EBV-related lymphoproliferative disease in Wiskott-Aldrich Syndrome patient

Case: Wiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. Discussion(s): We present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.Copyright © 2023 Elsevier Inc.

A Rare Cause of Enteritis in an Adult Male

Introduction: IgA vasculitis is more commonly seen in the pediatric population than in adults. Rarely IgA vasculitis is associated with malignancy, most commonly solid tumor malignancies, although there are case reports of association with hematologic malignancies. We report a case of large B-cell lymphoma mimicking IgA vasculitis in a 33-year-old immunosuppressed male with a prior history of IgA vasculitis. Case Description/Methods: A 33-year-old Caucasian male post renal transplant from reflux nephropathy on chronic immunosuppression was hospitalized for postprandial epigastric abdominal pain, nausea, vomiting and diarrhea. Two years prior, he was admitted for the same symptoms, palpable purpura of the lower extremities and elevated serum IgA. Enteroscopy had shown duodenal and jejunal ulceration with biopsies staining positive for IgA, confirming IgA vasculitis. He had complete resolution with a steroid taper. His current presentation had resulted in multiple hospital admissions, but empiric trial of steroids failed to alleviate symptoms. Vitals were normal and exam was notable for epigastric tenderness. Labs were notable for WBC 19.00 x103/cmm with normal differential, hemoglobin 9.2 gm/dL (prior 11.0 gm/dL), CRP 20.7 mg/L, serum creatinine 2.7 mg/dL (prior 1.5 mg/dL), and urinalysis with proteinuria, sterile pyuria, and hematuria. CTA abdomen/pelvis revealed thickening of the duodenum with shotty mesenteric lymph nodes without ischemia. Enteroscopy revealed an erythematous duodenum and jejunum (figure A). Jejunal biopsy (figure B) revealed CD20 positive cells consistent with DLCBL (figure C). He was seen by oncology and treated with R-CHOP but later unfortunately expired due to COVID-19 complications. Discussion(s): Non small cell lung cancer and renal cell carcinoma are most commonly associated with IgA vasculitis. It may also be seen in both Hodgkin and Non-Hodgkin lymphomas in adult patients. If IgA vasculitis occurs after a malignancy is diagnosed, it may indicate that metastasis has occurred. Malignancy associated IgA vasculitis is more likely to have an incomplete response to steroids and requires treatment of the underlying malignancy to achieve remission. Our case illustrates posterior probability error and premature closure cognitive biases. We should consider alternative diagnoses rather than anchor on prior diagnoses even when presentations are similar. Our case also highlights the importance of considering occult malignancy in adults with diagnosis of IgA vasculitis.

Superior Mesenteric Artery Thrombosis and Intestinal Ischemia as a Consequence of COVID-19 Infection.

COVID-19-associated arterial and venous thrombotic events are multifactorial in origin, resulting in significant morbidity and mortality. Intestinal ischemia due to thrombus is a rare manifestation of COVID infection. Here, we report the case of a patient who presented with fever, malaise, and diarrhea, and was found to be COVID-19 positive; his clinical course was further complicated by devastating thrombosis of the superior mesentery artery (SMA) associated with COVID-19 infection.

