Case 1 - 57-year-old female with a background of UC
Background
This patient presented with a six-day history of left leg swelling and discomfort. Duplex sonography and computerised tomography confirmed the presence of thrombus extending from the left common iliac vein to the left distal external iliac vein and into the left common femoral vein (Figure and Figure ).
Surgical Management
The patient received catheter-directed thrombolysis (CDT) using a 5F Fountain® catheter (Merit Medical Systems, UT, USA) positioned in the thrombus via a left popliteal vein puncture. Recombinant tissue plasminogen activator (r-tPA) was infused at a rate of 1 mg/h; after 72 h there was complete clearance of the thrombus (Figure and Figure ).
Final venography identified left common iliac vein and distal left external iliac vein stenoses. Therefore, venoplasty was performed at 18 atm using a 14 mm x 40 mm Atlas® balloon (Bard Peripheral Vascular, Temple, AZ, USA). The left iliofemoral segment was stented using closed cell stents (two 14 mm x 120 mm Vici Venous Stents® (Boston Scientific, Marlborough, MA, USA) with a bridging 14 mm x 90 mm Vici Venous Stent® (Figure ).
Post-operative Recovery and Surveillance
The patient was initiated on therapeutic low-molecular-weight heparin (12-hourly 1 mg/kg enoxaparin) for six weeks with a view to transitioning to long-term warfarin (international normalised ratio range 2.0-3.0) alongside thigh-length class II compression hosiery. Post-operative duplex sonography the following morning demonstrated patent stents with good flow. Surveillance sonography was initiated with scans at two weeks, six weeks, three months, six months, 12 months, and annually thereafter.
Post-stenting Complications
Five months following stent deployment, the patient presented with a refractory flare of UC necessitating a subtotal colectomy. Duplex sonography performed during the admission revealed an in-stent stenosis. Venoplasty (18 atm, 14 mm x 40 mm Atlas® balloon) was performed prior to the colectomy to reduce the risk of post-operative DVT and in-stent thrombosis. The procedure was successful and follow-up sonography revealed patent stents with no residual thrombus. The patient experienced no major complications and was continued on the post-stenting surveillance programme (previously described). The stents remained patent after 19 months.


Case 2 - 41-year-old male with a background of Crohn’s disease
Background
This patient presented with a 10-day history of left leg swelling and pain. Duplex sonography and venography confirmed occlusion from the left common iliac vein to the left common femoral vein (Figure and Figure ).
Surgical Management and Post-operative Recovery
The patient received CDT using r-tPA (infused at a rate of 1 mg/h) via a 5F Fountain® catheter positioned in the thrombus, accessed via the left popliteal vein. Following 72 h of treatment, the thrombus cleared.
Post-operative venography confirmed improved venous flow with no visible collateral veins and therefore stenting was not required (Figure ). There were no major complications following CDT and the patient experienced full symptom resolution. The patient was discharged on apixaban (10 mg twice daily for seven days, then 5 mg twice daily for six months). This post-operative management differed from case 1 as due to the absence of deep venous stenting, intensive long-term anticoagulation was not required.


An intact, 11 -year-old, mixed breed female dog, weighing 15 kg was admitted with signs of urinary obstruction and resistance to inserting a urinary catheter into the urethra. Signs of urinary obstruction had been recorded by the owner two weeks earlier. During this period, the patient was treated conservatively in another clinic, and after the clinical symptoms worsened, he was referred to the Department and Clinic of Surgery, Faculty of Veterinary Medicine of Wroclaw Environmental and Life Sciences. After admitting the patient to the clinic, vaginal and rectal examinations revealed a firm mass in the pelvic cavity at the level of the pelvic part of the urethra was perceptible. Abdominal palpation revealed a severely distended bladder. After a clinical examination and blood screening test, the patient was referred for ultrasound, CT, and endoscopy. The ultrasonographic examination revealed a strongly filled urine bladder, occupying almost the entire mid abdomen, and extending to the cranial abdomen. The ultrasound examination revealed only the initial, clearly extended (about 1.3 cm) section of the urethra, apart from the bladder. However, no cause of obstruction was visualized in the segment available for examination. The urethra and the wall of the entire bladder available for ultrasound examination did not show any hyperplastic changes.
Computed tomography examination showed well-contrasting, heterodense enlargement of the urethral wall extending into the lumen. The growth was about 5.5 cm long (taking up about 3/5 of the length of the entire urethra). The lesion was about 3 cm thick, significantly restricting the patency of the urethra (Fig. ). The part of the urethra in front of the tumor was approximately 1.5 cm in diameter. Cranially there was a 1.3 cm long, hypodense growth coming out of the tumor into the lumen of the urethra. Contrast CT examination did not reveal any metastatic changes, both local and distant. This also applied to the bladder, lymph nodes, and lungs.
Prior to surgery, vaginoscopy and an attempt of urethrocystoscopy was performed to localize the lesion that prevents the outflow of urine from the bladder (Storz rigid endoscope, diameter of 2.7 mm). Endoscopic examination showed no macroscopic changes in the lumen of the vagina and in the external exit of the urethra. During the attempt of performing urethrocystoscopy, a mass occluding the lumen of the urethra (0.5 cm from the external exit of the urethra) was found without the possibility of introducing the optics into the lumen of the bladder. During the same examination, a fine-needle biopsy was also performed for cytological evaluation of the examined lesion.
Based on the results of the clinical trials and additional examinations (only the distal part of the urethra was changed and no metastases), the owner of the animal was presented with possible options for conservative and surgical treatment. The owner of the animal did not consent for the removal of the tumor from the pathway of the pelvic symphysis osteotomy. At the same time, he accepted less invasive procedures with the possible risk of only palliative treatment. Therefore, it was decided to perform a pre-pubic urethrostomy and an attempt of removal of the altered part of the urethra by laparoscopy.
Patient was pre-medicated by intramuscular injection of medetomidine (Cepetor, CP-Pharma, Handelsges. mbH Ostlandring 13 31,303, Burgdorf Germany) at a dose of 10 µg/kg with butorphanol (Butomidor, Richter Pharma AG) at a dose of 0.1 mg/kg. Endotracheal intubation was performed after induction of general anaesthesia with propofol at a dose of 1 mg/kg intravenously to effect. After intubation, the epidural anaesthesia was provided with a lidocaine at a dose of 4 mg/kg (Warszawskie Zakłady Farmaceutyczne Polfa S.A. ul. Karolkowa 22/24; 01-207 Warsaw, Poland). General inhalation anaesthesia was maintained with isoflurane (IsoVet, Piramal Healthcare, United Kingdom) in 100 % oxygen using a circle system (Mindary Wato-Ex 65 Pro). Before placing the patient on the operating table, a catheter with a diameter of 1 mm was inserted into the bladder through which the residual urine was removed. The patient was placed in dorsal recumbency for the procedure (Trendelenburg position). After the surgical field was prepared, the procedure was started with the introduction of a 5 mm diameter optical trocar using the Hasson method in the Linea alba cranially to the umbilicus. All endoscopic equipment used for the laparoscopic procedure with a 5mm 30˚ scope manufactured by Karl Storz SE & Co. KG (Tuttlingen, Germany). After the insufflation of the abdominal cavity with an insufflator (Storz) and reaching a pressure of 8 mm Hg, optics were inserted into the abdominal cavity. Subsequently, under the control of the endoscope, two consecutive 5 mm and 10 mm diameter trocars were inserted caudo-laterally to the optical trocar in a triangular fashion (Fig. A).
After accessing the abdominal cavity, the pelvic part of the urethra was successively dissected from the surrounding tissues. For this purpose, different types of vessel-sealing devices (BiCision, BiSect, Erbe Vio 3, Tübingen, Germany) were used alternately. Preparation began with cutting the median ligament of the bladder. The vesicogenital and pubovesical pouches were then opened and bluntly prepared using laparoscopic forceps. The fatty tissue present in this place, surrounding the urethra was dissected and cut off. The vessels were closed successively using the previously mentioned vessel-sealing devices. This procedure revealed a considerable length of the pelvic urethra (Fig. A). Then, to improve visibility and facilitate the preparation (obtaining constant tension of the urethra without the need for an additional trocar), the urethra was suspended from the abdominal wall with a monofilament suture (Monosyn 0, Braun, Rubi, Spain). A situational suspension suture was introduced in the unchanged part of the urethra. This place was determined based on the macroscopic difference in the laparoscopic image of the dissected urethra (significant widening of the affected part). Additionally, intraoperatively, the difference in the structure (hardness) of the altered and unchanged urethra was assessed by very gentle squeezing with Maryland laparoscopic forceps along the urethra, starting from the bladder. Before cutting the urethra, the residual urine was once again removed from the bladder and the catheter was removed. A transverse urethral resection was performed using vessel-sealing devices (BiCision) in front of its thickening (affected part) and just behind the applied situational suture. After the urethra was cut transversely, behind the place of the previously conducted situational seam, the proximal part of the urethra was temporarily suspended to the abdominal wall. (Fig. B). The distal part of the urethra was dissected from the surrounding tissue maximally caudal up to the vaginal vestibule. This allowed for the coagulation of both cut edges of the urethra, which, combined with the earlier removal of urine from the bladder through the preoperative catheter, was aimed at limiting the possible spread of neoplastic cells. Using a speculum and per-vaginal palpating the course of this part of the procedure - initially palpable in the per-vaginal examination, movements of laparoscopic tools pressing on the wall of the vaginal vestibule, and then periodically visual inspection of cutting the opening of the urethra. After laparoscopic dissection of the urethra from the vaginal vestibule, the dissected distal part of the urethra was removed from the abdominal cavity through an opening in the wall of the vaginal vestibule using haemostatic forceps inserted from the side of the vaginal vestibule (Fig. C) The surgical wound in the vaginal vestibule wall was then closed with three endoscopically inserted simple interrupted sutures from abdomen cavity. The tightness of the performed sutures was checked intraoperatively by per-vaginal examination. Then, after making a small incision in the Linea alba, the proximal part of the urethra was led out. The rim of the urethra was levelled with scissors, where the coagulated part of the urethra was removed at the time of its previous transverse cut. The urethra was sewn to the skin with simple interrupted sutures (Monosyn 4 − 0, B. Braun, Rubi, Spain). The trocar wounds were closed with simple interrupted sutures on the fascia and muscles (Monosyn 2 − 0, B. Braun, Rubi, Spain) and the same sutures on the skin and subcutaneous tissue (Dafilon 2 − 0, B. Braun, Rubi, Spain) - Fig. B.
After surgery, the affected distal part of the urethra was sent for histopathological evaluation, as well as the fragment of the proximal part of the urethra (from the side of the bladder) obtained during the alignment of its edges prior to the pre-pubic urethrostomy.
Immediately after recovery from anaesthesia, the patient was able to get up and move without any problems. Controlled urination, without symptoms of incontinence, was found immediately after the anaesthesia subsided. The patient was discharged from the clinic the second day after surgery. Information about the dog’s health status was transferred to the clinic by the owner by phone, where no postoperative complications were noted for a period of the first 2 weeks. After this period, the authors had no possibility of direct supervision during treatment, despite the recommendations of regular monitoring in the clinic. Lack of contact with the owner was because he lived far away from the clinic and his advanced age. Unfortunately, it was only three months after the procedure that the owner returned to the clinic with the patient showing difficulty in moving and defecating, noting while for a period of 2.5 months he did not observe any negative changes in the dog’s behaviour. Another clinical (per rectum) examination showed the presence of a firm, strongly painful mass in the ventral part of the pelvis. Subsequent CT scan showed the presence of extensive recurrence in the form of a heterogeneous tumor covering the entire width of the medial and ventral pelvic cavity and extending to the posterior abdomen, ventral and right sided to the bladder (Fig. A). The enlargement completely included the pubic bones and the medial-ventral edges of the iliac bones. Additionally, metastatic changes in the lungs were visualized. The patient was euthanized, and an autopsy was performed.
A fine-needle biopsy performed before the surgery did not give a definite answer as to the nature of the examined lesion. However, the cytological specimens showed mainly erythrocytes, weakly eosinophilic, amorphous necrotic masses, few neutrophils, and single cells showing features of anisocytosis and anisokaryosis.
The microscopic examination of the histopathological specimens from both intraoperative specimens of the lesion, i.e., the fragment of the urethra from the side of the bladder together with the remaining removed tumor tissues, showed the weaving of a typical well-differentiated transitional cell carcinoma (carcinoma urothelial). Tumor cells were present in the incision line from the urethral opening to the vaginal vestibule. No neoplastic cells were observed in the connective tissue surrounding the urethral section in the incision line from the bladder side (Fig. A). The cytological and histopathological slides were observed under Olympus BX53 microscope couplet with Olympus UC90 camera. To take acquisition the cellSens Standard V1 software was used (Olympus).
At the site of the urethrostomy, an irregular thickening of the skin and subcutis, about 1 cm thick, with no signs of neoplastic infiltration was found. The neoplastic tissue, however, comprised the urethra, circumscribed the bladder neck, and grew irregularly around these structures, reaching dimensions of approximately 12 × 7 × 7 cm. The tumor did not penetrate the lumen of the urethra and the bladder, growing exophytically (Fig. B). Furthermore, the surrounding soft tissues (rectal intestine and uterine body) were not infiltrated but only pressed by the mass of the tumor. The hypogastric and sublumbar lymph nodes were swollen and bloodshot. The pubic bones and ilium bones at the site adjacent to the tumor were thickened with irregular surface. Small foci of distant metastases in the form of diffuse gray-white single nodules were observed under the pulmonary pleura and in the lung parenchyma. Histopathological examination of metastatic foci revealed neoplastic cells corresponding to the image of the primary tumor - transitional cell carcinoma - Fig. B.


