This patient was a 42-year-old man who had been admitted to several hospitals before being transferred to our hospital for further care. Acute epigastric pain was his initial complaint, and laboratory findings from nearby hospitals, which included routine blood tests, ALP, amylase, transaminase and creatinine, were normal (Table ). Computed tomography revealed a small amount of retroperitoneal exudation around the body of the pancreas. A combination of a proton pump inhibitor, anisodamine and tramadol was administered, but his symptoms recurred. Six days after onset, he visited another hospital for further care. His alanine transaminase and γ-GGT levels were elevated (118 U/L and 146 U/L, respectively), but his amylase and lipase levels were normal. Because peripancreatic exudation was observed on the CT scan, he was admitted with the diagnosis of acute pancreatitis. After admission, his creatinine level gradually increased (6 days after onset: 89.9 μmol/l; 7 days after onset: 93.9 μmol/l), and the urinary sediment examination showed the following: urinary protein: 2+; and hematuria: 0–2/μL. Nine days after onset, he complained of abdominal colic pain and had diarrhea, and new ascites was found on the plain abdominal CT scan. Eleven days after onset, enhanced CT revealed that the amount of ascites had increased. Fourteen days after onset, he began to have progressive oliguria. Twenty-one days after onset, his illness was aggravated, with a urine output of approximately 200 ml/d, a CRP level of 137 mg/L, a creatinine level of 275 μmol/l, an albumin level of 23.2 g/L and an ALP level of 202 U/L. Therefore, he was transferred to a third hospital that specializes in kidney disease. He began treatment with intermittent bedside hemodiafiltration because of water overload and symptoms of heart failure 24 days after onset. Twenty-five days after onset, he began to develop a fever, with a maximum temperature of more than 39 degrees. His hemoglobin and platelet counts were normal on admission but gradually decreased as low as 67 g/l and 10 × 109/l, respectively, after admission. Pathogen detection tests, including blood culture and the atypical pathogens and G/GM test, were negative. Hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative. HIV antibody and HHV-8 PCR were negative. The polyclonal light chains in both the blood and urine were increased. The levels of serum kappa and lambda light chain were 170 mg/l (3.30–19.40) and 208.25 mg/l (5.71–26.3), respectively (kappa/lambda: 0.82). However, the levels of IgG and IgA were within the normal range, and the levels of IgM and complement 3/4 were below normal. Antibodies, including ANA, RF, ANCA, and platelet-associated IgG, were undetectable. His serum VEGF and IL-6 levels were > 800 pg/ml (0.0–142.0) and 11.5 ng/ml (0.0–7.0), respectively. An abdominal puncture was performed, and 1000 ml of ascites fluid was drained 40 days after onset. The total number of cells in ascites was 121 and included 40 nucleated cells (34 mononuclear cells and 6 multinuclear cells). Total protein, albumin and glucose levels in ascites were 28.0 g, 14.4 g/l and 14.96 mmol/l, respectively. The IL-6 level in ascites reached 1022 pg/ml (0.0–7.0). Bone marrow biopsy showed marked hyperplasia of granulocytes and megakaryocytes, and reticular fiber staining was negative. PET/CT showed that FDG activity was increased in the bilateral neck, bilateral axillary areas, mediastinum, bilateral hilar lymph nodes, bilateral parailiac artery, and bilateral inguinal lymph nodes and did not reveal any carcinoma. Pathology of the lymph node puncture showed plasmacytosis. After ineffective antibiotic treatment with meropenem, he was given intravenous methylprednisolone (60 mg qd) 36 days after onset combined with intravenous immunoglobulin (20 g qd for 5 days). At the early stage of glucocorticoid therapy, his pleural effusion and ascites decreased significantly, accompanied by a general improvement. However, 46 days after onset, his temperature increased again, with a mild increase in bilirubin and a significant decrease in blood cells. Therefore, lymphadenectomy was performed, and histopathology showed a massive hemorrhage in the lymph nodes with a normal lymph node structure, decreased lymphoid follicles, an atrophied germinal center, a concentric circle arrangement in the partial mantle zone, the proliferation of small vessels, enlargement of the paracortical zone, and flaky or focal infiltration of mature plasma cells. These findings are consistent with the mixed histopathological subtype of iMCD. After a multidisciplinary consultation, the patient was diagnosed with iMCD and was believed to have hemophagocytic syndrome according to the decreased NK cell activity (14.09%) and increased soluble CD25 level (10,615 pg/ml). For further care, he was referred to our hospital which was famous for being specialized in hematology. Based on his clinical manifestations (fever, ascites, thrombocytopenia, lymphadenopathy and progressive renal insufficiency) and lymph node biopsy (atrophied germinal center and the proliferation of small vessels), we diagnosed the patient with TAFRO syndrome. As the CMV DNA contents of the serum and lymphocytes were increased (4.76 × 104 cp/ml and 4.25 × 106 cp/ml, respectively) 53 days after onset, ganciclovir was added to his treatment plan. With an improvement in renal function, hemodiafiltration was stopped 2 months after onset. However, proteinuria was still serious, with 24-h urine protein reaching 31 g, so renal biopsy was performed 3 months after onset. Histopathology revealed 11 glomeruli in which a membranoproliferative glomerulonephritis (MPGN) pattern was observed, with diffuse endocapillary proliferation, mesangial proliferation, fuchsinophilic protein deposition in the subendothelial and mesangial areas by Masson stain, double contours and microthrombosis seen in some capillary loops, vacuole and granular degeneration of renal tubular epithelial cells, and arterial endothelial cell proliferation with thickened walls and a narrowed lumen. Immunofluorescence showed two glomeruli with immune complex deposition (IgA ++, IgG +++, IgM ++, C1q ++, C3 +++, FRA -, Kappa ++, Lambda ++), which were deposited with clumps and granules along the mesangial zero and capillary wall. The IgG subtype detection of immune complexes showed IgG1 ++, IgG2 ++, IgG3 and IgG4 -. Electron microscopy revealed intramembranous, subendothelial and partially subepithelial electron-dense deposits and diffuse podocyte foot processes (Fig. ). His renal histopathology were consistent with those of cases with TAFRO syndrome reported in literatures, which further confirmed his diagnosis of TAFRO syndrome. One hundred twenty days after onset, therapy with intravenous rituximab (CD20 B-cell monoclonal antibody, from Roche) was initiated (375 mg/m2 once a week for the first month and then once evert 2 months). The patient has not been hospitalized since the fifth course of treatment. At the latest follow-up, his hemoglobin level was 133 g/L, his platelet level was 309 × 109/L, his creatinine level was 103 μmol/L, and his body temperature and urine volume were normal (Fig. ).


A 66-year-old woman was diagnosed with moderate nonproliferative DR with DME bilaterally a decade earlier. She underwent focal laser photocoagulation in both eyes, and the decimal best-corrected visual acuity (BCVA) in her right eye improved to 1.0, but it did not improve in her left eye. She did not agree to further therapy such as anti-VEGF for the left eye, because the BCVA in her right eye was good and the high cost of anti-VEGF agents. The macular edema in the left eye persisted for 4 years with a decimal BCVA of 0.3 and a central retinal thickness (CRT) of 598 μm (). Six months later, the macular edema was completely resolved (). One month before this ophthalmic visit, her glycemic control deteriorated to a glycated hemoglobin A1c of 7.4%, and her general physician prescribed 25 mg of oral empagliflozin, an SGLT2 inhibitor. The CRT in her left eye decreased to 253 μm () at one month after beginning the SGLT2 inhibitor treatment. Six months later (), her body weight was reduced, and the glycemic control was improved with the glycated hemoglobin A1c of 6.5% (). The CRT reduction was maintained for over two years without other ophthalmic therapy. The clinical course of the macular edema before and after the administration of the SGLT2 inhibitor is shown in . The final decimal BCVA improved to 0.8, and the CRT measured by optical coherence tomography (OCT) was 235 μm () at 30 months after commencing the SGLT2 inhibitor.


A 68-year-old woman was diagnosed with preproliferative DR 6 years earlier, and panretinal photocoagulation had been performed. However, the DME gradually developed beginning 5 years earlier. She was treated twice with intravitreal injections of ranibizumab and a sub-Tenon injection of triamcinolone acetonide in her left eye. In her right eye, she received 7 intravitreal injections of aflibercept and focal-grid laser photocoagulation. However, the DME persisted, and her decimal BCVA was 0.6 in the right eye and 0.3 in the left eye. The CRT was 519 μm in the right eye and 467 μm in the left eye ( and (B)). Oral dapagliflozin was administered to improve the glycemic control. At the beginning of the dapagliflozin, her glycated hemoglobin A1c was 7.0%; however, her glycemic control was exacerbated by overconsumption; although, the refractory DME was improved. Two months later, the CRT was thinner in her left eye (), and six months later, the CRT was reduced to 491 μm in the right eye () and 326 μm in the left eye (). Her BCVA was 0.6 in the right eye and 0.3 in the left. At six months, her body weight was reduced; although, the glycated hemoglobin A1c was elevated to 7.9% (). The clinical course of the macular edema is shown in . A sub-Tenon injection of triamcinolone acetonide was administered to her right eye at eight months. Her final BCVA was 0.8 in the right eye and 0.4 in the left eye, and the CRT was 378 μm in the right (), 305 μm in the left () at twelve months.


A 61-year-old woman was diagnosed with moderate nonproliferative DR without DME 7 years earlier. She had undergone bilateral cataract surgery 5 years earlier, and her BCVA had recovered to 1.0, but there was a gradual development of macular edema. She received 2 sub-Tenon injections of triamcinolone acetonide, 5 intravitreal injections of aflibercept, and focal laser treatment in her left eye. She received 1 intravitreal injection of aflibercept and a focal laser treatment in her right eye. Despite these treatments, the CRT was still 613 μm in the right eye () and 412 μm in the left eye (); although, the decimal BCVA was 1.0 in both eyes. Her BCVAs were maintained, and she did not agree to continue anti-VEGF therapy. Oral luseogliflozin 2.5 mg was administered, and the CRT of both eyes ( and (D)) began to decrease by two weeks after commencing the luseogliflozin. This reduction continued for six months. Six months later, her CRT was reduced to 451 μm in the right eye () and 273 μm in the left eye (). The BCVA was maintained at 1.0 in both eyes. Her body weight was reduced at six months, and the glycated hemoglobin A1c was reduced from 6.5% to 6.1% at six months ().