Appendicular flap transposition in case of the left ureters defects

Introduction & Objectives: The frequency of involvement in the oncological process of the ureters in case of pelvis tumors ranges from 15 to 20%. The use of the appendix as a plastic material for the reconstruction of extended ureteral defects (EUD), including left-sided ones, remains debatable. The main goal of this study is evaluating the clinical and functional results after EUD repair using patchy transposition of the appendix. Material(s) and Method(s): Since August 2019 to June 2021, 8 laparoscopic surgeries were performed to replace the EUD using flap transposition of the appendix. Of these, 6 on the left (75%), 2 on the right (25%). 7 women (87.5%) and 1 man (12.5%) were operated on. Mean age 53+/-10.6 years. Average BMI 25.9 kg/m2. Etiology EUD: 25% radiotherapy (n2), 50% iatrogenic surgery (n4), 12.5% (n1) primary ureteral cancer, 12.5% (n1) non-Hodgkin's lymphoma. In all cases, the first stage was a wide mobilization of the ileocecal angle, the appendix was disconnected with a 45 mm hardware suture, in case of left-sided lesion, the appendix was moved isoperistaltically under the mesentery of the sigmoid colon to the left side after preliminary maximum mobilization of the process on the vascular pedicle in the form of a "triangle". All patients received a 7Fr ureteral stent. CT urography was performed on the 3rd, 7th, 11th days. Dynamic nephroscintigraphy was performed on the 90th day. Result(s): The average length of diastasis is 4.6+/-1.7 cm. The average length of the mobilized appendix was 8+/-1.8 cm. Replacement of the ureter with an appendix and a flap of the bladder according to the Demel method was performed in 1 case (12.5%), according to the Boari method in 1 case (12.5%), in 6 (75%) cases an anastomosis was formed according to the "end-to-end" type. the end". The average duration of the operation was 251+/-40.9 min, blood loss was 121+/-56.7 ml. Median removal of the ureteral stent was 36+/-18.28 days. Duration of hospital stay was 14+/-5.2 days. Median follow-up 10+/-5.3 months. Early complications (<30 days): 2 cases of urinary edema (Clavien-Dindo II), 2 cases of ipsilateral hydronephrosis (Clavien-Dindo I-II). Late complications (>30 days): 1 case of partial failure of ureterocystoanastomosis against the background of Sars-Cov-2 infection (Clavien-Dindo IIIa), 1 case of non-functioning left kidney (Clavien-Dindo IVa). Dynamic nephroscintigraphy was performed in 68.4% of patients, the average isotope accumulation time was 4.23+/-0.25 minutes, the duration of the half-life was 14.26+/-0.52 minutes. Conclusion(s): Flap transposition with the appendix is a technically difficult but possible option for extended ureteral strictures. However, various pathological processes that have developed against the background of previous treatment potentially increase the risk of developing repeated strictures or anastomotic leaks. Therefore, given the small sample of patients, further research on this issue is required.Copyright © 2023.

Protease Activity in the Excretory-Secretory Products of Nymphal Stage of Linguatula Serrata: First Detection of a Metalloprotease

The aim of this study was to evaluate the presence of proteases and determine the main protease present in the excretory-secretory products (ESPs) from nymphal stage of Linguatula serrata. Infected mesenteric lymph nodes of goats were collected from Tabriz slaughterhouse, northwestern Iran. Recovered Linguatula serrata nymphs were immersed in culture medium (MEM), then ESPs were collected and protease activity in presence of specific inhibitors was assayed. Protease enzyme was fur-ther characterised by SDS-PAGE. The results of this study showed that the main protease in the ESPs from the nymphal stage of L. serrata was a metalloprotease that was resistant to heat. In conclusion, these data show that a major protease secreted by the larval stage of L. serrata exhibited properties that may play a role in the pathogenesis of L. serrata nymphs.Copyright © 2023, Trakia University. All rights reserved.

Ileal perforation in a tocilizumab-treated patient with rheumatoid arthritis in SARS-CoV- 2 infection

Introduction: Tocilizumab, a monoclonal anti-interleukin- 6 receptor antibody, has been widely used as a treatment for rheumatoid arthritis. Gastrointestinal perforation is a rare but critical complication that occurs in patients treated with tocilizumab. In the COVID-19 pandemic, tocilizumab has been recently highlighted for its beneficial effect in reducing the risk of death in severely ill COVID-19 patients. In this current study, we report the ileal perforation in a COVID-19 confirmed patient who had received tocilizumab for the treatment of rheumatoid arthritis. Case Presentation: A 57-year- old woman with a medical history of rheumatoid arthritis and hypertension presented to our emergency room with abrupt onset of severe abdominal pain and nausea. Physical examination revealed direct and indirect tenderness of the whole abdomen. She had a history of COVID-19 infection 1 month ago and recovered without severe complications. She also has been treated for rheumatoid arthritis, and the disease activity has been maintained low with the administration of tocilizumab since 2019. The latest administration of tocilizumab to the patient was 2 weeks ago. The plain radiograph of the abdomen showed intraperitoneal free air suggesting pneumoperitoneum. The abdominal computed tomography was also conducted to find the origin of free extraluminal air, and it revealed heterogenous wall enhancement of the ileal loop and the mesenteric haziness. The emergency surgery was performed, and the ileal perforation was noted. The small bowel segmental resection was performed through the surgical procedure. Conclusion(s): COVID-19 has been founded to cause gastrointestinal inflammation. The use of tocilizumab in COVID-19 patients should be carefully conducted because it could act as a permissive of gastrointestinal perforation. Furthermore, the physician should be aware of the possible complication of tocilizumab because early diagnosis and timely management are crucial to preventing high mortality complications.

