The patient was a 62-year-old man with a liposarcoma that had repeatedly relapsed. In February 2000, he underwent resection of a lipoma-like nodule on the left wall of the chest, but surgical pathology was not performed. In June 2004, he found a lump on the edge of the surgical scar. Three months later, a tumor was removed in the same hospital but again no tissue was sent for pathological examination. One month later, another mass developed on the left wall of the chest, and grew rapidly to attain dimensions of about 5 × 4 cm. He was admitted to a general hospital and underwent locally expanded, left wall excision on March 28, 2005. The surgical pathology indicated a pleomorphic liposarcoma with positive surgical margins. Then the patient underwent nine rounds of chemotherapy (combined pirarubicin, vindesine, and cyclophosphamide for the first three rounds; combined pirarubicin and dacarbazine for the second three rounds; and combined epirubicin and ifosfamide for the last three rounds). Radiotherapy (30 Gy) was delivered to the surgical area of the left wall of the chest after chemotherapy concluded. The liposarcoma recurred once more (on October 30 2014) 5 cm below the left nipple. Four weeks later, he underwent a repeat, locally expanded excision of the same wall. A pleomorphic liposarcoma with positive surgical margins was again confirmed by surgical pathology (). After two more rounds of chemotherapy (combined epirubicin and ifosfamide), he received a further 50 Gy of radiotherapy to the site. However, the incision cracked and did not heal. After a series of surgeries including expanded debridement, soft tissue repair using a latissimus dorsi myocutaneous flap, and skin grafting, the wound gradually healed. He detected a 1 × 2 cm painless scleroma above the scar on December 2, 2017. Three weeks later, he again underwent locally expanded excision at the same site. The fifth rib had been invaded by the tumor and was partially removed during operation. A de-differentiated liposarcoma with a negative surgical margin was confirmed by surgical pathology ().
On February 7, 2019, he experienced local pain and swelling on the left wall of the chest. The pain commenced as a pinprick, but then developed into a paroxysmal tear-like shape with a numerical rating scale (NRS) score of 6. The pain was not relieved by loxoprofen sodium tablets, and his sleep was severely affected. On April 8 2019 the patient was admitted to our oncology department for the first time. Positron emission tomography (PET)/computed tomography was performed early the following day and revealed a huge mass with irregular nodules and protrusions, of dimensions 10.5 × 5.4 × 7.2 cm, in the lower left wall of the chest. The boundary of the mass was unclear, and it was lobulated. The density was uneven, and local fat density shadows were evident. The average mass density was about 49.5 Hounsfield units. The mass exhibited enhanced fluorodeoxyglucose (FDG) metabolism, with an SUVmax of 15.07. The mass had invaded part of the pericardium, diaphragm, and interior of the left lung. The left fifth anterior rib was absent, and the cortex of the left sixth anterior rib was irregular. The FDG metabolism of the left sixth anterior rib was elevated, with an SUVmax of 3.2 (). The radiologist concluded that the patient could not receive any more radiotherapy. The thoracic surgeon considered that as the tumor was so large, and had invaded the pericardium, diaphragm, and lung tissue, the surgical risk was high and it would be difficult to ensure a negative surgical margin. Thus, surgery was not recommended at that time. On the same afternoon, we commenced apitherapy at the bulge of the left sixth rib (we used the bee Apis cerana fabricius).
We initially used only one bee to sting (). The NRS score dropped to 1 and the patient slept throughout the night. Then he underwent apitherapy on Mondays, Wednesdays, and Fridays; the dose was gradually increased to 18 bee stings each time over 6 weeks. The thoracalgia that had interfered with his sleep did not recur. Apitherapy focused principally on the chest wall area corresponding to the tumor mass indicated by PET/CT (). He commenced apatinib (Jiangsu Hengrui Medicine Co. Ltd.) on April 12 2019 (425 mg once daily). Apatinib is a specific molecular inhibitor of VEGFR-2 and exhibits antitumor activity both in vivo and in vitro (, ). We discontinued it on the weekends because the patient developed painful ulcers of the fingertips, heels, and throat after 4 weeks on the drug (). After another 2 weeks, we reduced apatinib to three times weekly because he complained of a constant sore throat. We increased the apitherapy dose from 18 to 50 bee stings each time, and discontinued apatinib because the sore throat and consequent dysphagia did not resolve within 3 weeks (). The sore throat and limb extremity ulcers disappeared after apatinib withdrawal. He was given intravenous infusions of camrelizumab (Jiangsu Hengrui Medicine Co. Ltd.), a PD-1 inhibitor that recently received conditional approval in China for treatment of relapsed or refractory classic Hodgkin lymphoma, non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma. He received the drug on June 19, July 10, July 31, August 21, and September 1 2019 (200 mg every 3 weeks). Apitherapy was discontinued on September 20 2019. Ten days later, he underwent repeat PET/CT () and then a complex surgery featuring enlarged resection of the chest wall tumor, thoracoplasty, and surgical repair of the chest wall, pulmonary, and diaphragm defects.
We completely removed the tumor along the outer margin of the mass. The mass dimensions were now 8 × 5 × 3 cm. Pathology showed that the mass exhibited a degenerative change characterized by hyaline degeneration of sections of the surgical specimens. Hemangiogenesis and chronic inflammatory cell infiltration were evident at the edge of the mass, but no tumor cells were found in the ribs or vessels or at the excisional margins of the pericardium, lungs, or diaphragm. Of all sections, only 41 consecutive sections exhibited residual tumor tissue. In the section with most such tissue, the tumor area was about 0.3 × 0.2 cm ().
Prior to the radical resection of October 7 2019, the patient had been battling his recurrent liposarcoma for 20 years, and had undergone many surgeries, chemotherapies, and radiation treatments. He was physically and mentally exhausted. At his request, we discontinued all antitumor therapy after surgery. The patient receives a medical re-examination every 4 months, and no evidence of tumor recurrence was apparent to his fourth follow-up (thus to 16 months after surgery) ().


The patient was a 51-year-old man with a history of renal failure due to acute rapidly progressive glomerulonephritis that had been diagnosed 2 years earlier and required treatment with artificial hemodialysis. He had been diagnosed with CD 35 years earlier and underwent ileocecal resection. He developed a CD-induced vesicoileal fistula and vesicosigmoid fistula and underwent right colectomy, sigmoid colectomy, closure of the bladder fistula, small bowel resection, and ileostomy 23 years earlier. After this operation, the estimated length of the remaining small bowel was 1 m. Since then, he had received home parenteral nutrition because of short bowel syndrome. He also underwent total colectomy 13 years earlier because he had developed extensive colitis. He currently desired renal transplantation for chronic renal failure and was examined in our hospital. Pre-transplantation colonoscopic examination led to a diagnosis of rectal cancer of the remaining rectum. He was then referred to our department.
On physical examination, his height was 150.7 cm, weight was 38.1 kg (dry weight), and body mass index was 16.8 kg/m2. A single ileostomy at the right lower abdomen and a scar from a midline incision extending from the epigastric to suprapubic region were observed. Digital examination could not be performed because of stenosis of the anus secondary to the previous anal fistula, which had cured and showed no evidence of canceration. On hematological examination, his blood urea nitrogen concentration was 43 mg/dL, creatinine concentration was 12.16 mg/dL (before hemodialysis), carcinoembryonic antigen concentration was 1.8 ng/mL, and CA19-9 concentration was 24.4 ng/mL. Colonoscopy showed a circumferential tumor at the remaining rectum (Fig. a), and biopsy revealed well-differentiated adenocarcinoma. A contrast enema revealed a 6-cm defect at the remaining rectum around the pritoneal reflection (Fig. b). Computed tomography examination revealed wall thickening of the remaining rectum but no swollen regional lymph nodes or distant metastasis. Magnetic resonance imaging showed that the estimated depth of wall invasion by the tumor was T2 because the muscle layer was continuous (Fig. c). The preoperative diagnosis of the rectal cancer was clinical T2N0M0, Stage I.
Severe intra-abdominal adhesions were expected because of the patient’s history of multiple surgeries; therefore, we performed an operation with both laparoscopic transabdominal and transperineal approaches. The transabdominal procedure and transperineal approach were carried out concomitantly. For the transabdominal approach, three ports were placed in the abdomen. One of the ports was placed in the umbilicus for scope insertion, and the other two were placed on the left side of abdomen for the laparoscopic operator. The transperineal approach was concurrently implemented. First, two purse-string sutures were placed to close the rectal lumen and prevent cancer cell dissemination. The scar due to the previous anal fistula existed, but could be easily dissected. After dissecting the perianal skin and perirectal soft tissue, a GelPOINT Path transanal access platform (Applied Medical, Rancho Santa Margarita, CA, USA) was inserted and an AirSeal System (CONMED, Utica, NY, USA) was used for carbon dioxide insufflation during the transperineal approach. In the transabdominal approach, adhesion of the small intestine and greater omentum to the abdominal wall was observed. Even after dissection of the intestinal and omental adhesion, it was difficult to recognize the wall of the remaining rectum because of the pelvic adhesion due to previous operations. Careful dissection of the rectum progressed laparoscopically. In the transperineal approach, the correct plane could be recognized and TME smoothly progressed. The influences of the inflammation of CD or chronic renal failure were none or very little to dissect the correct plane. The rectal dissection progressed along with the levator ani muscle, and the anococcygeal ligament was resected in the transperineal approach (Fig. a). Rendezvous of the abdominal space with the transperineal space was achieved on the dorsal side of the rectum. TME progressed from the posterior to lateral side of the rectum laparoscopically and transperineally. Preservation of the S4 nerve was confirmed in the transperineal approach. Finally, the anterior wall of the rectum was completely dissected after confirming the posterior wall of the prostate in the laparoscopic approach (Fig. b). The specimen was extracted from the perineal incision. Figure c shows the pelvic space after extraction of the specimen. Strong adhesion was observed in the pelvic floor. The operation was finished without conversion from laparoscopy to open surgery (Fig. d). The duration of the operation was 3 h 48 min, and the blood loss volume was 50 mL. No intraoperative complications occurred.
On gross examination of the resected specimen, the tumor was a flat and villiform mass classified as type 5 (Fig. a). The size of the tumor was 80 × 67 mm. Histologically, the tumor was a well- to moderately differentiated adenocarcinoma with foci of a poorly differentiated component (Fig. b). The background contained characteristic findings of CD: chronic inflammation through the rectal wall and noncaseous epithelioid cell granulomas with multinucleated giant cells in the submucosa (Fig. c). Therefore, we diagnosed the tumor as colitic cancer associated with CD. The pathological stage was pT2N0M0, Stage I. The resection margin was negative.
During the postoperative course, the patient developed a fever due to an intra-abdominal infection 3 days after the operation, which might be due to a retrograde drainage tube infection estimated by CT, and it was treated with antibiotics. He was discharged 21 days after the operation. No recurrence was evident 3 months after the operation, and no adjuvant chemotherapy was performed.