A 50-year-old postmenopausal woman, gravida 15, para 7, from a rural area in northwest Ethiopia presented to the University of Gondar Urogynecology unit after she sustained an ox horn injury to her genitalia 6 days prior to presentation. She initially had profuse bleeding from the injury site, but the bleeding stopped spontaneously and she did not seek medical care until she presented to our urogynecology unit. At presentation, she reported a history of failure to control urine and pain, and a foul-smelling discharge at the wound site. She had history of a mass protruding outside the vagina of 7 years duration that was progressively increasing and associated with difficulty in urinating for which she had not sought medical care. Following the injury she denied abdominal pain, abdominal distension or failure to pass feces and flatus. Her last menses was 2 years prior to the injury. She had no known history of other medical problems or illness.
On physical examination she was acutely sick looking, vital signs were within normal range and she had slightly pale conjunctiva. Her abdomen was flat, non-tender and with active bowel sounds with no palpable mass or sign of fluid collection. Evaluation of the genitourinary system revealed stage three POP with the leading point being the cervix. The anterior vaginal and posterior bladder walls were disrupted with visible draining of the left ureter. The wound was dirty and edematous with a whitish discharge (Fig. ). There was no involvement of the urethra and the distal one-third of the vagina in the injury. She had difficulty walking due to the pain from the wound. Otherwise there were no remarkable findings from her physical examination. Her hematocrit was 31.6%, and abdominopelvic ultrasound revealed a mild right-sided hydronephrosis with hydroureter. There was no sign of intra-abdominal or pelvic fluid collection. She was admitted to the urogynecology ward with a diagnosis of stage three POP, posterior bladder rupture and wound infection. The right ureteral orifice was identified and stented (Fig. ), and she received wound care twice daily.
Three months following admission, the wound was clean and well granulated and the edema had resolved. The right sacrospinous ligament fixation was then completed (Figs. and ).
Six weeks after the RSSF the ruptured bladder was repaired after adequate mobilization of the bladder (Fig. ). Both the ureters were identified and stented prior to the repair. Vaginal packing and transurethral catheter were left in situ. The vaginal packing and the urinary catheter were removed after 24 hours and 3 weeks, respectively. The patient was fully continent when discharged on postoperative day 21 following bladder repair and on postoperative day 63 following her RSSF.


A 73-year-old man with a history of persistent atrial fibrillation who had undergone pulmonary vein isolation 29 months earlier presented with palpitations. His electrocardiogram revealed a narrow complex, short R–P tachycardia consistent with AVNRT and he was referred to electrophysiology for RFA. The electrogram recorded during supraventricular tachycardia (SVT) induction can be seen in . The SVT was initiated with an atrio–His (AH) “jump” and shows a narrow-complex, short R–P, A-on-V tachycardia consistent with AVNRT. RFA of the slow-pathway region was initially attempted using a 4-mm, large, curved, nonirrigated ablation catheter (Blazer; Boston Scientific, Natick, MA, USA) set in the temperature-controlled mode. Initially, adequate temperatures were achieved with adequate power delivery (50 W and a temperature of 50°C–65°C). However, the desired ablation effect, an accelerated junctional rhythm, was not observed (.
With adjustment of the catheter position, a junctional rhythm was observed with ablation; however, the average power delivery was consistently less than 10 W despite a temperature cutoff of 65°C (.
Despite the creation of a total of 20 lesions, AVNRT was still able to be induced. The use of both a long sheath (SR0 curve) and a steerable sheath (Agilis medium curl; Abbott Laboratories, Chicago, IL, USA) did not improve results. The induction of junctional rhythm with ablation using the nonirrigated catheter indicated that the catheter position was in the appropriate location for slow-pathway modification of the atrioventricular (AV) node. It was noted that the power delivery was low during the creation of these lesions and it was decided that a deeper lesion might instead suffice and could be more durable. Therefore, no attempt was made to ablate in the proximal coronary sinus using the nonirrigated catheter.
To deliver more power to the slow pathway, the 4-mm nonirrigated catheter was removed and a 3.5-mm irrigated contact-force catheter (75 Tacticath; Abbott Laboratories, Chicago, IL, USA) was placed. Power was titrated between 20 W and 25 W and the flow was adjusted from the usual 17 mL/min down to the lowest programmable setting of 6 mL/min during ablation. Two new lesions were delivered in the same area where the junctional rhythm was previously induced, with successful induction of the junctional rhythm. These lesions are represented by white markers in . The ablation characteristics of the lesion set are summarized in .
At the conclusion of these lesions, AVNRT was no longer inducible, even with the infusion of isoproterenol, and an AV-node effective R–P interval was observed for the first time (600/470 ms). Ultimately, AV nodal Wenckebach occurred at 400 ms and the ventricular effective R–P interval was 600/210 ms. Therefore, it was decided that no further ablation was required.
The patient tolerated the procedure without any significant complications and was followed for 39 months postablation. There was no evidence of SVT on the patient’s personal electrocardiogram monitor (KardiaMobile; AliveCor, Mountain View, CA, USA) and no reported symptoms.


The first case concerns a 15-year-old boy, known with idiopathic end-stage kidney disease (ESKD) treated with peritoneal dialysis. He had no history of cardiac dysfunction. He was admitted on March 6th, 2020, for a deceased-donor kidney transplantation which was postponed because of fever for 3 days. He complained of fatigue, headaches, and loss of appetite. Characteristics and laboratory findings at admission and imaging results are noted in . A positive PCR for SARS-CoV-2 confirmed COVID-19 the day of admission. He was hospitalized for 10 days because isolation measures were not possible at home. He stayed paucisymptomatic and received supportive care with antipyretics besides his usual treatments for kidney failure. After 10 days, he was discharged home.
Twenty-three days after discharge, he was readmitted because of dyspnea (NYHA grade III), orthopnea, and hemoptysis. Laboratory findings and imaging results are shown in . Because of suspected alveolar hemorrhage, bronchoscopy was performed the day after admission. Repeated bronchoalveolar lavage ruled out alveolar bleeding. SARS-CoV-2 PCR on lower respiratory samples was negative. Because of progressive oxygen requirements after bronchoscopy and severe myocardial dysfunction on echocardiography, the patient was transferred to the intensive care unit for monitoring, inodilator therapy, and noninvasive ventilation (NIV) with rapid clinical recovery. NIV could be stopped, and supplemental oxygen was given by high-flow nasal cannula until day 4 of hospitalization. Endomyocardial biopsy was performed, but neither endomyocardial PCR nor histopathological analysis was suggestive for SARS-CoV-2 myocarditis. Cardiac MRI on day 8 revealed a dilated left ventricle with reduced ejection fraction of 30–35%. Coronarography revealed normal coronal anatomy.
While titrating heart failure therapy, he needed readmission in the medium care unit from day 9 to 12 because of an episode of relapse cardiac decompensation that needed to be managed by increasing ultrafiltration through peritoneal dialysis.
Between day 18 and 20, he developed a low-degree fever (maximum body temperature of 38.7°C axillary). C-reactive protein was low, and lymphocytosis was absent. Because of the suspicion of pneumonia, co-amoxiclav was empirically started. All cultures (blood, sputum, peritoneal fluid, and urine) yielded negative. Because of nocturnal hypoxemia, a polysomnography was performed revealing Cheyne–Stokes apneas secondary to heart failure. After 28 days, he was ready for a new discharge home. He is still under medical follow-up for his end-stage kidney disease and slowly recovering heart failure.
This patient was one of the first cases of paediatric SARS-CoV-2 infection in Belgium. In retrospect, we think he was one of the first cases of a MIS-C associated with a SARS-CoV-2 infection in Europe, with signs of viral or inflammatory myocarditis. At that time, little was known about the treatment of a MIS-C associated with COVID-19 infection, so no immunoglobulins or corticoids were administered during his stay.


The second case, a girl of 14 years old, known with Lennox–Gastaut syndrome, was admitted on April 28th, 2020, in our hospital for neurological observation after a severe concussion. The second day of admission, she developed high fever initially not responding to antipyretics, and she became generally unwell with a dry cough. The patient and her mother had COVID-19-like symptoms approximately a month prior to admission; unfortunately, no confirmation with PCR-testing for SARS-CoV-2 was obtained at that time. Additional characteristics, laboratory findings, and chest X-ray results are shown in .
Epileptic activity increased, and she needed seizure medication. Because of seizures and the risk of aspiration pneumonia, intravenous co-amoxiclav was empirically initiated. She gradually deteriorated needing oxygen therapy. Because fever persisted and inflammation parameters were rising, intravenous antibiotic therapy was switched to third generation cephalosporins. Cardiac ultrasound, ECG, and echocardiography were planned, as well as a chest CT which all showed signs of pericarditis (see ).
Our patient did not meet the criteria for Kawasaki disease but appeared to be an atypical Kawasaki-like shock syndrome. A trial of intravenous immunoglobulins (IVIGs) was administered. Although none of the cultures (blood, cerebrospinal fluid, urine, stool, and bronchial aspirates) yielded positive, antibiotics were continued for 10 days. Shortly after IVIG treatment, the patient clinically improved significantly although moderate fever persisted and inflammatory parameters dropped swiftly (as visualized in ). Oxygen therapy was interrupted, and all edema disappeared. In the light of clinical and laboratory improvement to normalization, there seemed no need for additional corticotherapy.
After hospital discharge, SARS-CoV-2 serology returned positive and diagnosis of MIS-C associated with COVID-19 was confirmed. She remains under medical follow-up for her epilepsy but recovered completely from PIMS-TS.