Mesenteric Adenopathy and Adenitis

Mesenteric adenopathy and adenitis are common causes of abdominal pain, requiring emergency admission to hospital. The term mesenteric adenitis is generally used to denote painful lymphadenopathy due to viral infection and is mostly associated with self-limiting viral infections. However, mesenteric adenopathy and adenitis can be associated with infection with SARS-Cov-2 or the human immunodeficiency virus in which setting these have a particularly poor prognosis. Recent advances in our understanding of the mesentery and the organisation of the human body shed new light on the position of mesenteric adenopathy and adenitis in disease in general. Both these abnormalities of the mesentery are observed in most diseases of the abdomen. The frequency with which they are observed means there is an increasing need to scientifically and clinically investigate both. Improved understanding of mesenteric adenopathy and adenitis is likely to greatly enhance our understanding of abdominal and systemic diseases in general. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Mesenteric Adenopathy and Adenitis

Mesenteric adenopathy and adenitis are common causes of abdominal pain, requiring emergency admission to hospital. The term mesenteric adenitis is generally used to denote painful lymphadenopathy due to viral infection and is mostly associated with self-limiting viral infections. However, mesenteric adenopathy and adenitis can be associated with infection with SARS-Cov-2 or the human immunodeficiency virus in which setting these have a particularly poor prognosis. Recent advances in our understanding of the mesentery and the organisation of the human body shed new light on the position of mesenteric adenopathy and adenitis in disease in general. Both these abnormalities of the mesentery are observed in most diseases of the abdomen. The frequency with which they are observed means there is an increasing need to scientifically and clinically investigate both. Improved understanding of mesenteric adenopathy and adenitis is likely to greatly enhance our understanding of abdominal and systemic diseases in general. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

TULAREMIA PRESENTING AS LARGE GI ULCERATION AND HEMORRHAGE

SESSION TITLE: Critical Care Infections SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Francisella tularensis is a zoonotic disease by an aerobic, gram negative coccobacillus. It is transmitted by exposure to infected animal or vectors in individuals who landscape or camp. Common symptoms are fever, chills, anorexia, and headache. Abdominal tularemia can present with abdominal pain, emesis, diarrhea, and rarely intestinal ulceration and hemorrhage. It is treated with aminoglycosides, fluoroquinolones and tetracycline. CASE PRESENTATION: 38-year-old male presented with fever, cough, anorexia, and black stool for 5 days. Patient worked as a landscaper. He has no pets, travel history or sick contacts. He does not take any medications at home. Physical exam was significant for sinus tachycardia and rhonchi of right upper lobe. Significant labs include WBC of 9.8 with 41% bands, hemoglobin 15.5, sodium 125, procalcitonin 27.3, and lactic acid 1.8. COVID-19, MRSA, Legionella and Pneumococcal urine antigen were negative. CTA chest revealed mass-like opacity in right upper lobe with multiple bilateral pulmonary nodules. Lower respiratory culture showed Candida albicans. Patient was empirically started on ceftriaxone and azithromycin. He was transferred to intensive care for worsening respiratory status and was placed on non-invasive ventilation on hospital day 1. Antibiotics were broadened to ceftaroline and levofloxacin due to suspicion of tularemia. Amphotericin B was added. Labs for Histoplasma, Blastomyces, TB, Leptospira, and HIV were negative. Patient then suffered a cardiac arrest on hospital day 2 after having large brown secretions pouring from his mouth. Cardiopulmonary resuscitation was initiated and patient was intubated and started on vasopressors with return of spontaneous circulation. Massive blood transfusion protocol was initiated. Emergent bedside upper endoscopy showed large blood clot adherent to duodenal ulcer. Interventional radiology planned on performing gastric duodenal artery embolization. However, patient suffered two more cardiac arrest with resuscitation efforts terminated per family request. Karius Digital Culture later was positive for Francisella tularensis. Autopsy revealed diffuse alveolar hemorrhage, hilar lymphadenopathy, and perforated duodenal ulceration with large adherent clot. DISCUSSION: Gastrointestinal tularemia is rare and usually from drinking contaminated water or oral inoculation of bacteria. Intestinal tract involvement can present with mesenteric lymphadenopathy and ulcerative lesions resulting in gastrointestinal bleeding with case fatality rate of 50%. Even though this is noted in the literature, to our knowledge no case reports have been published. CONCLUSIONS: Careful history taking and early identification of risk factors are important when severe tularemia infection is suspected such as in individuals with extensive outdoor activities. Treatment should be empirically initiated in high risk patients. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585636/ Reference #2: https://casereports.bmj.com/content/2017/bcr-2017-22125. Reference #3: Altman GB, Wachs JE. Tularemia: A pathogen in nature and a biological weapon. Aaohn Journal. 2002 Aug;50(8):373-9. DISCLOSURES: No relevant relationships by Maria Haider Baig

