A 74-year-old male with a history of previously excised melanoma metastatic to a mesenteric lymph node who had been in remission for 2 years before presenting for additional evaluation of persistently abnormal small bowel findings on a surveillance PET-CT scan. Patient reported feeling well without complaints. He had a medical history of hypothyroidism, GERD, lymphocytic colitis on loperamide therapy, and metastatic melanoma. He was originally diagnosed with melanoma on his back ten years prior to this presentation. His melanoma history includes a left axillary recurrence over 3 years prior to this presentation, initial adjuvant therapy with pembrolizumab that was discontinued after 2 doses due to lymphocytic colitis, and laparoscopic resection of a metastatic mesenteric lymph node that was excised 2 years prior to this presentation. The patient's other surgical, family, and social history are unremarkable.
Since his previous lymph node excision two years prior to this presentation, multiple surveillance PET scans had shown intense focal FDG uptake in the distal small bowel, deemed to likely be inflammatory in nature although melanoma recurrence and metastasis remained a possibility. The patient underwent PET-CT scan in the weeks prior to presentation which showed interval increased FDG uptake at the distal small bowel near the ileocolic junction (). This finding featured an SUVMax of 16.4, previously noted to be an SUVMax of 7.4 at prior PET/CT. Given recurrent findings, patient underwent capsule endoscopy which revealed ulcerated, nodular, congested, and erythematous mucosa at 6 hours, 26 minutes, and 12 seconds past swallowing capsule, with location deemed likely in distal ileum (Figures and ). Given this finding, patient underwent retrograde double-balloon enteroscopy (DBE) which showed ulcerated, edematous mucosa in the distal ileum at 95 cm from ileocecal valve (), with biopsies consistent with metastatic melanoma as confirmed by the presence of melanin in tumor biopsy and positive staining. The site of the lesion was marked with SPOT tattoo to allow for intraoperative localization. Patient underwent surgical resection of this area (), which also revealed the second area of ileal metastasis (2.8 cm of the ileum) separate from the tattooed area (2.6 cm), and seven lymph nodes removed were negative for metastatic melanoma. The surgical resection specimens also demonstrated the presence of melanin and had positive staining for melanoma (). Patient underwent surveillance DBE 8 months after initial procedure, which showed patent anastomosis and normal mucosa up to 110 cm from the ileocecal valve. Patient has undergone PET/CT scans every 3 months following surgical resection, and he was without evidence for recurrent or metastatic disease at his most recent clinic evaluation one year from surgery.


A 71-year-old man with cardiovascular risk factors significant for morbid obesity, diabetes mellitus type 2, hypertension, hyperlipidemia, Crohn's disease, deep vein thrombosis (DVT), multiple, pulmonary embolisms and an IVCF placement 8 years prior was referred to vascular surgery for management of 3.3 × 3.6 cm contained ruptured APA. The patient underwent a C.R. Bard Eclipse placement in 2011 after being admitted with a recurrent DVT, pulmonary embolisms, and multiple lower extremity hematomas while on coumadin. His medication was switched to apixaban during the index hospitalization, and he has not suffered another PE since.
A computed tomography angiography (CTA) in late 2018 revealed a protrusion of the struts of the IVCF with encroachment on the aortic wall and surrounding inflammatory changes. Because he was asymptomatic and a review of prior imaging revealed no change in the appearance over the preceding years, he was monitored. A CTA performed 2 years later for abdominal pain revealed a focal penetration of the aorta with pseudoaneurysm formation measuring 3.3 × 3.6 cm in diameter at the level of the inferior mesenteric artery (IMA) takeoff (). The infectious workup was negative. The patient refused IVCF removal, but consented to endovascular repair of the APA.
The procedure was performed in a hybrid room under general anesthesia. Systemic anticoagulation with bivalirudin was initiated after gaining percutaneous bilateral common femoral artery access. Aortogram confirmed the presence of the APA (, A). The IMA was selectively cannulated and embolized using Nester coils (Cook Medical, Bloomington, Ind) while preserving collateral flow via a branch to the internal iliac artery and arc of Riolan.
To avoid contralateral gate compression and difficulty cannulating in a nonaneurysmal aorta, we elected to precannulate the gate using a technique we have recently reported (, B). The remainder of the procedure was carried out in the standard fashion using a 23 × 14.5 × 120-mm Excluder Endoprosthesis and 18-mm limbs (W. L. Gore & Associates, Flagstaff, Ariz). Completion angiography demonstrated excellent exclusion of the pseudoaneurysm with no endoleak (, C). The patient's pain resolved and he was discharged home on postoperative day 1. The 1-month follow-up CTA demonstrated the endograft in good position, no flow within the pseudoaneurysm, and no endoleak ().


A 36-year old nulliparous female patient presented to our emergency department with acute lower abdominal pain, general discomfort, and elevated inflammatory markers. Her past medical history included obesity with a body-mass-index of 40, superficial vein thrombosis of the upper extremity and achilles tendon rupture. No bleeding abnormalities were reported. Cervical cancer screening including PAP smear was regularly performed and inconspicuous, most recently less than one year ago. On physical examination the patient presented significant rebound tenderness and involuntary guarding of the lower abdomen with a positive Blumberg sign. Speculum examination showed normal external female genitalia, normal vaginal epithelium, no abnormal discharge and a non-suspicious cervix. Significant cervical motion tenderness was observed during vaginal palpation. On vaginal ultrasound, the anteverted and anteflexed uterus showed no suspicious lesions. Bilateral adnexal masses with both cystic and solid aspects, remarkable hyperperfusion as well as free intraabdominal fluid were noted (Fig. a, b), suspicious for tubo-ovarian abscesses. During emergency laparoscopy, ruptured ovarian tumors with up to 8 cm sized cauliflower-like masses comprised of small cysts foremost of the right, but also of the left ovary were detected (Fig. a, b) and an enucleation of the cystic structures was performed.
On histopathological examination, a neoplasm with adeno-papillary growth of the inner female genital tract was described and the diagnosis of an eBOT with microinvasion of up to 1 mm was established. Following thorough postoperative discussion of the treatment options and their clinical impact, the patient decided against a fertility preserving approach favoring radical surgery including hysterectomy. Subsequently, laparoscopic staging was performed with hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy and extensive peritoneal staging. In final histopathological results, an unexpected, HPV-high risk associated, intracervical endometrioid adenocarcinoma of the cervix uteri with a transversal diameter of 12 mm was diagnosed so that this was attributed as the primary tumor with ovarian metastases (Fig. a-f). Consistent with HPV high-risk association, the tumor showed strong immunohistochemical expression of p16 in the ovary and in the endocervix. CT scan of the thorax and abdomen showed no other distant metastases so that a subsequent laparoscopic lymph node staging was carried out to excluded tumor-infiltrated pelvic or para-aortic lymph nodes. Accordingly, final histopathological assessment led to a tumor stage of pT1b1 with ovarian metastases, pN0, L0, V0, Pn0, G2, R0, FIGO IB1. As individual decision making, an extended adjuvant treatment was applied consisting of chemoradiation followed by chemotherapy with four cycles paclitaxel and carboplatin according to the protocol of the currently recruiting OUTBACK trial (NCT01414608).


Before presentation to our hospital, the 27-year old nulliparous female, was diagnosed with a left-sided endometrioid BOT at an external institution. She had already undergone fertility-sparing surgery with adequate staging procedures including left-sided salpingo-oophorectomy and omentectomy by open surgery. External histopathological findings revealed a single peritoneal implant in the left paracolic gutter. Three months later she presented for first consultation to our department with a highly suspicious contralateral ovary in vaginal ultrasound (Fig. a, b). On physical examination, the patient presented with no acute distress and a soft, nontender, nondistended abdomen. She denied any abnormal vaginal bleeding. Pelvic examination was unremarkable as well as cervical cytology. Vaginal ultrasound revealed a 7 mm thickness endometrium of with slightly inhomogeneity but without any suspicious lesions. The right ovary presented highly suspicious for malignancy consisting of cystic and solid aspects with abnormal perfusion.
According to her explicit request for fertility preservation, we performed a re-laparotomy with salpingo-oophorectomy of the right side and cryoconservation of healthy appearing ovarian tissue. To increase oncological safety in this constellation, hysteroscopy and curettage was additionally performed. Pathological evaluation revealed a progression of the previously diagnosed eBOT to a well-differentiated endometrioid ovarian carcinoma limited to the ovary and sized 25 mm, positive peritoneal washings and a corresponding FIGO stage IC3 with accompanying superficial endometriosis in peritoneal biopsies. Unexpectedly, uterine curettage revealed an endometrioid endometrial cancer (Fig. a-d). As a consequence, completion surgery consisting of a total abdominal hysterectomy, pelvic and para-aortic lymphadenectomy was performed. No further peritoneal lesions were noted. Histopathological examination diagnosed a moderately differentiated endometrioid endometrial cancer without extrauterine tumor growth with a corresponding FIGO stage IA (pT1a pN0 (0/65) L0 V0 Pn0 G2 R0). While both carcinomas of the ovary and of the endometrium displayed similar histomorphological and immunohistochemical characteristics, the possibility of an ovarian dissemination of the endometrial carcinoma could not be ruled out at this point. However, due to the limited extent of the endometrial cancer and the patient´s history of eBOT, it appeared more likely that two independent carcinomas developed synchronously. No mismatch repair deficiency was detected. Finally, an adjuvant mono chemotherapy consisting of six cycles carboplatin was recommended.


We analyzed a 21-year-old female patient showing linear verrucous lesions only in the right palmar area (A). Consanguinity of parents was evaluated and excluded. No other relatives (father, mother and sister) are affected by any dermatological condition. The patient had lesions that appeared since childhood. In our clinical examination, multiple, well demarcated, hyperkeratotic and yellowish streaks were evident in the right palm, following the Blaschko lines, but completely absent in the left palm (A). No similar lesions were observed in other cutaneous regions. Moreover, a complete screening of all skin district including flexures did not identify hyperkeratosis or ichthyotic lesions. Interestingly, the lesions have a nevoid distribution that intercross the palmar creases. They consist of three main stripes localizing across the radial longitudinal crease, just below the thenar eminence, another localized along the middle and thenar creases, and one more external from the hypothenar eminence to the distal transverse crease.
After this first examination, a further patient reevaluation was conducted to check the possible presence of leukoplakia and of signs of laryngeal squamous cell carcinoma (LSCC). This is because the molecular analysis showed the presence of a single nucleotide polymorphism (SNP) identified by rs14024 recently associated to an increased risk of LSCC []. The dermatological and otolaryngological screening did not reveal abnormalities.