A 62-year-old man presented with pain in the left wrist after falling off a ladder. Initial plain radiographs revealed a dorsal PLD (Fig. ). He had no specific medical conditions other than high blood pressure. Under general anesthesia, a 6-cm longitudinal skin incision was made on the dorsal aspect of the wrist, centered on the Lister tubercle. The incision was extended to the extensor retinaculum which was divided along the third dorsal compartment, and the extensor pollicis longus tendon was identified distally and retracted radially. The second and fourth compartments were reflected off the dorsal capsule. Elective neurectomy of the posterior interosseous nerve may be performed. The carpal bones were inspected using capsulotomy. A ligament sparing capsulotomy was done along the fibers of the dorsal radiocarpal and dorsal intercarpal ligaments.[ Bone or cartilage fragments were removed from the joint, which was irrigated to remove any hematomas or other debris.
Surgically, complete rupture of the SLIL and LTIL were confirmed (Fig. A). K-wires were placed into the scaphoid and lunate and used as joysticks to correct the intercalated segment instability pattern. This usually requires correcting scaphoid flexion and lunate extension and closing the scapholunate interval. In most instances, the midcarpal and lunotriquetral joints are reduced, with restoration of the normal alignment of the scaphoid and lunate. Prior to SLIL and LTIL repair, temporary intercarpal fixation was performed with K-wires to maintain the carpal relationship. One was used to stabilize the scaphoid to the capitate, and the other was used to stabilize the triquetrum to the capitate. Carpal alignment and K-wire positions were confirmed using the C-arm image intensifier. The dorsal SLIL and LTIL were carefully repaired using suture anchors (JuggerKnot Soft Anchor Suture; Biomet, Warsaw, IN) (Fig. B). However, ligament repair was difficult, unreliable, and insecure. In view of the likelihood of insufficient repair, we decided to perform IB augmentation using synthetic tape (FiberTape; Arthrex, Naples, FL). Three 0.054″ guide wires were placed into the distal pole of the scaphoid, central portion of the lunate, and the central portion of the triquetrum. Drill holes for the IB were created using a 3.0 mm drill bit. IB augmentation was performed using suture anchors (3.5-mm DX SwiveLock SL; Arthrex), and the anchors were inserted at 90° as insertion at an obtuse angle could reduce the pullout strength (Fig. C). Once good alignment of the carpal bones was confirmed on the C-arm intensifier, the K-wires were buried under the skin. The capsulotomy incision was closed, and the retinaculum was repaired with interrupted absorbable 2-0 sutures. The skin was closed using nylon sutures. Postoperative radiographs demonstrated a well-reduced carpal alignment (Fig. D).
A short-arm thumb spica splint was used for the first 2 weeks, and a short-arm thumb spica cast was used for the following 3 weeks. The cast and K-wires were removed 5 weeks after surgery. Rehabilitation, to restore motion and grip strength, commenced thereafter. The patient was able to return to his job 3 months after surgery. At the last follow-up, 14 months after surgery, he was pain-free and had returned to all activities. He showed excellent wrist range of motion, with flexion of 75° and extension of 65° (Fig. ). The last follow-up radiographs showed good alignment of the carpal bones and no arthritic changes (Fig. ).


A 75-year-old man presented with his right wrist pain after falling off a ladder. Initial plain radiographs revealed a dorsal PLD and a fracture of the ulnar styloid process (Fig. ). Concomitant injuries included fractures of the right 4th, 5th, and 6th ribs. He had no specific medical conditions other than benign prostatic hyperplasia.
The surgery was performed under general anesthesia. The surgical approach and method were similar to Case 1. Surgically, complete rupture of the SLIL and LTIL were confirmed (Fig. A). After the reduction of intercalated segment instability, temporary intercarpal K-wires fixation was performed to maintain the carpal alignment. The dorsal SLIL and LTIL were carefully repaired using non-absorbable sutures (Ethibond Excel; Ethicon INC., Bridgewater, NJ) (Fig. B). However, ligament repair was unreliable and insecure. Therefore, we decided to perform IB augmentation using synthetic tape as in Case 1 (Fig. C). Postoperative radiographs demonstrated a well-reduced carpal alignment (Fig. D).
A short-arm thumb spica splint was used for the first 2 weeks, and a short-arm thumb spica cast was used for the following 4 weeks. The cast and K-wires were removed 6 weeks after surgery. One K-wire broke and a part of wire remained in the bone, but there was no problem (Fig. ). The patient was able to return to his job 3 months after surgery. At the last follow-up, 10 months after surgery, he showed good wrist range of motion, with flexion of 60° and extension of 65° and modified Mayo wrist score was 90. The follow-up radiographs showed good alignment of the carpal bones and no arthritic changes.


A 55-year-old man presented with his left wrist pain. The patient fell off the ladder 4 days ago and was admitted via a private clinic. Initial plain radiographs revealed a dorsal PLD and a fracture of the radial styloid process (Fig. ). He had no specific medical conditions.
The surgery was performed under axillary anesthesia. The surgical approach and method were similar to Case 1 and 2. The fracture of the radial styloid process was reduced and fixed using 2 headless compression screws (DePuy Synthes, West Chester, PA) and a mini plate. We could confirm the complete rupture of the SLIL and LTIL in the surgical field. After repair of dorsal SLIL and LTIL using non-absorbable sutures, IB augmentation with synthetic tape was performed as in Case 1 and 2. Postoperative radiographs demonstrated a well-reduced fracture fragments and carpal alignment (Fig. ).
The postoperative immobilization method was the same as in Case 2. The cast and K-wires were removed 6 weeks after surgery. Rehabilitation, to restore motion, and grip strength, commenced thereafter. The patient was able to return to his job 3 months after surgery. At the last follow-up, 10 months after surgery, he was pain-free and had returned to almost all activities. He showed good wrist range of motion, with flexion of 65° and extension of 60° and modified Mayo wrist score was 90.


A 73 year-old-woman was presented at our department with a 2-month history of severe neck pain and a chief complaint of numbness in her arms. A cervical X-ray was previously performed, which resulted in no anomalies. The primary care provider advised her to have physiotherapy. Due to the worsening of the pain and complaints of weakness in her legs, she was admitted to the emergency department. Neurologic examination revealed a spastic paraparesis and numbness in all four limbs. A cranial nerve objective examination produced normal results. She was able to walk, with some difficulty, for short distances. In addition, her medical history reported urge incontinence. A general physical examination did not reveal any other signs or symptoms; no other conditions were referred. She confirmed that any history of cancer or smoking were not present.
Magnetic resonance images (MRIs) of the cervical spine showed an intramedullary mass at the level of C2–C6 vertebrae, a heterogeneous hyperintense signal on the T2-weighted sequence, with a heterogeneous pattern of contrast enhancement that extended for about 6 cm associated with a syringomyelic cavity, from the bulbar–medullary junction to the D5 level inferiorly (). Considering the correlation between these features and the patient’s history, the neuroradiologist made the diagnosis of anaplastic astrocytoma. The MRI of the brain and the preoperative chest X-ray were normal.
Based on the progressive neurological worsening and MRI images, surgical treatment was indicated. Surgery was performed with the aid of intraoperative neuromonitoring. The patient underwent a C3–C6 laminectomy procedure using a posterior approach. Intraoperatively, the dura appeared as intact. Once exposed to the spinal cord, a midline myelotomy was performed. The tumour appeared to infiltrate the spinal cord without any cleavage plane. The lesion was partially removed, and an extemporaneous biopsy was taken for histologic examination. A mild worsening of the intraoperative motor evocated potentials (MEPs) occurred during the procedure.
The histological analysis showed nervous tissue infiltration by poorly differentiated malignant carcinoma cells. These consist of epitheliomorphic cells, which are characterised by poor cytoplasm and medium-sized nuclei. In addition, frequent cellular spindling was present, as well as nuclear moulding and necrosis. The histologic examination was confirmed by immunohistochemistry, which resulted in CKAE1AE3++/CK7+/GFAP-/pS100-/HMB45-/TTF1++/chromogranin A + (dots on 60% of cells).
These findings highly suggest the presence of a poorly differentiated lung small-cell neuroendocrine carcinoma. The strong signal for the TTF1 marker is indicative of lung origin. The negativity for the CK20 marker is helpful for the differential diagnosis of the other metastatic small-cell neuroendocrine carcinomas, such as Merkel cell carcinoma, which would result as being positive for CK20 ().
The postoperative course was regular, with no additional neurological deficits compared to preoperative. In the following days, we performed a total-body computed tomography (CT) scan that revealed a small, solid mass in the superior segment of the right upper lobe of the lung (). Unfortunately, she presented a rapid worsening of her neurological status and prematurely died within three weeks due to a sudden increase in perilesional oedema at the bulb of the spinal cord, which compressed the respiratory centres.