Superior Mesenteric Vein and Portal Vein Thrombosis in a Patient With COVID-19: A Rare Case

A 68-year-old man was referred to the general surgeons on account of his abdominal pain of unknown cause. He had contracted COVID-19, 9 days prior. CT chest abdomen and pelvis revealed an extensive thrombus extending from the portal vein to the superior mesenteric vein. Further investigation ruled out haematological causes, and COVID-19 was determined to be the cause. He was treated with an extended course of therapeutic dose low molecular weight heparin under the guidance of the haematology team. He was discharged once he was clinically stable and pain-free, with a plan to be followed up by both the surgeons and haematologists. This case highlights the different ways in which COVID-19 presents, and the need for clearer guidance on the treatment and prevention of thromboembolism in COVID-19.

Coronavirus-2019 Disease with Pancytopenia with Leptospirosis and Herpes Simplex Virus Co-infection

Aim and background: COVID-19 pandemic has affected the whole world. Besides COVID, many infections may emerge during the course of the disease. Lymphopenia, use of immunosuppressants underlying comorbidities, and immune dysregulation secondary to SARS-CoV-2 could be the likely cause of the emergence such infections. We hereby describe a case of COVID-19 disease which presented with pancytopenia and was found to have Leptospirosis and Herpes Simplex Virus co-infection. Case summary: A 23-yearold postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital 2 weeks after a full-term normal vaginal delivery. She developed generalized convulsive status epilepticus on the 10th day of her delivery, which was managed elsewhere with anti-epileptic drugs (AEDs). During her hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic throughout the course of her illness and seizures remained well-controlled on AEDs. On admission to our hospital, she was fully conscious, alert with no focal neurological deficits. Notable findings on evaluation were pancytopenia with megaloblastic features, bilateral pedal edema, and hepatosplenomegaly. NCCT brain was done which was suggestive of subarachnoid hemorrhage (SAH) along bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of abdomen revealed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In the panel sent for pancytopenia workup, IgM anti-HSV 1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies were positive). Workup for tuberculosis was negative. Bone marrow workup revealed features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia with no evidence of hemophagocytosis. Subsequently, IV acyclovir, IV doxycycline, and iron replacement were added. She improved clinically after these therapies and was subsequently discharged in a stable condition. MRI brain with MR angiography and venography done before discharge showed T1 sulcal hyperintensities along bilateral parietooccipital regions suggestive of SAH which was not progressing (as compared to NCCT brain scan done at admission). On day 60 of telephonic follow-up, patient was doing well and leading normal life without any persistence or emergence of symptoms.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