We present a 48-year-old male who arrived at our academic level I trauma center complaining of left shoulder, back, and hip pain with corresponding flail chest. Initial workup identified several injuries, including a left pubic ramus fracture, a left sacral fracture, a left scapular fracture, a chronic right dislocated temporomandibular joint, a left basilar pulmonary contusion, a left hemopneumothorax, a small retroperitoneal hematoma without active extravasation, and flail chest. While flail chest was identified, the initial computerized tomography (CT) report did not identify all the patient’s rib fractures. He was not originally deemed an optimal surgical fixation candidate for several reasons related to the initial imaging: many of the fractures were too close to the corresponding transverse process for fixation, many of the fractures were in line with minimal displacement, and the costocartillage fractures were not readily discernible. Due to the extent of his injuries, the decision was made to admit him to the Surgical Trauma Intensive Care Unit (STICU).
On hospital day (HD) two, orthopedic surgery was consulted and recommended nonoperative treatment of his pelvic and scapular injuries. A thoracic epidural catheter was placed for pain management, and a chest tube was inserted for an enlarging hemothorax. The patient was transferred to a lower level of care but later developed respiratory distress and was readmitted to the STICU on BiPAP. On HD 10, he was intubated for further respiratory insufficiency and altered mental status. A repeat chest CT scan then revealed greater displacement and offset of the previously identified fractures as well as improved visibility of the costocartillage fractures (Table ). He was then deemed to be an appropriate surgical candidate on HD 13 and received surgical stabilization of rib fractures (SSRF) on the left side. He returned to the operating room on HD 15 for completion of SSRF. MatrixRIBTM plates and sternal locking screws (MatrixRIBTM Fixation System, DePuy Synthes, Raynham, MA) were used across six separate ribs in nine total locations (Table ). Other fracture locations were not deemed appropriate for fixation due to the patient’s body habitus and concern for damage to surrounding tissue. The procedures were without complications, and he returned to the STICU postoperatively.
He was able to be extubated on HD 16. On HD 40, the patient was reintubated for respiratory insufficiency but afterward became bradycardic with pulseless electrical activity (PEA) and required cardiopulmonary resuscitation (CPR) with the return of spontaneous circulation after two rounds of defibrillation. This corresponded to SSRF postoperative day 27. After his cardiac event, CT revealed hardware failure with one locking screw separating from a plate at the left costochondral junction and another along the sternum (Table ). The sternal plate had partial separation from the sternum as well (Figure ). An isolated hardware failure was also noted at the posterolateral segment of a rib close to the transverse process of the corresponding vertebrae. The screw in this instant was not freed to the same extent as was the sternal and costochondral segments and could potentially have been an imaging artifact. The patient ultimately died on HD 56 from PEA arrest.


A 28-year-old male with a past medical history (PMH) of type I diabetes mellitus and alcohol abuse presented to the emergency department (ED) with complaints of abdominal pain. His symptoms started on awakening that morning. He described it as a sudden onset epigastric pain, rated 10/10 and non-radiating. The patient also became nauseous and had episodes of non-bilious, non-bloody vomiting, which prompted his ED visit. The patient denied headaches, dizziness, chest pain, shortness of breath, diarrhea, dysuria, or neurological changes. In the ED, vital signs were remarkable for a temperature of 98.9°F, heart rate of 110 bpm, respiratory rate of 15 breaths/min, and blood pressure (bp) of 160/111 mmHg. Labs were remarkable for white cell count 20.3 k/uL, hemoglobin 17.4 g/dL, and serum lipase level 665 u/L. The lipid panel revealed a total cholesterol level of 1154 mg/dL, high density lipoprotein (HDL) of 23 mg/dl, with significantly elevated low density lipoprotein (LDL) and triglyceride level, such that it was too high to calculate due to lipemia. A CT scan of the abdomen without contrast revealed acute interstitial edematous pancreatitis primarily involving the pancreas body and tail. There was also acute peripancreatic fluid collection measuring 7 cm x 4 cm x 5 cm as seen in Figure .
Of note, the patient was admitted in 2019 with similar symptoms where he was diagnosed with hypertriglyceridemia-induced pancreatitis and was discharged on atorvastatin and gemfibrozil. During this evaluation, the patient stated that he is non-compliant with medications and that he now drinks an average of four cans of beer twice weekly.
Given hypertriglyceridemia, the patient was placed on strict nil per os (NPO) and transferred to the ICU for further management. IV fluid and insulin infusion were initiated for the management of recurrent hypertriglyceridemia pancreatitis. Frequent blood work was performed to monitor lipid panel and potassium level while on insulin infusion. About three days following treatment, the patient's symptoms started to improve on the current treatment. Repeat lipid panel showed an improvement of triglyceride level at 470 mg/dL, LDL of 177 mg/dL, and total cholesterol of 284 mg/dL. He reported having minimal to no abdominal pain; hence he was advanced to a clear liquid diet. He was placed on a low-fat diet, atorvastatin, and gemfibrozil for better lipemic control. While on current management, the patient's abdominal pain started to worsen again. He began to have multiple episodes of fever. His white cell count started to increase significantly, and his hemoglobin level decreased to 12.7 g/dL. A repeat CT abdomen was performed, which revealed an extensive hyperdense peripancreatic fluid with findings suggestive of hemorrhagic pancreatitis, with acute SVT and splenomegaly as seen in Figure . There were also new areas of non-enhancement within the pancreatic tail compatible with necrosis as seen in Figure .
The patient was started on meropenem, and hemoglobin levels were monitored frequently. The hepatobiliary surgery team was consulted, who recommended supportive management with antibiotics, IV fluid, and to advance diet as tolerated. Blood cultures were performed, which were negative. The patient’s symptoms eventually improved and his hemoglobin levels stabilized. He was gradually restarted on a consistent carbohydrate diet without any new complications. The patient was discharged with lipid-lowering medications and scheduled for an outpatient appointment.


A 63-year-old Caucasian man diagnosed with metastatic lung adenocarcinoma 5 months ago and receiving systemic chemotherapy and external radiotherapy to the right hip underwent routine eye examination. He had no history of known ocular disease and intervention and was asymptomatic. Best corrected visual acuities were 20/32 in the right eye and 20/20 in the left eye. Intraocular pressures were 15 mmHg and 17 mmHg in the right and left eyes, respectively. Anterior segment examination showed both eyes had moderate nuclear sclerosis. Fundus examination of the right eye revealed a relatively well-circumscribed whitish retinal lesion measuring 0.5 × 0.5 × 0.5 mm located along the inferotemporal vascular arcade. There was no apparent vitreous and choroidal involvement. The left eye had normal funduscopic findings with blunted foveal reflex. Spectral domain optical coherence tomography (SD-OCT) of the right eye showed a hyperreflective dome-shaped lesion occupying the inner retinal layers with few hyperreflective dots overlying the retina consistent with tumor cells in the posterior vitreous. The outer retina was compressed by tumor and partial choroidal shadowing was observed without clinical or imaging evidence for choroidal involvement. The lesion was hypofluorescent on fundus autofluorescence (FAF) imaging. Fluorescein angiography (FA) revealed early hyperfluorescence of the lesion, late staining, and no leakage. The tumor was flat and nonmeasurable on B-mode ultrasonography. Brain magnetic resonance imaging revealed normal findings. Based on the clinical and imaging features, a diagnosis of presumed lung carcinoma metastasis to the retina was made. At a follow-up examination 2 months later after completion of systemic chemotherapy, the visual acuity in the right eye was 20/60 due to the worsening of the cataract. Fundus examination revealed that the retinal lesion in the right eye had regressed completely. There were only focal irregularities in the inner retinal layers on SD-OCT (). The patient passed away 6 months after the diagnosis of retinal metastasis.


A 56-year-old male patient (weight, 82 kg; height, 168 cm) with glutaric acidemia type 2 was scheduled for laparoscopic cholecystectomy for cholecystolithiasis. He had a history of rhabdomyolysis with lumbago and brown urine as initial symptoms at the age of 44 years. At the age of 52 years, he was diagnosed with glutaric acidemia. He did not receive nutrition therapy, including fat restriction; however, he developed rhabdomyolysis approximately once a year and needed fluid therapy. His previous medical history included diabetes mellitus requiring medical treatment, cerebral infarction, and bronchial asthma. Preoperative examination for laparoscopic cholecystectomy led to a diagnosis of angina pectoris with three-vessel disease. Consequently, an off-pump coronary artery bypass grafting (CABG) was planned preceding laparoscopic cholecystectomy.
The preoperative serum creatine kinase (CK) and creatinine levels were within the normal range. Metformin hydrochloride, an oral hypoglycemic agent, was discontinued 2 days before the surgery. General anesthesia was induced using remifentanil (0.3 μg/kg/min) and midazolam (6 mg), with rocuronium (70 mg) administered as a muscle relaxant. Anesthesia was maintained using midazolam (0.03 mg/kg/h), dexmedetomidine (0.4 μg/kg/h), and remifentanil (0.1–0.5 μg/kg/min) with O2-air mixture. In addition to the standard intraoperative monitoring, direct radial arterial pressure, pulmonary artery pressure, transesophageal echocardiography, and electroencephalogram were monitored. Moreover, the arterial blood pH, glucose, serum CK, serum and urine myoglobin, and lactate levels were measured at 1-h intervals. Administration of 2 mg/kg/min glucose using 10% glucose solution was started from midnight of the day before surgery. It was continued throughout the operation and postoperatively in the intensive care unit (ICU) using 50% glucose solution. Continuous insulin administration was started when intraoperative blood glucose exceeded 200 mg/dL. The operation and anesthesia times were 8 h 2 min and 9 h 49 min, respectively. The myoglobin level started to increase just after surgery. In the ICU, the body temperature was 36.7°C, and postoperative shivering was not observed. Moreover, the serum potassium level was 4.0 mEq/L. The total in-out balance of volume was 2294 ml: intravenously infused fluid (crystalloid and colloids), 4260 mL (2260 mL and 2000 mL, respectively); cell saver autotransfusion, 1600 mL; estimated blood loss, 592 g; cell saver output, 2786 mL; and urine output, 178 mL. The patient was sedated using midazolam and dexmedetomidine; subsequently, postoperative analgesia was maintained through continuous fentanyl infusion. There was an increase in the Mm-CK levels to a maximum value of 2328 U/L, while the serum potassium level increased to 5 mEq/L on postoperative day (POD) 2. Further, the serum myoglobin level increased to a maximum value of 635.8 ng/mL on POD 4. Urine volume decreased to approximately 0.2–0.5 mL/kg/h, and serum creatinine increased to >4.0 mg/dL, which indicated acute renal failure. Consequently, continuous hemodiafiltration was started and continued up to POD 25 (Fig. a).
The patient underwent laparoscopic cholecystectomy 316 days after undergoing CABG. General anesthesia was induced using midazolam (3 mg), remifentanil (0.2 μg/kg/min), and rocuronium (60 mg). Transversus abdominis plane block was performed with an ultrasound linear transducer using 40 mL of 0.25% levobupivacaine after anesthesia induction. Anesthesia was maintained using sevoflurane (1.5%) and remifentanil (0.03–0.15 μg/kg/min). The operation and anesthesia times were 1 h 51 min and 3 h 30 min, respectively. The total infused fluid and urine volumes were 1170 mL and 100 mL (0.36 mL/kg/h), respectively. The glucose infusion rate was 2 mg/kg/min using 10% glucose solution, was started from midnight of the day before surgery, and increased to 4 mg/kg/min using 50% glucose solution when introducing anesthesia. There was a slight increase in the postoperative serum CK and myoglobin levels at a maximum value of 534 U/L and 213 ng/mL on POD 1, respectively. The increased CK and myoglobin levels were promptly normalized. The serum creatinine level was normal, and renal function was not impaired (Fig. b).