The first patient was a 43-year-old woman with a lengthy and complicated hospital course. She was admitted to our surgical department with symptoms of abdominal pain, nausea and vomiting for the previous two months. Her medical history was significant for a choledochal cyst operation 34 years ago; a Roux-en-Y hepaticojejunostomy after a post-cholecystectomy 27 years ago and finally a left salpingectomy plus a lower intestinal resection and end-to-end anastomosis that was performed 16 months prior to admission. Since that last operation, she had undergone several abdominal surgeries to control a biliary leakage. Eventually, she developed several enterocutaneous fistulae. The patient was on parenteral nutrition via a tunneled central venous catheter (CVC; Hickman catheter). In the preceding five months after admission to the hospital, episodes of bacteremia caused by multi-drug-resistant Acinetobacter baumannii, carbapenem-resistant Klebsiella pneumoniae, Morganella morganii, Enterococcus faecium, C. albicans and C. glabrata occurred. She received broad-spectrum antibiotic treatments (ertapenem, meropenem, colistin and teicoplanin) and antifungal drugs (fluconazole, caspofungin and anidulafungin) for multiple episodes of bloodstream infections.
Five months after admission to the surgical ward, the body temperature of the patient rose to 39.5 °C and leukocytosis (13,200 cells/µL) and high C-reactive protein levels (15.3 mg/dL) were detected. She had no symptoms potentially related to respiratory or urinary tract infections. A chest radiograph showed no pneumonia patch and the urinalysis was normal. Blood cultures from the CVC and peripheral vein were detected as positive for yeasts. The tunneled CVC was considered to be a possible infection source and therefore removed; the catheter, catheter blood and venous blood cultures were examined. Echinocandin-resistant C. glabrata and C. albicans were isolated from the blood culture in the fifth month after hospitalization (day 0). Caspofungin was administered (70 mg loading dose followed by 50 mg/day) when the yeast growth signal was reported on day −3 of the blood cultures until day 18. The antifungal treatment was not revised as multiple follow-up blood cultures remained sterile after the CVC removal with the clearance of the infecting C. glabrata and C. albicans strains at day 5.
The patient had a protracted and complicated hospitalization and died one year after admission due to a cerebral air embolization. This last incident of embolization was previously reported in a visual case presentation [].
The patient data were extracted from the hospital records retrospectively. The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of Hacettepe University (No.: GO-21/518).


A 36-year-old male patient presented with acute onset dizziness during work. He had poorly controlled type II diabetes mellitus for ten years and deep vein thrombosis in his right thigh two years earlier. The associated symptoms included left lower limb weakness and numbness. There was no recent traumatic injury. He also denied having a headache, fever, dyspnea, nausea, vomit, chest pain, or abdominal pain.
On physical examination, his temperature was 36.2 °C, blood pressure was 155/78 mmHg, heart rate was 99 beats/min, and glucose testing was 288 mg/dL. The Glasgow Coma Score (GCS) demonstrated that he was aware and alert (E4V5M6). His breath sound was clear, and his abdomen was soft without local tenderness. A neurologic examination showed a sensory and motor defect at bilateral lower limbs. Bilateral lower leg muscle power symmetrically decreased in proximal and distal limbs. There was no cranial nerve defect.
Initial laboratory evaluation revealed no significant infection pattern, including no increased white cell count, C-reactive protein, or neutrophil. Coagulation analysis showed no coagulopathy, and fibrin degradation product D-dimer (FDP D-dimer) test was within normal range. Biochemical analysis revealed no hepatitis, acute renal injury, or electrolyte imbalance (). The detail autoimmune antibody profile revealed positive results of APS, including lupus anticoagulant, anti-cardiolipin, and anti-β2 glycoprotein 1 antibodies ().
Brain computed tomography revealed no intracranial hemorrhage, dense MCA sign, hypodense lesion, or occupied lesion. Doppler of bilateral extremities was arranged to access peripheral arterial occlusive disease (PAOD) and revealed decreased flow velocity from bilateral common femoral artery to distal popliteal artery. There was no atherosclerosis formation at bilateral femoral and popliteal artery. An upstream lesion was suggested (). Lower extremity computed tomography angiography (CTA) showed occlusion of distal aorta and bilateral proximal common iliac arteries ().
This patient was diagnosed with acute aorto-iliac occlusive disease (AIOD), known as Leriche syndrome, which may be caused by antiphospholipid syndrome. Recurrent thromboembolic events at young age lead us to highly suspect genetic or autoimmune disease. Antiphospholipid syndrome was diagnosed based on positive result of anti-cardiolipin IgG/IgM and anti-β2 glycoprotein 1. Emergency bilateral transfemoral Fogarty catheter thrombectomy and bilateral common iliac artery stentings were done to rescue distal blood flow. After surgical intervention, follow-up CTA revealed proper vascular graft at abdominal aortic bifurcation and bilateral common iliac arterial regions with patency of the graft. Treatment with aspirin 100 mg per day, clopidogrel 75 mg per day, and warfarin 2.5 mg per day was prescribed in order to help prevent further thrombotic events. The patient was discharged and received outpatient department follow-up. After one year of follow-up, he presented with dyspnea and acute heart failure at our emergency department. Echocardiogram showed poor heart function (Left ventricular ejection fraction, LVEF: 23.2%) and abnormal wall motion. Cardiac catheterization exam showed akinesia of anterior wall and apex at left ventricle without coronary artery stenosis. The patient died due to multiple organ failure, even under percutaneous cardiopulmonary support (PCPS).


A 13-year-old male was diagnosed with full-blown CINCA due to a de novo variant of NLRP3 with high expressivity. Intense postFLAIR-enhancement was observed in the cochlea (arrows), vestibule, and semicircular canal, and strong enhancement involving the cochlear nerve (empty arrows) was also noted (Fig. a,b).


A 42-year-old female was diagnosed with DFNA34, a non-syndromic form of hearing loss due to an NLRP3 variant residing in the LPR domain possibly with lower pathogenic potential than CINCA syndrome. Although not detectable on postT1WI, postFLAIR revealed stronger enhancement in the cochlear nerve than in the cochlea (Fig. c).


A 38-year-old female was strongly suspected of having AID clinically. Although we defined some evidence that suggested mosaicism of a NLRP3 variant from this case, the presence of mosaicism was not confirmed yet, making this case 3 to be the one without detectable NLRP3 variant at this point. Minimal postFLAIR-enhancement was observed in the cochlea, but no demonstrable enhancement of the cochlear nerve was noted (Fig. d).


The patient was a 22-year-old male who presented to a rural hospital with a presumed high-voltage electrical injury of unclear etiology with an obvious evisceration. By report he was found walking in a dazed state unable to recount the mechanism for his injuries. He was transported via EMS to the local hospital where he was intubated and volume resuscitation was initiated. Based on the severity of his abdominal injuries, he was transported to the nearest regional level 1 trauma center for further management. Aeromedical transport was not available due to weather factors resulting in an approximately 105 min ground transport.
On arrival to our facility he was hemodynamically stable, and a primary survey did not reveal any immediately life-threatening physiologic abnormalities. He did have evidence of major abdominal and perineal injuries with evisceration (Fig. ) as well as apparent electrical injuries to his left upper (Fig. ) and bilateral lower extremities (Figs. , ). Given his unclear mechanism, CT imaging was performed to exclude other occult injuries. Imaging excluded major head, thoracic, spinal column or vascular injuries. He was then taken emergently to the operating room for abdominal exploration and other indicated procedures.
In the operating room, a midline incision was extended from the superior aspect of the evisceration wound to the xiphoid process. Abdominal exploration revealed full-thickness burns to the abdominal wall musculature with destruction of all muscular layers of the lower abdominal wall including the rectus abdominus, the posterior rectus sheath as well as portions of the internal and external obliques (Fig. ). While running the small bowel, five discrete areas of full-thickness coagulative necrosis were encountered. Examination of the pelvis revealed an intraperitoneal bladder injury to the dome of the bladder (Fig. ) with obvious coagulative necrosis to the area immediately surrounding the intraperitoneal injury (Fig. ). Multiple small bowel resections were performed, and the bowel was left in discontinuity. No attempt was made to reestablish bowel continuity due to the potential for extension of the areas of bowel necrosis and a desire to maximize length of small bowel that remained. Intraoperative consultation with urology was obtained and obvious areas of bladder necrosis were debrided. The bladder dome was closed in multiple layers with chromic sutures. A Foley catheter was left in place for bladder drainage after the repair was completed. No evidence of other hollow viscus injury, significant solid organ injury or retroperitoneal hematoma was observed. A temporary abdominal closure was then performed using a negative pressure abdominal closure system.
Following the temporary abdominal closure, our attention was then turned to the burned extremities. The patient appeared to have full-thickness circumferential injuries to the left upper extremity, left lower extremity, right lower extremity, and right foot with significantly decreased peripheral pulse exams. Intraoperative orthopedic and podiatry consults were obtained. Given the concern for compartment syndrome and potential constriction from the burned tissue, left upper extremity and bilateral lower extremity escharotomies were performed as well as right foot fasciotomies. Dry sterile dressings were applied to all wounds at the completion of the procedure. In its entirety, the initial operative procedure took 125 min. Following the procedure the patient was left intubated and arrangements were then made to transfer the patient to a regional burn center for further management. After a brief delay in setting up aeromedical transport, the patient was transferred via helicopter for further management with a 45-min transport time.
During his subsequent 2-month burn center admission, the patient required additional small bowel resections, but eventually had restoration of bowel continuity. The urinary tract injuries required vesicostomy, ureteral stenting, and revision of the original bladder repair. His clinical course was also complicated by vesiculocutaneous fistula and progression of his lower extremity injuries, eventually requiring right below knee and left transmetatarsal amputations. After successful abdominal wall reconstruction, the patient ultimately survived his injuries and was discharged from the burn center to a rehabilitation facility. More detailed information regarding his burn center hospital course is not available due to privacy issues raised by the burn center. He has subsequently been lost to follow-up at our facility.
Follow-up regarding the injury mechanism revealed that the patient was the driver of a motor vehicle which struck a power pole resulting in a downed high-voltage power line over his vehicle. By report he was initially uninjured, however when he attempted to exit his vehicle, he contacted the electrified auto frame resulting in his electrical injuries. He initially walked from the scene to a local house where EMS was contacted.