MIS-CM imicking Acute Appendicitis

Introduction: Abdominal pain is one of the most common complaints seen in the pediatric acute care setting. SARS-CoV-2 disease in children includes a hyperinflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are most common in pediatric acute SARS-CoV-2 infection as well as in MIS-C. Case Description: A 13- year-old female presented with diffuse lower abdominal pain for 3-days. Pain was 10/10 in intensity, worsened with movement, and had associated constipation, anorexia, nausea, and vomiting. Exam showed an ill-appearing female with labile vitals and generalized lower abdominal tenderness with good bowel sounds. Ultrasound suggested features of acute appendicitis but a follow-up CT did not visualize the appendix. She was admitted to the inpatient unit after routine screening revealed positive SARS-CoV-2 antibody but negative PCR. She received IV fluid bolus, narcotic analgesics, and ampicillin-sulbactam preoperatively. Within hours, she spiked high-grade fevers (101.4F), sustained hypotension, and tachycardia with concern for sepsis secondary to a possible ruptured appendix. She underwent emergency diagnostic laparoscopy which revealed bile-tinged fluid in the lower quadrant, a mildly inflamed appendicular tip without perforation, and thickened mesenteric nodes within the inflamed distal ileum. Intra-operatively, she had persistent hypotension requiring fluid boluses and vasopressors. Her admission labs revealed elevated inflammatory markers, deranged coagulation profile, and elevated cardiac enzymes. Her differential diagnosis was then revised to include MIS-C and severe sepsis. Antibiotic coverage was broadened to Vancomycin and Meropenem. An Echocardiogram showed mitral regurgitation with moderately to severely decreased right and left ventricular systolic dysfunction with an ejection fraction of 32.8% The patient was then transferred to the pediatric cardiac critical unit where she received treatment with IVIG, steroids, and anticoagulants. Her clinical status and lab studies improved with EF > 50%. She was discharged from the intensive care unit after 7 days and has had an uneventful follow-up. Discussion: Differential diagnosis for acute lower abdominal pain in an adolescent female is broad. Similar cases with predominant GI symptoms and later generalized multisystem involvement have been reported, however, most were managed conservatively. Two reports have been published on MIS-C presenting as acute appendicitis, but neither had significant cardiac involvement. Our patient's presentation can easily be confused with an acute surgical abdomen but the pathology report confirmed a congested appendix without any fecoliths supporting either inflammation or vasculitis as the cause for her presentation, which is in concordance with the hyperinflammatory state that has previously been described in patients presenting with a history of past SARS-CoV- 2 infections. Conclusion: MIS-C can mimic serious pediatric illnesses including sepsis, acute abdomen, and Kawasaki disease. Clinicians should have a low threshold for suspecting MIS-C, as prompt treatment can be lifesaving. Universal screening for COVID-19 infection with PCR and antibody tests can expedite the diagnostic evaluation of severely ill children. Showing reactive wall thickening of the cecum and small bowel loops (red arrow) and enlarged mesenteric lymph nodes (yellow arrow). The appendix could not be visualized here.

IMMUNE SYSTEM IN MOTION: A CASE OF ADULT-ONSET STILL'S DISEASE

CASE: A 23-year-old female with a history of congenital deafness and HLAB27 positivity presented for two weeks of diffuse arthralgias, fever, and nausea. She had a history of an erythematous rash around her eyes and upper chest that had resolved with prednisone;however, her other symptoms persisted. She denied known tick exposures, drug use, sick contacts, or travel, but had recently been hiking. On presentation, she was febrile to 38.8°C and tachycardic to 130 beats/min. Her labs were notable for an AST of 232 U/L, ALT of 266 U/L, LDH of 680 U/L, haptoglobin <10 mg/dL, and ferritin of 12,230 ng/mL, with no cytopenias or leukocytosis. Her CRP was 127 mg/dL and ESR was normal. Her troponin and BNP were both elevated, to 54 ng/L and 468 pg/mL respectively. ANA and RF titers was negative. Viral studies including EBV, CMV, and SARSCoV-2 as well as bacterial studies were negative. She was started on doxycycline for possible tick-borne infection, but titers returned negative. Echocardiography and chest x-ray were unremarkable. CT scan demonstrated nonspecific para-aortic and mesenteric lymphadenopathy. The patient's presentation and labs were consistent with adult-onset Still's disease (AOSD), meeting the Yamaguchi criteria for diagnosis. She was started on IV hydrocortisone and anakinra with symptomatic improvement. Her liver function testing worsened due to concerns for macrophage activation syndrome (MAS). She was treated with ruxolitinib with gradual improvement in her liver function, followed by tofacitinib. She made a full recovery on discharge. IMPACT/DISCUSSION: Due to its rarity, AOSD can be challenging to diagnose. This case highlighted the key manifestations and distinguishing characteristics of the disorder. The patient presented with fever, rash, and polyarthralgias. While the location of the rash in AOSD varies, the upper chest as seen in this case is typical. While this patient did not have cytopenia or leukocytosis, she did have elevated transaminases and a disproportionately elevated ferritin, a hallmark of AOSD. Importantly, ANA and RF titers were negative, which helps to differentiate AOSD from other autoimmune disorders. The case also demonstrated a feared complication of AOSD, MAS, a form of hemophagocytic lymphohistiocytosis that occurs in 10-15% of patients with AOSD. This case highlighted the importance of remaining vigilant for MAS, as the patient's liver function continued to decline despite symptomatic improvement. While MAS is difficult to diagnose, hyperferritinemia and pancytopenia are thought to be relatively strong indicators. CONCLUSION: AOSD is a rare and debilitating disease, with an illness script that has significant overlap with other diseases. In addition to the combination of polyarthralgias, rash, and fevers, a markedly elevated ferritin is a strong indicator of AOSD. ANA and RF titers will be negative. It is crucial to remain vigilant for complications of the disease, such as MAS.