A 35-year-old female patient with no past medical history presented with sudden onset of non-exertional, substernal, chest pain, radiating to left side of chest and left arm, associated with non-exertional dyspnoea, diaphoresis and palpitations. Past surgical history was non-significant. There was no family history of coronary artery disease, spontaneous coronary artery dissection, fibromuscular dysplasia, vascular or connective tissue disorders. Patient was an ex-smoker with five pack year smoking history, quit ten years ago, drinks three glasses of alcohol per week, and no history of recreational drug use. Patient was not on medications and had no known allergies. Vitals were stable at presentation. The physical examination was unremarkable. Labs were only significant for initial troponin level elevated to 4 ng/ml. Chest X ray was unremarkable. Initial ECG showed sinus bradycardia, ST segment elevations in leads V1 to V6 (Figure ). No changes were noted on serial ECG’s.
Differentials included acute coronary syndrome, myocarditis, pericarditis, spontaneous coronary artery dissection, aortic dissection, and pulmonary embolism. CT of chest, abdomen and pelvis with contrast did not reveal pulmonary embolism, aortic dissection or other vascular abnormalities. As chest pain was associated with elevated troponin level and ECG changes, ACS was high on the differential; coronary angiography was performed which showed 100% mid LAD coronary artery dissection (Video ), no significant coronary atherosclerosis was identified in the remaining vessels. Type 1 spontaneous coronary artery dissection of proximal to mid LAD coronary artery was diagnosed and as the patient became hemodynamically unstable, coronary angiogram was done to place a stent in proximal to mid LAD which was unsuccessful as the true lumen of the LAD coronary artery was not accessible on multiple attempts. Emergent CABG was done because of proximal to mid LAD coronary artery involvement and hemodynamic instability. An intraoperative trans-esophageal echo (TEE) before CABG showed 40% LVEF. Intraoperatively, dissection was noted to have started at the junction of proximal to mid LAD with severe thrombosis extending to apex. Left internal mammary artery grafting was done to proximal to mid LAD and coronary blood flow was restored. LVEF improved to 60% on intraoperative TEE, hemodynamically stabilized post CABG, and the patient was transferred to intensive care unit. Patient improved gradually during the hospital course and was discharged to home on dual antiplatelet therapy, atorvastatin and metoprolol. Patient was evaluated for extra coronary vascular abnormalities with CT angiography of head which did not reveal abnormalities. Four months later, patient was admitted to hospital with mild chest pain, concerning for recurrent SCAD. Patient was monitored in the hospital with serial troponins, ECG, which were not significant and as the suspicion was low, no coronary angiography was performed. Patient was counseled on recurrent chest pain, exercise regimen and follows as outpatient with no further complications.


A 28-year-old female with a past medical history of hypertension and smoking presented with acute onset of substernal substernal pressure-like chest pain for two days. Patient reported pain radiating to left arm, associated with palpitations and dizziness. Patient had no past surgical history, no family history of SCAD, premature CAD, and vascular disorders. Patient smokes three cigarettes per week, socially drinks alcohol, and has no history of recreational drug use. Patient was on hydrochlorothiazide, and had no known allergies. Patient was in significant distress but had an otherwise unremarkable exam. ECG showed minimal ST elevations in V1, V2 (Figure ).
Initial troponin I was elevated to 0.71 ng/mL. Patient was given aspirin, nitrate, beta-blocker and atorvastatin in emergency room and started on a heparin drip for ACS. Coronary angiogram showed 40-50% stenosis in the mid LAD with an aneurysmal segment and no involvement of other coronaries; stenting was hence deferred. TTE showed LVEF of 55% and no left ventricular wall motion abnormalities. Patient was discharged the next day on aspirin, beta blocker, atorvastatin, and nitrate. Two days later, she was readmitted with a similar presentation. Initial troponin level was elevated to 2.22 ng/mL. ECG showed nonspecific ST T wave abnormality (Figure ).
Patient was started on a heparin drip as well as a calcium-channel blocker for possible coronary vasospasm. Overnight she developed episodes of non-sustained ventricular tachycardia. Repeat left heart catheterization revealed Type 2 mid to distal left anterior descending spontaneous coronary dissection (Video ). Her fractional flow reserve was deemed to be 0.76 with intravascular ultrasound (IVUS) and the decision to continue medical management alone was made. Patient was discharged home on DAPT, beta-blockers, calcium-channel blocker, atorvastatin, and a follow-up with cardiology. Patient did not continue care with us and presence of other vascular or connective tissue disorders could not be excluded.


A 50-year-old woman with previously unknown psychiatric history was admitted to the emergency department at night in a state of confusion and psychomotor agitation. Her partner declared that during the morning, the patient suddenly developed motor stereotypies, hyperactivity, and fluctuations of both attention and consciousness. Although her partner denied that the patient had used any psychoactive drugs or alcohol previously, he reported an occasional consumption of diazepam oral solution for anxiety. The patient was not taking any drug therapy with medical prescription. Since psychomotor agitation was becoming more severe with the patient's risk of self-injurious conduct, intramuscular medication with delorazepam up to 6 mg was administered without any substantial modification of the symptomatology. Meanwhile, a CT scan without contrast, performed at the emergency room, was negative for acute neurological events, while toxicological screening of urine (research for opioids, cocaine, methamphetamine, cannabinoids, and benzodiazepines) was positive only for benzodiazepines. The patient's blood tests showed no significant alterations except for creatine phosphokinase (CPK), while the electrocardiogram detected no significant alterations except for a tachycardia (120 beats for a minute). After 2 h of intramuscular therapy with benzodiazepines, haloperidol, and promazine, the patient had no clinical improvement showing abnormal motor behaviors, disorganized thinking, echolalia, visual hallucinations, and total insomnia. Her partner was able to recover a series of tablets at home, of which phenibut, in its various commercial formulations (Fenibut, Anvifen, and Noofen) was the main ingredient (). Upon contacting the Poison Control Center, the clinical symptomatology presented by the patient was suspected to be related to phenibut withdrawal since the patient had started consuming phenibut in the previous months. It was subsequently possible to reconstruct that the interval between the last dose of phenibut and the onset of symptoms was about 3 days. The patient was, therefore, hospitalized in the psychiatric ward. Meanwhile, intravenous diazepam up to 30 mg and intramuscular haloperidol up to 5-mg therapy was administered. Following the recommendations for phenibut withdrawal syndrome from previous case reports (), a baclofen medication of up to 20 mg/day was started. This is because previous literature reported baclofen as a GABA-B agonist, which allows an alternative binding of GABA-B receptors and, therefore, an improvement on withdrawal (). A time course regarding the drug treatment and the dosages used is shown in .
Despite the therapy, the patient still spent two completely sleepless nights, experiencing visual hallucinatory disturbances, disorganized behavior, and thinking, with no clearly structured delusions. Psychometric rating scales were performed, with evidence of significant alteration of the mental state [Brief Psychiatric Rating Scale (BPRS) = 75, Hamilton Rating Scale for Depression (HAM-D) = 24, Mania Rating Scale (MRS) = 22, Positive and Negative Syndrome Scale (PANSS) = 102, and Global Assessment of Functioning (GAF) = 25]. Afterward, her mental status began to change from agitation, self-directed aggressiveness, and persecutory delusions to episodes of catatonia, during which she did not react to stimuli and appeared hostile and opposed to any therapeutic contact. Electroencephalogram (EEG) and magnetic resonance imaging (MRI) were performed, with the former showing rapid rhythms compatible with benzodiazepine therapy, and the latter exhibiting rare punctiform hyperintense signal alterations in T2-FLAIR affecting the bihemispheric subcortical white matter of non-specific gliotic significance. In the context of catatonia, the patient developed bladder globe and urinary tract infection with the consequent need for antibiotic treatment (ceftriaxone 2 g for 6 days). She never showed signs of kidney damage, and there was a progressive decrease in CPK (from 1,504 to 195 U/L). Instead, a picture of autonomic instability emerged, characterized by pressure peaks and tachycardia; therefore, atenolol treatment up to 10 mg/day was started, and this had positive effects on symptoms.
Meanwhile, it was possible to view previous health records, and the patient's medical history was reconstructed. She did not suffer from any major medical diseases, but she had been previously treated by private psychiatrists at the age of 36, for depressive episodes in the context of bipolar disorder with psychotic features. She had not been working for 20 years, and she had been living with her partner, living a mainly solitary life with few social interactions. Complete intercritical resolution of the depressive episodes was reported, with a return to the previous functioning. However, for cultural reasons, the patient continued to have magical thoughts. Amitriptyline and benzodiazepines were the last pharmacological therapy administered, prescribed 3 years before the current episode by a private psychiatrist and consumed by the patient without any medical supervision, which, due to her history of poor pharmacological compliance and her tendency to prefer natural remedies, may have not been taken correctly. She had no history of substance abuse, although a trend of excessive consumption of benzodiazepines was also reconstructed for anxiolytic and hypno-inductive purposes.
In light of the catatonic state, the therapy was changed from diazepam to intravenous lorazepam up to 12 mg/day (). Furthermore, since occasional lengthening of the QT interval was detected through ECG, haloperidol was replaced first with olanzapine, then with risperidone up to 6 mg in order to facilitate the management of psychomotor agitation with a daily QT monitoring. Gradually, the patient progressively showed a reduction in both disorganized thinking and agitation. In addition, psychotic symptoms, such as persecutory delusions and both visual and auditory hallucinations, slowly diminished until finally ending after 4 weeks. Atenolol therapy was stopped after 15 days, and the patient did not experience any further symptoms of autonomic instability.
After resolving the psychotic symptomatology, the patient showed positive recovery in regard to delusional thinking and hallucinatory phenomena, but she also experienced a few days of moderate expansive mood, which resolved after a few days. The patient revealed that she had been consuming phenibut in high dosage (up to 5 g/day) in the previous months in order to treat anxiety and insomnia that began during the COVID-19 pandemic quarantine. Therefore, the diagnosis of phenibut withdrawal was confirmed. Finally, psychometric rating scales were performed at the end of the hospitalization showing the following results: BPRS = 25, HAM-D = 5, MRS = 2, PANSS = 37, GAF = 80. We concluded on a diagnosis of withdrawal psychosis and mixed psychotic episode in the context of bipolar disorder. The patient was, therefore, discharged after 25 days of hospitalization, with a diagnosis of withdrawal psychosis and mixed psychotic episode in bipolar disorder, and with the following treatment: risperidone 6 mg and lorazepam 10 mg/day.
Although it was impossible to have a detailed view of her perspective during the entire hospitalization, at the time of discharge, the patient expressed feelings of relief and amazement concerning her well-being. She also said that she had lived “a nightmare” and that she not only had fear but also, in some moments, the certainty that it would never end. The patient gave her informed consent for the publication of the present case report.