Patient 1 was a boy aged 4 years and 3 months presenting with normal birth history, growth, and development (height, 115 cm; weight, 18 kg; body surface area, 0.73 m2; and head circumference, 50 cm). He showed normal facial features, physical development, and nutrition condition. Nine months after birth, the patient showed somnolence and right upper-limb shaking. Brain MRI showed probable metabolic encephalopathy. Mitochondrial DNA testing was negative. His condition improved after orally taking vitamins B1 and B2, and he had no subsequent developmental delay. At 4 years of age, he was referred to PICU at the Beijing Children’s Hospital for viral infection-induced lethargy, decreased muscle strength and limb tension, diaphragmatic weakness, and expiratory dyspnea; he had to undergo tracheal cannulation and mechanical ventilation for 8 days. Brain MRI showed abnormal signals in the bilateral basal ganglia, thalamus margin, hippocampus, midline frontal lobe, and temporal cortex. Diffusion-weighted imaging was limited (Fig. a), and the lactic acid levels in the cerebrospinal fluid (CSF) was normal. Muscle biopsy showed no abnormalities in mitochondrial respiratory chain enzyme activity. Combined with previous medical history, a diagnosis of aggravation of metabolic encephalopathy induced by infection was considered, but the possibility of necrotizing encephalopathy could not be ruled out. During treatment, immunotherapy for necrotizing encephalopathy and vitamin cocktail therapy for metabolic encephalopathy were given along with vitamin B1 (3.33 mg/kg/day) and vitamin B2 (1.67 mg/kg/day). Trio-exome sequencing was performed during his hospitalization. The patient's condition did not deteriorate further; he was transferred to the local hospital PICU for treatment for another 10 days and was taken off the ventilator. Later, the consciousness of the patient cleared and muscle strength recovered; however, low muscle tone, incomplete deep tendon reflex, and extrapyramidal symptoms remained. One-year follow-up showed that the patient survived, exhibiting normal intelligence and behavioral development, but muscle tone and tendon reflex were still decreased.


Patient 2 was a boy aged 2 years and 7 months. He presented with normal birth history and physical and mental development. He had influenza A virus infection-induced febrile illness, became convulsed, and fell into a deep coma. He was admitted to PICU. During the disease, the coma progressively worsened and limb paroxysmal tremors, shaking, and muscle tone increased with passive extension. In the initial stage, the possibility of ANE was suspected. Immunoglobin and methylprednisolone were administered. Vitamin treatment was not given during hospitalization. Brain MRI revealed multiple signal abnormalities in the bilateral basal ganglia, thalamus margin, and brainstem (Fig. b). However, the lactic acid levels in the CSF were normal. In the late stage of treatment, he and his parents’ blood were collected for genetic testing in the Center for Medical Genetics of Beijing Children’s Hospital. Four weeks after intubation, he was taken off the invasive ventilator and spontaneous breathing was maintained; however, cough and swallowing reflexes were weak.


A 20-year-old woman receiving interferon beta-1a for MS reported a visual field defect in the lower temporal quadrant of the left eye. Examination revealed a normal visual acuity of 20/20 in both eyes. Intraocular pressure was 15 mmHg in the right eye and 17 mmHg in the left eye. Anterior segment examinations were normal in both eyes. Pupils were equal, round and reactive to light with no relative afferent pupillary defect. Fundus examination of the left eye showed ischemic retinal whitening in the supra-nasal area, fluorescein angiography (FA) revealed BRAOs and subtle, segmental arteriolar wall hyperfluorescence (AWH) at the site of BRAO in the late phase (Fig. A). Fundus examination and FA of the right eye were normal. Retrobulbar optic neuritis due to MS was ruled out because the infra-temporal visual field defect reported by the patient corresponded to the area of the ischemic retina due to supra-nasal BRAO. Moreover, the patient did not have reduced visual acuity nor colour vision disturbances, and did not report any pain concomitant to eye movements which is characteristic for retrobulbar optic neuritis in the course of MS. Interferon beta-1a treatment was discontinued after 7 weeks because of its possible prothrombotic effect. A repeat FA performed two weeks later showed reperfusion of the occluded arterioles and resolution of the AWH (Fig. B).
The patient had increased thromboembolic risk due to hormonal contraception and cigarette smoking. A full laboratory work-up was done, including tests for connective tissue disease, vasculitis, borrelia, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV), cytomegalovirus (CMV), and factor V Leiden mutations. The results of laboratory studies (borderline lupus anticoagulant, leukopenia, decreased platelet count, slightly elevated D-dimer concentration, and prolonged activated partial thromboplastin time) were suggestive of antiphospholipid syndrome or lupus; however, further biochemical tests excluded these causes. Performed again with an interval of 12 weeks, anti-cardiolipin antibodies in the IgG or IgM class, lupus anticoagulant and antibodies against β2-glycoprotein were negative. Moreover, IgM and IgG antibodies against CMV were detected. Transthoracic echocardiography and carotid artery ultrasonography were unremarkable.
Treatment with glatiramer acetate was started 3 weeks after discontinuation of interferon beta-1a. After 2 weeks of glatiramer acetate therapy, we observed neurological worsening with fever, headache, impaired consciousness, left-sided weakness, and lower limb ataxia. Lumbar puncture revealed only a mild elevation of cerebrospinal fluid protein, no oligoclonal bands, and a negative encephalitis panel; meningitis was therefore ruled out. The brain MRI showed diffuse and limited hyperintense changes in fluid-attenuated inversion recovery (FLAIR) and T2 sequences located periventricularly in the subcortical white matter, mainly in the frontal and parietal lobes, in the pons, in the basal ganglia and in the corpus callosum. MRI revealed also post contrast leptomeningeal enhancement (Fig. ). Repeated FA showed new BRAOs and AWH in both eyes (Fig. C, D). Moreover, the patient reported hearing loss; however, pure tone audiometry was inconclusive because of the patient’s worsening condition. We also noted livedo reticularis and a maculopapular rash. SS was diagnosed based on these new findings. The diagnosis of MS was excluded, and glatiramer acetate therapy was discontinued. Treatment was started with Methylprednisolone (0.5–1.0 g) which was administered for 5 days; the total used dose was 3.0 g. Despite slight initial improvement, neurological deterioration occurred after 7 days when the steroids dose was reduced to 50 mg prednisone per day (a total used dose of 350 mg of prednisone). Neither plasma exchange (four courses) nor azathioprine improved the patient’s neurological condition. The patient’s neurological state improved only after use of a combination of corticosteroids, intravenous immunoglobulins, and azathioprine; visual acuity was 20/20 in both eyes, however in the fundus examination, BRAO’s in the peripheral retinal artery branches were still present in the right and left eye.


A 6-year-old male with eczema since the age of two was hospitalized for an acute eczema flare with low-grade fever and rigors. On arrival, the patient presented with a low-grade fever of 99.4°F with a physical exam notable for diffuse erythroderma with xerosis and open impetiginous lesions throughout the arms, trunk, and face. There were no pustules, vesicles, draining wounds, or extensive denudation. Before this, his eczema had been reasonably controlled with triamcinolone cream and frequent hydration with emollients. There was no history of recurrent viral or fungal infections involving the respiratory or sinus tracts. There was no personal or family history of fractures, skeletal abnormalities, cognitive abnormalities, or vasculitis. Further history elicited no known food allergies in the patient, but an egg allergy in the patient's father.
Initial lab testing showed leukocytosis (14,700 cells/μL) with 27.6% eosinophils and blood cultures positive for methicillin-sensitive Staphylococcus aureus. He was treated with intravenous clindamycin and eventually transitioned to oral clindamycin for a fourteen-day course. This initial infection resolved; however, three months later, the patient returned with recurrence of eczematous flares and suspected superinfection. He was treated with a fourteen-day course of oral clindamycin and cephalexin and a five-day course of prednisone. The patient's IgE drawn at this time was 7,460 IU/ml. Food allergen panel was significant for very high specific IgE to peanuts, egg whites, soybean, hazelnut, walnuts, almonds, and cashews. Chest imaging showed no pathology. A hyper-IgE NIH score [] was 27 (IgE > 2000 = 10 points, eosinophil count >800 = 6 points, mild characteristic facial features = 2 points, severe eczema = 4 points, history of severe nonpulmonary infection = 4 points, and increased nasal width = 1 point).
Despite topical steroids, topical clobetasol, topical tacrolimus, and aggressive skincare, the patient continued to have recurrent eczematous flares associated with cutaneous Staphylococcus aureus infection. Prophylactic cephalexin abated some symptoms, and the patient had no additional episodes of bacteremia. Repeat serum IgE level at this time was improved, but still markedly elevated at 3,464 IU/ml. A HIES targeted genetic panel was negative, indicating that the patient had no detectable pathogenic variants associated with STAT3, DOCK8, TYK2, and SPINK5. Given this negative finding, whole exome sequencing (WES) with chromosomal microarray was performed. Nonsynonymous variants of unknown clinical significance were found in the genes BCL11B, ZAP70, LYST, and PTPRC, all inherited from the patient's mother, all of which are related to the immune system or immunodeficiency. WES revealed heterozygosity of a pathogenic variant of the filaggrin gene (p.S3247X). The father's WES showed a similar heterozygous mutation in filaggrin despite only reporting alopecia totalis and egg and chicken allergy. Chromosomal microarray analysis showed a copy number gain of chromosome region 15q13.3, which did not contain genes associated with immune function. In addition to prophylactic antibiotics, the patient was started on dupilumab (200 mg every 2 weeks), resulting in fewer eczematous flares with no reported adverse events. At this time, the patient is off of dupilumab, but utilizes ultraviolet therapy every other day, topical steroids, and tacrolimus with nightly wet wraps, and still requires intermittent oral antibiotics for eczema control.