IMMUNOSUPPRESSION SECONDARY TO SEPSIS AND POSTACUTE CARE SYNDROME LEADING TO LATENT TUBERCULOSIS REACTIVATION

CASE: A 59-year-old Mexican-American man with hypertension and type II diabetes (Hemoglobin A1c 11.5) was admitted for sepsis and Acute Respiratory Distress Syndrome secondary to COVID-19 pneumonia. He was ventilator- dependent for 66 days. His clinical course was complicated by acute renal failure requiring hemodialysis, pulmonary embolism, and recurrent ventilator-associated bacterial pneumonia. He was discharged to a long-term acute care center four months after his initial presentation, but was readmitted two weeks later for abdominal pain and fever. CT abdomen revealed diffuse mesenteric nodular stranding and pelvic ascites concerning for peritoneal carcinomatosis. Biopsy of an omental nodule, however, showed necrotizing granulomatous inflammation and no malignant cells. No cultures were sent from the initial biopsy, so repeat sampling was performed and culture was positive for Mycobacterium tuberculosis complex. Treatment for active tuberculosis was initiated with subsequent recovery. IMPACT/DISCUSSION: Initial infection by tuberculosis occurs in the lungs, where alveolar macrophages encounter and phagocytose the bacteria. The macrophages initiate a cytokine response and recruit lymphocytes to form a granuloma, which segregates the infection within the host. The granuloma is then perpetually maintained by an ongoing immune response that is driven by monocytes and CD-4 T cells. Reactivation of tuberculosis occurs when the ongoing immune response is disrupted. Sepsis has profound and complex effects on the immune system, including marked inhibition of lymphocyte proliferation that leads to reduced levels of B cells, CD-4 T cells, and follicular dendritic cells. Signaling pathways are disrupted without these lymphocytes, which then leads to the dysfunction of the remaining leukocytes. Further, critically ill patients often suffer from post-intensive care unit syndrome. This syndrome is marked by persistent inflammation, which prompts an immunosuppressive response that suppresses T-cell function and leads to T-cell apoptosis. Both sepsis and post-intensive care unit syndrome predispose patients to opportunistic infection by attenuation of the usual immune response. In this particular case, the specific loss of T-cell function in both syndromes allowed this patient's latent tuberculosis to reactivate several months after his initial presentation with sepsis from COVID-19 pneumonia. This case highlights the importance of maintaining a high index of suspicion for opportunistic infection after critical illness. CONCLUSION: Sepsis and post-intensive care unit syndrome disrupted this patient's ability to maintain the immune responses that prevent the progression of latent tuberculosis infection. The diagnosis was delayed due to a lack of awareness of the profound immunosuppression that accompanies and follows critical illness. Providers must recognize these syndromes and the impact they have on immunity in order to diagnose and treat opportunistic infections in a timely manner.