An 80-year-old Caucasian male presented to our clinic for evaluation and management of a right parotid tail mass that had been present for several years and had significantly increased in size over the past two months. Computed tomography (CT) revealed a 3.4 × 2.7 cm mass, and subsequent ultrasound guided core biopsy was consistent with a low-grade oncocytic neoplasm. On surgical evaluation, the tumor was found to be superficial to the facial nerve branches, so a superficial parotidectomy was performed with dissection and preservation of the facial nerve. Intraoperative frozen section analysis was performed confirming benign pathology, and final pathology would confirm an oncocytoma, measuring 4.8 × 3.7 by 2.3 cm.
After resection, there was a considerable mass defect that required volume reconstruction. Once frozen section pathology confirmed a benign tumor, the mass defect was reconstructed using a level I and II lymphofatty packet of tissue mobilized off the posterior aspect of the submandibular gland and SCM, advanced posteriorly and superiorly, and secured to the parotid fascia.


A 58-year-old woman with a five-year history of a right-sided mass at the angle of the mandible sought evaluation after noting a recent increase in size with discoloration of the overlying skin. CT scan of the neck showed a mass measuring 3.2 × 2.9 cm involving the superficial lobe of the right parotid gland. Fine needle aspiration findings were consistent with a cystic lesion. On surgical evaluation, the tumor was found to be partially superficial and deep to the facial nerve branches. These were identified, dissected, and preserved while resecting the mass. Frozen section analysis demonstrated a papillary cystadenoma lymphomatosum tumor with cystic degeneration. Final pathology would confirm the frozen section diagnosis. The mass defect was reconstructed using a level I and II lymphofatty packet of tissue mobilized off the posterior aspect of the submandibular gland and SCM, advanced posteriorly and superiorly, and secured to the parotid fascia.


Case summary 1
A 60-year-old male presented with complaints of swelling over the right side of the face for 20 years. The swelling remained static initially, which gradually increased in size for the last five years and was not associated with any sudden increase in size. He had no pain complaint, difficulty in mouth opening, facial weakness, facial paraesthesia, halitosis, altered salivary flow, or discharge from the swelling during its progression.
On local examination, an ovoid mobile swelling of size 15x15 cm was noted below, behind, and in front of the right ear with obliteration of the retro-mandibular furrow and lifting of the right ear lobule with no local warmth or tenderness. The swelling had well-defined margins, a smooth surface, a variegated consistency predominantly fluctuant cystic area, and a firm solid area in its posterosuperior part. There were two soft outpouchings noted on the surface of swelling, which were compressible. The swelling was not fixed to the underlying muscles or the overlying skin except in the area of outpouching nodules. The skin over the swelling had normal facial hairs and had no dilated veins, scars, sinuses, or fistulae (Figure ).
His intraoral examination revealed a normal deep lobe, parotid duct, and its opening. There was no apparent facial asymmetry or weakness of facial muscles. Contrast-enhanced computed tomography (CECT) revealed a well-defined, hyperdense, fluid-attenuating cystic lesion of size 11x13x12 cm with an eccentric enhancing nodular solid component of size 4x5 cm in the right parotid region. The deep lobe of the parotid was normal. There was no involvement of the deeper structures and vessels of the neck. There was no significant lymphadenopathy (Figure ).
Fine-needle aspiration cytology (FNAC) from the lesion showed features suggestive of PA. The patient underwent a right superficial parotidectomy. Blair’s incision was given with a 5 cm extension in the cervical skin crease because of significant swelling. Intraoperatively, the facial nerve's zygomatic branch was found to be traversing through the cyst and was sacrificed. The rest of the branches were identified and preserved. There was an excess of thinned and redundant skin, which was trimmed to achieve cosmetically acceptable closure. Postoperative microscopic examination revealed PA without any evidence of malignancy (Figure ).
Case summary 2
A 63-year-old male presented with complaints of swelling in the right side of the neck extending to the right cheek for 15 years. There was no sudden increase in the size of the swelling. He had no other complaints similar to Case 1.
On local examination, an irregular, non-tender, mobile swelling of size 10x8 cm was noted below, behind, and in front of the right ear with obliteration of the retro-mandibular furrow and lifting of the right ear lobule. The swelling had well-defined margins, a smooth surface, and variable consistency with cystic and solid areas admixed. It was not fixed to the masseter, sternocleidomastoid, or overlying skin. The skin over the swelling and his intraoral examination were clinically unremarkable. There was no evidence of facial palsy or lymph nodes in the neck.
Magnetic resonance imaging (MRI) of the neck showed a well-circumscribed, solid-cystic lesion within the posteroinferior part of the right parotid gland's superficial lobe with no extension to the deep lobe measuring 8.5x6.4x8 cm. Peripheral solid areas of the lesion along the superior and medial aspects show diffusion restriction with post-contrast enhancement. There was a presence of T2 intermediate to hyperintense signal with scattered T1/T2 hyperintense cysts. A T2 hypointense T1 intermediate to mildly hyperintense cystic component of the lesion (measures 4.0x3.8 cm2) with possibilities of mucoid content was also noted. The lesion was abutting the retromandibular vein and displacing it anteriorly. There were no suspicious deep cervical lymph nodes noted (Figure ).
FNAC showed differentials of WT and lymphoepithelial cyst. He underwent right superficial parotidectomy with standard Blair’s incision. Meticulous dissection was done to identify and safeguard the facial nerve and its branches. During his immediate postoperative period, he developed facial nerve neuropraxia, which was resolving well with physiotherapy. The histopathology of the specimen revealed features of WT (Figure ).


A 71-year-old man presented with a right breast lump that was noticed three weeks prior to the clinic appointment. His background history included gastroesophageal reflux, chronic kidney disease, repair of right inguinal hernia, and excision of basal cell carcinoma of the abdominal wall. Clinical examination revealed a dent in the skin and a palpable 3-cm lump in the axillary tail.
Mammogram (Figure ) showed a 25-mm suspicious lesion in the right axillary tail, which was also visualized on ultrasound (Figure ), along with a suspicious lymph node in the right axilla. Imaging-guided core biopsies were taken from both; the histopathology was consistent with grade 1 invasive ductal carcinoma, and ER 0, PR 0, and HER 2 negative as well. Mastectomy with axillary clearance was performed after consultation with breast MDT (multidisciplinary team). The post-operative histopathology revealed 23-mm, grade I, triple-negative invasive ductal carcinoma (Figure ) with lymphovascular invasion, Ki67 10%, one out of nine lymph nodes showing metastatic disease, and the final staging as T2N1M0. The MDT advised for annual surveillance for five years.


A 26-year-old female was admitted to our hospital following a 3-week history of anorexia, fatigue, and dark urines. She denied taking alcohol, recreative drugs, or any medications and had no family history of liver disease. On examination, except for jaundice, the patient had no signs of chronic liver disease, was alert, oriented, and afebrile. Blood pressure was 112/65 mmHg, and pulse rate was 88 beats per minute. At admission, blood tests showed mild AST elevation (3 times the upper limit of normal, ULN), normal ALT, low alkaline phosphatase (43 IU/L [N: >46], high gamma-glutamyltransferase (GGT) at 190 IU/L [N: <38], and elevated total bilirubin (128 μmol/L [N: <2] with a conjugated form of 52 μumol/L [N: 0.5–9.5]. Albumin level was 26 gr/l [N: 28–35]. Coagulation parameters were altered, with an elevated international normalized ratio (INR) of 2.34 and factor V 44% [N: >70]. Cell blood count demonstrated normal leucocytes and platelets, but low hemoglobin value of 67 gr/l [N: 120–160] with a high reticulocyte count of 293 G/L [N: 20–120)]. In the absence of overt bleeding, anemia was predominantly related to hemolysis with undetectable serum haptoglobin, high lactate dehydrogenase (LDH) [], and negative Coomb's test. Further testing excluded hepatitis A, B, C, and E, as well as autoimmune hepatitis, based on normal total IgG level and absence of antismooth muscle antibodies. The ceruloplasmin level was 0.22 gr/l [N: 0.2–0.6]. No biliary tract disease or vascular alterations were detected on abdominal echography. Acute hepatitis due to WD was considered as the most likely diagnosis. Histological features observed at liver biopsy obtained by the transjugular route were consistent with the diagnosis, showing cirrhosis associated with chronic inflammatory changes, mild (10%) macrovesicular steatosis, and few ballooned hepatocytes. Increased hepatocyte copper-associated protein deposition was observed in periportal areas using Victoria blue stain (). A quantification of 8071 μg/gr in liver tissue [N: 10–35] was consistent with a massive accumulation of copper [, ]. Additional studies included a major increase in serum and urinary copper values of 2205 μg/l [N: 70–175] and 4130 μg/24 h [N: 15–60], respectively. A slit-lamp examination was inconclusive regarding Kayser–Fleischer's ring. Brain magnetic resonance imaging (MRI) was not performed at that time. Thus, according to the Leipzig score [, ], a diagnosis of AWH with cirrhosis and liver insufficiency was made, and a combined treatment of oral D-penicillamine (1200 mg/d) and zinc gluconate (90 mg/day) was promptly initiated on day 1 after admission. However, the following days were associated with a rapid clinical deterioration and majoration of hemolytic anemia with low hemoglobin levels in the range of 60 to 70 gr/l, necessitating repeated blood transfusions (). At this stage, with a MELD score of 31, the patient did not reach Clichy criteria for urgent LT [, ] (no hepatic encephalopathy and a factor V level of 35%). Nevertheless, a WD prognostic index [] of 11 indicated a poor prognosis with medical treatment alone. Therefore, considering the role of massive copper overload in the severe hemolysis coexistent with acute liver and renal failure (serum creatinine 177 μmol/l [N: 44–80]), we decided to combine conventional chelation therapy with a mechanical method to rapidly remove excess serum copper. In spite of a very limited experience in the literature, a multidisciplinary team including hepatologists, nephrologists, and intensive-care specialists decided to use the Molecular Adsorbent Recirculating System (MARS) (MARS-Flux, Gambro, Lund, Sweden) as an albumin-based dialysis able to remove free exchangeable copper molecules in addition to other albumin-bound toxins associated with liver failure []. This technique has been preferred to therapeutic plasma exchange (TPE), reported to bring benefits as a bridge for liver transplantation in anecdotal reports [, ], because the use of fresh frozen plasma replacement would have influenced coagulopathy as a criterion to decide urgent listing [].
MARS is a hemodialysis system coupled to a closed circuit containing an albumin-rich dialysate with a carbon filter and an anion exchanger. The device aims to mimic the liver detoxification mechanisms at the hepatocyte membrane level. The plasma albumin loaded with toxins will, at the level of the MARS filter, transfer the albumin-bound toxins via a membrane permeable to toxins but not to proteins (cut-off 30 kDa) [], therefore minimizing the depletion in hormones, proteins, and platelets. From a technical point of view, MARS therapy is coupled with hemodiafiltration using the MARS Prismaflex system which includes both one filter in contact with blood (MARS-FLUX) and one in contact with albumin. The MARS set also includes one adsorber column filled with carbon charcoal (diaMARS AC250) eliminating nonpolar compounds (i.e., fatty acids) and another column filled with ion-exchanger resin (diaMARS IE250) to eliminate anionic molecules including bilirubin and copper. The MARS system was administered to our patient using a 13F dialysis catheter in the femoral vein according to the manufacturer's recommendations adapted to our institution's guidelines. A total of 9 MARS dialysis sessions (each session lasting 6–8 hours) were administered starting from day 6 to day 17, with an excellent clinical tolerance, no bleeding complications, and only a marginal decrease in platelet count. depicts the MARS device and the dark-brown-colored adsorber cartridge filled with copper. The patient rapidly recovered from hemolysis, as no further blood transfusions were necessary after day 7 (see ). The evolution of WD prognostic index during the hospitalization is depicted in . On day 21, the MELD score was 14, hemoglobin level was 87 gr/l, LDH had decreased from 2004 U/L to 327 U/L [N: 87–210], and the patient's general condition was good. She left the hospital on a combined treatment of penicillamine 1200 mg/d and zinc gluconate 90 mg/d and received also dietary counseling. At the outpatient visit 3 weeks later, hemoglobin was 133 gr/l, and the urinary copper excretion value was reduced at 1080 μg/24 h compared to baseline measure (−74%). Determination of serum copper level was not repeated thereafter. The brain MRI scan did not show T2 hyperintensity in basal ganglia.