A man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. The patient had no significant medical or family history. The performance status was 0. The results of blood tests on admission were unremarkable, including tumor markers, such as carcinoembryonic antigen, carbohydrate antigen 19–9, and cytokeratin 19 fragment. Upper gastrointestinal endoscopy revealed a type 2 tumor (biopsy-confirmed NEC) spanning the endothelial cell junction to the abdominal esophagus (Fig. ). Histopathological examination of the biopsy confirmed a diagnosis of esophageal NEC. Preoperative contrast-enhanced computed tomography (CT) and positron emission tomography (PET)-CT scans showed no distant metastasis, and esophagectomy was planned. Thoracoscopic esophagectomy with three-field lymph node dissection, gastric tube reconstruction, and feeding jejunostomy tube placement were performed. The operative time was 493 min, and the blood loss was 20 mL. Histopathological examination confirmed a diagnosis of esophageal NEC with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. Immunohistochemistry revealed a Ki-67 labeling index of 3–30%, with 23 mitoses per high-power field. Tumor cells were positively stained for synaptophysin, CD56, neuron-specific enolase, P40, p53, and cytokeratin 7, and negatively stained for chromogranin A, cytokeratin 20, and CK20 (Fig. a–d). The positive rate of programmed death-ligand 1 (PD-L1) expression was ≤ 1%. The patient was wild type for the UGT1A1*6/*28 polymorphisms. The postoperative course was good, with no complications.
The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. No recurrence was subsequently observed.
A PET-CT scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex (Fig. a, b). The patient was diagnosed with metastatic esophageal NEC postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was simultaneously started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). The protocol of the combination therapy for NEC was approved by the Institutional Review Board of International University of Health and Welfare Hospital (Approval No. 21-B-28), and the patient provided written informed consent. The only adverse event during treatment was Grade 1 myelosuppression. After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a PET-CT scan was performed to evaluate the treatment response according to the Response Evaluation Criteria in Solid Tumors (Version 1.1) []. The scan showed disappearance of all lesions, and a complete response was considered to have been achieved (Fig. a, b). Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.


A 50-year-old Chinese male presented to the hospital in December 2020. A month ago, while he was undergoing a routine physical examination before the surgical excision of his right eye pterygium, a large anterior mediastinal mass was found. A contrast-enhanced computed tomographic scan revealed a smoothly marginated anterior mediastinal mass measuring 3.1 × 1.4 cm. It was a multi-lobulated, soft-tissue mass with slight homogeneous enhancement after intravenous contrast (Figure ). The patient had no complaint of physical discomfort and denied symptoms of ptosis, diplopia, facial or limb weakness, slurred speech, or dysphagia.
The patient's past history was significant for HIV positivity, radius fracture, and pterygium. HIV infection was diagnosed in April 2018 (probably due to unsafe sex in January 2018) with initial CD4+ T-cell counts of 480 cells/μl. The patient had been treated with antiretroviral therapy (ART) ever since then, consisting of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate. CD4+ counts elevated to 514 cells/μl in April 2020 and the CD4+/CD8+ ratio was 1.17 at that time. During the course of HIV infection, he reported no history of opportunistic infection or neoplasia. Fracture of his right radius occurred in July 2017 due to high force impact, after which internal fixation was done with implanted plates. Surgery was conducted to excise his right eye pterygium in November 2020 after complaints of visual compromise for 1 year.
Laboratory examination reported negative acetylcholine receptor (AchR) antibodies and normal electromyography. No hepatitis B antigen or antibody was detected. Right before surgery, the patient's leukocyte count and differential lay within the normal range, with a slight increase in monocyte percentage. Complete excision of the lesion with total thymectomy was undertaken by video-assisted thoracoscopic surgery (VATS). A well-encapsulated, firm mass of size around 4 × 3 × 2 cm was found in the left thymus. The tumor was stage I in the Masaoka–Koga staging system. Histopathology revealed type B3 (WHO, 2015) thymoma with foci of necrosis. The polygonal cells showed diffuse staining with AE1/AE3 cytokeratin and CD19, and negative for desmin and CD34. Immunohistochemical stains were focally positive for CD3 and CD5, and sporadically positive for terminal deoxynucleotide transferase (TdT) and CD20 (Figure ).
Right after surgery, the patient's leukocyte counts elevated to 15.74 × 109/L, with the predominance of neutrophils. Lymphocyte dropped to 0.79 × 109/L. Before he was discharged, leukocyte count and differential came back to normal. Chest radiograph showed good lung recruitment with no effusion or gas present. Two weeks after surgery, his lymphocyte subpopulations were as follows: CD4+ T cell = 879 cells/μl, CD4/CD8 = 1.26, CD4 + CD45RA-/CD4+ = 42.9% (N = 57 ± 11.4%), CD4 + CD45RA+/CD4+ = 57.1% (N = 43 ± 11.4%), CD4 + CD28+/CD4+ = 100% (N = 92.5 ± 7.5%), CD8 + CD28+/CD8+ = 80.5% (N = 48.8 ± 11.6%), CD8 + DR+/CD8+ = 17.5% (N = 15.05 ± 8.75%), CD8 + CD38+/CD8+ = 27.1% (N = 44.9 ± 12.5%). As type B3 thymomas have more probability of recurrence, the patient was suggested for radiation therapy afterwards.


A 60 year old male, chronic smoker with underlying diabetes mellitus, hypertension and chronic kidney disease was admitted to Hospital Melaka, Malaysia. He was presented with sudden onset of shortness of breath for a one-day duration associated with failure symptoms of orthopnoea, paroxysmal nocturnal dyspnoea and bilateral lower limb swelling for two months prior to admission. He was compliant to the restriction of fluid of 500 cc/day and denied any past medical history of ischemic heart disease or bronchial asthma. There was no chest pain, palpitations, or profuse sweating. Furthermore, he denied having fever, cough or other symptoms suggestive of infection from home. The patient denied a history of recent travel, exposure to wild animals or recreational water sources or contact with ill patients.
Initial physical examination revealed a sallow appearance; he was tachypnoeic with a respiratory rate of 32 breaths/min, hypertension with blood pressure of 183/120 mm Hg, and hyperglycaemic (GM: 12.3 mmol/L). Auscultation of the lung revealed bi-basal crepitations. Dual rhythm and no murmur were noted upon cardiac examination. Bilateral pedal oedema was palpated up to knee levels. Arterial blood gas taken when the patient was on high flow mask 15 L/min showed type I respiratory failure (pH: 7.31 mm Hg, PCO2 37 mm Hg, PO2 37 mm Hg, HCO3: 18.6 mmol/L, SO2 of 95%) and hence, he was started on non-invasive ventilation (CPAP PEEP:7.5, FiO2:1.0). The patient was treated for Acute Pulmonary Oedema with Non-ST-Elevation Myocardial Infarction (NSTEMI), with underlying chronic kidney disease approaching end stage renal failure (ESRF) with renal anaemia. This was evidenced by the ST depression over lateral leads (I, II, AVL, V5 and V6) with poor R wave progression, presence of cardiomegaly and lung congestion on a chest radiograph and elevation of troponin I from 1.47 to 2.35. On day two of admission, the patient’s condition deteriorated as shortness of breath worsened after dialysis and crepitations were heard over bilateral lungs up to the upper zone on auscultation. Hence, he was intubated in view of persistent type I respiratory failure and persistent desaturation despite post haemodialysis.
Laboratory tests revealed a white blood cell count of 22,300 cells/mm3. There was a predominance of neutrophilia with a differential of 93.4% neutrophils, 1.4% lymphocytes, 3.5% monocytes and 1.5% eosinophils. The C-reactive protein value of 103.5 mg/L indicated the presence of ongoing active bacterial infection and inflammation. Cardiac echocardiogram suggested heart failure with the ejection fraction of 50% with mildly impaired left ventricular systolic function. Neither clots nor pericardial effusion were noted. Repeated chest radiograph post-intubation revealed left upper and right lower zone consolidation suggesting pneumonia. Hence, he was started on intravenous (IV) amoxicillin/clavulanate empirically and the blood culture was sent to the laboratory for further examinations. Subsequently, the empirical antibiotic was escalated to IV piperacillin/tazobactam 2.25 g four times/day to cover for hospital-acquired pneumonia due to a worsening of consolidation over bilateral lung fields on the chest radiograph taken on the third day of admission. However, his condition did not improve with the antibiotic prescribed.
The aerobic blood culture bottle was positive after 48 h of incubation; however, no organism was observed via Gram staining. Greyish, mucoid colonies were observed on blood agar after 24 h of incubation at 37 °C under aerobic condition. Repeated Gram staining of organisms from the aerobic blood culture bottle after re-incubation for 48 h yielded Gram-negative coccobacilli which appeared singly and in pairs, similar to those cultured from blood agar. F. philomiragia was identified using the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (Score value: 2.16) and confirmed by 16S rDNA sequencing [] (Accession no. LR999753). MALDI-TOF mass spectrometry was performed in-house using the MALDI Microflex LT system (Bruker Daltonik GmbH, Bremen, Germany). The 16S rDNA gene was amplified with three pairs of overlapping primers, sequenced in both directions, aligned and compared with other sequences in the Basic Local Alignment Search Tool (BLAST) database []. The patient was started on oral tablet doxycycline 1 mg twice daily for Fransicella bacteraemia on day six of admission. His condition improved after commencement of doxycycline and IV furosemide. Additionally, the fluid overload picture and consolidations on a chest radiograph improved as well. He was discharged well on day 26 of admission, after completing one week of piperacillin/tazobactam (to cover empirically for hospital acquired infection) and two weeks of doxycycline.


A 72-year-old man presented with a 4-week history of headache and neck pain, with a weight loss of over 20 kg in 6 months. A computed tomography (CT) of the craniovertebral junction (CVJ) and the cervical spine was done, which revealed an osteolytic lesion of the odontoid with signs of instability (differential diagnosis (DD) metastasis, DD rheumatoid arthritis, DD spondylodiscitis) (Fig. a and b). MRI was not possible due to the presence of a pacemaker.
As history, the patient had a mitral valve insufficiency and coronary heart disease, with stent implantation 11 months ago (the patient takes clopidogrel), had an arterial fibrillation with a pacemaker, was hypertensive, and had a renal insufficiency.
Firstly, he was given a Philadelphia collar and analgesics.
Because the patient had severe secondary diseases, we had to find a strategy to solve these problems in one surgery.
An approach through midline incision from posterolateral which can be done in same sitting during posterior craniocervical stabilization was necessary.