RARE CASE OF ILEOCOLIC MESENTERY PRIMARY MELANOMA WITH LIVER METASTASIS

Purpose/Background: Although GI melanoma is commonly a metastatic disease, it is very unusual to see the mesenteric mass of the cecum and terminal ileum as the primary origin of melanoma. Hypothesis/Aim: This is a case report and presentation showing a rare occasion of primary melanoma in the cecum and the terminal ileum mesentery along the ileocolic pedicle causing cecal complete bowel obstruction. Methods/Interventions: The reported case is a rare occasion of large bowel obstruction near the cecum resulted from primary mesenteric melanoma invading into the wall of the descending colon. Primary melanoma of the GI tract is still controversial and only a limited of cases have been reported in the literature. We added a review of the other published case reports to this case report using Endnote. Results/Outcome(s): This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt this was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient service and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/ mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. She had also intraoperative liver biopsy that demonstrated metastasis of the melanoma to the liver. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. Limitations: Case report study with reported cases reviewed. Conclusions/Discussion: Large bowel obstruction could be related to unusual diagnoses like melanoma of the bowel mesentery. Although, primary GI melanoma is rare this showed the possibility of such diagnosis. (Figure Presented).

SARS-CoV-2-INFECTED MACAQUES EXHIBIT MICROBIAL TRANSLOCATION ACROSS INTESTINAL MUCOSA

Background: Gastrointestinal symptoms and viral RNA (vRNA) in stool have been described in human SARS-CoV-2 infections. However, intestinal pathology and related inflammation have not been extensively described in humans or animal models. Here we investigate the effect of SARS-CoV-2 infection on the gut mucosa and inflammation in rhesus macaques (RM) and humans. Methods: Fourteen adult RM were infected with US/WA-1/2020 SARS-CoV-2 instilled intranasally and intratracheally. Animal clinical features (mass, temperature, etc.) and samples (nasal swabs, throat swabs, blood, stool, etc.) were collected at baseline and up to day 10 post-infection at necropsy. RNA was extracted from swab and stool samples and vRNA measured by qRT-PCR. Plasma samples were assessed for inflammatory biomarkers by ELISA. Tissues collected at necropsy were fixed and evaluated for microbial translocation through immunohistochemical (IHC) staining of bacterial products;H&E staining was also performed. Tissues were additionally collected from uninfected RM and processed in the same manner. Human plasma samples from individuals with moderate COVID-19 were collected at early infection and recovery time points and assessed for inflammatory biomarkers. Results: SARS-CoV-2 infection of RM did not induce fever nor weight loss over five percent. vRNA was detected in all animals in nasal and throat swabs. vRNA, including subgenomic RNA indicative of viral replication, was also detected in stool samples. Scores for translocating bacteria in colon sections stained by IHC for bacterial products were higher for SARS-CoV-2 infected RM than uninfected controls. Additionally, follicles made up a higher percentage of total mesenteric lymph node area in SARS-CoV-2 infected animals than control RM. Furthermore, soluble CD14 in plasma increased significantly from baseline to day 10 of SARS-CoV-2 infection (p=0.0006) and decreased significantly in humans from early infection to recovery time points (p=0.0295). Conclusion: Thus, adult RM experienced mild to moderate SARS-CoV-2 infections yet demonstrated evidence of microbial translocation. Humans similarly demonstrated evidence of microbial translocation that decreased upon recovery from COVID-19. These data suggest gut pathology in SARS-CoV-2 infection may be contributing to systemic inflammation in COVID-19.

Correlation of Clinical and Histopathological Findings with Viral Variant in the Gastrointestinal Tract of COVID-19 Autopsy Cases

Background: Initial evidence has shown the occasional presence of SARS-CoV-2 in enterocytes in the intestines of patients with COVID-19. Our aim is to further assess the clinical and pathologic changes in the gastrointestinal tract caused by the highly contagious Delta (B.1.617.2) variant as compared to viral variants originating earlier in the pandemic. Design: Intestinal samples from 32 patients with death due to COVID-19 were obtained at autopsy. Decedents were males and females, with an age range of 32-73 years. Twenty-one of the decedents self-identified as Black/African American, eight as Caucasian, and three as Hispanic. Two groups were differentiated by viral genome RNA sequencing from autopsy tissue: those with Delta variant (n=16), and those with non-Delta variant (n=16). SARS-CoV-2 expression in the intestine was evaluated by immunohistochemical (IHC) detection of the SARS-CoV-2 nucleocapsid protein (N-protein). Results: Clinically, the Delta group reported diarrhea more frequently (25%) as compared to the non-Delta group (6%). Patients in the Delta group had a shorter time interval between the onset of gastrointestinal symptoms and death (mean = 19 days), as compared to the non-Delta group (mean = 25 days). Histologic examination revealed mostly normal to mild, non-specific chronic inflammation within the epithelium and lamina propria in both groups. Macrophages with positivity for N-protein IHC were present beneath the epithelium, most notably within the Delta group. N-protein positivity occurred most frequently in small submucosal and mesenteric blood vessels. Patchy positivity for N-protein in enterocytes was seen frequently in cases of Delta variant in which the time from initial symptoms to death was short (<14 days). Figure 1 - 11 Conclusions: As in prior studies, intestinal microscopic changes in COVID-19 were minimal, though our findings indicate that SARS-CoV-2 may be detected within enterocytes more frequently in the Delta group. Patients with the Delta variant experienced both a higher rate of diarrhea and a shorter interval between gastrointestinal symptom onset and death. Whether increased Nprotein in enterocytes is a result of the Delta variant itself, or earlier intestinal sampling relative to symptoms in this group, remains to be determined. Autopsy studies can add to our understanding of the effects of COVID-19 on the digestive system, by allowing a greater volume of tissue sampling, as well as temporal sampling relative to disease onset that is not always possible at endoscopy.