A 51-year-old male diagnosed with opioid and stimulant use disorder was receiving injectable opioid agonist treatment (iOAT) with hydromorphone (Sandoz Inc. 50mg/ml solution) at a community clinic in Vancouver. Prior to receiving iOAT he reported injecting illicit opioids and smoking crack cocaine daily for over two decades and had multiple prior oral OAT attempts. He was prescribed 200mg of hydromorphone three times per day (600mg total per day), since August of 2014 (with dose adjustments). He had trialled diacetylmorphine (pharmaceutical grade heroin) in February 2015 but preferred hydromorphone. Hydromorphone supported him to stop his illicit opioid injection however he reported ongoing daily crack cocaine smoking, on average 1015 rocks per day. He presented to his physician with the goal of reducing his crack cocaine use in January 2020.
His medical history included numerous conditions that were aggravated by smoking crack cocaine including diagnoses of hepatitis C, chronic obstructive pulmonary disease, and pulmonary hypertension. He had developed pulmonary embolism as a result of deep vein thrombosis moving to his lungs. The clot damaged the veins in both of his legs, and he developed associated chronic leg wounds. The ongoing use of crack cocaine contributed to poor wound healing. He reported engaging in drug dealing daily to support his use. He was motivated to reduce his crack cocaine use in order to: (1) limit his spending on cocaine, with a longer-term goal of saving money and; (2) to minimize its physical health burden. He reported that crack cocaine use helped him with remaining alert to accomplish daily tasks, and as such found it difficult to cut down on his crack cocaine use.
A trial of sustained-release dextroamphetamine sulfate (Dexedrine ) (See Fig.) was offered following the clinics dextroamphetamine dosing protocol (Table ) and was taken at the clinics on-site pharmacy (See Fig.). This was his first time receiving treatment for stimulant use disorder. Prescribing began on January 24th 2020 at 15mg twice per day, though the patient was advised to begin with one capsule and could increase to two if the dose was tolerated (i.e. no or mild side effects). On February 1st 2020, the patient reported tolerating 15mg of dextroamphetamine twice per day and did not report experiencing any adverse effects (e.g. sleeping problems, agitation, changes in appetite, etc.). He reported that his crack cocaine cravings were reduced, but not eliminated. The patient and physician decided together to increase the dose and a prescription for dextroamphetamine 30mg twice per day was written.
On February 23rd 2020, 4weeks after beginning the prescription, he reported less cravings and clinically significant reductions in use, from 1015 rocks daily to between 1 and 2 rocks on average two days per week. He reported having stopped his daily drug dealing as it was no longer required to support his crack cocaine use. He was meeting his self-identified therapeutic goals of reducing his crack cocaine use and reducing his spending on crack cocaine. The patient reported that dextroamphetamine helped him to feel energized, a feeling that he had previously been seeking from crack cocaine. Clinical improvements were witnessed in his abscesses and chronic wounds, which began to heal. In addition, care providers noted that he became more cognitively alert and was more engaged and interested in conversations. On May 18th 2020, the patient discontinued the medication, stating it was no longer required to maintain the reductions in cocaine use he had attained. Upon the most recent clinical visit on October 5th 2020, the patient reported having maintained the significant reductions in cocaine use, and the prescribing physician (SM) reported persistent clinical improvements in the patients physical health, cognition and social functioning. For example, the patient maintained his reduction of crack cocaine use, and experienced persistent improvements in mobility, and reduced edema (swelling) of the legs.


The patient was a 59-year-old man with a 12-year history of hemodialysis due to diabetic kidney disease. The patient had a history of failed bilateral arteriovenous fistula and underwent placement of an arteriovenous graft in his left arm 2 years ago for hemodialysis. The patient experienced syncope during hemodialysis. Electrocardiography showed complete atrioventricular block and was transported to our hospital for further treatment. Temporary PMI was immediately performed via the right internal jugular vein, and the patient was admitted for permanent PMI the following day.
Permanent PMI was planned in the right chest because of presence of the graft in the left arm. Right subclavian venography was not performed because the patient had experienced an allergic reaction to iodinated contrast 2 years prior. Instead, we decided to introduce a 0.035-inch guidewire into the right subclavian vein (SCV) for puncture.
During the procedure, a 5-Fr sheath was inserted from the right femoral vein. A 0.035-inch Radifocus wire® (Terumo) with the support of a 4-Fr Judkins right (JR) catheter® (Medikit) was introduced. However, we could not pass the guidewire to the right SCV. Thus, SCV occlusion was suspected. Carbon dioxide digital subtraction angiography (CO2-DSA) was performed using the JR catheter at the right brachiocephalic vein (Figure ), which showed total occlusion of the right SCV. To determine occlusion length, venography from the basilic vein was performed. A 5-Fr sheath was inserted into the right basilic vein using ultrasound-guided puncture. The 0.035-inch Radifocus wire was inserted with the support of a 4-Fr Glidecath® (Terumo). The guidewire successfully passed to the distal end of the SCV, and CO2-DSA was performed (Figure ).
Since the patient had a graft in the left arm and a prior history of failed bilateral arteriovenous fistula, a transvenous pacemaker was implanted on the right side. A leadless pacemaker was an alternative option, but because of a prior allergic reaction to iodinated contrast, there was a risk of developing an allergic reaction. The occlusion length was short, so EVT to the right SCV was decided.
A 0.014-inch guidewire (Gladius® Mongo® PV ES; Asahi Intecc) with the support of a 4-Fr Glidecath was introduced via the right basilic vein and penetrated the occlusion successfully before being advanced into the superior vena cava. A 5.0 × 40-mm Mustang® balloon (Boston Scientific) could not pass the occlusion. We predilated the lesion using a 2.0 × 40-mm Coyote® followed by a 4.0 × 40-mm Coyote (Boston Scientific). Using the Glidecath, we changed the Gladius Mongo PV ES to a 0.035-inch Radifocus wire. The 5.0 × 40-mm Mustang passed the lesion, and balloon angioplasty was performed. Then, we used a 21-G micro-puncture needle (Cook) to puncture the right SCV. However, puncture was not successful as venous blood could not be drawn. Vein elastic recoil was considered, and we decided to puncture the balloon instead.
The 5.0 × 40-mm Mustang was dilated in the SCV. Using a 21-G micro-puncture needle attached to a 2.5-mL syringe, we punctured the balloon under the guidance of fluoroscopy. On successful puncture, almost all diluted contrasts were aspirated into the syringe (Figure ). The guidewire was inserted; however, the guidewire alone could not pass into the vein, and both the balloon and guidewire were pushed. Subsequently, the guidewire was successfully advanced into the SCV (Figure ). This sequence of procedures is named the balloon-target puncture technique.
We used the one-puncture two-sheath technique to introduce two 7-Fr peel-off sheaths (Medikit) into the SCV and successfully implanted the pacemaker (Figure ). The SelectSecure™ MRI SureScan™ lead (Medtronic) was implanted using a C315 S10 guiding catheter into the right ventricular septum, and the CapSureFix Novus MRI™ SureScan screw-in lead was implanted into the right atrial appendage. The procedural duration was 2 hours 25 minutes, and the fluoroscopy time was 36 minutes. No perioperative complications occurred. The patient was discharged after 1 week.