A 4-year-old boy presented with his parents at the Outpatient Clinics of our Department, following resection of a congenital nodule from the arch of his right foot two months earlier, elsewhere. According to the history, this skin lesion was present since birth as a macroscopically solid, asymptomatic and painless nodule that slowly increased in size, measuring –before excision- about 0.8 mm in diameter ().
The histopathological evaluation of the specimen revealed a dermal and subcutaneous spindle cell neoplasm with moderate cellularity. The majority of the cells were elongated, with eosinophilic cytoplasm and ovoid nuclei with minimal pleomorphism, arranged in interconnected fascicles with a plexiform pattern. Intermixed with these cells, there was a small subset of medium-sized, ovoid or round cells. Their cytoplasm was eosinophilic and the nuclei were ovoid, with mild pleomorphism and distinct nucleoli. These cells were arranged in clusters along with a few osteoclast-like giant cells and hemosiderin deposition (). There was no mitotic activity. The lesion extended to the surgical margins. On immunohistochemical stains, the neoplastic cells were immunoreactive for vimentin, CD34 and CD10. The medium-sized, ovoid and round cells and the osteoclast-like giant cells were positive for CD68. A diagnosis of PFHT was made on the basis of the histologic features.
Due to positive margins, a wider excision was performed under general anesthesia, with 2 cm excisional margins around the existing scar and down to the underlying muscle fascia. The defect was covered with a full-thickness skin graft harvested from the left groin area. The immediate postoperative period and wound healing of both operated areas on the foot and the donor site was uneventful (). The pathology report following re-excision was negative for residual tumor.
Approximately four months later, the patient presented with palpable lymph nodes in both groin areas. An ultrasound scan of both inguinal sites was performed reporting enlarged lymph nodes, which showed reactive features and were negative for tumor. On follow-up, seven months postoperatively, the clinically palpable groin lymph nodes subsided and a computed tomography scan of the thorax, abdomen, and pelvis showed no pathology. On 52 months’ follow-up, there was no evidence of local recurrence, regional lymphadenopathy or distant metastases ().


A 2-year-old boy initially presented with no speech, poor social interaction skills and repetitive behaviors consistent with ASD based on the DSM-IV criteria, which also fulfilled the DSM-V criteria. The patient was the second child born to healthy and unrelated Thai parents. He had one older sister with normal development. His birth weight was 3,600 g with no perinatal complications. He first stood with support at 10 months, but did not walk without support until the age of 27 months. He was unable to hold a spoon and feed himself until 45 months of age. He never developed verbal language skills. His growth curves were within normal ranges, including head circumference, except he had been overweight since 2 years of age (). His BMI at 10 years was 29.7 kg/m2 (>97th centile, Z score = 3.79). He had no hypopigmentation, and had never shown signs of seizure, ataxia or hypotonia. He usually walked on tip toes. He had poor eye contact and had a repetitive behavior in constantly spinning the wheels of a toy car. He engaged in hand-flapping whenever he was happy. He had no self-injury nor aggressive behaviors. He liked to bite things (i.e., clothes, drinking straws). At the age of 5 years, he was assessed using the Autism Diagnosis Observation Schedule (ADOS)-Module 1 by a developmental pediatrician. His scores for communication were 4 (cutoff = 4), 8 for reciprocal social interaction (cutoff = 7), and 1 for repetitive behaviors (). The scores were consistent with a diagnosis of autistic disorder. At 10 years of age, he had a non-verbal IQ rating of 42 (Stanford Binet Intelligence Scales-Fifth edition) and the Vineland Adaptive Behavior Scales-II showed moderate deficits in all three domains, communications, daily living skills and socialization. We also observed that his autistic features evolved as his social interaction skills improved over time. For example, at 11 years of age, he liked to play with his peers and parents, although he still could not speak understandable words.
Initially, he was tested for common genetic causes of ASD, which revealed normal karyotyping and normal CGG repeats on the FMR1 gene. Electroencephalogram (EEG) was also normal. Following the recommendations from the International Standard Cytogenomic Array (ISCA) and the American College of Medical Genetics (ACMG) for the use of CMA, he was screened with the CMA at 10 years of age to look for pathogenic CNVs. Written informed consent was obtained from the patient’s parents for publication of this case report.


A client-owned 12-year-old female blend dog was presented with a several-month history of walk with flexed knees and hips, reduced activity with pronounced abstaining from climbing and descending the stairs, and with occasional urine incontinence. The dog weighed 19 kg (4–5 kg more than average) and had not received any medication beforehand.
During general examination, the dog was found to be conscious, oriented in space, with a normal posture of the head. The dog repeatedly supported body with forelegs, while hind legs were kept down, on the side. The perineal region was wet, most likely from urine.
On orthopedic and neurological examinations (), hind limb paresis with a mild drift of lumbosacral part, which was in a slight kyphosis, was noted. When the animal was placed to stand up on the hind legs, disturbed proprioception was observed, and quickly the dog rested again. Deep and superficial sensibility, retrieval reflex, and patellar reflex were preserved, while the crossed extensor reflex was slightly reduced. The stiffness was detected during each knee flexion with audible crepitation, which indicated osteoarthritis (OA) of both knees. Regarding hip flexion and extension, nothing abnormal was detected. During palpation of the lumbosacral region, the dog expressed discomfort and pain. The lordosis test (performed in a lying position) was positive; the animal felt pain. The enlarged urinary bladder was detected by palpation, which was released by pressure. Perineal reflex was preserved. The tone of the tail was decreased. Since the dog had no pain except the one that was elicited during physical examination (PE), and since she had had several episodes of gastritis in the past, no analgesic therapy was prescribed. A short video from that period was provided by the owner ().
Following described assessments, an X-ray and magnetic resonance imaging (MRI) were performed. The animal was anesthetized only during MRI due to her age and our technical limitation to complete these examinations consecutively. That is why the animal was poorly positioned on the radiograph image (), but nevertheless, an asymmetric lumbosacral transitional vertebra with ossification on the left side was clearly seen (indicated by an oblique arrow), as well as a reduced intervertebral space L7-S1 (indicated by a horizontal arrow). On the sagittal MRI of the lumbosacral region (), the IVD L7-S1 was seen as protruded and hypointense compared with the bright signal from normally hydrated discs. The disc protrusion was also seen on the transversal MRI section (). Based on these results, as well as on orthopedic and neurological findings, this case was diagnosed as DLSS, accompanied with OA of both knees.
There is currently no consensus on treatment selection for dogs with DLSS, and available options most often involve aggressive surgical techniques (). We decided to try a new and least invasive procedure, using cultured autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs). These cells hold enormous potential as therapeutic agents in vivo, especially for regenerating damaged tissues in diseases of the locomotor system (, ).
The adipose tissue collection and AT-MSC therapy were approved and certified by the dog owner with signed informed consent. The AT collection was performed using anesthetics, and AT-MSC therapy was performed using sedatives, which excluded the pain, suffering, fear, and stress of the animal, following the standards of good veterinary practice, the guidelines of good laboratory practice, the European Parliament Directive, the Council of 22 September 2009 (2010/63/EU), and the European Convention for the protection of vertebrates intended for experimental and other scientific purposes (ETS 170).
Around 10 g of subcutaneous adipose tissue from the paralumbar region (on the borderline of the middle and caudal lateral abdominal region) was collected through the 5-cm-long incision while patient was under general anesthesia using medetomidine hydrochloride (Domitor, Orion Pharma, Espoo, Finland; 10 μg/kg IM) and Propofol (Diprivan, Astra Zeneca, Macclesfield, UK; 1.5 mg/kg IV).
The isolation, culture of AT-MSCs for the treatment, and differentiation of cells for control of the stemness were performed as previously described (). A total of 91.8 × 106 cells resuspended in 3 ml of PBS were transplanted as follows: paravertebrally at the level L7-S1, a 30.6 × 106 cells were injected into each, left and right side with a 0.8 × 40-mm needle; while intraarticularly into each knee, a 15.3 × 106 cells were injected with a 0.6 × 30-mm needle. During this procedure, the animal was sedated with medetomidine hydrochloride (Domitor, Orion Pharma, Espoo, Finland; 20 μg/kg IM). Following the application of AT-MSCs, the dog was not subjected to any physiotherapy treatment. Until the next PE, rest and restraint from physical activity under the owner's supervision were the only recommendations.
Clinical evaluation consisted of PE of the patient (). Also, the assessment for lameness at walk and trot, using a numeric rating scale, has been performed as previously described (). Briefly, the clinical outcome measures were expressed by a numeric rating scale based on a veterinary assessment questionnaire. The scale ranged from 1 to 6, where 1 was marked as the best, normal condition (without the lameness) and 6 as the most severe (the animal cannot walk or trot). The evaluation was performed initially, upon admission of the patient (baseline) and at specified intervals after the treatment with AT-MSCs, supplemented with assessments of the owner (). There were no detected adverse reactions to the described treatment.
As it is presented in , at first check-up performed 30 days after the treatment, the dog walked with stiff hind legs, occasionally weight bearing. Palpation of the lumbosacral region was less painful. The lordosis test (performed in a standing position) was positive but less than before the treatment. Stiffness during the flexion of both knees still existed, with audible crackling. The urinary bladder was of normal size and did not leak under the pressure. The tail had a normal tone. According to the owner, the dog was walking but with difficulties, could not run, turning was performed with an effort to maintain the balance of the backside, had problems when trying to get up and lie down, and it was difficult for the animal to take a position to urinate.
After 60 days of AT-MSC injection, the animal moved normally without the stiffness of the hind limbs. The knee stiffness was lesser than during previous examination. According to the owner, getting up and lying down was easier for the dog, and the position to urinate was almost normal.
Ninety days post-AT-MSC treatment, the animal functioned normally, with a desire to run and play, albeit cautiously. The mild stiffness of both knees remained at full flexion, with crepitation.
Once a year, the owner informed the veterinarian about the condition of the dog, which was unchanged compared with the examination that was performed on the 90th day after the AT-MSC treatment.
After 3 years posttreatment, the animal was re-examined. It was found that the dog still felt well, without any problems during the movement or with the balance, and without pain throughout the lordosis test. Slight restraint was observed during running. At full flexion, the mild stiffness of both knees was still present but painless. Videos from that period were provided by the veterinarian (, ).
The final follow-up was performed 4.5 years after the treatment. The dog was still feeling well, with signs of slightly slower walking and turning and a bit less willingness to climb the stairs. Video from that period was provided by the veterinarian (). Eight days after this examination, the dog died of old age.