A 3 year old adult female Yucatan pig acquired from an approved research vendor arrived healthy to the research facility. The pig was never enrolled into the study for which it was ordered, and at the time, there were no concurrent studies to allow transfer to another experimental protocol. Therefore, the experimentally naive animal was then transferred to the institutional holding protocol. For the purposes of interim group housing and future re-homing or adoption, a bilateral ovariectomy was performed via a midline laparotomy (~ 20 cm incision length). The animal was anesthetized with Telazol (4 mg/kg IM) and Xylazine (2 mg/kg IM) and maintained intubated with isoflurane anesthesia (2–3%). The surgical site was prepared with removal of all hair and a triple surgical scrub using chlorohexidine and alcohol. Peri-operative cefazolin (20 mg/kg, IV, once) was administered, and aseptic surgical technique was maintained throughout the procedure. 0-Vicryl® (polyglactin 910) miller knots were used for ligation of each ovarian pedicle. For added security, each pedicle was double ligated in this manner. Three-layer closure of the incision was accomplished using PDS II® (polydioxanone)6 in a simple continuous pattern (size 2 for linea alba, size 0 for subcutaneous tissue, and size 2 − 0 for intradermal). Pre-operative analgesia was provided with Buprenorphine SR (0.2 mg/kg SQ once), meloxicam (0.4 mg/kg, SQ, once), and a local incisional block (5 mL 2% Lidocaine). Post-operatively carprofen (4 mg/kg, PO, q24) was provided for 3 days. The surgery and post-operative period were uneventful.
Approximately 4 months later (122 days post-surgery), a small nodule (~ 1 cm in diameter) developed on the left paralumbar fossa with the surrounding 3–4 cm of skin warm and mildly hyperemic. Fine need aspirate of the nodule revealed clear serous fluid. Cytology did not reveal any cellular infiltrates and protein assessment was not performed at that time. All other physical exam findings were unremarkable. A presumptive diagnosis of a cyst or seroma was made based on these findings.
By one month after this (146 days post-surgery), both paralumbar fossa had developed 2–5 nodules present on each side. Fine need aspirate yielded caseous material indicating abscessation. In-house cytology demonstrated numerous degenerate neutrophils admixed with cellular debris. No bacteria, fungi, or parasites were identified on cytology. Due to worsening presentation, treatment including amoxicillin (15 mg/kg, PO, q12) and carprofen10 (4 mg/kg, PO, q24) were instituted. Despite two weeks of treatment, there was no improvement and the affected area on each side measured 8 cm x 8 cm with multifocal abscesses present. The surrounding area was still warm and mildly hyperemic, and the immediate area was becoming hyperpigmented (Fig. ).
Due to this progression, anesthetized debridement, bloodwork, culture, and cytology were elected (166 days post-surgery). The animal was anesthetized as previously described. An intravenous catheter was placed in the right auricular vein and cefazolin5 (20 m/kg, IV, q12) and enrofloxacin (5 mg/kg, IV, q24) started. These antibiotics were continued for four days after debridement. Oral carprofen therapy was continued throughout this period. All abscesses were sterilely lanced and flushed with dilute betadine and sterile saline and allowed to heal open. Aerobic, anaerobic, and fungal cultures were submitted to an external laboratory9, but all yielded no growth. Cytology taken at time of debridement was unchanged and characterized by neutrophilic inflammation. A complete blood count and serum chemistry was performed on in-house analyzers.10 Complete blood count results indicated a chronic inflammatory process with a mild non-regenerative anemia and a shift in the leukocyte percentages with neutrophils comprising 73% of the total white blood cells and lymphocytes only 22% (Table ). The elevated creatinine kinase is attributable to a traumatic blood collection. The low sodium was determined to be spurious secondary to a needed machine maintenance for that particular analyte (Table ). All other complete blood count total numbers and serum chemistry values were within normal ranges.
Approximately 2 weeks after the surgical debridement during cleaning of the area (177 days post-surgery), a small biopsy was collected from one of the draining tracts which included fibrous material (Fig. a). Histologically, foreign material was identified in the core of the tissue (Fig. b). Reviewing the animal’s record, it was concluded at the observed lesions were likely a result of a reaction to the pedicle ligatures made with 0-Vicryl® during the ovariectomy. No other foreign materials had been introduced to the animal during its ovariectomy or any time thereafter.
As a suture-related pseudoinfection causing a sterile inflammatory process, all antibiotics were discontinued, and the animal was maintained on intermittent carprofen10 (4 mg/kg, PO, PRN) and buprenorphine HCl (0.03 mg/kg, SQ, PRN) to control pain and discomfort. Further, more invasive surgical debridement was not elected. Despite supportive care, the animal developed intermittent mild hindlimb lameness which alternated limbs depending on which paralumbar fossa was more severely affected with abscesses and draining tracts at the time. Eventually, the animal became generally more agitated and aggressive to care takers. Because of this change in behavior and lack of response to treatment, euthanasia was elected approximately 5 months after initial presentation and 9 months after ovariectomy. For euthanasia, similar sedation was used as for debridement, and the animal euthanized (Beuthanasia-D®, 4.5 mg/kg, IV). At necropsy (241 days post-surgery), numerous abscesses ranging from 3 to 7 mm diameter were present bilaterally in the skin and subcutaneous fat (Fig. a). These lesions occasionally extended in a linear fashion deep into the subcutis and through the body wall (i.e. draining sinus) (Fig. b). Ovarian pedicles were bilaterally fibrotic and mineralized with linear tracks of fibrotic tissue connecting the ovariectomy site with skin lesions. Minor abdominal adhesions were multifocally present (i.e. post-surgical adhesions). While scarring was present from the linea alba closure, there was no indication grossly of a similar foreign body reaction or remaining suture from the surgery in that area. Tissue sections were fixed with 10% formalin, paraffin embedded, and sectioned for hematoxylin and eosin staining.
Histologically, there were typical signs associated with a foreign body reaction including multifocal small pyogranulomas (Fig. a). These were observed throughout the skin which consisted of a necrotic core containing degenerate neutrophils, epithelioid macrophages and numerous foreign body type giant cells surrounded by fibroplasia and chronic inflammatory cells. In a few sections, distinct multi-nucleated giant cells surrounded a refractile material (Fig. b). In some of these pyogranulomas, the center contained Splendore-Hoeppli bodies composed of antigen antibody complexes (Fig. c).


A 33-year-old male patient was admitted to the hospital because of ‘the numbness of the left upper limb for 3 h with dyskinesia of the left limb for 50 min’. The patient had a history of hypertension, smoking, and drinking. The physical examination showed that the muscle strength of the left upper limb reached 0 grade and the muscle strength of the left lower limb reached 3 grades. Digital subtraction angiography (DSA) showed a large number of mural thrombus in the C1 segment of the right internal carotid artery(RICA) (Fig. a). After the transcatheter thrombus aspiration and stent thrombectomy, the patient’s blood vessels were recanalized, while the vessel wall of the RICA was not smooth (Fig. b). By now, the patient's symptoms have been significantly improved. Four days after operation, the three-dimensional (3D) T1 volumetric isotropic turbo spin echo acquisition (VISTA) sequence showed a high signal in the lumen of the RICA (Fig. c). Curved planner reconstruction(CPR) showed a high signal in the vessel wall of the RICA (Fig. d). The vessel wall magnetic resonance imaging (VW-MRI) showed the components of hematoma in the vessel wall (Fig. a). One month after antiplatelet therapy (oral aspirin 100 mg once a day and oral clopidogrel 75 mg twice a day), VW-MRI showed the disappearance of hematoma in the vessel wall (Fig. b). So far, the patient is in good condition and is subject to regular follow-up. clopidogrel.


A 33-year-old man with allergic rhinitis and asthma under treatment with inhaled and nasal corticosteroids, and with a known allergy to Dermatophagoides pteronyssinus and Dermatophagoides farinae .
He experienced an anaphylactic reaction at the age of 25 years, with facial and lip angioedema, dyspnea, cough and dysphagia minutes after ingestion of a mushroom pizza. No other suspected triggers were present, such as drug intake or stings. He also denied physical exercise or alcohol intake in the hours before the episode. He stopped eating mushrooms and any food containing mushrooms.
The patient reported two posterior episodes of lip angioedema, without any other symptoms after accidental contact with mushroom sauce.
Measurements of serum total IgE (ImmunoCAP™, Phadia, ThermoFisher Scientific, Uppsala, Sweden) and specific IgE (ImmunoCAP™, Phadia, ThermoFisher Scientific, Uppsala, Sweden) to airborne allergenic sources ( D. pteronyssinus , D. farina e, Lepidoglyphus destructor , cat and dog dander) molds ( Aspergillus fumigatus and Alternaria alternata ) and mushroom were carried out.
We also performed skin prick tests with commercial extracts (LETI Laboratories, Madrid, Spain) of D. pteronyssinus (100HEP/mL); D. farinae (100HEP/mL); L. destructor (10HEP/mL); pollens from Olea europaea (30HEP/mL), Corylus avellana (30HEP/mL), and Platanus occidentalis (30HEP/mL); cat and dog dander (30HEP/mL); A. fumigatus (150ug protein/mL); A. alternata (30HEP/mL); Cladosporium herbarum (150ug protein/mL); Candida albicans (125ug protein/mL); pollen from grass mixture (30HEP/mL); cow's milk (1,600ug protein/mL), egg (1,400ug protein/mL); wheat flour (1,900ug protein/mL); tomato (10HEP/mL) and mushroom (10HEP/mL). Histamine was used as positive control (10mg/mL).
Besides skin testing with commercially available extracts, a prick to prick test with raw and cooked A. bisporus was also carried out.
A sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblotting assay was performed to assess the molecular mass of the IgE-binding proteins from A. bisporus .


The patient was a 19-year-old woman with no comorbidities other than asthma. She was a non-smoker. She had been treated for severe asthma with high doses of inhaled corticosteroids plus long-acting β2-agonists, antileukotriene, theophylline, and antihistamine. The patient participated in cheerleading as an extracurricular activity at her college. During cheerleading, she experienced asthmatic attacks, which became increasingly frequent, and she therefore sought medical consultation. The patient wanted to continue cheerleading and enquired about strengthening her treatment. However, she did not want to take regular corticosteroids or antibody agents. She refused biological treatment owing to the cost associated with long-term continuation and the desire to have children. Therefore, the patient decided to undergo BT.
Chest computed tomography (CT) showed a thickened bronchial wall (Fig. a); the percentage forced expiratory volume (%FEV) was 86.2%, and exhaled nitric oxide was 45 ppm. Blood test results revealed the following: 515 U/mL, IgE; 8900/μL, white blood cell count; and 143/μL, eosinophils. The patient received 30 mg/day prednisolone for 3 days before BT treatment and continued it for 1 day post-BT treatment. The sessions for the right and left lower lobe were properly completed at 3-week intervals, and the BT activation numbers were 31 and 24 times, respectively (Fig. a).
After the second BT session, she developed more sputum and cough. During the third session, white secretion and saccular bronchodilation appeared in the left lower bronchus (B9 and B10) (Fig. b). At the same time, bronchial washing was performed. Her CT also showed saccular bronchodilation in the affected bronchus (Fig. b). Aspergillus fumigatus was detected in the bronchial lavage culture. Oral itraconazole administration was started, and serum β-d-glucan and aspergillus antigen were found to be negative. Five months later, the subjective symptoms and CT findings improved (Fig. c). Although respiratory function remained unchanged (%FEV, 88%), exhaled nitric oxide reduced to 15 ppm. After BT, the inhaled steroid dose was reduced owing to a remarkable improvement in asthma symptoms. The patient was able to continue her cheerleading activity without exacerbations.