This patient, a five-year-old African-American female, fell at school and developed severe left knee pain. Three days after falling, the patient's mother contacted her primary-care physician where she reported her daughter's severe left knee pain that prevented her from walking and had worsened since the initial injury. At this point, the patient's left knee was also warm and erythematous. She and her daughter were referred to her local emergency department where radiographs of the patient's left knee were conducted and were read as unremarkable with no signs of trauma (). The patient was, therefore, diagnosed with a left knee sprain and was treated conservatively with pain control (ice and NSAIDs) and NWB without further intervention.
Eleven days later, the patient was seen by her primary-care physician for her persistent limp and intermittent pain, although her swelling had resolved. Anteroposterior view of the pelvis and bilateral frog lateral radiographs were ordered to rule out any hip pathologies, which could also cause an antalgic gait. All films were read by an attending radiologist and were deemed unremarkable. Relying on these reads, the primary-care physician recommended the patient to continue supportive care (NSAIDs and ice for pain, nonweight bearing for left lower extremity) and to refer to an orthopedist if symptoms persisted.
Despite these treatments, the patient's pain and limp persisted, and the patient then sought a referral to a general pediatric orthopedist for further work-up. Although the child's pain had slightly improved, her limp remained. She described her left knee pain as worse at night but responsive to acetaminophen and ice. She had never felt anything like this before prior to her initial fall. Both the patient and her mother denied fever, weight loss, fatigue, malaise, or recent infection. On physical exam, her left knee did not have a palpable mass, muscle atrophy, or edema, but was tender to palpation. Given concern for the persistent pain and antalgic gait, repeat radiographs of the left knee were also ordered by the orthopedist and showed aggressive poorly defined lytic lesion centered within the left distal femur metadiaphysis extending up proximally 6 cm superiorly from the metaphysis with associated interrupted superior periosteal involvement (). A radiologist reviewed these findings and agreed with the orthopedist that based on these radiographic findings, there was concern for a primary bone malignancy. Arthrocentesis of the left knee was performed to rule out a possible infectious etiology, which was negative. Acute-phase reactants including c-reactive protein, sedimentation rate, and leukocyte count were all within normal limits. Magnetic resonance imaging (MRI) and needle biopsy were ordered to establish diagnosis. Contrast-enhanced MRI examination showed a enhancing mass centered in the distal femoral metaphysis approximately 7 cm in craniocaudal dimension with aggressive periosteal involvement (). Needle biopsy of the left distal femur was performed at the site of the lesion, and pathology demonstrated cores of tumor tissue consisting of pleomorphic tumor cells with frequent mitoses, foci of necrosis, regions of chondroblastic differentiation, and rare small foci of malignant osteoid production, consistent with the diagnosis of osteosarcoma. Additional imaging, including chest computerized tomography (CT) and whole body Positron Emission Tomography (PET), was obtained for tumor staging and demonstrated no evidence of distant metastases.
The patient was then referred to an orthopedic surgeon to discuss treatment options including oncologic and operative interventions. Given the concern for pathological fracture and possible subsequent contamination of healthy tissue from this tumor, the patient was placed in a knee immobilizer to limit weight bearing (NWB LLE with walker). The patient and her parents were referred to an oncologist to determine a chemotherapy plan. A typical treatment plan of osteosarcoma involves surgical resection and six cycles of chemotherapy (two cycles preoperatively as neoadjuvant therapy and four cycles postoperatively) with high-dose methotrexate, doxorubicin/dexrazoxane, and cisplatin.
Operative treatments were discussed between the family and the attending orthopaedic surgeon in great detail including potential risks and benefits, and the family chose to proceed with Van Nes Rotationplasty. Radical resection of the left distal femur 17 cm from the joint line with femur/tibia osteoplasty with internal fixation and Van Nes Rotationplasty of the left lower extremity and left sciatic neuroplasty was performed. The procedure lasted around eight hours long without complications. Estimated blood loss was 100 mL or less. The patient was transferred to the PICU for monitoring postoperatively. There were no wound complications postoperatively, and the patient received trimethoprim-sulfamethoxazole and cefepime for antibiotic prophylaxis. Nine days later, the patient was discharged with referrals to physical therapy and the appropriative postoperative wound care instructions.
The patient was treated with chemotherapy for five months postoperatively and responded well. Since finishing chemotherapy treatments, the patient has continued with physical therapy and has been fitted for a lower extremity prosthetic. Postoperative radiographs have demonstrated appropriate healing of the rotationplasty (). Six-month postoperative Positron Emission Tomography (PET) showed no evidence of local or distant metastatic disease. There was minimal uptake in the left lower extremity at the location of the rotationplasty. The procedure with the appropriate adjuvant chemotherapy was deemed successful.


A 76 y.o. female with a left open distal tibia/fibula fracture following trauma sustained after a fall from stairs, had reconstruction with a contralateral free gracilis muscle flap. During harvest, the course of the pedicle to gracilis muscle was found to be entirely intramuscular through adductor longus, requiring a perforator flap type of dissection to free up the 7 cm long pedicle. This practice added significant difficulty in raising the flap and increased the length of time of the overall procedure. Regrettably, this gracilis muscle flap subsequently failed 4 days post op. A decision to re-do the reconstruction with an ipsilateral free gracilis muscle flap was made, giving the team the opportunity to compare the anatomic variation of the pedicle to gracilis with the opposite side. On this occasion, the course of the pedicle was the one commonly encountered, that was in the intermuscular septum between adductor magnus and adductor longus muscle, ensuring a speedy and uneventful dissection. The outcome was successful.


A 74 y.o. female with a left open distal tibia/fibula fracture following trauma sustained after a fall from own height, had reconstruction with a contralateral free gracilis muscle. Again, during flap harvest the gracilis pedicle was found to have an intramuscular course through adductor longus, however, this time the course was partly intramuscular – 3 cm of pedicle length. Although the dissection was not as tedious as in Case 1, it still added in surgical effort and operative time. The outcome was successful.


A 65-year-old woman was admitted with pain in the right iliac fossa for three days. Laboratory tests showed elevated C-Reactive Protein (106 mg/L; normal value range <5 mg/L) and white blood cell count (11.400/mm3; normal value range 410.000/mm3). Contrast-enhanced computed tomography (CT) with sagittal (), axial () and volume rendering (VR) () views revealed perforated retrocecal appendicitis (white arrow) with an abscess (, white star). An intraluminal metallic foreign body with the typical shape of a hemostatic clip was found (, blue arrow). Review of the medical data revealed that the patient had undergone a colonoscopy six weeks previously with a somewhat hemorrhagic resection of a polyp of the cecum requiring two hemostatic clips (). One of these had migrated in the appendix causing its perforation. Surgical dissection of the parietal abscess (, white star) found the clip () and was completed by radical appendicectomy.


A 50-year-old Caucasian female with a history of pulmonary embolism, morbid obesity [body mass index (BMI) 48], chronic abdominal pain, and high grade papillary carcinoma of the bladder (T3bN1) status post chemotherapy, radical cystectomy, and Indiana pouch creation presented to the emergency department with altered mental status and a 3-day history of decreased urine output, foul-smelling urine, nausea, vomiting, and anorexia. She had been hospitalized multiple times in the past for urosepsis, hypokalemia, enterocutaneous fistula, abdominal wall abscesses, and cellulitis. She was most recently hospitalized 3 months prior for altered mental status and was successfully treated with piperacillin–tazobactam that was deescalated to oral ciprofloxacin after a urine culture grew pansensitive Escherichia coli and Proteus vulgaris. Notably, she performs in-and-out catheterization through her umbilicus several times per day to drain urine from the Indiana pouch.
On physical examination, the patient was belligerent and oriented only to place and person. Neurological examination was grossly normal by observation, but limited by severe patient combativeness. The patient was swinging wildly at staff and screaming during intake interview and examination. History obtained from her mother revealed that at baseline she was a pleasant and well-adjusted individual. Her abdomen was tender to palpation, but without distention or rigidity. A large midline scar was present without erythema or purulence.
Laboratory studies demonstrated hyperammonemia (289 μmol/L), hypokalemia (2.8 mmol/L), hyperchloremia (115 mmol/L), nonanion gap metabolic acidosis, normal liver function studies, mildly elevated creatinine (1.36 mg/dL), chronic leukopenia (2.8 × 1000/mm3), and thrombocytopenia (71 × 1000/mm3). Urinalysis showed increased pH (8.5) and pyuria with many bacteria. Urine cultures grew 10,000 to 50,000 colony forming units (CFU)/mL Enterococcus faecium. Blood cultures were negative. Arterial blood gas was unable to be obtained owing to her mental status.
Computed tomography (CT) imaging showed postsurgical changes of radical cystectomy with ileocecal diversion in the right lower quadrant; there was also ileolithiasis present (Fig. ). CT of the head was unrevealing.
The patient was initially admitted to the general medicine service, but because of significantly altered mental status and combativeness with concern for airway protection, the patient was ultimately transferred to the medical intensive care unit (ICU) for continued management. Of note, she had presented 3 months prior with similar symptoms that resolved quickly with a course of piperacillin–tazobactam with transition to oral ciprofloxacin. Because of this, she was empirically started on piperacillin–tazobactam, but was changed to daptomycin once urine cultures showed Enterococcus growth, and ultimately transitioned to vancomycin thereafter. She was treated with antibiotics for a total of 5 days. Her hyperammonemia was treated with lactulose, and her hypokalemia and nonanion gap metabolic acidosis were treated with potassium citrate.
Ultimately, she returned to her baseline mental status within 3 days and was discharged on lactulose and potassium citrate. Her discharge laboratories tests were notable for an ammonia level of 108 μmol/L and persistent hyperchloremic metabolic acidosis (Table ).


A 60-year-old female with a history of depression, chronic obstructive pulmonary disease, heart failure with preserved ejection fraction, hypertension, hyperlipidemia, and non-epileptiform seizure disorder presented to the emergency department (ED) for altered mental status after reports of seizure-like activity occurring at home. The patient was taking alprazolam at home but ran out of all her medications two weeks prior to admission. After arriving to the ED in a post-ictal state, she went into respiratory distress and required intubation. The patient was loaded with levetiracetam and admitted to the intensive care unit. Alprazolam was also started as it was thought that it may be likely that the patient’s episode was a result of benzodiazepine withdrawal. The patient was then extubated and transferred to the internal medicine floor for prolonged long-term electroencephalography (EEG) monitoring with video recording. The patient continued to have episodes of seizure-like activity while on levetiracetam that did not abate even when switched to phenytoin. These episodes were associated with chewing motions, head and body shaking, and rocking movements. During the majority of the seizures, the patient had low-amplitude generalized shaking episodes of the body with some rocking movements back and forth. All seizures appeared to be quite similar and lasted between 12 and 39 minutes. EEG revealed three episodes of clinical and electrographic seizures originating from the right hemisphere, maximal in the temporal region. These events were associated with prolonged and distinctive focal slowing in the right temporal region (Figure ).
Brain magnetic resonance imaging (MRI) was negative and did not reveal any abnormal intracranial enhancement (Figure ).
Serum thyroid function test showed thyroid-stimulating hormone (TSH) of 10.00 mIU/L (reference intervals: 0.45-5.33 mIU/L), free thyroxine (FT4) of 0.76 ng/dL (reference intervals: 0.7-1.70 ng/dL), and anti-TPOAb of 310.9 IU/L (reference intervals: 0.20-9.0 IU/L). Our patient’s workup also included a negative NMDA (N-methyl-D-aspartate) receptor panel to rule out autoimmune encephalitis. The findings on EEG along with an elevated TPOAb were suggestive of HE, and thus treatment with steroids was initiated. Given the indications for HE, the patient was treated with oral methylprednisolone 500 mg twice a day for five days. Her symptoms improved significantly and neuropsychiatric symptoms fully resolved. Endocrine was also consulted and recommended that the patient start levothyroxine 50 mcg daily. The patient was discharged in a stable condition, and follow-up visits over the next few months did not reveal any recurrence in seizures.