Here, we describe a 9-month-old boy, born from nonconsanguineous parents, with past medical history of cutaneous Langerhans cell histiocytosis (LCH) diagnosed at 2 months of age. He was admitted to our institution with an exacerbation of cutaneous lesions, fever, vomit, hypoalbuminemia, diarrhea, and generalized edema; hence, an extended study of the disease is performed confirming the diagnosis of systemic LCH. Treatment was started with prednisone and vinblastine following the LCH-III international protocol, and after 1 month of disease progression, the patient started with Ara-C and cladribine (LCH-S 2005). After the third cycle of Ara-C and cladribine, the patient presented with a complete hematological remission of LCH. However, high ferritin levels (2,800 ng/mL) and triglycerides (280 mg/dl), bone marrow hemophagocytosis, low NK cytotoxicity, and elevated sCD25 levels were detected. As the patient fulfilled five of eight HLH diagnostic criteria (), HLH treatment was included resulting in a control disease with a decrease in the CD25s levels and normalized ferritin levels, with recovery of NK cell cytotoxicity.
Due to LCH progression, the patient (16 months of age) received allogeneic transplant (donor father), being referred again (5 months later) with loss of the chimera, Adenovirus infection, and hemophagocytic syndrome. Then, the patient required multiple treatments including cyclosporine, vp16, corticosteroids, gammaglobulins, ribavirin, cidofovir, and finally alemtuzumab, with control of viral reactivation and secondary hemophagocytic (March 2013 receives last dose of alemtuzumab), currently out of treatment, asymptomatic, without active disease ().
During the loss of chimera episode and HLH reactivation, impaired NK cytotoxicity was observed with a recovery after treatment (). The direct sequencing of the genes involved in primary HLH (PRF1, UNC13D, STXBP2, STX11, and RAB27A) only revealed one low-frequency (MAF=0.0005) maternally inherited heterozygous variant in the STXBP2 gene (c.568C>T/p.R190C). The study included primers for sequencing flanking regions of up to 20 nucleotides, where intronic changes with functional consequences are usually located, excluding alterations such as mutations in intron 1 of the UNC13D gene. To rule out any other potential pathogenic defects associated to HLH, we performed an NGS targeted gene panel containing 427 PID-causing genes (see full gene list in ). Results confirmed the presence of the R190C heterozygous variant in the STXBP2 gene. No additional pathogenic mutations in HLH-associated genes or in other genes related with the clinical phenotype of our patient were found. STXBP2-R190C has been described () and recently characterized () leading to a severe deleterious effect on STXBP2 function. We performed a careful clinical and molecular evaluation of the patient providing additional arguments for the STXBP2-R190C pathogenicity.


A 50-year-old male was referred to our care from a private facility after being diagnosed with stage I (according to International Staging System [ISS]) kappa light chain MM.
In April 2020, he presented with severely worsening non-traumatic left-sided upper back pain, radiating to the midline and down to his mid-lower back. Further evaluation showed multiple lytic lesions in bones - largest at T6 and mild compression deformities at T8 and T10 along with hypercalcemia (13.5 mg/dl), AKI (creatinine: 1.7 mg/dl, blood urea nitrogen: 34.1, and glomerular filtration rate: 45.3 ml/min), and mild anemia. He also had a right lower lobe pulmonary embolus without evidence of right ventricular strain at that time. He was hospitalized and was treated with intravenous hydration, zoledronic acid, and apixaban. He was started on prephase treatment with 40 mg dexamethasone intravenously for six days for suspected MM.
Further laboratory results are as follows: Urine 24-hour protein excretion was increased with monoclonal protein present in urine protein electrophoresis. Serum protein electrophoresis showed no monoclonal protein; however, the kappa/lambda light chain panel showed an increased immunoglobulin kappa light chains of 1378 mg/dl and an increased kappa/lambda ratio (K:L) of 233.59. Beta-2 microglobulin levels were also increased at 3.0 mg/dl, albumin was normal at 3.5 mg/dl, and lactate dehydrogenase (LDH) levels were normal. The immunoglobulin (Ig) levels were low (IgG: 627 mg/dl, IgA: 25.6 mg/dl, and IgM < 26 mg/dl). Peripheral blood smear showed normocytic anemia and bone marrow aspirate, and biopsy confirmed the presence of 32% of clonal plasma cell population with cytoplasmic kappa light chain restriction. Fluorescence in situ hybridization (FISH) showed TP53 gene deletion at 17p13.1 and translocation (11,14) resulting in the fusion of CCND1 (BCL1) at 11q13 with immunoglobulin heavy chain gene (IGH) at 14q32 (Figure ).
On presentation, his Eastern Cooperative Oncology Group (ECOG) performance status was one, and Karnofsky performance score was 90%. Treatment was initiated with bortezomib, lenalidomide, and dexamethasone along with allopurinol and valacyclovir for infectious prophylaxis. The patient’s pain was managed with as-needed narcotics. The treatment was well tolerated without any major complications other than mild neuropathy that was treated with gabapentin. After completing four cycles of chemotherapy, he was evaluated for autologous stem cell transplant and consented for stem cell mobilization and collection. However, mobilization was held because he tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). After recovery from the COVID-19 infection, he was diagnosed with depression and anxiety with suicidal ideation, for which he received treatment with antidepressants. It was decided to hold on to the transplant transiently until the patient recovers.
In January 2021, his K:L increased to 67.47, and he was initiated on lenalidomide and dexamethasone considering his disease progression. After treatment, his K:L transiently decreased to 40.69; however, it increased to 99.64 in April 2021. Repeat bone marrow biopsy showed 80% plasma cell proliferation (Figure ), and FISH detected t(11,14); a gain of 1q and chromosome 5; and loss of chromosome 13, p53, and 5q. He was started on pomalidomide and subcutaneous daratumumab in anticipation of a bone marrow transplant in the future. Shortly after, he developed left-sided Bell's palsy with no other neurological deficits. CT of the head revealed subdural hematoma possibly secondary to thrombocytopenia, which was managed conservatively with serial head CTs. Apixaban and pomalidomide were discontinued, and he received platelet transfusions to maintain a platelet count of >50,000 cells/mm3.
Several months later, he was admitted to the hospital with double vision and slurring of speech. On clinical examination, he was alert and oriented; cranial nerve examination showed left-sided Bell’s palsy along with left sixth nerve palsy and right-sided tongue deviation with no sensory or motor deficits. CT brain without contrast showed right anterior para alpine subdural hematoma measuring approximately 2 mm in thickness, which is unchanged from prior along with chronic left holohemispheric subdural hematoma with areas of new acute intracranial hemorrhage, consistent with acute on chronic subdural hematoma. He could not complete MRI because of his severe back pain. He required no acute intervention, and he received packed red blood cell (RBC) and platelet transfusions for pancytopenia to keep platelets > 100,000 cells/mm3 and hemoglobin > 7 g/dl.
A week later, he was hospitalized again for hyponatremia and ground-level fall. He also complained of dysphagia and difficulty opening his right eyelid. Complete neurological examination revealed bilateral multiple cranial nerve palsies, involving the third nerve on the right, minimal eye movement in any direction on the left, bilateral seventh nerve, and tongue deviation to the right along with mild (-4/5) weakness in the right upper and lower extremities. He also developed progressive weakness and urinary retention during hospitalization. His K:L was > 500; however, his beta-2 microglobulin, albumin, and LDH levels were normal. CT of the brain showed scattered calvarial lucencies, which is compatible with the known diagnosis of MM. CSF analysis showed increased protein of 1088 mg/dl, five white blood cells (WBCs), and 230 RBCs, and flow cytometry did not show any aberrant immunophenotype. MRI of the brain was done after pain control, which revealed poorly enhancing soft tissue infiltrating the cavernous sinuses bilaterally and diffuse smooth dural enhancement with extensive calvarial and skull base marrow replacement along with left subacute to chronic frontoparietal subdural hematoma (Figure ). MRI spine revealed diffuse epidural enhancement of the thoracic and lumbar spinal segments, more pronounced at T9-T10 and L5-S1. The neuro-oncology team reviewed the MRI and stated that the clinical and MRI findings are consistent with diffuse epidural involvement of MM. The patient received three cycles of cranial radiation. However, he could not tolerate the whole course of treatment due to severe back pain and claustrophobia. He opted for hospice and palliative care.


A 63-year-old man presented with gross hematuria and urinary retention. He had no remarkable medical or family history. His serum prostate-specific antigen (PSA) was 4.58 ng/mL, and urine cytology was class 3 (atypical urothelial cells). Since cystoscopy revealed a papillary tumor in the prostatic urethra, we performed transurethral resection of the prostate. The pathological diagnosis was poorly differentiated adenocarcinoma with Gleason score of 5 + 4 = 9 with DCa (Fig. ). Magnetic resonance imaging showed local invasion of the left lobe of the prostate and bone metastasis of the left trochanteric section of the femur (Fig. ). Although he was treated with androgen deprivation therapy (ADT), 10 months later, the disease became castration-resistant prostate cancer. At this point, the PSA level was 3.66 ng/mL and serum NSE was 9.6 ng/mL. Then, we administered three courses of docetaxel (75 mg/m2) as the second-line therapy. Since the serum PSA level was decreased to 0.54 ng/mL, the patient was treated with a combination of 160 mg of enzalutamide and intensity-modulated radiation therapy (IMRT) consisting of 78 Gy administered in 39 fractions for the prostate and 40 Gy administered in 14 fractions for the left femur as the third-line therapy, which decreased the PSA level to be nadir of 0.03 ng/mL. After the combination therapy, enzalutamide was continued for 13 months, and when the serum PSA increased to 0.35 ng/mL, four courses of cabazitaxel (25 mg/m2) were administered as the fourth-line therapy. Despite multimodal therapy, positron emission tomography/computed tomography (PET/CT) showed viability of the left trochanteric section of the femur. Thus, we performed left femoral head replacement, and we confirmed the absence of viable cancer cells pathologically. After 1 year, he was treated with local radiation of 60 Gy administered in 25 fractions because the PSA level increased to 0.76 ng/mL and pelvic lymph node metastasis was noted. At this point, we performed targeted genome sequencing of the tumor specimen from the transurethral resection and re-evaluated the immunochemistry findings. We identified PTEN p. R233fs*10, RB1 loss exons 18–27, and TP53 p.R249G mutations by genome sequencing (Table ), and the patient was found to be positive for synaptophysin by immunohistochemistry (Fig. F). Currently, he is undergoing chemotherapy with cabazitaxel, and his PSA/NSE level was around 0.20/9.0 ng/mL.