Case 1 (D1): a 7-year-old male donkey, weighing 150 kg was examined and treated within 2 h after being burned. The donkey was kept in a small pen (10 × 10 m) with three other donkeys. Upon physical examination, the body condition score (BCS) was 3/5, tachycardic 64 beats/min (reference range 36–52), tachypneic 30 breath/min (reference range 12–28), furthermore, the donkey had congested mucous membranes. There were burn marks over the lips, face, ears, dorsum, and both front limbs. All serous exudate was observed over the coronary bands in front limbs, but had a normal gait. Immediate treatment included flunixin meglumine 1.1 mg/kg intravenously (IV) (83 mg/mL, Febrectal, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile); hosing with tap water (13 o 15°C) all over the body for 30 min to protect the tissue, and bandage with sterilized gauze and liquid paraffin gauze dressing over the neck and back prior to transportation to the clinic 2 h later (A).
Approximately 12 h after the incident, the estimated TBSA was approximately 40–50%. Most of the affected areas were classified as deep second-degree burns with some small areas of third-degree burns on the distal area of the front limbs and face. There was also facial, abdominal, and limb edema. The donkey was eating and drinking with difficulty (dysphagia—possibly caused by edema and pain). He was placed on IV fluids with Hartmann’s solution 10 mL/kg bwt/h (Lactated Ringer’s solution, Baxter, Toongabbie, New South Wales, Australia) for 3 h until he was stable and started to eat and drink. Both eyes had bilateral corneal ulcers and uveitis (B), with signs, such as epiphora, blepharospasm, corneal edema, and episcleral congestion. Treatment with ophthalmic antibiotic ointment containing zinc bacitracin 400 iu/g, neomycin sulfate 3.5 mg/g, and polymyxin B sulfate 6000 IU/g q 12 h (Oftabiotico, Saval S.A. Laboratory, Santiago, Chile), ophthalmic atropine sulfate drops q 12 h × 2 days (10 mg /mL, Atropina 1%, Saval S.A. Laboratory, Santiago, Chile), and dextran-70 lubricant drops 1 mg with hidroxipropilmetilcelulosa 3 mg (Tears Naturale II, Alcon Laboratory Chile Ltd.a., Santiago, Chile) was initiated several times a day. The eyes were treated with triple antibiotic ointment for six weeks, and natural tear drops for four weeks.
A topical cream of sulfanilamide with zinc oxide was applied to the coronary bands (sulfanilamide 5 g, zinc oxide 5 g, vitamin A 250,000 IU, vitamin D2 90,000 IU/100 g, Pomada Sulfavitaminada, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile).
Respiratory distress was observed, characterized by tachypnea, nostril flaring, and cough—a suspected result from smoke inhalation; therefore, treatment with corticosteroid, dexamethasone sodium phosphate 0.2 mg/kg IV (5,26 mg/mL, Hasyun, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile) was administered. A parasympatholytic drug and beta-2 agonist inhalation therapy by aerochamber (Aerofacidose Aerocamara A.E., Chile Laboratory S.A. Teva, Santiago, Chile), using ipratropium bromide 0.8 µg/kg q 6 h (250 µg/mL, Atrovent, Boehringer Ingelheim International GmbH, Rhein, Germany) and albuterol 2 µg/kg q 4 h (100 µg/doses, Sinasmal SF Salbutamol, Chile Laboratory S.A. Teva, Santiago, Chile) were also administered. The aerochamber was placed in one nostril and the opposite side was occluded (). Airway endoscopy was performed the second day (1800PVS9150, PortaScope, FL, USA), and mild to moderate irritation with hyperemia of the mucous membrane from a common nasal meatus, and the first part of a ventral nasal meatus of both nostrils, as well as mild hyperemia in the pharynx and trachea, were observed. The cough resolved within 48 h of treatment; therefore, the bronchodilators were discontinued after three days.
Complete blood cell count and serum biochemistry profile were performed on the second and eight days post rescue (Biosystems BA400, Biosystems S.A., Barcelona, Spain). The first analysis, done at day two, revealed: neutrophilia, increased alkaline phosphatase, muscle enzymes creatine kinase, aspartate aminotransferase and triglycerides, decreased total protein and albumin, increased glucose, and decreased total calcium and chloride concentration. Slightly cloudy serum was observed in the clotted blood sample ().
The second analysis at day 8 showed increased alkaline phosphatase, aspartate aminotransferase. Blood analysis was repeated on day 15 of the hospitalization and all of the parameters were within normal limits (). Antibiotics therapy was initiated with procaine g penicillin 20,000 IU/kg + dihydrostreptomycin 15 mg/kg q 24 h intramuscular (IM)/7 days (200,000 IU procaine G penicillin + 250 mg dihydrostreptomycin sulfate/mL, (Pentril, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile).
During the hospitalization time period (90 days), the burn surfaces, appetite, and pain level of the donkey were monitored. The donkey appeared more comfortable, with good appetite, and showed interest in socializing with other donkeys and his environment; these responses became evident since day 7 in the clinic. The edema (described) was observed since the first day of the rescue and decreased after 6 days, the skin became dry and sensitive to touch, and he experienced hair loss on his legs, neck, and back.
Flunixin was given daily for pain control for 10 days since the rescue (3 days, 1.1 mg/kg q12 h, then 7 days, 1.1 mg/kg q 24 h IV), and continued with a natural product (devil’s claw 726 mg + Yucca schidigera extract 954 mg + vitamin B12 10 mcg/ 10 mL, Bute-Less Paste, Absorbine, Massachusetts, MA, USA), 5 mL oraly q 24 h/15 days, supplement to discomfort and pain relief. Omeprazole 2 mg/kg per os q 24 h/4 weeks (20 mg tablets, Omeprazole, Chile Laboratory S.A. Teva, Santiago, Chile) was given for treatment and/or prevention of gastric ulceration.
During the following 2 weeks, the eyelids, ears, and back became dry, hairless, and painful, and there was a loss of elasticity (). Topical treatment with aloe vera gel was initiated twice daily to exposed areas before washing and debridement. The pinna of both ears developed ulcers and contracture of the cartilage.
Daily skin care initially required sedation xylazine 0.5 mg/kg IV, with butorphanol tartrate 0.01 mg/kg IV (10 mg/ mL, Torbugesic, Zoetis, NJ, USA) as potent analgesic for the first six days in the clinic. On day seven, sedation and potent analgesic for treatment was no longer required. Local anesthetic instillation with lidocaine hydrochloride was used in some affected areas on the back and face (20 mg/ 1 mL, Lidocalm, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile).
Wounds were lavaged every 24–36 h, for debridement of devitalized tissue, and dead skin was removed with sterile scissors or a hypodermic needle. The blisters were left intact, however, gauze dressing with impregnated paraffin (Jelonet) was used in some areas where blisters opened. Local antibacterial drugs were used every 24 h. The wounds were lavaged with chlorhexidine gluconate solution (2 g/100 mL, Inveclor, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile) and diluted in water with sterilized gauze using gloves and triclosan (0.3%/100 g, Sanigermin, Sanitas S.A. Laboratory, Santiago, Chile). A variety of topical products were used in conjunction with the dressings for the following weeks: cream of Buddleja globosa (Matihorse, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile), raw honey, aloe vera, and nitrofurazone cream (0.2 g/100 g, Furasep Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile). Nitrofurazone was used in areas with exudation and erythema and, locally, raw honey on areas with less exudation and erythema. Dry skin areas were treated with Jelonet, and then it was changed to Buddleja globosa cream. Fly repellent was used around wounds (dichlorvos 1250 mg + triclosan, 500 mg/ 100 g, Moskation larvicida spray, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile).
Three weeks later, the donkey developed pruritus, which was treated with chlorpheniramine maleate 0.5 mg/kg IV (50 mg/mL, Histamil, Troy Laboratories Pty. Limited, Glendenning, Australia) as needed.
After 2 months, a thin layer of skin started to regrow. Exuberant granulation tissue on some areas was periodically de-bulked. After 3 months, all treatments were discontinued, and most of the burned areas had healed, but the area of the face and front limbs were without hair growth. At this time, the only product used on his legs and body was aloe vera gel. His coronary bands from the front limbs did not separate significantly, but a horizontal line of damage was evident around the hoof wall (1 cm below the coronary band), walk, and trot sound.


Case 2 (D2): a 15-year-old female donkey, 120 kg, was examined with D1. The jenny appeared anxious and painful. Upon physical examination, her BCS was 3/5, she was tachycardic (72 beats/min), tachypneic (30 breath/min), and had congested mucous membranes and muscle tremors. Burns over her face, neck, back, perineal area, vulva, and coronary band swelling of the left hind limb were observed. She was transported to the clinic with the other affected animals and was treated, as per case 1.
Her burns were classified as second-degree, with some areas with third-degree (perineal area); estimated TBSA approximately 40–50%. She had bilateral corneal ulcers and uveitis, and her eyes were treated with the same antibiotic ointments and regime as case 1. The left coronary band was inflamed and a serious exudate was present; therefore, topic cream with sulfanilamide + zinc oxide was applied. She was five-months in gestation, which was closely monitored at the clinic. Intravenous fluids with Hartmann’s solution were administered at the same rate as described above, as well as flunixin and omeprazole. Fluids were discontinued on the second day at the clinic, when the laboratory report indicated adequate hydration. Moreover, she was eating hay with a good appetite at this time.
Complete blood cell count and serum biochemistry profile were performed in the clinic similar to D1. The first blood analysis, taken at day two, revealed: neutrophilia, increased alkaline phosphatase, muscle enzymes creatine kinase, aspartate aminotransferase, triglycerides and cholesterol, decreased total protein and albumin, increased glucose, and decreased mineral calcium and chloride concentration. Slightly cloudy serum was observed in the clotted blood sample ().
Antibiotic therapy started with procaine penicillin + dihydrostreptomycin IM, and for the skin, aloe vera cream, at the same doses rates described in D1. The wounds from the skin were periodically lavaged and cleaned using disinfectant, and a similar topic cream, as described in D1, removing the devitalized tissue when necessary (sedation and potent analgesic, described in D1, were previously used). The pinna of the left ear also developed ulcers and permanent cartilage contracture, as D1. A second blood analysis performed eight days post rescue showed increases in alkaline phosphatase and aspartate aminotransferase. Concerning the third blood analysis performed on the 15th day of hospitalization, all parameters were within normal limits (). Pruritus was evident on day 10; therefore, the antihistamine product used was the same as D1. Over the next 2 weeks, her wounds continued to improve and the burns re-epithelialized rapidly ().
The left coronary band lesion, increasing in size and lameness, was graded 2/5. Radiographs were taken, which revealed no sign of distal phalangeal rotation. Flunixin meglumine (1.1 mg/kg) for pain was continued, daily, for 12 days (3 days 1.1 mg/kg q12 h, then 9 days 1.1 mg/kg q 24 h IV), and the supplement for pain relief was the same dose rates as D1. After six weeks, she could canter when turned out into a paddock in the evenings, or early mornings, when the outdoor temperatures were cooler. His left coronary band from the hind limb did not separate, but a horizontal line of damage was evident around the hoof wall (1 cm below the coronary band).The jenny was discharged after 3 months of hospitalization. She was doing well on her 3- and 8-month pregnancy checks. She foaled a healthy donkey foal after 13 months of gestation (range of 11–14.5 months) [].
Cases 3 and 4 (D3–D4): the next two cases were a 12-year-old female donkey, 160 kg, and a 5-year-old male, 110 kg. Both were examined at the site of the fire, as described for both previous cases (D1 and D2). They both had a BCS of 2/5, were tachycardic, and small burn areas with hair loss on their heads (noses and cheeks), as well as necks, were observed. Their TBSAs were approximately 5% and the burn areas classified as first degree. These two donkeys were in the same paddock with the others; however, they were less affected. Cases D1–D2 were tied up to a fence, close to the burning vegetation until the rope was burned by fire, while cases 3 and 4 were free. This most likely explains the severity of the injuries in the first two cases.
D3 and D4 were also hosed with tap water all over their bodies, and moved to the same clinic. They were also treated with flunixin meglumine for 3 days and the burn areas were treated with aloe vera as the previous two cases. Superficial burns healed without complication. The areas affected became dry between 5 and 8 days. The wounds from the skin were periodically lavaged and cleaned using disinfectant, and similar topic cream, as described in D1, was used. It was necessary to use xylazine and butorphanol tartrate for wound management for 2 days after they arrived at the clinic. After 3 weeks, most of the burned areas healed ().
The hematologic and biochemical analyses of D3–D4 performed two days after the recue showed no abnormalities (). They showed no signs of discomfort and had good appetite. They were treated for 5 days and then discharged from the clinic to a free ranged pasture.
All of the donkeys were fed alfalfa hay and grass (Medicago sativa and Lolium perenne), 1.7% daily of their bwt in dry matter (DM) intake, which is equivalent to 2.6 kg D1, 2.1 kg D2, 2.7 kg D3, 1.9 kg D4 per day (). What was also given daily included: vegetable oil, 30 mL, and 20 mL of multivitamin and mineral oral supplements for horses containing: copper 150 mg, cobalt 6 mg, potassium 330 mg, magnesium 70 mg, manganese 130 mg, zinc 370 mg, iron 1000 mg, calcium pantothenate 170 mg, folic acid 35 mg, biotin 0.08 mg, vitamin: A 80,000 IU, B1 200 mg, B2 100 mg, B6 35 mg, B12 400 µg, D2 12,000 IU, E 150 IU, sucrose 50 G, choline chloride 675 mg, and selenium 3.1 mg/ 100 mL (Equifort, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile). All were orally de-wormed with fenbendazole 7.5 mg/ mL (10 g/100 mL, Lombrimic, Drag Pharma Laboratory Chile Invetec S.A., Santiago, Chile).