A 39-year-old female came to our clinic complaining of gradual loss of visual in the left eye for 5 months. She had been diagnosed with acute retinal necrosis in the right eye, and wide-field photograph of the right eye showed patchy and diffusive retinal necrotic lesions (Fig. ). Pars plana vitrectomy was performed due to retinal detachment of the right eye 5 months earlier. The visual acuity in the left eye at the time of initial presentation was 20/20. In the meantime, she noticed floaters in her left eye. Superior retinal necrosis had been detected and it was recorded in her previous medical chart. The aqueous fluid from the left eye was positive for herpes zoster virus (VZV). She received repeated (nine rounds) intravitreal ganciclovir injection (3 mg/0.1 ml) into her left eye, one injection every 2 weeks, and systemic antiviral therapy for 5 months. The patient noticed a decrease in the visual acuity of the left eye and was referred to our clinic.
When the patient came to our clinic, her best corrected visual acuity was 20/400 OS, 20/33 OS. The intraocular pressure was within the normal range in both eyes. There was no inflammation in the anterior chamber, and the lens was normal in the left eye. There was no posterior necrotizing involvement and no macular edema or exudation in the left eye. Indirect ophthalmoscope examination revealed pigmentary change in the superior peripheral retina of the left eye. Slight abnormality of the interdigitation zone in the fovea area of the left eye was detected on OCT. Angio-OCT revealed normal capillary density of superficial retinal capillary, deep retinal capillary, outer retina, and choriocapillaris layers in the left eye (Fig. ). The Humphrey visual field (central 24–2 threshold test) showed massive visual field damage in the left eye. The amplitude and implicit times of pattern visually evoked potential (VEP) and flash VEP were within the normal range in the left eye. The amplitudes of dark-adapted flash electroretinography (ERG) were slightly low in the left eye. Photopic single-flash response showed decreased amplitude of a-wave and b-wave in the left eye. The amplitudes of photopic 30-Hz flicker were decreased in the left eye. Trace arrays showed subnormal multifocal electroretinography (mERG) with decreased amplitudes for the left eye. The three-dimensional topography map showed a blunted foveal peak (Fig. ).


A 19-year-old female patient, with Fitzpatrick II skin color, who was a non-smoker, sedentary, free from comorbidities or drug allergies, and was taking oral contraception regularly, presented with an esthetic complaint of combination telangiectasias on the lateral surface of the left thigh. She was told that she needed to use skin moisturizer and take pycnogenol 200 mg/day orally for at least 15 days before undergoing a procedure. Detailed photographic records were taken and the patient was given a consent form with detailed information about the treatment and its possible complications. When she returned 15 days later, the patient underwent conventional sclerotherapy of the combination telangiectasias on the lateral surface of her left thigh, using a solution containing glucose 65% and polidocanol 0.5% (to a total volume of 1.5 mL).
She developed a large expanse of telangiectatic matting (approximately 10 x 15 cm) in the area surrounding the vessels that had been treated, about 2 days after the procedure (). An augmented reality venous Doppler ultrasound examination of the region did not show varicose veins or feeder veins that could be linked with the complication.
Initial management consisted of reassuring the patient and instructing her not to expose herself to sunlight and prescribing oral and topical pycnogenol. Additionally, three sessions of intense pulsed light were administered at 540 nm/17 J/15 ms (similar parameters to those used to treat rosacea), with 21-day intervals between sessions. In the opinions of the same evaluator and of the patient, there was no more than mild attenuation of the condition ().
In view of this, the patient was instructed to administer topical brimonidine tartrate 0.5% daily. After 7 days of regular use of this medication, considerable improvement was observed (). A joint decision was taken to continue applying the medication for a further 7 days, with very satisfactory results (). After 14 days’ use, we withdrew the medication and continued the follow the patient up clinically. She is satisfied and both the telangiectasias and the telangiectatic matting have completely disappeared. The initiative to treat with brimonidine tartrate was based on use of Mirvaso® to treat rosacea, which has a pathophysiology that has certain similarities with matting. Because it is difficult to source, the medication was ordered from a compounding pharmacy. The patient has been in clinical follow-up for 6 months () and no rebound effect has been observed to date.


The patient was a 71-year-old man who had a history of chronic obstructive pulmonary disease, right upper lobectomy for lung cancer and partial liver resection for hepatocellular carcinoma. He underwent subtotal esophagectomy for upper esophageal cancer with 3-field lymph node dissection via video-assisted thoracic surgery (VATS), followed by retrosternal reconstruction. The 4.0-cm-wide gastric conduit was created extracorporeally and pulled up to the neck via the retrosternal route. The remnant cervical esophagus was fully mobilized and transected near skin level. An end-to-end hand-sewn anastomosis was fashioned and placed above the manubrium by pulling the conduit down from the abdominal cavity to straighten the digestive tract.
On postoperative day (POD) 2, he developed septic shock and underwent reoperation after emergency endoscopy revealed necrosis of the conduit. During the second operation, the tip of the conduit above the manubrium was found to be necrotic from strangulation as a result of compression by the SCJ (Fig. ). The necrotic conduit was removed, and an esophageal fistula was constructed in the left side of the neck for a second reconstruction to be performed later.


In this case, a 50-year-old woman underwent two cycles of neoadjuvant chemotherapy (fluorouracil and cisplatin) and subtotal esophagectomy for middle esophageal cancer with 3-field lymph node dissection via VATS, followed by retrosternal reconstruction. The gastric conduit was 4.0 cm wide, and the reconstruction procedure was the same as in case 1. The anastomotic site was determined by indocyanine green (ICG) fluorescence imaging before pulling up. After the anastomosis, the tip of the conduit appeared pale with the trace of the upper end of the manubrium as the clear boundary (Fig. a). Although re-anastomosis was considered, it was not performed because ICG fluorescence imaging had indicated adequate blood flow at the anastomotic site.
She developed anastomotic leakage on POD 8, which was confirmed endoscopically on the ventral side of the tip of the gastric conduit, which had been pale intraoperatively (Fig. b). We determined the cause of the anastomotic leakage to be circulatory disturbance at the tip of the conduit behind the SCJ. She recovered with cervical drainage, but developed anastomotic stenosis afterwards.


The patient was a 71-year-old man who underwent three cycles of neoadjuvant chemotherapy (fluorouracil, cisplatin and docetaxel) and subtotal esophagectomy for lower esophageal cancer with 2-field lymph node dissection via VATS, followed by retrosternal reconstruction with a 3.5-cm-wide gastric conduit. Although sufficient blood flow to the anastomotic site had been confirmed by ICG fluorescence imaging, the tip of the conduit looked pale after anastomosis. Anastomotic leakage developed on POD 5. Endoscopic findings indicated that the cause of leakage was circulatory disturbance at the tip of the conduit behind the SCJ, as in case 2. He recovered with cervical drainage, but also subsequently developed anastomotic stenosis.