CHILAIDITI SYNDROME IN A 49-YEAR-OLD MALE WITH COVID-19 INFECTION – CASE REPORT

The authors illustrate a case of a 49-year-old male patient admitted to our Emergency Department with dry persistent cough, fever, chills, vague abdominal discomfort and a recent history of dyspnoea and fatigability, symptoms suggestive of COVID-19 infection. Physical examination showed mild abdominal distension and no signs of peritoneal irritation. The patient was tested positive for COVID-19 and d-dimers were also found positive, raising a strong suspicion diagnosis of pulmonary thromboembolism as a complication of SARS-COV-2 infection, which required an immediate CT scan. No signs of pulmonary thromboembolism were present on the CT scan. Apart from bilateral pulmonary condensation areas having a ground glass pattern with a peripheral distribution, which are the characteristic radiologic feature of SARS-COV-2 infection, the CT scan also revealed the anterior interposition of the colon between the liver and diaphragm, this being highly suggestive for Chilaiditi Syndrome.

ON THE CUSP-ID OF VALVULAR DISEASE: CARCINOID'S UNEXPECTED ROLE

Background: Primary causes of tricuspid regurgitation (TR) account for 8-10% of cases, whereas secondary causes account for >90%. Given this disparity, there is paucity of data to help guide treatment. Case: A 55-year-old man presented with DOE, fatigue, and diarrhea. He initially presented to urgent care to be tested for COVID-19, however, was found to have a pulsatile neck and was sent to the emergency department. Further history significant for lethargy, bilateral lower extremity swelling, and PND. On presentation, he was normotensive and tachycardic to 110 bpm. Pertinent physical exam findings included facial erythema, severe jugular venous distention with prominent C-V waves, a holosystolic murmur without radiation, and 2+ lower extremity pitting edema. Pertinent laboratory studies include NT-Pro-BNP of 802 pg/mL (reference range, 15 - 125 pg/mL). Infectious workup was positive for SARS-CoV-2. Transthoracic echocardiogram (TTE) demonstrated preserved ejection fraction of 55-60%, dilation of the right atrium and ventricle with normal function, and a small pericardial effusion. Evaluation of the tricuspid valve showed wide-open regurgitation with thickened and restricted leaflets. Decision-making: Given concern for carcinoid valvular disease, oncologic workup was performed that revealed a serum serotonin of 1493 ng/mL (reference range, 21-321 ng/mL), 24-hour urine serotonin of >300 mg/24 hr (reference range, 0.0-14.9 mg/24 hr), and chromogranin A of 806.7 ng/mL (reference range, 0.0-101.8 ng/mL). PET/CT demonstrated Dotatate uptake within the liver and mesenteric lymph nodes. Percutaneous liver biopsy confirmed metastatic well-differentiated neuroendocrine tumor, grade 1. He was started on octreotide and furosemide for symptomatic management. Currently, he is pending endoscopic tricuspid valve replacement which will be guided by decreased tumor progression. Conclusion: Carcinoid heart disease, while rare, represents an important etiology of valvular dysfunction. Despite a well-recognized clinical entity, establishing a diagnosis and making an individualized treatment plan remains a significant challenge utilizing several subspecialties.