In May 2018, a 15-year-old boy with early childhood autism presented at the Department for Special Care Dentistry at Witten/Herdecke University. Although the teenager lived in an assisted living facility for children and young people with disabilities, his relationship with his family was good, especially with his mother. His mother also accompanied him, as his guardian at that time, during the actual treatment, by a dental student in clinical training, that we report on here. During the other appointments (regular check-ups, pretreatments, meetings), the patient was consistently accompanied by the same caregiver from the assisted living facility. According to both, the boy’s mother and his caregiver, he was not taking any medication regularly. In an assessment of the boy’s social interaction skills, it became clear that while his speech comprehension was good, verbal communication was not feasible because he did not speak. He could use a talker and construct two to three word sentences with it. In this way, he expressed wishes and interests in the context of leisure and family. Surprisingly, he showed little to no signs of refusal whatsoever concerning sounds, lights, and smells in the clinic. Perhaps also because an element of joy for him was water. Sounds or touching water had a calming effect.
An intraoral examination showed that he had a complete set of caries-free permanent teeth. The only clinical finding was a coronal enamel-dentine fracture without pulp exposure in the area of the incisal edge of tooth 11 (). There were no visible signs of a vestibular fistula. Further clinical examinations, which included percussion, palpation, and sensitivity testing were inconspicuous. Since the radiographic examination did not show translucency in the apical region of tooth 11 (), an “uncomplicated crown fracture of tooth 11” was diagnosed. At the time of the initial examination in the Department for Special Care Dentistry (May 2018), there were no bruise marks on the patient’s face or other body parts and no signs of intraoral abnormalities such as bleeding, swelling, or injuries, for example, from a fall. There had been no way of establishing from the people in the boy’s social environment as to when and how the enamel-dentine edge of the tooth might have broken off. Obviously, the trauma to this tooth had occurred at some previous time and the cause could no longer be determined. The patient’s caregivers (residential caregiver and mother) were informed that restoration of tooth 11 was feasible. Although they welcomed the prospect of possible treatment, especially because of the poor aesthetics of the chipped tooth, they also pointed out, several times, that the general medical and social characteristics of the boy might make treatment difficult.
A therapy plan was determined together with the patient’s mother and his caregiver, who were both also attachment figures for him. The proposal was to, first, adapt the patient to the dental setting before beginning with the actual restorative treatment. Initially, this was to be done in several short desensitization sessions in mostly familiar surroundings that were to be carried out by an experienced dentist, who was also a lecturer for the Department of Special Care Dentistry (P.S.). One of the patient’s attachment figures was to be present during these sessions (either the mother or the caregiver). If the desensitization sessions proved successful, and the patient tolerated intraoral examination and dental cleaning, the restorative measures were to be carried out in awake state by practicing elements of modified (or extended) behavioral facilitation (tell-show-feel-feel-do). Both the patient’s mother and his caregiver were informed about all aspects of the therapy and agreed to the treatment plan. They also consented to the patient being treated by supervised dental students in clinical training. According to plan, the supervising lecturer conducted several control and examination sessions, followed by a session with professional dental cleaning, with the aim of promoting patient cooperation. As part of the preparatory sessions, the patient was primed to also accept being treated by dental students. First, the student who was later to fulfill the role of “dental assistant” (L.J.) was, therefore, introduced to the patient during one of the preparation sessions. There, she performed a professional teeth cleaning for the patient. This measure also served to test if the patient was ready to accept being treated by other persons. At the next appointment, therefore, the patient was already familiar with this dental student, and then the student who was to be the dental operator (M.D.) for the tooth restoration was introduced to the patient as a “new” member. Furthermore, the patient was assured by P.S. and L.J., both of whom the patient was already familiar with, that he would also see them again during the restorative treatment session. After the supervising lecturer was of the opinion that the patient would be sufficiently cooperative for an invasive and time-consuming treatment in awake state, an appointment was made for the restoration of tooth 11 by a 5th year dental student in clinical training (M.D.). Because it is general practice in Germany for dentists to work together with dental assistants, dental students also take turns assisting each other while treating patients. In the present case, therefore, this role of dental assistant was undertaken by another 5th year dental student (L.J.). The therapy in the case reported here was performed during October 2019, with the student M.D. as the sole dental operator. During the restoration, the supervising dentist had only briefly been present in the treatment room to welcome the patient and to say goodbye to him, and, later, to check the finished restoration.
The aim of the operating dental student was to produce an aesthetically pleasing restoration of tooth 11 based on a standard approach for fillings of anterior teeth [,,]. To this end, first, a palatal layer key made of kneadable silicone (Honigum-Putty, DMG Chemisch-Pharmazeutische Fabrik GmbH, Hamburg, Germany) was made. This required situation impressions of the anterior defect and the adjacent teeth, which were also made with kneadable silicone. Then, the silicone impressions were filled with hard plaster (dentostone®220, Dentona AG, Dortmund, Germany). Afterwards, a composite shade (Filtek XTE, 3M Espe GmbH, Seefeld, Germany) was used, chairside, to model an approximation of the final situation (so-called mock-up) on the hard-stone model. The young patient observed the procedure with great interest, throughout. In the spirit of promoting cooperation, the tell-show-feel-feel-do behavioral technique was used, and it was even possible to involve the patient in the manufacturing process. After the two dental students (operator and assistant) had shown the patient how to knead the silicone mass after its two individual components had been mixed together, he was shown how the palatal key was placed on the plaster model (tell, show, feel). The patient was also given a small portion of the silicone mass, which he attached (feel, do) to the front of the hard plaster model (vestibular side). Both parts of the silicone key (vestibular and palatal) could, thus, cure simultaneously. In keeping with the structured behavioral approach, the hardening process was observed together with the patient, and then he was allowed to visually and haptically inspect the cured silicone key ().
The aim of the above-mentioned preparatory measures was to gain the patient’s cooperation in the subsequent intraoral treatment of his anterior tooth. After determining the tooth color (VITA A3), the enamel margins of the defect were first chamfered with rotating instruments (Diamant 863G and 833G, both green and red ringing, Hager & Meisinger GmbH, Neuss, Germany) (). Palatinally, only the refraction of the enamel prisms was performed, while an approximately 2 mm wide bevel was prepared vestibularly. Because the defect was only medium sized and the rotating instruments were used only briefly, there was no necessity for local anesthesia. Furthermore, in agreement with the supervising lecturer, the operating dental student deliberately avoided using a rubber dam, as this procedure could easily have been too much for the patient to tolerate. Since treatment in anterior regions of the oral cavity is feasible with only relative drainage, cotton rolls and permanent suction were the drainage method of choice in this case. In a next step, the tooth surface was prepared for an adhesive bond with the composite resin restorative material using an enamel-etching technique. For this purpose, 36% phosphoric acid gel (DeTrey Conditioner 36, Dentsply Sirona GmbH, Bensheim, Germany) and a multi-bottle adhesive system (Optibond FL, Kerr GmbH, Biberach, Germany) were used.
The restoration filling was built up in partial steps using different composite materials (enamel mass, body mass, dentine mass-Filtex XTE). First, a thin layer of enamel mass was placed in the layering guide, adapted, and then light-cured, intraorally, to create a thin enamel shell on the palatal side. A small core consisting of body and dentin materials could, subsequently, be built up in this shell. Then, this core was also coated with enamel on the vestibular side. In a last step, the filling was finished with a carbide finisher (HM48LU 012, Hager & Meisinger GmbH, Neuss, Germany) and polished with polishing wheels (Sof-Lex™, 3M Espe GmbH, Seefeld, Germany) and ceramic polishers (9771f and 9771C, Hager & Meisinger GmbH, Neuss, Germany). The total time needed for the restoration per se was about 45 min. This time estimate did not include the time required for welcome and farewell of the patient and a short pre- and debriefing session, or time spent answering interim questions from the patient’s mother. Because the patient had become very restless during the final polishing process, high gloss polishing could not be completed during the treatment session and had to be done in a subsequent control session (). The recall was set at a quarterly interval.
Written and signed consent to publish the images and the personal information about the patient in this case report was obtained from the mother of the patient (legal guardian till summer 2020) and the new state legal guardian (since summer 2020).


A 3 months and 26-day old infant male had a seven-day history of fever, rhinorrhea, nasal flaring, and wheezing prior to his death, during the Covid-19 pandemic. No medical attention was sought for the infant’s illness, but he was treated at home with tepid sponge for his fever. There was no complete resolution of his flu-like symptoms as they persisted even onto his death. The infant was delivered at term, vaginally with no adverse events. There was no history of maternal diabetes in pregnancy or HIV. Mother’s antenatal clinic visits were uneventful. The infant was discharged with mother 24 hours after delivery. On the day of the infant’s demise, he was breast fed and placed in his crib on his abdomen. Thirty minutes later the infant was discovered dead by his mother. An autopsy was mandatory.