A 53-year-old male presented to the emergency room with a one-day history of nausea, vomiting, and epigastric pain. The patient’s pain was severe in intensity and located in the mid-epigastric region with no reported abdominal trauma. His pain was associated with constant nausea and two episodes of non-bilious and non-bloody emesis episodes. He denied any febrile episodes, gastrointestinal overt bleeding, and chronic weight loss. He did not have any history of cigarette smoking, alcohol abuse disorder, or illicit drug usage. His past medical history was significant for essential hypertension being treated with oral lisinopril 20 mg daily. On physical examination, he was hemodynamically stable with body temperature, blood pressure, and heart rate of 37.3 °C, 140/90 mmHg, and 84 beats/min, respectively. Abdominal examination revealed tenderness to palpation in the epigastric region without rebound tenderness or guarding. At this point, our differential diagnosis was broad which included viral gastroenteritis, peptic ulcer disease, acute pancreatitis, acute cholecystitis, and choledocholithiasis.
The following investigations were normal or negative: complete metabolic panel, urinalysis, lipid profile, electrocardiogram, and chest X-ray. A complete blood count showed a slight increase in white blood cell count to 12,000 cells/mm3 and serum lipase level was elevated at 1028 U/L. Calcium levels were 9.5 mg/dl (within the reference range), triglycerides were 54 mg/dl (reference for age <150 mg/dl), blood ethanol levels within normal limits, HIV test was nonreactive and IgG4 test was negative. Ultrasound of the abdomen showed no acute sonographic abnormality, no gallstones, and no ductal dilation. A CT scan of the abdomen showed pancreatic inflammation and pancreatic necrosis (Figure ).
Diagnosis of acute necrotizing pancreatitis was established on the basis of physical examination, elevated serum lipase levels, and imaging findings, and conservative management was initiated with goal-directed intravenous fluid support (Lactated Ringer's at 250 ml/hr), early enteral feeding, and pain control. Diet was cautiously advanced over the course of hospitalization. As lisinopril was thought to be the possible cause of necrotizing pancreatitis, it was added to his list of allergic medications, and a different class of antihypertensive medication was commenced.
Outcome and follow up
The patient showed gradual clinical improvement and was discharged home on day 7. He was noted to be asymptomatic on subsequent outpatient visits.


A 93-year-old man living in a nursing home presented to our emergency department with altered mental status, which occurred suddenly over the previous one hour. An initial history elicited from the nursing home staff failed to identify any risk factors. Examination revealed hypotension and severe hypoxia with oxygen saturation of 85% on 15 liters per minute oxygen with a non-rebreather mask. Chest radiograph showed infiltrates in the right upper lobe, but contrast computed tomography (CT) showed no pulmonary embolism. Suspecting an occult organ pathology, we ordered CT of the abdomen and pelvis, which demonstrated a left femoral neck fracture. Further inquiry of the nursing home staff revealed that the patient had fallen earlier on the same day, striking his hip on the floor. A point-of-care transthoracic echocardiogram (TTE) revealed an enlarged right ventricle, severe tricuspid regurgitation, and numerous white floating dots moving toward the right atrium from the inferior vena cava (IVC) ( and ), leading to the diagnosis of fat embolism syndrome (FES). Intravenous crystalloid and oxygen administration were initiated, but the patient expired five hours after admission despite supportive care.


A 74-year-old female presented to the emergency department for progressive left leg weakness that had resulted in multiple falls. An electrocardiogram (ECG) was obtained per . The ECG had a fixed frequency square wave artifact in all leads, not present on previous ECGs. The patient reported no implanted pacemaker and no neural stimulator, but he was wearing a BioTel event monitor (BioTelemetry, Inc, Malvern, PA), which had been placed in the prior month for syncope. The nurse turned off and removed the event monitor and replaced the ECG machine main cable. A repeat ECG was unchanged. The nurse then exchanged the room’s cardiac monitor leads. A repeat ECG showed complete resolution of the artifact, shown in . The initial set of cardiac monitor leads showed no visible damage but appeared to be the cause of this unique artifact.


A 39-year-old Russian woman was admitted to the hospital because of severe, progressively worsening dyspnea and hoarseness for 1 month. She was diagnosed with chronic rhinosinusitis with mild ulceration of the nasal mucosa at the Russian medical clinic 2 months prior, with aggravated nasal blockage and blood-mixed nasal secretion despite symptomatic treatment. One month later, the patient complained of dyspnea and hoarseness without cough, sputum, fever, and chills. She was a never-smoker, with no other significant medical or operative history.
Upon examination, saddle nose and nasal mucosal edema were observed. Other abnormal findings, including skin lesions, were not observed. On auscultation, a severe wheezing sound without crackles was noted in both upper lung fields. Blood examination revealed elevated C-reactive protein (3.55 mg/dL) and erythrocyte sedimentation rate (66 mm/h). The full blood counts (including red cell count, white cell count, and hemoglobin), renal function, and urine analysis were within the normal range. Chest radiography revealed no remarkable findings, and paranasal sinus X-ray showed maxillary sinusitis with a mucosal thickening. On chest computed tomography (CT), there was no abnormal findings in the lung parenchyma; however, there was a diffuse thickening of the lower laryngeal and upper tracheal wall from the cricoid cartilage level to the medial level of the thyroid gland (A,B).
We suspected GPA with upper respiratory tract manifestations, such as nasal discharge, saddle nose, and SGS. Serology showed positives values for c-antineutrophil cytoplasmic antibody (C-ANCA) (3+) and proteinase-3-ANCA (PR3-ANCA) (38.5 units). Anti-nuclear antibody, rheumatoid factor, and any viral markers revealed negative results. We planned to perform a biopsy of the nasal mucosa and examine bronchoscopy. Histological examination of the nasal mucosa revealed necrotizing granulomatous inflammation (A).
Bronchoscopy revealed an irregular luminal narrowing of the subglottic area and upper trachea by 50% (A). Finally, the patient was diagnosed with GPA with SGS based on the diagnostic criteria as defined by the American College of Rheumatology []. The patient received steroid pulse therapy (intravenous methylprednisolone, 1000 mg for 3 days) followed by oral prednisolone. Additional bronchoscopy was performed 5 and 12 days after steroid pulse therapy, and the upper trachea inflammation was improved (B). On the follow-up chest CT scan, the diffuse thickening of the trachea wall improved, and she was discharged with a low dose of oral steroids.
However, 5 months after discharge, the patient complained of aggravated dyspnea upon reduction of the oral steroids. She received an increased dose of steroid (methylprednisolone 1 mg/kg/day) with cyclophosphamide in Russia due to an aggravated dyspnea. She was hospitalized again, and bronchoscopy showed a severe SGS with an 80% level (C). An emergency tracheotomy was performed, and we discussed additional medical and surgical treatment of the severe SGS. First, carbon dioxide (CO2) laser surgery for luminal widening was conducted in four directions of the subglottic area, the front, back, left, and right, via laryngomicroscopic surgery, because the stenosis lesion was close to the vocal cord (approximately 1.5 cm).
Additionally, intralesional steroid injections were also performed (D). Although she received an increased dose of steroid, cyclophosphamide, and intratracheal interventions, she complained of dyspnea again 7 days later, and bronchoscopy showed a 70% level of SGS (E). She was transferred to the intensive care unit and mechanical ventilator support was provided due to the risk of respiratory arrest; however, this was ineffective. We discussed the surgery strategy with the thoracic surgery team. As a result of visual inspection in the operating room, a 70% level of SGS was identified immediately under the cricoid cartilage. The area where repetitive narrowing occurred despite several treatments was completely removed, and the resection length was approximately 2 cm. Special attention was paid to maintaining adequate ventilation of the patient during surgery, and paratracheal area dissection was carried out with caution to prevent excessive tension of the trachea resection and anastomosis site. Surgery followed by tracheal cannula removal was successful, and she was discharged with low-dose steroids and cyclophosphamide (F).
Two years later, the patient was admitted for dyspnea again, and a chest CT scan revealed several round or lobular nodules with central necrosis in both lungs (A,B). Bronchoscopy revealed no SGS but bronchial obstruction due to necrotic inflammatory change on the right middle lobe. Bronchial biopsy was performed on the right middle lobe. Necrotizing granulomatous inflammation was also observed on histopathological examination (B). Owing to frequent recurrence of GPA, rituximab (375 mg/m2 of body surface area) was administered with steroids weekly for 4 consecutive weeks, which led to regression of dyspnea, and the dose of steroid was tapered from 60 to 10 mg/day without relapse of SGS after 12 months of follow-up.


A 76-year-old woman (height, 149 cm; weight, 55 kg; body mass index, 24.8 kg/m2) suddenly experienced severe left femoral pain when walking with a T-cane. After this event, the patient was brought in a wheelchair to our hospital.
When the patient was 7 years old, she underwent several surgeries for septic arthritis and osteomyelitis of the left hip (Table ). After that, she could live a normal life without any hip pain. However, the left hip pain gradually increased in her late 20s, and she was diagnosed with severe left hip joint destruction. Subsequently, she underwent femoral head replacement surgery with an acrylic prosthesis when she was 31 years old (45 years previously). Her hip pain was relieved for over 30 years. When she was 70 years old, she had difficulty walking without a T-cane because the left hip pain recurred, and she noted a leg length discrepancy, which gradually increased. She had not gone to the hospital before this sudden onset of left hip pain. She had a medical history of hypertension and dyslipidemia, which are controlled by oral administration.
Physical examination of the left hip showed no active motion and remarkably limited passive motion due to severe hip pain. An anteroposterior radiograph showed severe bone stock loss with upper migration of the prosthesis in the acetabulum. Obvious prosthesis loosening was recognized in combination with the thinning of the femoral cortex (Fig. ). A lateral radiograph showed a periprosthetic fracture of the femur (Fig. ), and computed tomography demonstrated marked bone loss with a flimsy and fragmented acetabular roof (Figs. , ).
We took into account several factors, including the imaging findings, patient’s age, activities of daily living before the injury, and the patient’s choice before selecting a procedure. We decided to perform a Girdlestone resection arthroplasty by removing the acrylic prosthesis and conducting internal fixation of the periprosthetic fracture.
During the surgery, we recognized the severely loosened prosthesis and removed it easily by hand. There was granulation tissue formation around the implant. The femoral cortex was extremely thin, in which we could confirm the fracture site. For internal fixation, we combined an intramedullary nail (T2 femoral nail, Stryker Corporation, Kalamazoo, Michigan, USA) with plate fixation (NCB distal femur plate, Zimmer Biomet Holdings, Warsaw, Indiana, USA). In particular, a locking screw of the plate was placed through the intramedullary nail to reinforce the fixation (Fig. , arrow). We placed allografts around the fracture site and the proximal part of the nail to fill the defect. The top of the nail was covered with a cement block so that it would not irritate the acetabular bone or other soft tissues. Finally, several cerclage wires were placed around the plate and femur. The removed implant showed remarkable wear-out, especially in the acrylic head (Fig. ).
Physiotherapy was started the day after the surgery. Range of motion exercise for the hip was started as soon as possible. For the first 8 weeks after the surgery, toe-touch weight-bearing was permitted. After increments in partial weight-bearing, full weight-bearing was permitted 12 weeks after the surgery.
After 2 years and 9 months of follow-up, bone union was observed on radiography (Fig. ). The patient could live with negligible pain in her left hip, walking with the T-cane indoors and crutches outdoors. The Harris hip score of her left hip at the last visit was 74. No unanticipated events occurred during the follow-up.


