Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

Pediatric Inflammatory Multisystem Syndrome (Pims) and Dengue Fever during Sars-Cov-2 Pandemic

Intro: The COVID-19 pandemic continues to spread worldwide, and it is likely to overlap with the dengue epidemics in tropical countries. Although most children and young people who develop COVID-19 have no symptoms or very mild ones at the time, we now know that a small number develop Paediatric Inflammatory Multisystem Syndrome (PIMS) a few weeks afterwards. Due to overlapping of clinical and laboratory features, it may be difficult to distinguish PIMS from dengue fever. So this study was undertaken to analyse the clinical features and laboratory investigations in these patients. Method(s): We retrospectively studied the case records of 21 patients diagnosed as pediatric inflammatory multisystem syndrome (based on WHO case definition) and dengue fever (either NS1 antigen positive or IgM antibody positive). A total of 106 patients were diagnosed with dengue fever. Out of these SARS-CoV-2 antibodies were positive in 57 patients. However, only 21 patients full filled the case definition for multi-inflammatory syndrome in children (MIS-C). Clinical features and laboratory investigations were entered in a proforma and results analysed. Finding(s): Out of 21 children's maximum children were older than 10 years age (76.2%). Commonest finding on abdominal sonography was gall bladder wall edema followed by ascites. Thrombocytopenia was seen in 18 (85.7 %) patients at admission and in 14 (66.7%) platelets were less than 50000/mm3.LDH was raised in 19 (90.4%), Ferritin in 18 (85.7%) and D-Dimer in 13 (61.9%) of patients (Table 2). Fever was seen in all the patients,17 (80.9%) patients had shock on admission. Rash was seen in 15 (71.4 %) of the patients. All the patients were discharged. Conclusion(s): Many of clinical features are common to both diseases. However, increased levels of serum ferritin, d-dimer and CRP are more commonly seen in pediatric inflammatory multisystem syndrome due to covid as compared to lower platelet counts which are more frequently seen in dengue fever patients.Copyright © 2023

Scientific debrief: cirrhosis

Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.

Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).

A Combined Method Based on the FIPV N Monoclonal Antibody Immunofluorescence Assay and RT-nPCR Method for the Rapid Diagnosis of FIP-Suspected Ascites

Feline infectious peritonitis (FIP), which is caused by feline infectious peritonitis virus (FIPV), is a fatal and immunologically mediated infectious disease among cats. At present, due to the atypical clinical symptoms and clinicopathological changes, the clinical diagnosis of FIP is still difficult. The gold standard method for the differential diagnosis of FIP is immunohistochemistry (IHC) which is time-consuming and requires specialized personnel and equipment. Therefore, a rapid and accurate clinical diagnostic method for FIPV infection is still urgently needed. In this study, based on the etiological investigation of FIPV in parts of southern China, we attempted to explore a new rapid and highly sensitive method for clinical diagnosis. The results of the etiological investigation showed that the N gene of the FIPV BS8 strain had the highest homology with other strains. Based on this, a specific FIPV BS8 N protein monoclonal antibody was successfully prepared by expression of the recombinant proteins, immunization of mice, fusion and selection of hybridoma cell lines, and screening and purification of monoclonal antibodies. Furthermore, we carried out a time-saving combination method including indirect immunofluorescence assay (IFA) and nested reverse transcription polymerase chain reaction (RT-nPCR) to examine FIP-suspected clinical samples. These results were 100% consistent with IHC. The results revealed that the combined method could be a rapid and accurate application in the diagnosis of suspected FIPV infection within 24 hours. In conclusion, the combination of IFA and RT-nPCR was shown to be a fast and reliable method for clinical FIPV diagnosis. This study will provide insight into the exploitation of FIPV N antibodies for the clinical diagnosis of FIP-suspected ascites samples.