A 29-year-old homemaker spontaneously delivered her first child at full term in the end of September 2018 ().
She breast-fed the baby. Three months later, she noticed a tendency toward constipation and distress in the epigastrium. She first noticed diarrhea mixed with blood at 20 weeks postpartum (). The number of diarrhea episodes increased to 20 times/day in a few days and abdominal pain began to appear. A local doctor referred her to a tertiary care hospital, where she was hospitalized at 21 weeks postpartum ().
Her past history was noncontributory except for palm exanthema at the age of 26. There was no family history of IBD. She reported not eating any foods that would likely cause diarrhea. Her family (husband and baby) did not have diarrhea. She did not take any supplements or medications.
Her height was 165 cm and body weight was 60 kg. She was afebrile. Physical examination was noncontributory except for mild tenderness in the left lower abdomen. Neither anal fistula nor anal skin tag was observed. Blood test disclosed a mild elevation of C-reactive protein (). Colonoscopy revealed diffuse inflammation from the rectum to the proximal descending colon with multiple yellow-white color spots (). Ulcer was not observed. Biopsy specimens revealed crypt abscesses, goblet cell depletion, and mononuclear cell infiltration (), which were consistent with findings of UC. Stool culture for pathogen, CD Chek (Techlab C. Diff Quik Chek Complete, Techlab Inc, VA, USA), and cytomegalovirus antigenemia were negative. At this point, moderate UC (initial episode) with left-sided colitis in the extent was diagnosed. Sulfasalazine 4.0 g/day was prescribed (). Her symptoms gradually improved, then bloody stool disappeared. She was discharged after 2 weeks hospitalization. Soon after discharge, sulfasalazine was replaced by mesalazine (3.2 g/day), and she resumed breast-feeding (). Because she wanted to be free from medication, she asked her doctor to refer her to another tertiary hospital based on the information of PBD in IBD.
She underwent 12 days of educational hospitalization for UC at 27 weeks postpartum (). At that time, there were no symptoms. C-reactive protein was normal and fecal occult blood was negative (). A lacto-ovo-semi-vegetarian diet (1700 kcal/day) with fish once a week and meat every other week, a kind of PBD, was provided. She experienced PBD and had a dietary guidance of PBD. Colonoscopy at the end of hospitalization revealed restoration of vascular patterns which confirmed endoscopic remission of UC (). She requested a lower dose of medication. Considering her excellent condition and our assertion that diet is generally more important than medication in the quiescent stage in IBD, the mesalazine dose was gradually decreased to 0.4 g/day on discharge (). She was advised to continue PBD after discharge.
An interview and questionnaire on lifestyle and dietary habits revealed a dietary change during the postpartum period. Midwives recommended Washoku for pregnancy and for lactation. Washoku is a traditional Japanese diet prevalent before dietary westernization and is similar to a presco-vegetarian diet. After delivery, she stayed at her parent’s home for about 3 months. Her mother prepared Washoku at the midwife's recommendation. She subsequently returned to her own home at 14 weeks postpartum (). She had a feeling of being released from childbirth. She prepared meals by herself. Although she was aware that the quality of the meals deteriorated, she had urges to eat sweets and cheese. She felt a tendency of constipation and distress in the epigastrium. This dietary change was assessed by plant-based diet score (PBDS). The score dropped from 25 to 9 (, ).
After the educational hospitalization, she was glad to be able to resume breast-feeding. She was well, then she completely stopped taking her medication 3 weeks after discharge. Her PBDS one month after the discharge (35 weeks postpartum) was 40, the highest score (). The values of hemoglobin and erythrocyte sedimentation rate became normal (). She has remained in remission without medication to the present (February 2020).
The patient has provided informed consent for publication of the case.


We received an endometrial biopsy of a 35-year-old female with a parity index of G4P3L3A1. The patient complained of polymenorrhea and leucorrhea for 2 years. Her medical history included an abortion two years ago. Her first delivery was by lower segment cesarean section because of a breech presentation, and the last delivery was full-term normal delivery seven years ago. A recent pelvic ultrasonography depicted heterogeneous and hyperechoic contents within the uterine cavity, along with multiple calcific deposits suggestive of osseous metaplasia of the endometrium ().
The histopathology of the endometrial biopsy showed an endometrium with bony remnants (A). The bony remnants showed mature degenerated osteocytes, bone tissue, and calcification (B).
The endometrial stroma showed a florid chronic inflammation predominantly composed of plasma cells and a few lymphocytes. Therefore, the report of chronic endometritis with osseous metaplasia was rendered. After a few days, we received the same patient’s hysterectomy specimen, which showed intrauterine bones in the endometrial cavity ().


An obese 31-year-old woman came to our hospital because of worsening dyspnea. She reported progressive exertional dyspnea associated with chest pain for two days but denied having a fever or any other pulmonary symptoms. The patient endorsed painless swelling of the right leg four days prior. She denied previous medical diseases and was not taking any medication or oral contraceptive pills. None of her family members had a history of vascular thrombosis. The patient denied recent immobilization, including long-distance travel. Her vital signs were: heart rate 110 bpm, blood pressure 135/77 mmHg, body temperature 36.80C, respiratory rate 30 per minute with oxygen saturation of 92% on room air. Her blood test results were demonstrated in table ; briefly, she had mild leukocytosis, lymphocytopenia, and elevated D-dimer and pro-BNP.
Her electrocardiogram (EKG) illustrated normal sinus rhythm, S1Q3T3 pattern, and anterolateral T wave inversion (right ventricular strain) (Figure ). Chest X-ray (CXR) had no significant infiltration (Figure , left). Computed tomography (CT) pulmonary angiography showed prominent bilateral pulmonary emboli and peripheral alveolar infiltrations (Figure , right). Doppler vascular sonography of bilateral lower extremities found occlusive intravenous thrombosis of bilateral popliteal veins.
She was started on a heparin drip, admitted to the medical intensive care unit, and received catheter-directed thrombolysis for the treatment of PE. She did not receive any specific COVID-19 medication. On admission day 4, her dyspnea and hypoxia were resolved, and she was discharged on a 6-month course of oral anticoagulant.


A 10-year-old girl attended with her father after she was referred to Paediatric Dentistry Clinic for diagnosis and treatment. The main chief complaint was the discoloured front teeth. Furthermore, bullying at school was occurring due to her teeth appearance. In addition, general teeth sensitivity was affecting the upper central incisor, especially during brushing and temperature change. A detailed dental and medical history was obtained from the child as well as the parents. Dental family history revealed that the relatives did not suffer from similar dental conditions. However, the patient was born prematurely at 8 weeks, and she was in an incubator for the first 8 weeks of birth. This was followed by a good recovery leading to not requiring any medication or hospitalisation during her first few years after her birth. Upon intraoral examination, we noted a mixed dentition stage, with partially erupted teeth, and caries-free primary and permanent teeth (except for the mobile upper right first primary molar). Regarding the occlusion, we noted a class II division one incisor relationship, skeletal class II relation with increased vertical proportion, midline shift to the left side, and an 8 mm anterior open bite, and the child was occluding solely on the left first permanent molar. The hypoplastic phenotype was affecting the enamel of both dentitions (more prominent in permanent dentition) with demarcated yellowish-brown discolouration at the incisal third of lower incisors, upper central incisors, first molars, and primary teeth. The features obtained from both clinical and radiographic examination were consistent with a possible diagnosis of hypoplastic AI (Figures –). A dental panoramic tomogram (DPT) taken showed all permanent teeth and hypoplastic defects affecting the teeth, including the unerupted second molars ().
The treatment planning was based on preserving the remaining tooth structure until the patient can reach the age when she can receive a definitive treatment, keeping in mind the need to relieve the symptoms including sensitivity, improve the occlusion, and aesthetic demands. Following discussion with the child and parents, it was agreed to use a noninvasive approach with no tooth structure removal. The treatment plan was divided into a prevention, restorative, and maintenance phase. In the prevention phase, enforcement of oral hygiene instructions was done at every visit. Sodium fluoride varnish 22,600 ppm (Duraphat, Colgate, USA) was applied to reduce dental sensitivity for three consecutive weeks to reduce teeth sensitivity, protect and prevent remaining structures from future loss, and, at the same time, to avoid caries development [, ].
During the planning visit, orthodontic consultation was obtained. Due to the skeletal open bite tendency of the patient combined with class II and the increased vertical proportion, the orthodontic treatment may include skeletal anchorage device or orthognathic surgery. It was recommended to delay the orthodontic treatment and reevaluate the case after one year, so a referral to Orthodontic department for periodic follow-up until treatment is initiated was done.
Restorative treatment was done for the permanent incisors and first molars. A direct composite veneer was performed to the upper and lower incisors: following the manufacturer's instruction, an adhesive system was applied (Optibond Solo plus, single component, Kerr Co., CA, USA). The enamel shade was applied in the cervical region, and shade A2 and shade A1 were used to the middle and cervical thirds (GRADIA® Anterior, GC corporation, USA) Finishing and polishing procedures of the restorations were performed using sequential Sof-Lex discs (3M ESPE, Seefeld, Germany). Regarding the first molars, the upper right and lower left were affected more by posteruptive breakdown when compared to the other two molars. As a result, a preformed metal crown (stainless steel crowns; 3MTM ESPETM, St Paul, MN, USA) was done and cemented using glass ionomer cement (Aquacem®; Dentsply, Milford, DE, USA). The other two molars were restored by composite, as the remaining enamel was sufficient to perform a retentive filling (Figures and ).
Follow-up was done for 15 months. The treatment showed a maintained tooth structure, good oral hygiene, and eruption of premolars ().


A 40-year-old female patient (weight 55 kg) was scheduled to undergo laparoscopic ovarian cystectomy under general anesthesia. In the past, she underwent ovarian cystectomy and appendectomy under general anesthesia without any adverse reactions. Her clinical and laboratory examinations were normal. There was no history of allergy.
In the operating theater, the patient received 2 mg of midazolam and 100 µg of fentanyl both intravenously (i/v). General anesthesia was induced with propofol 200 mg i/v and cisatracurium 5 mg i/v. Five minutes later, 1.5 g of cefuroxime i/v was administered for the infection prophylaxis. Within a few minutes after the cefuroxime injection, face flushing and redness of the eyes were observed. Her heart rate rapidly increased to 135 bpm and BP was 39/29 mm Hg. The anaphylactic reaction was suspected. The patient was intubated and treated as anaphylactic shock until vital signs recovered. When vital signs were stabilized, the residual neuromuscular blockade was reversed by 2 mg of neostigmine. The operation was postponed.
Anaphylaxis to cefuroxime was suspected. After 4 weeks, skin tests with amoxicillin, ampicillin, benzyl penicillin, and cefuroxime were performed according to the ENDA requirements. Skin tests were negative. Then, an oral provocation test with cefuroxime was performed. It was also negative. Later, the patient was tested with other perioperative drugs cisatracurium, fentanyl, midazolam, and propofol. Skin prick and intradermal tests were performed with the nonirritative concentrations of the drugs () []. The skin prick test wheal larger than 3 mm accompanied by erythema compared with a negative response to the control saline solution was considered as positive. The intradermal test was considered positive when the size of the initial wheal increased by at least 3 mm in diameter after 20 min or increased twice that of the post-injection wheal. Late reading was performed for the following 24 h. Histamine was used as a positive control while a saline solution was used as a negative control.
Skin tests with cisatracurium and other NMBAs (atracurium, rocuronium, and suxamethonium) were performed due to existing cross-reactivity between them (). Skin prick tests with cisatracurium () and atracurium () were positive. Cisatracurium was identified as the cause of anaphylaxis. Skin tests with other drugs used and latex were negative.
The consent for case report publication and pictureusage was obtained from the patient.