A 55-year old male presented to an academic medical center in February 2020 with a six-week history of increasing midline back pain. He had a history of chronic mid- and lower back pain as the result of degenerative disc disease, however his pain had abruptly worsened in the 6 weeks prior to presentation. Pain was worsened with trying to sit up straight or walk. Pain was partially relieved with acetaminophen, ibuprofen, and oxycodone 5 mg tablets taken as needed. He reported no associated fevers, chills, or night sweats. He did not recall a febrile illness prior to the onset of symptoms. He did report anorexia and 15-pound weight loss in the last 6 weeks. His medical history included chronic obstructive pulmonary disease, chronic hepatitis C infection, hyperlipidemia, generalized anxiety disorder, and lumbar degenerative disc disease. His surgical history was notable for cervical spine laminectomy in the remote past. His social history was notable for heavy and ongoing tobacco use with a 60 pack-year smoking history. He denied alcohol or illicit drug use including intravenous drug use.
He was afebrile and hemodynamically stable on presentation. Physical exam revealed a gaunt Caucasian male in moderate distress due to pain. Poor dentition was noted. His cardiopulmonary examination was unremarkable. On spinal examination, no bony tenderness was elicited upon palpation of the thoracic and lumbar spine, however paraspinal tenderness was noted in the lumbar spine. Neurologic examination including strength and sensation of the lower extremities was intact. Babinski reflex was downward bilaterally.
MRI with and without gadolinium contrast revealed abnormal enhancement of the lower endplate of the L2 vertebral body as well as diffuse enhancement of the L3 vertebral body with irregularity of the upper endplate. This abnormal enhancement extended to the intervertebral disc. Findings were suggestive of discitis with osteomyelitis not excluded. Additionally, there was enhancement and thickening in the anterior epidural space measuring 2 mm × 4 mm which may represent epidural abscess or hematoma (Fig. ). Laboratory evaluation including CBC with differential and comprehensive metabolic panel was unremarkable. Sedimentation rate was 36 mm/hr. and C-reactive protein was 30.1 mg/L. Blood cultures were sterile.
Based on initial results of clinical, laboratory, and radiographic evaluation, antibiotic therapy was withheld. CT-guided aspiration of the L2-L3 disc was performed for culture and histopathology. Gram stain revealed Gram variable rods. Histopathology revealed fibrocartilage with degenerative changes and acute inflammation suggestive of discitis (Fig. ). He was seen in Infectious Diseases outpatient consultation, initially offered intravenous antibiotic therapy however patient requested oral antibiotic therapy for empiric treatment of discitis. He was started on treatment with cephalexin 1 g by mouth three times a day as well as linezolid 600 mg by mouth twice a day. (Initially, prior to the revelation of RBF infection, linezolid was chosen (in addition to cephalexin) because Gram stain revealed Gram-positive rods. The intention was to cover Corynebacterium spp. and coagulase-negative staphylococci, skin flora which tend to have resistance to beta-lactams but susceptibility to vancomycin or linezolid.) Cultures were sent to a reference laboratory, with growth noted on Mueller-Hinton media with 5% sheep blood. The organism was identified as Streptobacillus moniliformis by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF). On further history, it was revealed that patient had two pet rats and had sustained numerous bites in the last 1 year prior to symptom onset. In vitro susceptibility testing using broth microdilution revealed low MIC for penicillin (< 0.06 μg/ml), ampicillin (< 0.12 μg/ml), and ceftriaxone (< 0.06 μg/ml), with elevated MIC > 4 μg/mL for gentamicin. The patient’s symptoms dramatically improved with cephalexin so a decision was made not to switch to oral or IV penicillin. Linezolid was discontinued after 2 weeks once culture results were available. He completed 6 weeks of oral cephalexin therapy with dramatic improvement of back pain. The patient was offered TEE to evaluate for endocarditis. However, he declined to have the test done as this coincided with the onset of CoVID-19 pandemic.


A 50-year-old male agricultural worker consulted his primary care physician with dyspnea, cough, and fever, which had started one month before this consultation. He was a current smoker with no significant past or family history. His body temperature was 37.3°C, and his oxygen saturation was 92% in room air. Chest radiography and computed tomography revealed a right pleural effusion and large tumor that was dominant in his right main bronchus. There were multiple enlarged mediastinal, right hilar, and bilateral cervical lymph nodes. There were multiple small nodes in his left lung (Fig. A-C). Metastases were detected in his liver and left adrenal gland. Intravascular thrombi were found in the superior vena cava and right subclavian vein (Fig. B, C). His serum tumor marker levels were slightly elevated (neuron-specific enolase, 18.2 ng/mL; cytokeratin fragment, 6.3 ng/mL), and his D-dimer titer was high (14.7 μg/mL). However, other serum workup results were normal. Thoracoscopic pleural biopsy and ultrasound-guided needle biopsy of the left cervical lymph node (Fig. D) were performed. A microscopic examination of the pleural mass and cervical lymph node lesions revealed tumor proliferation of only spindle and giant cells (Fig. D). On immunohistochemical examination, the tumor cells were positive for CK AE1/AE3, vimentin (Fig. E), and CK7; weakly positive for TTF1 and CK5/6; and negative for CK20, p40, WT-1, and calretinin. Histopathological examination of the biopsies suggested LPC. Based on these results, the patient was diagnosed with progressive cT4N3M1c stage IVB LPC. There were no mutations of oncogenic driver genes (epidermal growth factor receptor, ROS1, and BRAF); however, the percentage of PD-L1-positive cells was 100%. A combination of atezolizumab (1200 mg), carboplatin (AUC6), and nab-paclitaxel (100 mg/m2) chemotherapy was administered. Apixaban (10 mg), an anticoagulant, was initiated. The tumor was invading areas superior to the carina, which were likely to get totally obstructed; therefore, 30 gray palliative radiation therapy of the mediastinal lesion was initiated simultaneously. A sudden onset of dyspnea and desaturation were observed one week after treatment initiation. Obstruction of the trachea by the tumor was suspected, and bronchoscopy was performed. The tumor had invaded the left bronchi (Fig. A); therefore, the tumor was excised with biopsy forceps, and additional APC therapy with 30 watts of electronic energy was administered to relieve symptoms and prevent further tumor invasion. Although no change was observed in the first two weeks after atezolizumab initiation (Fig. B), histological examination of the excised lung fraction revealed necrosis of the tumor cells (Fig. F, G). After two cycles of combination therapy, the invading tumor could be excised easily using biopsy forceps (Fig. C). Macroscopic examination of the excised tumor tissue showed severe necrosis (Fig. H). Histological examination showed sparse degenerated residual tumor cells in the abundant necrotic tissue, indicating a marked therapeutic effect (Fig. I, J). The patient has maintained a good response to triweekly atezolizumab therapy after four treatment cycles (Fig. E-G). Moreover, he achieved near-complete remission of the LPC without any recurrence, even after he was followed up for one year.


A nine-year-old girl was referred to the Pediatric Emergency Department for worsening headache episodes that began about a year previously associated with vomiting. Clinical evaluation showed she had no neurological abnormalities. Ophthalmological evaluation was then performed with the finding of signs of intracranial hypertension. Urgent brain computed tomography (TC) was performed, showing the presence of obstructive triventricular hydrocephalus caused by a voluminous median expansive cerebellar lesion (A). Brain and spinal magnetic resonance imaging (MRI) confirmed the presence of an intra-axial vermian lesion that came to lick the cistern of the quadrigeminal lamina (B–F).
The patient was then urgently subjected to endoscopic third ventriculocisternostomy neurosurgery with clear improvement of the intracranial hypertension and resolution of headaches and emesis. A few days later, the girl underwent suboccipital craniotomy surgery with macroscopically complete removal of the lesion. The post-operative course took place in the absence of significant complications. A brain MRI performed twenty-four hours after surgery documented the complete removal of the mass (G).
Histological examination revealed a biphasic hypocellular neoplasm, composed of synaptophysin-positive monomorphic small/medium-sized cells with a rounded nucleus and clear cytoplasm, that were focally arranged around small vessels (perivascular pseudorosettes) or around a fibrillar core (neurocytic rosettes). The glial cells consisted of spindle- or stellate-shaped astrocytic cells with elongated to oval nuclei forming a compact fibrillar meshwork with occasional Rosenthal fibers and oligodendroglial-like cells with round nuclei and clearly staining cytoplasm were present. Numerous microcalcifications were present. The proliferation index (anti-Ki67) was about 1%. In light of the identified findings, a diagnosis of low-grade mixed glioneuronal neoplasm with histological characteristics suggestive of the glioneuronal tumor forming rosettes of the IV ventricle (grade I according to WHO) was performed (A–C).
Two years after diagnosis, a nodular lesion in the surgical field was discovered on a follow-up MRI (H). The patient therefore underwent a second neurosurgery with complete removal of the mass from a macroscopic point of view (I). Histological analysis confirmed the recurrence of the same neoplasm (D–F).
Eight months after the second surgery, an MRI documented a second recurrence at the local level (L). The girl was therefore a candidate for proton therapy program (M). The proton treatment was carried-out for one month (A–C). Dose distributions of the 3-fields proton plan, optimized with single-field-optimization (SFO) technique to deliver 54 Gy relative biological effectiveness (RBE) in 30 fractions (1.8 Gy RBE per fraction).
Three years after the end of proton therapy, the patient has no evidence of further disease recurrence during the MRI performed at follow-up (N).