On April 6, 2020, a 56-year-old woman was admitted at the Emergency Unit of the Azienda-Socio-Sanitaria-Territoriale (ASST) Papa Giovanni XXIII (Bergamo Hospital, Italy) and then transferred 12 days later to the Intensive Care Unit of the same hospital because of severe respiratory distress secondary to COVID-19 that, after a short unsuccessful trial of Continuous Positive Airways Pressure (CPAP), required intubation for invasive mechanical ventilator support (). Clinical course was complicated by a urinary tract infection and an Aspergillus super-infection of the lower respiratory tract that fully recovered with specific antimicrobial therapy. Mechanical ventilator support was weaned on May 18 and was followed by a 5-day course of CPAP. Then, she was transferred to the rehabilitation unit on June 8, 2020. However, only 4 days later, on June 12, 2020, she was again admitted to a COVID unit of the same hospital because of cough and worsening dyspnea. At admission, her body temperature was 36.5°C; blood pressure, 98/69 mmHg; heart rate, 98 beats per minute; respiratory rate, 28 breaths per minute; partial artery CO2 pressure (PaCO2), 32 mmHg; and partial artery O2 pressure (PaO2) in room air, 59 mmHg. PaO2 promptly increased to 96 mmHg with 4 L/min oxygen delivery through a low-flow nasal cannula. Diffuse, bilateral crackles could be auscultated at lungs bases. Laboratory workup showed macrocytic hyperchromic anemia (hemoglobin 9.2 g/dl, MCV 99.3 fl MCH 33.2 pg) with increased C Reactive Protein (11.2 mg/dl, reference range, 0–1 mg/dl), but with a procalcitonin level that was in normal range (0.03 ng/ml). Serum protein electrophoresis showed moderately increased alpha-1, alpha-2 globulins, and beta globulins with only 4% of gamma globulins (reference range, 11.1–18.8%). Flow cytometry found only two CD3- CD19+ B cells per µl (reference range, 200–400 cells/µl) in peripheral blood. There were <3.8 AU/ml of anti-SARS-CoV-2 S1/S2 IgG (Liasorin SARS-CoV-2 IgG chemiluminescent assay [CLIA], Diasorin; negative <12 AU/ml) and 0.02 index of anti-SARS-CoV-2 N IgG (Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay [CMIA]; negative < 1.2 index, ). Quantitative real time polymerase chain reaction (qPCR) failed to detect SARS-CoV-2 nucleic acid in two nasopharyngeal swabs, but qPCR detection of SARS-CoV-2 RNA in a bronco-alveolar lavage (BAL) performed on June 14, after transfer to a sub-intensive care unit, confirmed viral invasion of lower respiratory tract (). Blood and urinary cultures and extensive laboratory workup for concomitant viral, bacterial or fungal infection were irrelevant. Trans-thoracic echocardiography excluded valve vegetations. Chest computed tomography (CT) scanning showed ground-glass opacities in the dorsal regions of the upper lobes and the right lower lobe, sub pleural consolidations with air bronchogram in the right lower lobe, diffuse traction bronchiectasis, and reticular pattern interstitial abnormalities. This clinical picture was associated with remarkable increases in serum-induced C5b-9 deposition and thrombi formation on cultured human microvascular endothelial cell (HMEC-1) line () (). Plasma Fibrinogen concentration, von Willebrand Factor (vWF) antigen and activity and D-dimer levels () were also remarkably increased.
Patient’s family and remote history was irrelevant. Notably, on April 2019, she had been diagnosed with a double-hit diffuse large B-Cell lymphoma that was successfully treated with the first-line protocol of the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (R-GMALL) that included six cycles of chemo-immunotherapy with rituximab 375 mg/m2, dexamethasone, vincristine, methotrexate, etoposide, and citarabine followed by two additional doses of Rituximab 375 mg/m2 every 21 days after completion of the last cycle. This treatment regimen was completed on December 2019.
Seven hundred milliliter of a saline solution of anti-SARS-CoV-2 N IgG (Index 8.8, ) were obtained (after filter washing at the end of the DFPP session) from a 61-year-old male ABO competent adult donor who, according to the clinical and laboratory criteria issued by Consiglio Superiore di Sanità on February 28, 2020 (), had definitely recovered from COVID-19. He never received blood component transfusions and had negative acid nucleic testing for HAV, HEV, and B19 Parvovirus. The donor was found to have an adequate titer of anti-SARS-CoV-2 S1/S2 (84 UA/ml) and anti-N IgG (7.74 index, ). He provided written informed consent to donation and to the DFPP procedure. The procured IgG concentrated solution was frozen and stored in order to be slowly thawed at 4°C and infused as soon as a consenting ABO competent potential recipient with severe COVID-19 would have become available. The donation was tested as required by the Italian legislation for plasma intended for clinical transfusion (HIV, HCV, HBV nucleic acid, and serology testing, syphilis).
On June 16, 2020, 82 days after symptoms onset, the identified consenting patient received (in the context of an ongoing study approved by the Local Ethical Committee and registered at NCT04346589) a single intravenous infusion of this high titer (4+) anti-S1/S2 and anti-N IgG-enriched cryosupernatant solution without premedication. Plasma cryoprecipitate, which spontaneously separated from cryosupernatant during the thawing procedure, was discarded to avoid the infusion of pro-thrombotic factors—including fibrin, fibrinogen, von Willebrand factor, and others—to the recipient. The IgG-enriched solution was infused in 4 h without acute reactions or signs of fluid overload or cardiovascular instability.
High titer (IgG 4+) of anti-S1/S2 and anti-N IgG were detected by the chromatographic immunoassay qSars-CoV-2 IgG/IgM Cassette Rapid Test (Cellex) in recipient circulation as early as 24 h after the infusion of the IgG enriched solution. Ten days later, the presence of antiviral immunoglobulins was documented by chemiluminescence immunoassay (CLIA) LIASORIN SARS-CoV-2 S1/S2 IgG test (DiaSorin) and subsequently confirmed by chemiluminescence microparticle immunoassay (CMIA) Alinity SARS-CoV-2 IgG (Abbott) detection of anti-nucleocapsid antigen (N) circulating IgG. Serum levels of anti-SARS-CoV-2 N IgG antibodies, which were almost undetectable before antibody infusion, sharply increased at post-infusion day 1 and then slowly and progressively declined at post-infusion days 7, 14, and 21 (). However, following the infusion antibody titer largely exceeded the upper limit for test positivity (index 1.2) up to day 21 ().
The fully exogenous origin of circulating anti SARS-CoV-2 IgG was consistent with failure to detect circulating antiviral IgM antibodies and, even more convincing, by persistent depletion of CD3- CD19+ B cells in peripheral blood (3 cells/µl). On June 23, just 7 days after antibody infusion, the patient was transferred to a low intensity care Medicine Unit. Notably, in one BAL specimen collected on July 1, 15 days after antibody infusion, SARS-CoV-2 RNA could not be detected by qPCR. Two additional nasopharyngeal swabs tested after the infusion failed to detect any nucleic viral material.
In parallel with viral clearance, patient’s respiratory distress promptly improved after antibody infusion. Her peripheral oxygen saturation (SpO2) in room air increased to 96%. PCR decreased from 11.2 to 0.7 mg/dl. IL-6 titer, after peaking (60.5 pg/ml) 1 day after the infusion, progressively dropped to normal levels (2.64 pg/ml) just 8 days after the infusion. Similarly, plasma fibrinogen concentration, vWF antigen and activity, and D-Dimer levels (), which were remarkably increased before antibody infusion, slightly increased at post infusion day 1 and then progressively decreased on subsequent visits. In particular, D-dimer levels decreased to normal range at post infusion days 14 and 21 (). A CT imaging 13 days after the infusion showed a marked decrease of the consolidation areas with unmodified reticular abnormalities and bronchiectasis. Consistently, ex vivo serum induced C5b-9 deposition and thrombi formation on HMEC-1 line, after an initial acute increase the day after antibody infusion, progressively decreased, and eventually normalized (, respectively).
On July 8, 22 days after antibody infusion, and 104 days after disease symptoms onset, the patient was discharged in good health and without chronic sequelae. At 6 months after discharge, she was symptom-free, and a CT imaging showed an almost complete resolution of diffuse interstitial lung involvement. However, hypogammaglobulinemia (IgG concentration: 400 mg/dl) and lymphocytopenia (lymphocyte count: 900/mm3) did not recover. Notably, flow cytometry continued to document B-cell depletion from the circulation (two CD3− CD19+ B cells per µl).


A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. She had been diagnosed with ALL 2 years before this event and was in the process of receiving maintenance treatment under the Japan Adult Leukemia Study Group ALL202-U protocol []. Her headache and nausea had started after receiving an intrathecal chemotherapy (methotrexate, cytarabine, and prednisolone) 2 weeks before; thus, she initially interpreted the headache as post-lumbar-puncture pain and consumed painkillers (loxoprofen and tramadol) that partially relieved her symptoms. However, her symptoms continued, and by the time of her visit to our clinic, she also developed other symptoms, such as photosensitivity, appetite loss, left temporal and eye pain, and tinnitus. She had no gastrointestinal symptoms or fever during the 2 weeks. She had no medical history before her diagnosis of ALL and had only one episode of septic shock with lung abscess during her course of chemotherapy, which was caused by Klebsiella pneumoniae. She was on prophylactic antimicrobials, including atovaquone (leukopenia due to trimethoprim-sulfamethoxazole), fluconazole, and acyclovir. Notably, she had eaten undercooked beef 2 days prior to admission. On admission, the patient experienced acute distress, had a body temperature of 36.2 °C, blood pressure of 130/88 mmHg, pulse rate of 87/min, respiratory rate of 18/min, and oxygen saturation measured by pulse oximetry of 100% on room air. The patient did not have neck stiffness, jolt accentuation, or any other neurologic deficits, such as cranial nerve abnormality, ataxia, or muscle weakness in her extremities. She had no abdominal tenderness or normoactive bowel sounds. Laboratory findings were the following: white blood cell count, 2400/μL (neutrophils, 58%; lymphocytes, 27.5%; monocytes, 11.5%); hemoglobin level, 11.5 g/dL; platelet count, 336,000/μL; blood urea nitrogen level, 10.2 mg/dL; creatinine level, 0.48 mg/dL; and C-reactive protein level, 3.74 mg/dL. Computed tomography of the brain did not reveal any abnormalities. Incidentally, her neutrophil count had been hovering around 1000/μL, a month prior to her admission. Her headache was so intense that we started intravenous patient-controlled analgesia with fentanyl.
On day 2, her temperature rose to 38.0 °C and jolt accentuation was observed. Lumbar puncture was performed, and CSF analysis showed a cell count of 71 (polymorphonucleocytes 59.2% and mononucleocytes 40.8%), protein level of 87 mg/dL, and glucose level of 82 mg/dL (serum glucose 124 mg/dL). No bacteria were observed under gram staining. We empirically initiated ampicillin 2 g intravenously (IV) every 4 h and ceftriaxone IV 2 g every 12 h. Her symptoms gradually improved. On day 4, spiral gram-negative rods were detected in blood cultures obtained on admission, and ampicillin was discontinued. On day 6, blood and CSF cultures revealed C. fetus, which was identified by an aerobic bottle, BacT/ALERT (bioMérieux, Inc., Durham, NC). The minimum inhibitory concentrations (MICs) of this strain measured by E-test (bioMérieux) were as follows: meropenem, 0.064 μg/mL and cefotaxime, 16 μg/mL. Stool cultures were negative on day 9, and we switched from ceftriaxone to meropenem 2 g IV every 8 h (Fig. ). We excluded other metastatic foci, such as infective endocarditis, splenic or renal abscess, septic pulmonary emboli, or infected aneurysm. We continued meropenem for 3 weeks, and she was discharged without neurological sequelae.


An 8-year-old female child was referred to Inkosi Albert Luthuli
Central Hospital (IALCH) from a provincial hospital with a
4-month history of chronic purulent sputum, severe weight loss and
constitutional symptoms. There was no tuberculosis (TB) contact but
her 6-year-old brother had similar symptoms. They lived on a farm
at Nkonjeni in rural KwaZulu-Natal, South Africa. She was assessed
as having pulmonary tuberculosis and commenced on 4-drug
anti-tuberculosis therapy (rifampicin/isoniazid/pyrazinamide and
ethambutol) at the provincial hospital. The diagnosis of TB was based
on the clinical presentation and chest radiology .
GeneXpert and TB cultures were negative. The erythrocyte
sedimentation rate (ESR) was greater than 140 mm/hr, monocytes
2.56 ×109
/L and the globulin fraction was 37 g/L. Her HIV test was
negative.
After 2 months of TB treatment, the patient deteriorated and
presented to the provincial hospital with severe respiratory distress.
A chest X-ray showed a right pleural effusion, a thoracentesis
yielded pus and an inter-costal chest drain was inserted. She
developed respiratory failure, and she was referred to the
paediatric intensive care unit (PICU) at IALCH for mechanical
ventilation. On examination, she was clinically wasted, weighed
24 kg (z-score between –2 and –3), was in respiratory distress,
displaying pallor, clubbing and axillary lymphadenopathy. She
had absent breath sounds on the right hemithorax with left-sided crackles. Abdominal examination revealed a 7 cm firm
hepatomegaly with 3 cm splenomegaly. She was encephalopathic
with meningism. An initial assessment of disseminated TB was made.
She was intubated and ventilated. TB treatment was continued, and
ethambutol was changed to ethionamide. Meropenem was added
to the treatment. An urgent computed tomography (CT) brain
scan showed age incongruent cerebral and cerebellar involutional
changes with no basal enhancement or hydrocephalus or features
of raised intracranial pressure . Lumbar puncture showed
lymphocytes of 28, neutrophils of 12, no erythrocytes, glucose 1.1
mmol/L, protein 2.5 g/L and chloride 122 mmol/L. Admission
blood results: white blood cells were 45.3 ×109
/L, with predominant
neutrophilia of 35 ×109
/L and monocytes of 4.99 ×109
/L, Platelets
were 1169 ×109
/L, ESR >140 mm/hr and procalcitonin 52 ng/dL.
Gene Xpert and TB culture were negative. A CT chest scan showed
destruction of the right lung with bronchiectasis and cavities . Endotracheal aspirates and pleural fluid cultured Nocardia
spp. sensitive to meropenem and co-trimoxazole. An assessment
of disseminated nocardiosis was made. The patient was treated
with meropenem and high-dose co-trimoxazole and after 7 days of
therapy she showed signs of improvement, was successfully extubated
and transferred to the infectious diseases unit to continue with both
antibiotics and TB treatment. A month later, she developed generalised
tonic-clinic seizures and decreased level of consciousness (Glasgow
Coma Scale (GCS) score 7/15) and localising sign of dilated left pupil.
She was then re-ventilated and transferred back to PICU. An urgent
CT brain showed active tetra-ventricular hydrocephalus with transependymal seepage. An external ventricular drain was inserted by
the neurosurgeons; however, the patient continued to deteriorate and
demised on the ventilator.
Her 6-year-old brother was admitted to the infectious diseases unit with
a persistent cough with no involvement of the central nervous system.
His sputum cultured Norcadia spp. sensitive to imipenem, ceftriaxone
and co-trimoxazole. He was treated with ceftriaxone and high-dose cotrimoxazole. He recovered completely and was discharged home.