A 24-year-old male presented to our ED with complaints of right flank pain, with sudden onset, and rapid progression. The pain was localized to the right flank. There was no associated radiation of pain, fever, hematuria, or history of trauma. He also complained of two episodes of vomiting. He had been on regular medication for hypertension and chronic renal failure.
Upon arrival, the patient was afebrile, blood pressure (BP) was 114/70, pulse rate was 88 beats/min, room air saturation 100%, and respiratory rate was 22 breaths/min. Systemic examination of the abdomen was soft with tenderness over the right lower quadrant, with a palpable mass over the renal angle. Another systemic examination was unremarkable. Blood investigations revealed hemoglobin (Hgb) 10.7 g/dL (baseline Hgb 13.7 g dL), creatinine 222 umol/L, urine microscopy blood 3+, and protein 3+ (Table ).
Given his persistent pain over the flank region, with renal dysfunction, a noncontrast computed tomography-kidney ureter bladder (CT-KUB) was performed, showing enlarged right kidney with perinephric fat stranding and isodense lesion in the perinephric space, showing a CT density of recent bleed [(45-50 Hounsfield unit (HU)] (Figure ).
The patient was hospitalized for further workup and management and was started on analgesics and antibiotics. After two days of hospitalization, the patient underwent an MRI abdomen with contrast, showing a large perinephric hematoma (arrowhead) and a small hemorrhagic cyst (arrow) in the anterior renal cortex communicating with perinephric hematoma (Figure ).
He was treated symptomatically. The patient was pain-free and hemodynamically stable. The urology team was consulted, who advised for conservative management and close observation. He did not have a further fall in Hgb or worsening of renal function. Further workup for other causes, like vasculitis, were negative.
On the eighth day of admission, ultrasound imaging of the kidney revealed an estimate of 208 cc of perinephric fluid collection (Figure ).
As the patient improved symptomatically, he was discharged with outpatient follow-up. Follow-up ultrasounds done in the first and third weeks after discharge demonstrated regression of hematoma. Follow-up ultrasound done after three months postdischarge demonstrated complete resolution of hematoma, and no evidence of malignancies was detected (Figure ).


A 35-year-old African American male with a 20-year history of type 1 AIH, liver cirrhosis, primary sclerosing cholangitis, and esophageal varices presented with a two-day history of confusion and bizarre behavior. He had been recently diagnosed with HCC and was taking lactulose and lenvatinib 12 mg daily two weeks prior to presentation. He was not able to titrate his bowel movements with lactulose at home due to chemotherapy-induced diarrhea, which resulted in missing two doses of lactulose. The patient was subsequently diagnosed with hepatic encephalopathy secondary to lactulose non-adherence in the setting of chemotherapy-induced diarrhea. During his hospital course, the patient was treated with lactulose and rifaximin, which resolved his encephalopathic symptoms. He is currently being evaluated for a liver transplant and is being monitored closely by his oncology team at a tertiary care center.
Case background
The patient was diagnosed with type 1 AIH at the age of 15 following a liver biopsy, which showed cirrhosis and inflammatory activity consistent with AIH. To manage recurrent AIH episodes, he was prescribed azathioprine, prednisone, and propranolol by a gastroenterologist at a tertiary care hospital. Unfortunately, due to complex social determinants of health including insurance coverage issues and unwanted medication side effects, he was mostly non-adherent to the management plan. Due to the patient’s multiple gastrointestinal comorbidities, a series of surveillance tests were prescribed in 2013, including an outpatient MRI, AFP monitoring, and surveillance abdominal ultrasounds every six months to screen for cholangiocarcinoma and primary liver cancer. However, insurance coverage challenges prevented the patient from maintaining consistent follow-up.
Approximately one month prior to his hospital presentation with hepatic encephalopathy, he was diagnosed with HCC. This was determined after a workup for presentation with bilateral lower extremity and testicular swelling yielded the presence of a hepatic mass (4.91 by 3.93 mm) seen on MRI with a right portal vein thrombus (Figure ).
Laboratory studies were notable for elevations in AFP (8418.2 ng/mL) and bilirubin (6.7 mg/dL). Subsequent percutaneous needle biopsy of the liver confirmed the diagnosis of well-differentiated HCC, with biopsy positive for arginase-1 and negative for cytokeratin-7. Subsequent CT of the chest, abdomen, and pelvis with contrast for staging was performed one month after the initial diagnosis. While it demonstrated no evidence of metastatic disease, it did reveal progression of the hepatic mass to 5.15 by 3.83 mm (previously 4.91 by 3.93 mm) along with central invasion of the tumor (Figure ).
With these findings, our patient was diagnosed with stage IIIB HCC.


A 7-year-old girl was referred to our centre for evaluation of short stature. She was the product of a second-degree consanguineous marriage. She had two elder sisters, aged 16 and 18 years, who had similar morphological features and a brother aged 14 who was healthy (). The sisters had attained menarche at 14 years of age. Anti-natal and peri-natal periods were uneventful. Her birth weight was 2.1 Kg. The parents reported a poor gain in height since birth. She had a history of two fractures on trivial trauma; one involving the right tibia and one involving the left radius at 4 and 5 ½ years of age respectively. The fractures took a long time to heal. Height and weight were plotted on the Indian Association of Paediatrics growth chart for Indian girls aged 5-18 years (). On physical examination, her height was 84 cm [-5.6 standard deviation score (SDS)], and the head circumference was 68.5 cm (). The mother’s height was 158 cm, and the father’s height was 172 cm, thus her target height was 158.5 cm. The affected sisters at 16 and 18 years of age were 110.5 and 114 cm, respectively and both were below the 5th centile. The height of the unaffected elder brother was 158 cm, approximating to the 50th centile. The brother had not reached a final height. The sibling sisters have attained final height, as the epiphyses were fused. Notably, the final heights of the sibling sisters was less than expected, even for patients with Pycnodystosis. The medical records of the index case showed that her height velocity had been 1.2 cm/year for the last two years. She was pre-pubertal. She had facial dysmorphism with frontal, occipital bossing and limited mouth opening (). She had short hands with short and stubby fingers with dystrophic nails (). Her anterior fontanelle had not closed and measured 1.8 cm. The fontanelles of the affected sisters had closed. Examination of the oral cavity revealed hyperdontia, multiple caries and a grooved palate. Hepatosplenomegaly was present.
Laboratory examination revealed normal haematological parameters. The serum calcium, urea, creatinine, phosphorus, alkaline phosphatase, intact parathyroid hormone and 25 (OH) vitamin D levels were normal. Her IGF-1 level was 56 µg/L (normal range: 58-367 µg/L for a seven-year-old girl). A GH stimulation test was carried out with clonidine and revealed a peak value of 1.1 ng/mL, indicating GH deficiency. Her basal and adrenocorticotropin hormone stimulated cortisol levels were within normal limits. Serum thyroxine (T4) was 6.5 µg/dL (normal value: 4.6-12 µg/dL), and TSH was 3.2 mIU/mL. Serum IGF-1 for the affected sister aged 16 years was 182.6 µg/L (normal range: 127-541 µg/L) and of the sister aged 18 years was 201.2 µg/L (normal range: 121-486 µg/L); both had normal thyroid function profiles. Radiographic examination revealed generalised osteosclerosis. The medullary cavities were absent in the long bones. Skull radiography revealed frontal and occipital bossing, non-fusion of sutures with obtuse mandibular angle, absence of mastoid air cells and small ‘J’ shaped sella turcica (). Terminal phalanges of hands showed acro-osteolysis (). Magnetic resonance imaging of the sella revealed a hypoplastic anterior pituitary with a volume of 121 mm3 (<5th centile for age) () and a typical posterior pituitary bright spot. Arterial blood gas analysis did not reveal any hypoxia. Polysomnography did not show any evidence of obstructive sleep apnoea. Audiometry and ophthalmic examination were normal.
Molecular testing of the CTSK gene showed a homozygous missense variant CTSK:C.890G>C. The parents were found to be carriers of the same variant. Consent could not be obtained from the affected sisters and the unaffected brother for genetic testing due to the financial constraints of the family. The parents were counselled regarding their carrier status, and the siblings were advised regarding the benefits of genetic testing.
The index case was offered conservative and symptomatic management. Orthodontic and endodontic treatment was provided for caries and malposition of teeth. Counselling regarding oral hygiene, fracture prevention and other psychiatric aspects of the disease were undertaken.
In light of the GH deficiency, rhGH was administered at 0.16 mg/kg/week. An IGF-1 level was repeated after four weeks, which was still low. Based on the IGF-1 response, the dose was gradually increased to 0.48 mg/kg/week. An incremental IGF-1 response and increase in height velocity ruled out GH resistance. Compliance with treatment was good on regular monitoring. On follow-up, a repeat evaluation of her thyroid axis after three months of treatment revealed a T4 of 3.1 µg/dL and TSH of 9.2 mIU/mL. She was started on levothyroxine replacement of 50 µg/day and after two months of replacement therapy the T4 had normalised to 10.4 µg /dL and the TSH was 4.9 mIU/mL. At the end of 18 months of treatment, her height was 97 cms with a 9 cm increase in stature over the first year of treatment and four cms over the next six months. Her height velocity was 8.7 cm/year over 18 months, and there was a gain of 1 SDS in height over this treatment period. There was no adverse effect on GH treatment.
Informed consent was obtained from the guardian.


