by WES.


A 64-year-old heavy smoker male patient was admitted for the first time to our urology department for hematuria and dysuria. His past medical history was unremarkable. He had a transurethral resection of the prostate 5 years ago. He did not have any familial history of urothelial or bladder cancer. Physical examination and blood tests were normal. In the emergency room, an abdominal and pelvic ultrasound showed a thickening of the right lateral wall of the bladder with mild right side hydronephrosis (). On cystoscopy, a large tumor was found on the anterior and right lateral walls of the bladder, with invasion of the bladder neck and the prostate. The anatomopathological study of the tumor showed a neoplastic proliferation of large malignant polygonal cells with dark, irregular nuclei and frequent mitosis. A second component made of cylindrical cells was also present. Muscular invasion was documented with multiple necrotic areas (). Immunohistochemistry showed high positivity for CD56 marker and synaptophysin, minor and heterogenic positivity for cytokeratin 7, and negativity for cytokeratin 20 and CDX2 (Figures –). Overall, the histopathological study corresponded to LCNC with minor adenocarcinomatous component. Disease extension was assessed using computed tomography (CT) scan of the thorax, abdomen, and pelvis. A 6 × 3.5 cm mass of the anterior and right lateral walls of the bladder was identified, with diffuse infiltration of the perivesical fat and multiple necrotic iliac lymph nodes bilaterally (). Neither visceral nor bone metastasis was identified. Initially, the patient refused the treatment and was lost to follow-up. Two months later, he was readmitted to the hospital for similar complaints and additional pelvic pain. Blood tests were normal. A new CT scan revealed an increase in the size of the tumor, occupying now the majority of the bladder lumen, a persistent right hydronephrosis, and no new secondary lesions. The tumor was resected again, until the appearance of the muscular layer of the bladder, and the patient was discharged after stabilization. A later PET CT confirmed the previous findings of locoregional disease (tumor of the bladder base with infiltration of the prostate gland and a diffuse metastatic bilateral iliac chain and retroperitoneal lymph nodes) and denied secondary lesions. The multidisciplinary team meeting decided for radiotherapy and chemotherapy using cisplatin and etoposide every 21 days. Four months later, after the completion of four cycles of chemotherapy, the patient underwent new assessment for disease extension (). CT scan showed progression of the disease with the tumor occupying now the totality of the bladder lumen, infiltration of the anterior abdominal wall, and subcutaneous liquid collection measuring 33 × 36 mm. A similar left retrovesical mass of 60 × 38 mm along with multiple para-aortic and mediastinal lymphadenopathies with central necrosis was also found. A few months later, the patient died in the oncology department after recurrent admissions for different complications.


A 45-year-old male, right-dominant, Caucasian patient had a right primary anterior shoulder dislocation after a car accident. Due to burns at the left flank of about 9% of the body surface area caused by the car accident, the patient underwent several skin reconstructions. He had no previous shoulder pathology or other illnesses. The shoulder was reduced in an outside trauma clinic followed by conservative treatment. At 4 months after trauma, the patient presented initially in our institution with posttraumatic stiffness (passive range of motion (ROM): forward flexion 40°, abduction 30°, external rotation 0°), decreased sensation of the fingers 4 and 5, impaired strength with atrophic interosseous muscles, and palpatory distinct, painful ossifications in the axilla, and conjoint tendons. Electroneurography showed evidence for isolated proximal functional disorder of the ulnar nerve with all other nerves intact. We discussed the therapeutic options and first decided to try and exhaust conservative treatment. 9 months after the trauma, the patient presented with deteriorating symptoms and with constantly palpable and painful HO in the axilla and around the conjoint tendons. Plane radiographs and magnet resonance imaging (MRI) showed unaltered HO (). The shoulder stiffness had worsened with a fixed internal rotation position of the arm (passive ROM: forward flexion 35°, abduction 35°, external rotation -15°). The impaired sensation of the fingers 4 and 5 as well as the reduced strength of the interosseous muscles remained unaltered. Consequently, a surgical intervention was indicated. Preoperative, radiation was applied for recurrence prophylaxis. Computer tomography (CT) diagnostics revealed pronounced HO throughout the axillary recess, partially encasing neurovascular structures, conjoint tendons, and the subscapularis muscle (). Surgical procedure using a deltopectoral and transaxillary approach included resection of HO, neurolysis of the brachial plexus including the axillary artery, tenolysis of the conjoint tendons, and tenotomy of the long head of the biceps. The tendons of the pectoralis major, pectoralis minor, and latissimus dorsi were temporarily detached for complete removal of the HO and neurolysis. The whole ventral side of the subscapularis muscle appeared ossificated, which could explain the fixed internal rotation position of the shoulder. After HO removal (), flexion and abduction improved intraoperatively. In addition, external rotation improved from -15° to 40°. Postoperatively, the patient was treated with indomethacin 150 mg for 4 weeks for recurrence prophylaxis and painkillers. Physiotherapy was initiated on the first postoperative day with no restriction in ROM but limited strength for 6 weeks. 9 months after surgery, the patient reported an improvement of both pain (preoperative VAS 7 to postoperative VAS 0) and function (preoperative Constant score 18 points to postoperative Constant score 72 points). Also, neuropathy of the ulnar nerve was regressive with only slight numbness of the fourth finger.