A 2-year-old boy presented with a slow growing mass under the tongue for 6 months. He was born without any anomaly. The development status was within average except delay speech due to the mass at floor of mouth. The physical examination revealed left sublingual cystic lesion measuring 1.0 × 1.0 cm. Ankyloglossia was found (). Cervical lymph nodes could not be palpated. Magnetic resonance imaging (MRI) demonstrated multi-lobulated cystic mass, size about 3.15 × 2.1 × 2.9 cm, which showed hypersignal intensity on T2 weighted image, hyposignal intensity on T1 weighted image, T1 fat suppression, T1 fat suppression with gadolinium involving left sublingual, submandibular, pharyngeal and parapharyngeal spaces (). The provisional diagnosis was lymphatic or venous malformation.
The operation was performed under general anesthesia. Frenotomy was performed. Complete cystic removal was successful with minimal leakage of cyst wall ( and ). However, sclerosing agent was injected at surgical site to prevent the residual undetected cystic malformation. Macroscopic examination of the specimen showed a multi-lobulated cystic cavity with leakage of fluid content (). Pathological examination was demonstrated a unicystic lesion lined by ciliated pseudostratified columnar and cuboidal cells. No goblet cells were discerned. Subepithelial stroma revealed fibrovascular tissue. There was no other mesenchymal component such as smooth muscle bundles and cartilages (). The final diagnosis was bronchogenic cyst. No postoperative complication was found. The long-term course was uneventful with no signs of recurrence at 1 year.


A 59-year-old man with a past medical history of atrial flutter status-post ablation, hypertension, osteoarthritis, and depression presented to the emergency department (ED) with a three-day history of a burning, erythematous rash involving the neck, forehead, and cheeks. He denied any history of allergies or taking new medications. He did report applying a new hair dye to his scalp and beard. No other environmental exposures were identified. Apart from an elevated blood pressure, all other vital signs were within normal limits. He was diagnosed with allergic contact dermatitis and was discharged home with a Solu-Medrol dose pack, ranitidine, loratadine, and instructions to return to the ED if symptoms worsened.
Six days later, he returned to the ED with worsening asymmetric facial swelling (right > left), difficulty breathing, dysphagia with upper and lower lip swelling, and an erythematous rash with wheals on his bilateral upper extremities and neck. Labs were notable for a leukocytosis of 16.5 cell/L with an unremarkable basic metabolic panel and venous blood gas. Bedside laryngoscopy was performed by ENT showed normal mucosa, no pooling of secretions, and no laryngeal edema. He was admitted for angioedema and started on dexamethasone, famotidine, diphenhydramine. His lisinopril was discontinued out of an abundance of caution in the setting of angioedema of unknown etiology. On hospital day 1, he became febrile, tachycardic, and tachypneic with hypoxia. Repeat laryngoscope examination showed the increased base of tongue fullness, pooling of thick clear secretions, and laryngeal edema.
He was naso-tracheally intubated for airway protection and was started on broad spectrum antibiotics, including vancomycin and cefepime for possible sepsis. A computed tomography scan of his neck showed extensive soft tissue swelling and edema with extension to the anterolateral neck. Dexamethasone, famotidine, and diphenhydramine were continued during his entire. Blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA) in two bottles and his antibiotics were narrowed to vancomycin. He was started on continuous renal replacement therapy (CRRT) for worsening renal failure. Dermatology was consulted for possible PPD allergy from recent hair dye use. PPD patch test was not performed as he was on systemic steroids and the yield was thought to be insignificant. On hospital day 3, he developed upper and lower lip mucosal lesions with necrotic erosions and overlying hemorrhagic crust. He was started on Valtrex for presumed (and eventually confirmed) herpes simplex virus 1 (HSV-1) infection. On hospital day 5, he showed significant clinical improvement with discontinuation of vasopressors and transition to intermittent hemodialysis. However, on hospital day 6, he became febrile to 107 F with a worsening metabolic profile including refractory hyperkalemia with prolonged PR and QRS intervals unresponsive to medical therapy and CRRT. His creatine phosphokinase was elevated to >22,000 units/L, and he developed bullous lesions with serous drainage of his right lower extremity as well as erythema and induration of his left axilla. Given his clinical deterioration and concern for compartment syndrome, emergent bedside fasciotomy was performed with no evidence of necrotic muscle. Shortly after the procedure, the patient went into cardiac arrest and expired.


An 87-year-old woman was admitted to Tokuyama Medical Association Hospital because of two syncopal attacks within past 2 days, from which she recovered in a few minutes without residua. She had been treated for a long time for chronic renal failure, of which cause was suspected to be hypertensive and arteriosclerotic renal disease without diabetes mellitus. She had been given with calcium polystyrene sulfonate 4 g, azocemide 30 mg, benidipine hydrochloride 8 mg, telmisartan 40 mg, doxazosin mesylate 0.5 mg, and febuxostat 10 mg every day for hypertension and renal failure. Moreover, she had severe constipation, for which three kinds of laxatives had been given, including dioctyl sodium sulfosuccinate 90 mg mixed with casanthranol 45 mg, magnesium (Mg) oxide 660 mg (containing Mg 398 mg) and sennoside 12 mg every day, among which Mg oxide was started 4 months before.
On admission, her blood pressure was 113/84 mmHg with heart rate 78/min, regular. She looked somewhat obtunded, although she showed correct orientation and ordinary conversations with mild dysarthria and was judged to have normal consciousness. She could not stand up and walk due to mild muscle weakness of the lower limbs. Electrocardiography (ECG), chest x-ray studies, and Holter ECG for 24 h were all within normal limits. Head magnetic resonance imaging (MRI) computed tomography, including diffusion-weighted modality, revealed a few old lacunar infarctions in the white matter of the cerebral hemispheres, without abnormal intensity lesions in the basal ganglia and frontal lobes. Electroencephalography (EEG) disclosed diffuse and slow wave (6–7 Hz) basic activities, suggesting cerebral hypofunction rather than an impaired consciousness. Laboratory examination of serum on hospital day 1 disclosed a decrease in albumin (3.5 g/dL) and an increase in blood urea nitrogen (49.0 mg/dL), creatinine (2.59 mg/dL), K (5.2 mEq/L) with a decrease in eGFR (14.0 mL/min/1.73 m2) (Table ), a slight increase in C-reactive protein (CRP, 1.8 mg/dL) and normal aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transpeptidase (γ-GTP), Na, Cl and glucose concentrations. Complete blood counts (CBC) revealed a decrease in red blood cells (RBC, 298 × 104/mL), hemoglobin (Hb, 9.8 g/dL), and hematocrit (Ht, 29.9%); an increase in white blood cells (WBC, 10.5 × 103/mL) with increased stab and polymorphonuclear WBC percentage (80.5% in total); and normal platelet count. Urinary examination revealed mild proteinuria (< 100 mg/dL) without other abnormalities.
Her hospital days were uneventful until the 10th hospital day, when she began to show queer involuntary movements. While she sat to eat meals holding chopsticks with the right hand, her right arm suddenly dropped. Then, she again elevated the right arm, followed by sudden drops and difficulty to eat. Her left arm also dropped when elevated. While she was sitting on the bed, her neck sometimes dropped forwards and the trunk fell ahead. When she was standing with help, her legs lost power suddenly, falling without aids. Therefore, she was obliged to be bed-ridden. She said the phenomena were very troublesome, although she could not tell whether she had experienced such abnormal involuntary movements in the past. On neurologic examination, it was clear that these symptoms were asterixis, and when her arms were kept elevated by an examiner, typical flapping tremor was seen in both hands. Her intellectual function was evaluated with the revised Hasegawa dementia scale (HDS-R) [], which was verbal cognitive test known to be as useful as the mini-mental state examination (MMSE). In the clinical practice, an HDS-R score of 25–30 suggests normal cognition, 20–24 mild cognitive impairment, 15–19 mild dementia, 10–14 moderate dementia, and –9 severe dementia. Her score was 10, moderately low. She showed mild dysarthria. Deep tendon reflexes were decreased in the upper limbs and absent in the lower limbs without extensor plantar reflexes. Muscle tonus was normal in all limbs. Muscle strength was normal at the beginning, however, followed by transient loss of power due to asterixis. Sensory functions were obscure because the exact answers were not obtained.
In this case asterixis involving neck, trunk and all limb muscles were obvious, and because of lack of focal neurologic signs, metabolic causes were suspected of. Serum ammonium was 30 μg/dL (normal 30–80) on hospital day 10; therefore, hepatic failure and portal systemic shunt were excluded. At this time renal failure increased in severity because there were a more increase in serum urea nitrogen (101.2 mg/dL), creatinine (3.10 mg/dL), uric acid (8.5 mg/dL), and K (6.9 mEq/L) with decreased eGFR (11.5 mL/min/1.73 m2). CBC revealed a more decrease in RBC (263 × 104/mL), Hb (8.9 g/dL), and Ht (26.4%), and a mild increase in WBC (9.7 × 103/mL). Other serum electrolytes were examined at this time, revealing a slight decrease in Ca (4.4 mEq/L, normal 4.5–5.5), and an increase in inorganic P (3.7 mEq/L, normal 1.6–2.7) and Mg (3.6 mEq/L, normal 1.6–2.1).
The cause of asterixis might be azotemia from the literature []. However, we considered hypermagnesemia would be more important. Mg oxide 660 mg per day had been given as one of the laxatives for the past 4 months, and it was withdrawn immediately after hypermagnesemia was detected. Thereafter, her asterixis gradually improved, and on the 17th hospital day asterixis of the neck and trunk disappeared, and upper and lower limbs dropped less frequently than before, and with mild flapping tremor of the fingers. At this time, serum Ca was 4.3 mEq/L, inorganic P 3.5 mEq/L, and Mg 3.1 mEq/L, still showing an increase in Mg concentration. Renal failure was unchanged in severity. Surface electromyography (EMG) exhibited asterixis of the arm muscles, because while the right arm was elevated, irregular lapses of the contractions of m. triceps brachii appeared, and while the forearm was kept elevated by an examiner, the loss of power of the wrist extensor muscles was demonstrated (Fig. ). Based on these data, the most probable cause of asterixis seemed to be hypermagnesemia. Until the 24th hospital day, asterixis completely disappeared. However, she showed weakness of the hands with grip power 1 kg on the right and 3 kg on the left, and weakness of flexor and extensor muscles of the feet. There was hyperalgesia of bilateral hands and feet. Her gait needed assistance. At this time, serum Ca was 4.2 mEq/L, inorganic P 2.2 mEq/L, and Mg 1.9 mEq/L, showing a slight decrease in Ca concentration and normal inorganic P and Mg concentrations. Renal failure slightly improved because the serum urea nitrogen was 55.2 mg/dL, creatinine 1.95 mg/dL, K 5.3 mEq/L, and eGFR 19.2 mL/min/1.73 m2.
As to drug therapy after admission, calcium polystyrene sulfonate was increased from 4 g to 10 g every day on admission in order to lower serum K, and other drugs were not changed except for the withdrawal of magnesium oxide on the 10th hospital day. Concerning renal failure, hemodialysis therapy was explained to the patient and her family, although they did not ask it and rehabilitation alone was continued.