We present the case of a 16-year-old girl with an alleged history of fall, who was admitted to Acharya Vinobha Bhave Rural Hospital (AVBRH), Datta Meghe Institute of Medical Sciences (DMIMS) Deemed To Be University (DU), Wardha, Maharashtra, India, with the complaints of pain and swelling over the left thigh. She had no history of loss of consciousness, vomiting, or seizures, and had a Glasgow Coma Scale of 15/15 following the event; necessary investigations confirmed that she had suffered a left midshaft femur fracture. An open reduction internal fixation (ORIF) femur interlock nailing was done. She was then referred to physiotherapy for further management (Table ).
Clinical findings
She was examined in a supine position with both shoulders at the same level. Following this, the left leg was abducted and slightly externally rotated, and knee extended with pillow support below knee and leg and ankle where ankle was slightly plantar flexed. The swelling was found to be present on the left mid-thigh and operative site (Tables -). On palpation, there was a rise in local temperature with non-pitting edema. She also had extreme kinesiophobia with a Tampa Scale score of 67 and a visual analog scale (VAS) score of 10/10 [].
Medical management
An ORIF femur interlock nailing with one proximal screw and one distal screw locking was done. Stainless steel wire was also used in the reduction procedure (Figure -). Figure - presents images that depict the patient's postoperative rehabilitation process.
Goals
Postoperative
The short-term goals were to prevent respiratory complications, reduce pain and edema, maintain and increase joint range of motion and strength, promote early mobility, avoid pressure sores, encourage walking (non-weight bearing), and enable the patient to carry out ADLs independently [-].
The long-term goals were to promote independent walking with and without the walker (partial/full weight-bearing), static and dynamic balance, to promote indoor and outdoor mobility, independent ADLs, and ergonomics (Figure ).
Therapeutic management
Phase I (Zero to Two Weeks)
Phase I exercises revolved around counseling, knee and hip strengthening, non-weight bearing, and mobility of joints. Active range of motion, knee flexion exercises, and lower limb isometrics were initiated immediately after the surgery. The management of effusion and edema was carried out by frequent cryotherapy and limb elevation. Active control of the musculature of the knee extensor and the hip abductor were concentrated in immediate strengthening. Open chain exercises such as simple hip abduction, extension, and flexion exercises were done for strengthening a non-weight-bearing position. Throughout these exercises, the emphasis was placed on sustaining a powerful contraction of quadriceps with the leg in a completely extended posture. The knee extension was performed actively in a sitting position, without weight (open chain). It would also aid to avoid an independent quadriceps operation. This continued with non-weight-bearing with a walker.
Phase II (Two to Six Weeks)
In phase II, many aspects of the phase I regimen were continued as needed. Weight-bearing with a walker proceeded further to encourage toe contact (10% weight). Phase II interventions involved the advancement of phase I exercises to improve weight-bearing tasks, some gait retraining, recreational activities, and strength-conditioning initiation.
Strengthening advanced toward further weight-bearing activities until the patient began to display the ability to bear weight. More non-weight-bearing activities like knee extension with resistance bands ranging from 900 of flexion to 300 of flexion were started. Hip-strengthening progressed further by the introduction of exercises like abduction and flexion of the hip in a standing position. Training activities in phase I was repeated with increased resistance and more frequency.
Phase III (6-12 Weeks)
In order to improve mobility, balance, proprioception, and agility training, the focus of the exercises was on increasing the power of the lower limb by partial weight-bearing activities during phase III.
Power progression, gait normalization, and an eventual shift to performing desired activities were concentrated on. The increase in the intensity of the exercise implemented by enhanced resistance with progressive resisted exercises (PRESs) focused on strengthening the patient's condition. Furthermore, the advancement of weight-bearing to a level of 50% with or without an assistive tool, and strengthening exercises like step-ups on a single leg, were also initiated. Emphasis was continued to be placed on impairments that caused functional limitations, in particular the extension of knee and abduction of hip activities. The static balance development was done by ensuring that stable platform activities were advanced to make stable and unstable surfaces more dynamic, and training was enhanced by stressing the need to practice a more normal gait pattern. Along with backward-walking, gait-training exercises progressed to side-stepping activities with necessary help.
Phase IV (12-18 Weeks)
Throughout phase IV, in addition to improving mobility, coordination, fitness conditioning, and proprioception, the focus was also on exercises to improve full-weight strength bearing functions in the lower limb.
Strength improvement, gait normalization, and an eventual shift to desired activities were continued to be pursued in this stage. In terms of reinforcement, improvement in the intensity of the initiated exercises by enhanced resisted PRESs was also implemented. Similarly, for weight improvement of up to 100% with or without the walker, individuals usually pursue tasks like step-up, half lunges, and mini squat. For more closed-chain exercises like lateral walking with resistance, the strengthening of hip abduction was also advanced. Functional restricting impairments, targeted specifically by knee extension and hip abduction practices, were also an area of focus. Balancing and proprioception training progressed as single-leg tasks when full weight-bearing was carried out with or without the aids. Exercises with a solid platform with the transition of static balance to more active single-leg exercises on stable and precarious surfaces along with rehabilitation were implemented with an emphasis on practicing a more normal gait pattern.
Limitations
Kinesiophobia leads to a vicious cycle of pain-avoidance and fear, which severely affects the ability of the patient to perform any movement and activities that involve the operated limb; hence, the initial range of motion exercises was difficult.


We herein report the case of a 77-year-old male, with a remote history of smoking who underwent open radical cystoprostatectomy with bilateral extended pelvic lymph node dissection with an ileal conduit urinary diversion (Bricker) for a high-grade muscle-invasive urothelial bladder carcinoma (pT2HG). The patient was diagnosed after a transurethral resection of bladder tumor performed 3 months before his radical surgery; concomitant urethroscopy showed no suspicious inflammatory or neoplastic lesions. Preoperative thoracic, abdominal and pelvic computed tomography (CT) showed no signs of suspicious nodal involvement nor distant metastatic spread. Abdominal and pelvic magnetic resonance imaging (MRI) highlighted no stigmata of extravesical extension of tumor. The patient declined neoadjuvant chemotherapy and was therefore programmed for radical cystoprostatectomy.
On definitive pathology, the patient was found to have a poorly differentiated, high grade, urothelial carcinoma (UC) infiltrating the bulk of the muscularis propria and extending to the perivesical fat. Foci of carcinoma in situ and lymphovascular invasion were present. No pathologic lymph node invasion was demonstrated, compatible with a tumor node metastasis (TNM) classification of pT3N0M0. The prostate displayed three microfoci of intraparenchymatous Gleason 6 (3 + 3) adenocarcinoma, with no tumoral implication of the seminal vesicles. The surgical specimen presented negative surgical margins and negative distal ureteral margins.
The patient consulted 5 months after his surgery for a subacute onset of a painful penile induration and reported episodes compatible with stuttering priapism. He had a good performance status. Physical examination revealed a semi-erect penis and a considerable penile induration in regard of the corpora cavernosa. CT imaging of abdomen and pelvis identified isolated nonspecific, poorly limited, hypodense lesions of corpora cavernosa ( & ). Incisional biopsy of the palpated lesions revealed a poorly differentiated carcinoma with poor evaluation of surgical margins due to fragmentation of tissue specimen. No further imaging was performed due to financial impeachments.
A total penectomy was performed, which revealed a bulky invasion of the corpora cavernosa by a UC, with a secondary extension to the corpus spongiosum and a focal involvement of the urethra. Tumoral vascular emboli were present within the specimen ( & ). Surgical margins were negative, including the remaining proximal urethra.


A 60-year-old female presented with a nodular lesion in the lateral side of the left knee, measuring 2 cm, painful on palpation, that appeared two years before. She underwent a resection in 2013 and the histology confirmed MCS, with positive margins (Figure ). The patient then underwent a local excision after 45 days and the histology found a residual MSC with free margins. Four years later, in November 2017, she presented with an inguinal node, and fine-needle aspiration was performed and confirmed positive cytology for malignancy, compatible with metastasis of basaloid neoplasm. Immunohistochemical staining suggested metastasis of MSC. A computed tomography (CT) of the pelvis showed heterogeneous lymph nodes enlargement, with intense enhancement of contrast, the 2 biggest in the left inguinal region, measuring 42 x 27 mm, and in the left external iliac chain, measuring 31 x 27 mm (Figure ). There was no evidence of other sites of disease. After a multidisciplinary discussion, she underwent inguinal and iliac lymphadenectomy in February 2018, with four of nine lymph nodes harvested with metastasis of basaloid neoplasm in the left inguinal region, with extracapsular spread (7.5 cm); two of four lymph nodes in the pelvic region, without extracapsular spread (1.0 mm); and one of one lymph node in the left external iliac region, with extracapsular spread (5.2 cm). Due to the number of involved lymph nodes and the presence of extracapsular spread, adjuvant three-dimensional conformal radiation therapy in the left inguinal and iliac region was performed, with a total dose of 48Gy in 20 fractions of 240cGy (Figure ), until May 2018. It was not performed any systemic therapy. The patient developed mild lymphoedema on her left leg after the treatment, which was controlled with clinical measures. She is being followed with periodic exams, including pelvic and thoracic CTs, and shows no sign of disease until March 2020.


A 59-year-old male with a significant history of chronic alcoholism presented to the emergency room after an upper arm fracture on light gardening. X-ray of the shoulder showed a spiral fracture of the proximal diaphysis of the humerus with displacement and angulation of the distal fractured bone (). During the orthopedic surgery evaluation, the patient reported dyspnea on exertion and increasing abdominal girth. These alarming symptoms prompted a referral to cardiology for preoperative clearance. The patient got admitted for the pre-op workup. His past medical history was significant only for chronic alcohol abuse. He denied smoking and use of illicit drugs. His family history was noncontributory and negative for bone or liver disease. His vitals on admission were the following: temperature of 97.1, blood pressure of 160/65 mmHg, respiratory rate of 18 breaths per minute, and pulse rate of 60 beats per minute. Pertinent physical findings included mildly enlarged liver on palpation, grade IV/VI systolic murmur at the aortic area, and scattered basilar rales. There was no splenomegaly, jaundice, or lymphadenopathy.
Laboratory workup showed hemoglobin 11.8 g/dL, white blood count 5,700/mm3, platelets 115,000/mm3, BUN 14 m/dL, creatinine 0.62 mg/dL, calcium 8.7 mg/dL, albumin 2.7 g/dL, total proteins 8.4 g/dL, prothrombin time 14 seconds (control 10-13 seconds), activated partial thromboplastin time 34 sec (control 27-37 seconds), alkaline phosphatase 172 IU/L, ALT 71 IU/L, AST 107 IU/L, LDH 224 IU/L, total bilirubin 1 mg/dL, alpha-fetoprotein 8.7 ng/mL, hepatitis C antibody reactive, and hepatitis C viral load of 1,626,714. Computerized tomography (CT) scan of the shoulder () showed an oblique comminuted fracture of the proximal humerus shaft as reported on X-ray in the emergency room. However, the fracture appeared to traverse through an ovoid lucency measuring approximately 5.5 × 2.8 cm within the proximal humerus shaft (). No discrete tumor or soft tissue mass was seen but was likely obscured by hemorrhage from the fracture. CT scan of the abdomen and pelvis (Figures –) revealed cirrhosis with portal hypertension, showing four liver lesions, with the largest measuring 3.1 cm, typical of HCC and another one hypoattenuating large lesion, measuring 5.8 × 5.2 cm, atypical for HCC. Staging scans did not reveal metastatic disease in the chest.
The differentials considered based on radiological features were a primary bone tumor or metastasis of an unknown primary or hepatocellular carcinoma. The patient underwent an open reduction and internal fixation of the right humerus with a bone biopsy at the fracture site with no postoperative complications. The biopsy results showed the presence of HCC (Figures and ). The patient was recommended to start radiation to the humerus and sorafenib after recovery from surgery.