Patient two, aged 35 years old, is the younger sister of patient one and was also, diagnosed with PD when she was three years old.
Clinical examination found on the lower limbs, several ulcers, dry necrotic lesions, and retractile atrophic scars, bilateral genu valgum, irreducible equinus associated to varus of the right foot and valgus of the left one (Figure ), and fixed toes deformities: supra-adductus of fourth toes and of the right second toe (Figures , ). The patient is walking in a wheelchair. Spine and upper limbs examination were normal. Knees and ankles radiography x-rays showed diffuse demineralization, bilateral genu valgum, fusion, and dislocation of the tarsal bones (Figure ).


An 11-year-old girl with no prior history of ocular trauma, surgery, or vascular lesions presented with a 1-month history of swelling lesions involving the conjunctiva of the right eye. There was a swelling bulge of approximately 3 mm × 3 mm in the corner of the right eye that had led to increased secretion, itching, and rubbing. After treatment with levofloxacin eye drops, the secretion was reduced, but the swelling and itching continued with slight bleeding. Bleeding occurred intermittently, and the tumour increased gradually. When the patient registered at our hospital, the bulge was increased. Physical examination revealed normal vision in the two eyes and a red mass of approximately 10 mm × 5 mm that protruded from the conjunctiva near the inner canthus without eyelid swelling; and no conjunctival hyperaemia (Fig. ). The mass was brittle with slight oozing and a pedicle connecting to the conjunctiva, whose surface seemed to have sleeve-like scabs with pus-like adhesion. The boundary of the mass was clear. The anterior chambers and the pupils of both eyes were normal. The conjunctival cylindrical mass was excised completely during general anaesthesia. The peripheral and basal tissues around the mass were brittle and easily bled. When the mass was removed, vascular proliferation around the base could be seen near the caruncle and was destroyed by cauterization. With regular dressing changes daily, the wound healed nicely. The pathology report showed that the surface was covered with squamous epithelium, the interstitium showed clustered proliferation with small blood vessels, and there was a small amount of inflammatory necrotic exudate. Immunohistochemistry results were as follows: Glut(−), WT-1(+), SMA(+), CD 31(+), CD 34(+), D2–40(−). This was consistent with granulomatous capillary haemangioma (Figs. , , , , , , ). After 6 months of follow-up, there was no recurrence (Fig. ).


Ten-year-old spayed female Miniature Schnauzer that presented with a 3-week history of nasal discharge and a 10-day history of right front limb lameness. On physical examination, ulcerative lesions on the left nasal planum and right paw pad were observed, along with swelling of the tongue and palate. Biopsy of the hard palate, nasal planum and tongue demonstrated mucosal hyperplasia with suprabasilar clefting, focal ulceration and mild lymphoplasmacytic interface inflammation. Moreover, there was marked pigmentary incontinence in the nasal planum. These findings were most consistent with pemphigus vulgaris.


A 9-year-old spayed female Labrador Cross with a history of ulcerative stomatitis presented to the emergency room due to difficulty prehending food. On physical exam, ulcerations were noted along the face, ears, and inguinal skin. The area was very sensitive to touch. A skin biopsy was taken, revealing a thickened epidermis with acanthosis. In the stratum spinosum and stratum granulosum, there were ragged and ruptured foci and clear spaces, suggestive of vesicle formation. Along the dermo-epidermal junction, there was edema, pigmentary incontinence, and moderate inflammatory interface dermatitis. These findings were consistent with pemphigus erythematosus.


Seven-year-old female spayed German Shepherd Cross presented with a 1.5 year history of nasal and periocular depigmentation and crusting. Physical examination demonstrated thick yellow crusting on the ear flaps, around both eyes, above the nasal planum, and in multifocal areas along her flanks. She has previously responded well to steroids but has discontinued due to adverse side effects. Histopathologic evaluation showed moderate lymphoplasmacytic interface dermatitis with pigmentary incontinence. Moreover, marked eosinophilic and neutrophilic, subcorneal and exudative dermatitis with infrequent ghost acantholytic cells were observed. Clinical and histologic findings were consistent with pemphigus erythematosus.


Twelve-year-old male neutered Portugese Water dog presented with a 10 month history of nasal crusting, ulceration and allergic rhinitis. On physical exam, crusting was observed on the nasal planum with erosion and depigmentation. The canine patient was initially diagnosed with mucocutaneous pyoderma, however his condition was unresponsive to antibiotic treatments and later progressed to involve the foot pads. Histopathologic evaluation demonstrated suprabasilar neutrophilic pustules with rafts of acantholytic keratinocytes. Additionally, there was superficial dermal and interface inflammatory infiltrate composed of lymphocytes and plasma cells. These findings were consistent with pemphigus foliaceous disease.


A 19-year-old woman with pain and swelling in her right parotid gland was referred to Shohada Hospital (Tehran-Iran) with no underlying diseases. She has complained of a mobile mass on the parotid region for a duration of 3 months. In her clinical examination, the oral mucosa and overlying skin were observed as intact with normal color. The patient's magnetic resonance imaging (MRI) indicated a high signal of a lobular-contoured, as a 4 × 2.5 cm solid mass lesion in the superior lobe of her right parotid gland (Figure ). A fine needle aspiration biopsy was performed by a maxillofacial surgeon and then a pathologic report indicated an unknown type of soft tissue malignancy. The primary diagnosis and the surgical treatment plan were discussed for the patient and a written consent was then obtained from her. At the operation session, following conducting the frozen-sections evaluation, malignant spindle cell tumor was diagnosed. Thereafter, a total parotidectomy was performed. As well, the gross examination of the specimen revealed a solid creamy mass with an almost well-defined border, invading the superficial lobe of the parotid gland. In addition, the permanent microscopic sections demonstrated a malignant neoplasm composed of fascicles of atypical spindle-shaped cells with large pleomorphic vesicular nuclei, prominent nucleoli, and clear-to-pale eosinophilic cytoplasm arranged in a storiform pattern (Figure ). Multinucleated giant cells and lymphocytic infiltration were observed as well. Notably, mitotic activity was about 4/10 HPF. By performing an immunohistochemically analysis, it was found that the atypical cells were HMB45 (Figure ) and S100 positive (Figure ). However, other markers such as Myo D1, Desmin, PanCK, and CK5/6 were negative. The microscopic feature along with IHC findings was consistent with the result of melanoma diagnosis.
To discover the primary origin of the recent melanoma lesion, a comprehensive past medical history was taken from the study case. As a result, we found that she had a history of congenital scalp pigmented nevus with no pathological consultation or any report of metastasis after 2 years (Figure ). Considering the possibility that the scalp lesion may be the origin of metastatic malignant melanoma, we suggested her to undergo excisional biopsy of the newly developed scalp lesion. In this regard, the patient was referred to the dermatology department for both consultation and performing the excisional biopsy operation. Thereafter, the newly formed scalp lesion was surgically removed. As well, the gross examination of the specimen showed safe border margins (0.6–1 cm) as well as a pigmented lesion in the center. Sections also demonstrated skin tissue with dissipated pigments from the epidermis to deep dermis. Moreover, the proliferation of atypical spindle cells scattered in the stroma was arranged from the superficial epidermis to hypodermis with vesicular nuclei and eosinophilic nucleolus (Figure ). Of note, the mitotic activity was about 1 in 10 HPF. In this patient, immunohistochemical staining showed the HMB45 intense positivity, but Ki67 was estimated as lower than 5%. Therefore, according to all these findings, the diagnosis of malignant melanoma was confirmed. After a month, she underwent parotidectomy due to swelling and pain in the left parotid gland. The histopathological report showed the same malignant melanoma. Thereafter, adjuvant chemotherapy and radiotherapy were performed for her during 6 and 4 sessions, respectively. She followed her disease by administrating complementary medicines too (homeopathy). After 18 months of follow-up, the lesion has not recurred and she has still been on a regular follow-up program.


An 80-year-old woman was diagnosed with RA in 2010 based on polyarthritis, high serum C-reactive protein levels, positive for anti-cyclic citrullinated peptide (CCP) antibody, and rheumatoid factor (RF). She was first treated with methotrexate (MTX), followed by a switch to golimumab (GLM) monotherapy due to chronic kidney disease (CKD). She was also taking epoetin beta pegol (the last dose of both was 12 days before vaccine administration) for renal anemia due to CKD stage G5A2 and daily levothyroxine sodium hydrate for Hashimoto's disease. Four days after the second dose of the BNT162b2 vaccine, headache, nausea, loss of consciousness, and purpura appeared, for which she was admitted to our emergency department. Blood tests revealed marked thrombocytopenia (0.8 × 104/μL) despite a last count of 11.2 × 104/μL, and brain computed tomography (CT) revealed subarachnoid hemorrhage. No cerebral aneurysm or apparent thrombosis was observed. Platelet counts were 0.3 × 104/μL despite frequent platelet transfusion, and the patient died from intracranial re-bleeding 3 days after admission. There were no autoantibodies, including anti-nuclear antibody or anti-dsDNA antibody, but only platelet-associated immunoglobulin G (PA-IgG) was as high as 206 ng/107 cells (standard value <46 ng/107 cells).


A 77-year-old man was diagnosed with RA in 2006 with positive anti-CCP antibodies and RF; MTX was used but was changed to GLM in 2016 (the recent dose interval was 6–7 weeks; the last dose was 5 weeks before vaccine administration) and maintained in remission. The patient was receiving epoetin beta pegol and zinc acetate hydrate for hypertension and chronic renal failure. Four days after the first dose of the BNT162b2 vaccine, the patient developed left upper and lower limb paralysis and was rushed to the emergency room. The blood test revealed a platelet count of 5.6 × 104/μL despite the last count of 11.1 × 104/μL, and the brain CT showed right frontal lobe subcortical hemorrhage and subarachnoid hemorrhage in the central sulcus. There were no significant thrombotic findings. Transient thrombocytopenia recovered spontaneously after a few days, and the patient was transferred to the hospital for rehabilitation. The results of the PA-IgG test were negative.


A 79-year-old man diagnosed with RA in 2019 with positive anti-CCP antibodies and RF had a long history of hypertension. He developed primary ITP (PA-IgG negative) at the time of sarilumab induction and the latter was therefore substituted with prednisolone (PSL) 20 mg/day and intravenous immunoglobulin. Five days following the first dose of the BNT162b2 vaccine, the patient visited the outpatient clinic with no signs of bleeding but with a low platelet count of 4.7 × 104/μL despite a last count of 15.2 × 104/μL. The patient was deemed to have a flare of ITP, and PSL was increased from 9 to 15 mg/day, and tacrolimus 2 mg/day was added. At his firm request, a second vaccination was administered, after which the platelet count increased to 16.0 × 104/μL. The PA-IgG level following the second vaccination was 75 ng/107 cells.
The clinical course of all cases is presented in .