A 62-year-old female patient, agitated, disorientated, with hypothyroidism and hypertension, was hospitalized due to a syncopal episode. The clinical examination was inadequate due to hemodynamic instability.
Upon arrival, laboratory analyses showed WBC 35×109/L, hematocrit 25%, RBC 3,2×109/L, C-reactive protein level 418.9 mg/L, procalcitonin level 0.7 ng/mL, lactate dehydrogenase value was 746 U/L, and body temperature was 33°C, which led to a diagnosis of sepsis.
The echocardiography showed a 20-mm pericardial effusion and the color Doppler scan showed passable internal and external carotid arteries as well as vertebral arteries; however, left internal jugular and subclavian veins showed the presence of sizeable fresh coagulum. The aortic root was of regular dimension, and the ascending aorta was 39 mm, without sings of aortic dissection. To make the diagnosis, a multi-slice computed tomography (MSCT) was performed.
Computed tomography with contrast agent was performed and a 58×58 mm PAA with a 10 mm proximal neck, partially deriving from the aorta and partially from the brachiocephalic trunk, was discovered ( and ). It contained a 22-mm circumferential coagulum, which was in sternal contact and compressing the brachiocephalic trunk. Due to the high risk of rupture of the pseudoaneurysm, it was decided that the patient undergoes surgery despite the septic condition.


A 38-year-old man with no major comorbid conditions presented to the emergency room (ER) with the symptoms of cough of 3 days' duration. He had nausea and loss of appetite.
He also reported subjective fevers at home. Upon presentation, he denied shortness of breath, but worsening cough prompted him to seek medical attention.
On initial evaluation, he did not appear dyspneic and his oxygen saturation was 92% on room air. His initial chest roentgenogram (X-ray) revealed the bilateral interstitial infiltrates. He was hospitalized for monitoring of his respiratory status. His nasopharyngeal PCR swab for SARS-CoV-2 was positive, and he was given oral hydroxychloroquine and azithromycin. His laboratory parameters were significant for aspartate aminotransferase (AST) of 44 U/dL, lactate dehydrogenase (LDH) of 410 U/dL, C-reactive protein (CRP) of 32 mg/dL, and ferritin of 900 ng/dL. His random blood glucose and fasting glucose levels were 176 gm/dl and 116 gm/dl, respectively. His hemoglobin A1C (HbA1C), performed 2 weeks after presentation, was 6.1%, suggesting previously undiagnosed prediabetes. He remained clinically stable and had no worsening of his respiratory status, his oxygen saturation on room air improved to 96%, and he was discharged from the hospital on day 6.
A week after the hospital discharge, he reported new-onset diarrhea and mild abdominal pain. His symptoms started 2 days after discharge. He stated that his abdominal pain radiated to back and improved on bending forward. There was no worsening of abdominal pain with meals. His stool consistency was loose and he had 5 to 6 bowel movements per day. He denied any blood in the stool. He also denied nausea and vomiting. Stool Clostridium difficile toxin and glutamate dehydrogenase antigen (GDH) were negative. Fecal leucocyte stain was negative, but fecal fat was reported to be positive. Repeat evaluation of fecal fat remained positive. Due to persistent abdominal pain, serum lipase was performed, and it was found to be approximately 3 times the upper limit of normal (176 U/dL). He declined computed tomography (CT) of the abdomen. He had an ultrasound of his abdomen performed previously 6 months earlier which revealed fatty liver. Fecal elastase test was reported to be 110 μ/gm of stool. Given the possibility of exocrine pancreatic insufficiency (EPI), he was initiated on pancreatic enzyme replacement with 2 tablets of delayed release pancrelipase capsule comprising 36000 (36 K) units lipase with each meal. Oral omeprazole 40 mg once a day was also added. His diarrhea resolved with the initiation of pancreatic enzyme supplementation. He reported recurrence of diarrhea with discontinuation of pancreatic enzyme supplementation. Symptoms once again resolved with resumption of pancreatic enzyme therapy.


A 53-year-old man with a history of hypertension and obesity presented with cough, fever, and shortness of breath of 4 days' duration. He also reported diarrhea for 2 days. He had 5-6 episodes of nonbloody watery bowel movements daily. The worsening shortness of breath prompted him to seek medical attention. He drank alcohol occasionally and had reported 2 to 4 drinks in one year. He was a nonsmoker. On initial assessment, he had mild respiratory distress, with oxygen saturation of 88% on room air, pulse of 112 beats per minute, and blood pressure of 164/92 mmHg. His chest X-ray revealed perihilar infiltrates. Electrocardiogram showed left ventricular hypertrophy, and subsequent echocardiogram revealed ejection fraction of 62%.
He was hospitalized for monitoring of his respiratory status. He was initiated on oral hydroxychloroquine and azithromycin. He required venti-mask with the FiO2 of 50% to achieve oxygen saturation of 96%. His laboratory results at the time of presentation showed lactate dehydrogenase (LDH) of 450 U/dL, CRP of 42 mg/dl, ferritin of 870 ng/dL, and d-dimer of 380 U/dL. His alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were 88 U/dL and 65 U/dL, respectively. He had random blood glucose of 98 gm/dL at the time of presentation. Fecal leucocytes were negative. Stool tested negative for the GDH and Clostridium toxin A and B. However, his fecal fat was positive. His serum lipase was elevated to 132 mg/dL on 5th day of hospitalization. He did not report any abdominal pain, but CT scan of the abdomen with IV contrast done for the evaluation of the elevated lipase revealed findings suggestive of mild acute pancreatitis. There was no pancreatic necrosis or peripancreatic collection. He was also noted to have liver steatosis with a fat sparing liver lesion. The ultrasound of the abdomen did not reveal any gallbladder stones. His pneumonia improved, and he was discharged home. He reported persistent diarrhea. He was initiated on pancreatic enzyme replacements. The result for fecal elastase could not be obtained due to insufficient stool specimen collection. Patient reported resolution of diarrhea after initiation of oral pancreatic replacement therapy. He noticed recurrence of diarrhea with discontinuation of the pancreatic enzyme replacement therapy.


A 69-year-old man with a history of hypertension and compensated diastolic congestive heart failure (CHF) presented with cough, shortness of breath, malaise, fever, and severe myalgia of 5 days' duration. He was a nonsmoker and denied any alcohol use in the past. He had oxygen saturation of 78% on room air, and his X-ray chest revealed bilateral infiltrates. His nasopharyngeal swab test was positive for SARS-CoV-2. He was monitored in the critical care setting and required high-flow oxygen. His lactate dehydrogenase (LDH) level was 680 U/dL, ferritin was 972 ng/dL, and CRP was 56 mg/dl, and his liver function test revealed elevated transaminases with ALT and AST of 68 U/dL and 92 U/dL, respectively. He also developed acute renal insufficiency with a serum creatinine of 3.1 mg/dL. His random blood glucose was 210 gm/dL and fasting blood glucose was 172 mg/dL. He was given amoxicillin/clavulanic acid, azithromycin, and hydroxychloroquine. Four days into his hospitalization, he developed periumbilical abdominal pain and nonbloody water diarrhea with 5 to 6 bowel movements per day. Initially, diarrhea was considered to be a SARS-CoV-2-related symptom. Stool test for Clostridium difficile toxin was negative. His fecal leucocyte was negative as well; however, the fecal fat stain test was positive. His serum lipase level was elevated (189 mg/dl). His respiratory status precluded from obtaining a CT scan of the abdomen. He was empirically managed with pancreatic enzyme replacement for possible exocrine pancreatic insufficiency. He was given oral pancreatic enzyme supplement 4 capsules with each of them consisting of 8000 units of lipase. His symptoms improved after one day for the pancreatic enzyme replacement initiation. His respiratory status improved, and he was discharged with a follow-up tele-health appointment. Patient was lost to follow-up upon discharge.


A 50-year-old Caucasian man, nonsmoker, was referred to our clinic with the chief complaint of floaters in his left eye for the past 3 days, with no significant family history. He had been diagnosed with bipolar disorder 8 years earlier and was taking olanzapine, fenofibrate, and bisoprolol. He had no other systemic disease or risk factors for CRVO.
Upon examination, his best-corrected visual acuity (BCVA) was 0.7 in the left eye and 1 in the right eye, with normal pupillary reflexes and with no relative afferent pupillary defect (RAPD) in either eye. His intraocular pressure (IOP) was 18 mmHg in his right eye and 20 mmHg in his left eye. Slit-lamp examination of the anterior segment of both eyes was normal, without cataracts. The fundus showed signs of CRVO, with tortuous and dilated retinal veins and hemorrhages, with subhyaloid hemorrhage and intraretinal hemorrhage in the posterior pole and superior and inferior retina, without macular edema (Fig), confirmed by optical coherence tomography (OCT) (Fig. ). In the fundus examination, there was no sign of neovascularization elsewhere (NVE) or at the disc level (NVD).
In fluorescein angiography and OCT angiography (Fig. ), although we could not completely visualize the posterior pole because of the large subhyaloid hemorrhage, there was no significant capillary nonperfusion area or ischemic area, with no posterior segment neovascularization, and we could not detect any leakage to confirm macular edema.
Although we could not completely exclude the ischemic classification of thrombosis because of subhyaloid hemorrhage, other findings such as visual acuity and the type of thrombosis seemed to be nonischemic (Fig. ).
We ruled out other probable differential diagnoses and risk factors which lead to CRVO through complete physical exam including blood pressure control in 24 hours, chest X-ray and whole-body computed tomography scan to identify any other hemorrhage, and blood analysis including complete blood count (CBC), glucose, urea, creatinine, lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein, prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT), fibrinogen level, proteins, antiphospholipid antibodies (APA), homocysteine blood level, antithrombin III, protein C and S, factor V Leiden, prothrombin mutation, angiotensin-converting enzyme (ACE) level, other autoantibodies, and human leukocyte antigen (HLA)-B51.
Finally, we confirmed the probable side effect of olanzapine as another antipsychotic medication in his recent CRVO which was not previously reported.
We discontinued olanzapine to prevent any further complications related to this drug, and we added salicylic acid with an anticoagulant dose of 100 µg per day.
In the second follow-up visit after 2 months, his BCVA was 0.7 in the left eye and 1 in the right eye. His IOP was 16 mmHg in his right eye and 18 mmHg in his left eye.
Gonioscopy was performed by Goldmann gonioscopy, and the presence of neovascularization in the angle was ruled out. His fundus showed signs of exudation of previous subhyaloid and subretinal hemorrhage in the superior juxtapapillary zone, without any NVE.