A 10-year-old boy presented to the emergency room with 2 days of abdominal pain initially over the peri-umbilical region and later localizing to right iliac fossa (RIF) with an episode of non-bilious vomiting. Physical examination revealed low-grade temperature (100°F) and tenderness with guarding overRIF.
Hematological tests showed polymorph nuclear leukocytosis with left shift without eosinophilia. Biochemical tests and urinalyses were normal. Abdominal radiographs were unremarkable. Ultrasonogram (USG) abdomen could not visualize the appendix, but reported significant probe tenderness inRIF.
With clinical impression of AA, he underwent diagnostic laparoscopy under general anesthesia.
Intraoperatively, a retro-cecally located appendix was found that was mildly inflamed with surface congestion more towards the tip (with visible leash of prominent vessels) and a healthy base as shown in .
There was no perforation, peritoneal reactive fluid or pus and no omental reaction. Aware of his clinical presentation, a possibility of other pathologies like Meckel diverticulum, mesenteric lymphadenitis and any other small bowel lesions were thought of. On walking the bowel beyond 2 feet proximal to Ileo-Caecal Junction (ICJ), no other obvious lesions were found. Laparoscopic appendectomy was performed. Specimen was retrieved in a plastic bag in an attempt to avoid contamination.
Histopathologically, gross examination confirmed the operative findings showing a 5.5 × 0.7 cm appendix with venous congestion over the serosal surface. Microscopically, the section showed mild congestion and a luminal parasite with features compatible with Enterobius vermicularis as shown in . The specimen was reported to be an AO. He had an uneventful postoperative period and was discharged the next day. At follow up a week later, he had recoveredwell.
The histopathological finding came as a diagnostic surprise, since historically he never complained of appendiceal colic (AC), anal pruritus or worm defecation in the past. Moreover, eosinophilia was also not observed in the peripheral smear. Attributing his symptom complex to manifestation of AO, he was treated with a single dose of albendazole to be repeated after 2 weeks. His family members were also advised a similar treatment course. At 1 year follow up, he remained symptomfree.


A 10-year-old boy presented with history of peri-umbilical pain later migrating to right upper abdomen for 3 days and associated three episodes of non-bilious vomiting. He did not have fever, nausea or anorexia. He was moving bowel and bladder normally. Physical examination revealed tachycardia (110 beats per minute) and tenderness over entire right upper quadrant associated with rebound tenderness. Hematological tests were unremarkable. Biochemical tests were normal. Abdominal radiographs were unremarkable. USG abdomen showed a blind ending tubular, non-compressible, non-peristaltic structure measuring 9.5 mm, suggesting an enlarged appendix with its tip located in the sub-hepatic region as shown in .
With clinical impression of SHA, he underwent an emergency diagnostic laparoscopy under general anesthesia. Intraoperatively, findings were confirmed, an inflamed turgid appendix with its tip just beside the gall bladder in the sub-hepatic region was noted with a healthy base as shown in .
Laparoscopic appendectomy was performed as shown in .
Histopathologically, gross findings included an 8 cm long appendix with cut section showing lumen filled with fecal material. Microscopically, the section showed suppuration, edema and congestion along with peri-appendiceal inflammation and focal areas of destruction of the muscular layer suggestive of gangrenousAA.
He had an uneventful postoperative period and was discharged the next day. At follow up a week later and 1 year later, he was doingwell.


A 13-year-old boy presented with sudden onset RIF pain for a day associated with vomiting, nausea and anorexia without fever. He was moving bowel and bladder normally. Physical examination revealed guarding and rebound tenderness over RIF. Hematological tests showed polymorph nuclear leukocytosis. Biochemical tests and urinalyses were normal. Abdominal radiographs were unremarkable. USG abdomen showed a blind ending tubular, fluid-filled, non- compressible, non-peristaltic structure in RIF measuring 13 mm, suggesting an enlarged appendix with mucocoele formation as shown in .
In view of known associations of mucocoele with malignancy, he underwent open appendectomy as shown in . No visible or palpable mass lesion was found intraoperatively. Histopathologically, gross findings included an 8 cm long appendix with cut section showing lumen filled with purulent material and thinning of wall (2 mm) without an obvious mass lesion as shown in . Microscopically, the section showed suppuration, edema and congestion along with mucosal erosions. The lumen was filled with neutrophils and fibrinoid material. Peri-appendiceal inflammation was noted along with focal areas of destruction of the muscular layer suggestive of gangrenousAA.
He had an uneventful postoperative period and was discharged the next day. At follow up a week later and 1 year later, he was doingwell.


A 20-year-old female presented to the emergency department with a complaint of subjective fevers, intermittent chest pain, nausea, vomiting, and a new diffuse morbilliform rash. The patient had recently recovered from a SARS-CoV-2 infection two months prior, where her only complaint was cough and she had no other post-COVID-19 syndrome symptoms. On physical examination, the patient was febrile at 39.6 C, hypotensive with a blood pressure of 80/50, and tachycardic with a heart rate above 130. The patient had no respiratory symptoms, and oxygen saturation was normal. The patient was noted to have elevated jugular venous distension, normal rhythm with the absence of any murmur, normal breath sounds on bilateral lung fields, a diffuse morbilliform rash on her left arm, and no peripheral lower-extremity edema.
An electrocardiogram showed sinus tachycardia with an extreme right axis deviation and evidence of right ventricular hypertrophy (Figure ). Laboratory workup was notable for leukocytosis of 25,700 per uL, elevated brain natriuretic peptide of 1757 pg/mL, elevated troponin of 1.270 ng/mL, and high inflammatory markers (erythrocyte sedimentation rate 106 mm and D-dimer 3369 ng/mL). Chest X-ray and CT angiogram were unremarkable. The patient was admitted to the medical intensive care unit for hemodynamic monitoring and vasopressor support. Blood cultures and remaining infectious workup for bacterial and viral causes were negative. Repeat SARS-CoV-2 polymerase chain reaction from the nasopharyngeal swab was negative. A swan catheter was placed to determine the etiology of her shock. On placement of swan catheter, her hemodynamic data while on 5 mcg/min of norepinephrine revealed a right atrial pressure of 8 mmHg, pulmonary artery pressure of 25/15 mmHg, and a pulmonary capillary wedge pressure of 16. Her cardiac output per Fick’s equation was 6.7 L/min, and her cardiac index was 4.0 L/min/m2. An echocardiogram was performed and it showed normal left ventricle (LV) chamber size and moderately decreased systolic function with an estimated ejection fraction of 35-40% (Figure ). The right ventricle chamber size was normal with mildly reduced systolic function. A CMR image was ordered to evaluate for infiltrative causes of heart failure. CMR revealed increased T2 signal in double inversion recovery and triple inversion recovery sequences consistent with myocardial edema seen predominantly in the entire septum (Figure ). The LV was noted to be mildly dilated with a reduced LVEF. The presence of a small pericardial effusion was also noted without evidence of pericardial enhancement. The presence of a reduced LVEF, myocardial edema in the absence of necrosis, and pericardial effusion were highly suggestive of acute/subacute myocarditis.
Given that the patient was in septic shock on presentation to the emergency department, she was adequately fluid resuscitated and subsequently started on vasopressor support. Cardiology was consulted, and given the clinical and imaging findings, the patient was highly suspected to have MIS-A. Due to the high risk of post-MIS complications such as aortitis and coronary aneurysms, the patient was started on Decadron IV 6 mg for 10 days followed by one-month taper on discharge. The patient was able to be weaned off vasopressor support within three days and was eventually discharged in a normal state of health. Prior to discharge, a CT angiogram of coronary arteries was ordered and it showed no atherosclerosis, aneurysms, and significant aortic inflammatory changes (Video ).


A three-year-old bed-ridden girl presenting a chronic neurologic condition (Zika syndrome) was admitted to treat an episode of tracheitis. She had been submitted to tracheostomy and gastrostomy two years before to treat chronic pulmonary aspiration, recurrent episodes of pneumonia, and swallowing incoordination. A plastic cuffed tube continually inflated at low pressure was prescribed, as the child needed intermittent positive pressure ventilation.
The patient presented two self-limited bleeding episodes through the tracheostomy in a 48h interval, initially attributed to aspiration trauma. A new episode 48 hours after the initial report with bright projectile blood suggestive of arterial bleeding was then described by the mother, requiring a surgical evaluation. The patient did not show physiological instability or severe anemia.
A provisional diagnosis of TIF was made by the pediatric surgery team. An immediate angiotomography confirmed the diagnosis and revealed a TIF affecting the bifurcation of the innominate artery (IA) and the right tracheal wall, with a small pooling of contrast next to the fistula.
The patient was treated by the endovascular placement of four expanded polytetrafluoroethylene (PTFE)/nitinol stents (Viabhan®) in the right carotid (5×50 and 6×100 mm) and right subclavian arteries (5×25 and 5×100 mm), crossing the transition to the IA in Y configuration (). A stent (5×25 mm) accidentally migrated, staying next to the iliac bifurcation. This dislocated stent was not retrieved, since the team considered that removal attempts implied an unfavorable risk-benefit ratio. No neurological worsening, right arm ischemia, or complications related to the migrating stent were detected after surgery. Angiographic control, including a new angiotomography four months after surgery, showed normal blood flow in the right carotid and right subclavian arteries.
Anticoagulants were prescribed for two months (subcutaneous enoxaparin 20 mg bid). Five months after surgery, the patient remains asymptomatic, without new bleeding episodes, as well as infectious, thrombotic, or ischemic complications related to the stents.


A 58-year-old woman with a remote history of an excised right arm melanoma with negative axillary lymph nodes presented to our hospital’s emergency department with slurred speech and worsening left facial droop over two weeks following her second dose of a COVID-19 vaccine. She had received no further chemotherapy or radiation after her resection eight years prior and had appropriate follow-up. Following the second dose of a COVID-19 vaccine, she developed high-grade fevers and malaise and new-onset left facial weakness. The patient’s symptoms were attributed to a post-vaccination Bell’s palsy and she was recommended no further workup. Fevers and malaise resolved spontaneously over the next 24-48 hours as is typical with post-vaccination symptoms, but the facial weakness persisted until approximately two weeks later when she developed acute worsening of her facial droop with associated slurred speech, drooling, and new-onset left arm and leg weakness. She was taken to the emergency department and underwent stroke evaluation including computed tomography (CT) of the head which demonstrated a 3.4 cm right intraparenchymal hemorrhage with a 3 mm midline shift. CT angiography of head and neck did not demonstrate any abnormalities. Complete blood count, comprehensive metabolic panel, and coagulation factors did not demonstrate any overt abnormalities. Contrast-enhanced MRI of the brain demonstrated a large hemorrhagic cavity in the right frontal lobe with an enhancing focus along the right superolateral margin representing a hemorrhagic mass (Figure ). The patient was taken promptly to the operating room for hematoma evacuation and excisional biopsy of the enhancing lesion. Final pathology was consistent with a metastatic malignant melanoma, with immunohistochemical profile demonstrating positive staining for HMB-45, Melan-A, and S100.


A 52-year-old woman with a medical history of hypothyroidism and breast cancer presented after developing severe headache and neck stiffness associated with intermittent high-grade fevers to 102ºF four days after her first dose of a COVID-19 vaccine. Her primary care physician initially recommended monitoring of her symptoms and the use of over-the-counter analgesics which provided relief of her fevers. Her headaches persisted and the patient was prescribed a short course of methylprednisolone which reduced their severity. Symptoms returned two days after completion of the steroids and the patient was prescribed a second course of steroids and was sent for computed tomography (CT) of the chest and head which demonstrated a lesion arising within the corpus callosum. Contrast-enhanced MRI demonstrated a 5.8 cm heterogeneously enhancing mass with cystic and necrotic changes centered within the splenium of the corpus callosum (Figure ). Pre-operative laboratory tests were overall unremarkable except for a mild anemia (hemoglobin 10.1 g/dL) and mild decreased calcium at 8.2 mg/dL. The patient underwent a biopsy which demonstrated an IDH-wildtype, World Health Organization Grade IV glioblastoma, with positive staining for glial fibrillary acidic protein (GFAP), negative staining for IDH-1, and rare positive staining for p53. The patient was ultimately transferred to our facility for definitive treatment.


Figure shows the family tree of the family studied.
The proband is a 13-year-old boy (III1). Pregnancy and birth were unremarkable. Birth weight was 3.3 kg and length 53 cm (5th centile). The mother was 36 years old during the pregnancy. The proband started walking around 2 years old. Significant speech delay was noted by the parents at 3 years of age, but they did not consult for a specialized examination. The child came to medical attention again at the age of 6 due to his global developmental delay and suspected ASD. Indeed, he presented with autistic features such as abnormal behaviors, namely sensory and motor stereotypes (triggered in emotionally charged situations) and compulsive behavior. He has mild-moderate ID (according to the Weschler intelligence scale for children, third edition, WISC-III). In summary, these behavioral findings, along with the developmental delay and dysmorphic features suggest an ASD, according to the Autism Diagnostic Interview, a standardized investigator-based interview, and Autism Diagnostic Observation Schedule, a semi-structured, standardized assessment of social interaction, communication, play, and imaginative use of materials for individuals suspected of having an ASD.
The phenotypic manifestations included craniofacial dysmorphism with highly arched eyebrows, hypertelorism, strabismus, proptosis and downslanted palpebral fissure, thick alae nasi, short philtrum and large central incisors, everted upper lip, narrow mouth, prominent and large ears with uptilted lobules, and retrognathia. His height was 161 cm and weight 78 kg. He has no siblings.
No history of epilepsy was reported. The neurological examination was normal, and no structural abnormalities were observed on the MRI or the EEG. Hearing and sight functions as well as the skeletal X-rays were unremarkable. The urine and blood metabolic screening results were within the normal limits. There was no urogenital or limb malformation. He had no tremors, no picking, no joint stiffness, no feeding difficulties, and no kyphoscoliosis, according to the criteria described by Beunders et al. []. He did not have any sleep disorders.
The mother of the proband is 49 years old (II2). Pregnancy was uneventful and birth weight was 2.9 kg (5th–10th centile). Her early development was normal, and she walked at the age of around 1 year. Her pubertal development was within the normal limits. The patient had a height of 156 cm (between third and tenth centile) and weighed 76 kg, with a head circumference of 52 cm. The psychological evaluation with the Wechsler Adult Intelligence Scale, third edition (WAIS-III) indicated that her verbal IQ falls within the borderline range (70 to 85). The evaluation of social cognition revealed disturbances in attributional style, theory of mind and emotional recognition. No psychiatric evaluation of a possible ASD was carried out in the absence of clinical signs. She leads an independent life and lives with her husband. No genetic or psychiatric information was available regarding the proband’s father, who exhibited no particular phenotype or behavior.
She presents with short stature, facial dysmorphism with highly arched and thick eyebrows, short philtrum and slightly posteriorly rotated ears. She has arched feet and shallow palmar creases (Fig. ).
Since the age of 45, she developed delusional ideas with an erotomaniac component. She was convinced that a choirmaster loved her. She was consumed by the idea that every object or drawing she came across were signs that he had left for her as proof of his love. She had a severe interpretive and delusional experience.
The diagnosis of erotomania was made according to the clinical criteria set by the International Classification of Diseases, eleventh edition (ICD-11) (F22.0) and to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) (297.11). The latter allowed to specify the predominant type of delusional disorder.
There were no urogenital or limb malformations. She had no tremors, no picking, no joint stiffness, no feeding difficulties, according to the criteria described by Beunders et al. []. There was no family history of substance-alcohol use. She wore a corset for kyphoscoliosis. She did not present with any sleep disorders or epileptic seizures. Brain MRI and blood screening were within the normal limits.
Aunt 1 is 50 years old (II3). Pregnancy and childbirth were unremarkable. Birth weight and birth length are not known. Her early development was unremarkable. The patient has a height of 160 cm (between third and tenth centile) and weighs 78 kg. The psychological evaluation using WAIS-III indicated an IQ within the normal range. The social cognition evaluation did not reveal any disturbances in social cognition but revealed high levels of social anxiety, severely impacting her daily life. She lives in her mother’s home and is not married. She has a job.
This patient presents dysmorphic features such as heart-shaped face, soft fine hair, highly arched eyebrow, a high broad forehead, a bilateral ptosis, large front teeth, kyphoscoliosis and mild micrognathia. No urogenital or limb malformations, nor tremors/picking/feed difficulties/sleep disorders were documented.
Concerning the psychiatric phenotype, Aunt 1 presented serious social anxiety, as has been evaluated during various specialized interviews by several psychiatrists but did not required any medication or supplementary psychiatric evaluations. The blood screening results and brain MRI were unremarkable.
Aunt 2 is 45 years old (II4). She was born at term and pregnancy and delivery were both unremarkable. Birth weight and length were not available. The patient has a height of 155 cm (between third and tenth centile) and weighs 61 kg. A lack of eye contact was noted at 6 months of age with global hypotonia and little social interaction. Mild motor and significant speech delay were evident during childhood.
She presents facial dysmorphism with ptosis, minor hand and feet anomalies. Low anterior hairline, narrow sloping forehead, prominent nasal bridge, broad nasal tip, low hanging columella, prominent eyes with bilateral ptosis, arched eyebrows, small mouth orifice, thin upper lip, high narrow palate, micrognathia and kyphoscoliosis were observed, corresponding to the characteristics of the AUTS2 syndrome. She has been followed for scoliosis since early adulthood. She presented feeding difficulties and severe sleep disorder.
She presented mild-to-moderate ID with behavioral problems such as self-harming and aggressivity without psychotic symptoms (verbal IQ < 35, WAIS-III). She had limited eye-contact with severe communication impairment (no verbal language with the use of gestures or grunts to communicate). Psychiatric medication associated Risperidone (2 mg/day), Fluoxetine (20 mg/day), Loxapine (150 mg/day).
The grandmother is 76 years old (I2). We do not have any early information on pregnancy, birth and childhood, which it would appear were within the normal limits. There was notably no language delay. She went to school, worked all her life and apparently never presented any difficulties in her social interactions.
She does not have dysmorphic features. The patient has no abnormal cognitive features, no psychiatric diagnosis has ever been made. Blood screening showed no abnormalities.
As we can see in Fig. , her husband (I1) is dead and there is no information available about his birth, development, or cognitive abilities. We learn from the family that he presented qualitative deficiencies in his social interaction and communication.
The patient and the parents of the patient gave their written informed consent before participating in this study, and this study was approved by the ethical institutional review board of Le Vinatier hospital.
The karyotyping result for this patient was 46, XY. Array comparative genomic hybridization (CGH) did not show any unbalanced chromosomal rearrangement. The patient was investigated with a diagnostic gene panel of 450 genes whose mutations cause Mendelian neurodevelopmental disorders, including intellectual disability and autism spectrum disorder. Such a 450-gene panel for intellectual deficiency showed a heterozygous duplication of a single nucleotide, Chr7(GRCh37): g.70236569dup, ENST00000342771.4: c.1769dup in exon 11 of AUTS2, leading to a frame shift expected to produce a premature stop codon, p.(Met593Tyrfs*85). No additional pathogenic or likely pathogenic variant was found in any of the other genes of the panel. The history, clinical and behavioral findings support the recurrent phenotypical features of “AUTS2 Syndrome”.
Sanger sequencing showed that the AUTS2 variant was found, in the heterozygous state, in the mother, aunt 1 and aunt 2 but was absent in the grandmother.
All neuropsychological evaluations were performed by trained neuropsychologists (EP and FH).
Table summarizes the characteristics of the five members of the family carrying the AUTS2 variant.


A 62-year-old non-Asian Spanish man was admitted to the emergency room for abdominal pain of epigastric origin, which evolved over the next 3 days to diffuse pain with constipation, but with no fever or vomiting. He had a 32-pack-year smoking history and had completed disulfiram treatment for alcohol cessation 10 years previously. He had residual pain in lower limbs after lumbar disc herniation surgery 15 years previously, for which he was taking naproxen, and had a medical history of a mild factor XII deficiency. He had no other relevant medical, surgical, or family history. On physical examination, palpation showed he had a contracted abdomen, with lividity and signs of peritonism but with no signs of deep vein thrombosis in the lower limbs. Blood pressure was 112/88 mmHg, heart rate 122 beats per minute, and temperature 35.8 ℃. There were no other findings on physical and neurological examination. A thoracoabdominal computed tomography (CT) scan revealed “findings suggestive of intestinal perforation (probably in the upper hemiabdomen), without being able to clearly identify the point of perforation.” Laboratory parameters in the emergency room showed glucose 123 mg/dL, urea 238 mg/dL, creatinine 4.29 mg/dL (previously, normal), total bilirubin 1.45 mg/dL (conjugated 0.91 mg/dL), and amylase 111 mg/dL. Sodium and potassium were in normal range, and the hemogram was also normal. Intravenous fluid resuscitation and empiric antimicrobial therapy with piperacillin–tazobactam 3.375 g/8 hours intravenous for 10 days, fluconazole 400 mg/24 hours for 6 days, and vancomycin 1 g/12 hours for 4 days were started. The patient underwent urgent surgical intervention, which revealed generalized peritonitis, perforation at the pylorus, necrosis of the greater omentum, and an abundance of free fluid in all abdominal quadrants (surgical intervention consisted of pyloric suture and resection of the greater omentum). The pathology report revealed “pyloric wall with signs of perforation and epiplon with adiponecrosis, microabscesses and exudative-fibrinoid serositis.” In the immediate postoperative period, the patient had a low level of consciousness and saturation of up to 80%, with acute lung edema observed on the CT scan (“extensive bilateral pulmonary consolidations associated with bilateral pleural effusion and evidence of anasarca due to probable fluid overload/decompensated heart failure”). The patient was intubated to achieve oxygen saturation > 98% with an FiO2 of 0.4. The patient was sedated and on analgesic, responding to painful stimuli. Hemodynamically, he was mostly stable with a need for norepinephrine at 0.3 mg/kg/minute and tension readings of 123/73 and 90 beats per minute. However, liver function progressively worsened, reaching total bilirubin levels of 4.15 mg/dL. Likewise, the patient was in acute renal failure AKIN III, with diuresis dependent on furosemide at 30 mg/hour, creatinine levels > 4 mg/dL, and urea > 290 mg/dL. The patient presented poor postoperative course, with progressively higher fluid outflow through abdominal drains and abdominal sepsis, as revealed by symptoms and microbiology (Klebsiella pneumoniae was isolated in blood culture; Enterococcus faecalis and Escherichia coli in the drains; E. coli and Streptococcus anginosus in the surgical wound), which raised suspicion of perforation of the previous surgical suture. As intraabdominal pressure increased progressively, the patient underwent a second surgical intervention at 9 days after the first surgery, which revealed a biliopurulent contamination in the peritoneal cavity caused by a previous dehiscence from a pyloric suture line. Therefore, based on intraoperative findings, duodenal exclusion was performed by gastric antrectomy followed by retrocolic Roux-en-Y (end-to-side) gastrojejunostomy and jejunojejunal distal (side-to-side) anastomosis. Cholecystectomy was then followed by external drainage of the common bile duct by placement of a T-tube, to prevent cholecystitis. Splenectomy was performed because of intraoperative bleeding.
The patient remained intubated and sedated, maintaining good saturation. He also had hemodynamic stability without vasoactive amines. However, total bilirubin levels continued to rise (from 4.15 to 6.8 mg/dl), and the patient continued to exhibit anuria, with urea 291 mg/dl, creatinine 4.02 mg/dl; pH 7.35, HCO3- 26.5 mmol/L, pCO2 47 mmHg, and normal anion gap (AG). The patient began treatment with an infusion of caspofungin for 13 days at 50 mg/24 hours, meropenem for 21 days at 1 g/8 hours, and again with vancomycin for 6 days. As the patient again presented very poor postoperative evolution, with fecal contamination of the abdominal drainage, a third surgery was performed 4 days after the second one, in which the patient underwent partial colectomy (due to the intraoperative ischemic appearance of the colon) and resuture of the pyloric repair. Pathological anatomy showed gastric and duodenal dehiscence, with an ischemic appearance of the transverse colon and perforations, foci of hemorrhagic necrosis (both mucosal and submucosal), secondary gangrenous inflammation, and multiple intestinal ulcerations related to calcified phlebosclerosis of the submucosal vessels. After the third intervention, the patient was in stable but serious condition. Hemodynamically, the patient was stable, with some hypertensive peaks (160/70 mmHg). Bilirubin levels improved, down to 2.19 mg/dl; however, the patient continued to have poor kidney function that required hemodialysis sessions at 6 days after the third surgery. Due to the improvement in respiratory function, extubation was carried out but failed due to weakness in the musculature. For this reason, a tracheostomy was performed at 29 days after admission. Teicoplanin was delivered at 3 days after the third surgery, at 400 mg/12 hours for 6 days by isolation in surgical wound exudate of Enterococcus gallinarum. An infusion of ertapenem and ampicillin at 1 g/24 hours and 1 g/6 hours, respectively, was started at 16 days after the third surgery but was suspended because of a skin rash. Linezolid infusion (600 mg/12 hours) was also started at 20 days after the last intervention in order to treat for Gram-positive bacteria. In the last days of life, the patient showed increased overall deterioration, with disconnection to his environment, oscillation between normothermia and hypothermia, and systolic blood pressure < 70 mmHg, which forced hemodialysis to be suspended. Furthermore, despite hemodialysis, creatinine peaks continued at 8.11 mg/dl, and urea at 190 mg/dl. After receiving palliative care, the patient died, 35 days after admission. No autopsy was requested.


A 44-year-old female with past medical history significant for anxiety, seizure disorder, hypothyroidism, and multiple provoked and unprovoked DVTs and PE for which she took 75 mg oral dabigatran twice daily presented to the ED with fatigue and shortness of breath. According to the patient, she was unable to walk from her bed to the bathroom without feeling winded. She also had sharp chest pain whenever she took a deep breath with pain radiating to the right side of her neck. She presented with similar symptoms and was admitted to the hospital two days prior and was diagnosed with a DVT of the left lower extremity and PE of the right pulmonary artery. She was discharged home after one night in stable condition with a prescription for 150 mg twice daily dabigatran, which was double her previous dosage.
She had been taking her dabigatran for the last five years; however, over the past two months, she had multiple interruptions in taking it as she was instructed to stop taking dabigatran four days prior to and following a recent spinal surgery that was rescheduled multiple times. She also occasionally uses marijuana, smokes half a pack of cigarettes most days for the past 10 years, and drinks alcohol a couple of times a month. She denied oral contraceptive use.
A complete review of systems was performed and was significant for left inner thigh pain that was slowly worsening in the last few days. Vital signs obtained were oxygen saturation of 99% on room air, blood pressure 142/95 mmHg, temperature 37.2°C, pulse 98 beats per minute, and respiratory rate 18 breaths per minute. She often required deep breaths between words when talking. She was not in acute distress, however. Her physical exam was significant for tachycardia, tachypnea, and tenderness to palpation over the left thigh with no obvious deformities, swelling, or rashes seen.
Differential diagnosis included but was not limited to PE, acute coronary syndrome, pneumothorax, aortic dissection, pericarditis, pneumonia, pleurisy, and gastro-esophageal reflux. The initial diagnostic workup was remarkable for leukocytosis and elevated troponin (Table ). A d-dimer was not obtained as the patient's pre-test probability of having a PE was too high, meaning we would have obtained a computed tomography angiogram (CTA) of the chest regardless.
Computed tomography angiogram was significant for bilateral PE in the distal left main pulmonary artery extending into the left lower lobe pulmonary artery branches as well as distal right main pulmonary artery extending into the upper and lower lobes. The heart was at the upper limit of normal size (Figure ).
An echocardiogram demonstrated preserved left ventricular function with an ejection fraction of 55% and was significant for a right ventricular systolic pressure of 57 mmHg and left pleural effusion. Bilateral lower extremity ultrasound re-demonstrated extensive left lower extremity DVT from left common femoral, superficial femoral, popliteal, and deep calf veins. The electrocardiogram demonstrated sinus tachycardia.
In consultation with hematology, a heparin drip was initiated. The patient was subsequently admitted to the medical floor. The patient was not a candidate for ekosonic endovascular system (EKOS) due to oral anticoagulation and showed an elevated international normalized ratio (INR). She was bridged to warfarin due to the patient's preference for no longer being on dabigatran. Hematology suggested that clot formation was likely secondary to medication non-compliance (intermittent medication use) rather than the failure of dabigatran. The patient’s hospital course was complicated by multiple episodes of hematemesis as well as hematochezia that were addressed and resolved. She was ultimately bridged to warfarin and discharged home with oxygen as well as follow-up with hematology.


A 38-year-old man presented to the surgery clinic with complaints of upper abdomen pain for 1 year. The pain was dull aching with episodes of increased severity lasting for 1 to 2 hours. The pain was relieved with oral analgesics. This was associated with occasional black tarry stools. The patient also complained of easy fatigability, breathlessness, and palpitations. He had a history of repeated blood transfusions for severe anemia. He was a chronic smoker and tobacco chewer.
His clinical examination revealed pallor. The rest of the examination was unremarkable.
The patient had severe anemia with hemoglobin of 5.7 g/dL for which he was transfused with two units of packed cells. Subsequently, his hemoglobin improved to 8.3 g/dL.
UGIE showed a 1 × 1 cm polyp with central umbilication along the greater curvature of the body of the stomach. There was no active bleeding. The mucosa of the rest of the stomach appeared normal. An impression of a gastrointestinal stromal tumor or NET was kept. The serum chromogranin A (CgA) level was 304 ng/L (normal value = 28–94 ng/mL).
Contrast enhanced computed tomography (CECT) showed evidence of a hyperenhancing polypoidal lesion along the greater curvature measuring 1.1 × 0.7 cm (
). There were no enlarged lymph nodes visualized. Gd-68 DOTATATE scan showed a somatostatin receptor (SSTR) expressing small polypoidal soft tissue density in the body of the stomach along the greater curvature (
).
Subsequently, the patient underwent resection of the polyp under a second endoscopy (
) which was sent for histopathological examination (HPE).
HPE showed a polypoidal structure lined by gastric mucosa (
). The mucosa and submucosa were infiltrated by a tumor that was arranged in an acinar pattern. The tumor cells were monomorphic with a moderate amount of cytoplasm and salt and pepper nuclear chromatin. Occasional mitotic figures were seen. The base of the polyp was free of tumor cells. The tumor was diffusely positive for synaptophysin and CgA on immunohistochemistry (
). Ki-67 index was 3%. The impression made from the above findings was NET of the World Health Organization (WHO) grade II.
The patient was immediately relieved of symptoms following polypectomy and was discharged 2 days later. His hemoglobin after 2 weeks on follow-up was 10.5 g/dL. He is currently asymptomatic.