Medicinal bismuth: Bismuth-organic frameworks as pharmaceutically privileged compounds

Historically organometallic compounds have been used to cure certain diseases with limited applications. Although bismuth belongs to the category of heavy metals, many of its derivatives have found applications in modern drug discovery research, mainly because of its low toxicity and higher bioavailability. Being an eco-friendly mild Lewis acid, compounds having bismuth as a central atom are capable of binding several proteins in humans and other species. Bismuth complexes demonstrated antibacterial potential in syphilis, diarrhea, gastritis, and colitis. Apart from antibacterial activities, bismuth compounds exhibited anticancer, antileishmanial, and some extent of antifungal and other medicinal properties. This article discusses major synthetic methods and pharmacological potentials of bismuth complexes exhibiting in vitro activity to significant clinical performance in a systematic and timely manner.Copyright © 2022 Elsevier Ltd

Mortality on Liver Transplant Waiting List: Analysis of a Transplant Center in Colombia

Introduction and Objectives: Cirrhosis and acute liver failure have a high mortality rate and liver transplantation is the only treatment that has shown improvement in the survival of these patients, being 90% in the first year after transplantation and 80% in five years. Currently, in our center there are 95 patients on the liver transplant waiting list, being the largest in the country. The availability of an organ is of key importance and is directly related to the morbidity and mortality of our patients. This study aimed to determine direct and indirect variables that affect mortality on the waiting list in our transplant center. Material(s) and Method(s): We did a retrospective observational study in which we reviewed the clinical charts of the 116 patients who died in the liver transplant list between 2015 and 2021. We described the stage of cirrhosis, its complications and the cause of death. For the analysis of the results, we performed a statistical description. Result(s): Between 2015 and 2021, 116 patients died on the liver transplant waiting list. The cause of cirrhosis was autoimmune disease in 42%of the patients, 75% were CHILD C and 39.7% had MELD >25. The main cause of death was an infection, and the main complications of cirrhosis were ascites (84.5%), encephalopathy (59.5%) and variceal hemorrhage (39.7%). Between 2020 and 2021, COVID-19 infection was documented in 16.7% of deceased patients. Conclusion(s): Infection in patients on the waiting list is the main cause of death before transplantation. It has been documented in the literature that one-year mortality, according to the Meld score, is 30% and 50% for scores of 20-29 and 30-39, respectively. Because of this reason, liver transplantation is the only alternative to impact the survival of these patients. The pandemic contingency affected the care of patients with terminal liver disease, reducing the number of transplants performed because of the lower donation rate. Being pioneers in Colombia of living donor transplantation, it was possible to mitigate the low availability of organs during the Covid-19 pandemic, and in 2020 -2021, 38% of the transplants performed in our center were from a living donor.Copyright © 2023

Expert perspectives for the pharmacist on facilitating and improving the use of albumin in cirrhosis.

PURPOSE: Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review. SUMMARY: Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance. CONCLUSION: Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites.

Unusual initial presentation of childhood acute lymphoblastic leukemia as massive ascites and pleural effusion in post-COVID-19 setting: a case report.

Acute lymphoblastic leukemia (ALL) in children typically presents with nonspecific manifestations such as fever, fatigue, lethargy, joint and bone pain, and bleeding diathesis. Ascites and pleural effusion as an initial presentation of ALL, although described, is exceedingly rare. However, this unusual initial presentation becomes much rarer in the post-coronavirus disease 2019 (COVID-19) setting. Herein, we aim to highlight such a rare initial presentation of childhood ALL that warrants clinical attention. Case Presentation: Two months following a COVID-19 infection, a 3-year-old male patient presented to the hospital with severe abdominal distention associated with occasional dyspnea. Physical assessment revealed a critically ill and pale patient with a distended abdomen and decreased air entry on the right side of the chest. Laboratory testing showed pancytopenia. Imaging studies confirmed the presence of massive ascites and pleural effusion. Bone marrow aspiration revealed CD10-positive pre-B-cell ALL. The patient was treated with chemotherapy and achieved complete remission. Conclusion: Rare manifestations of relatively common diseases create a barrier to prompt and effective detection and medical intervention. Although ascites and pleural effusion are rare conditions in ALL children patients, the occurrence of these pathologies in this particular patient, especially following COVID-19 infection, is an exceedingly rare event.

Atypical Presentation of Burkitt Lymphoma With Isolated Peritoneal Involvement and Association With Refractory Type B Lactic Acidosis and Hypoglycemia Secondary to the Warburg Effect.

Lactic acidosis is considered to be one of the most common causes of high anion gap metabolic acidosis in hospitalized patients. Warburg effect can present with type B lactic acidosis and is considered to be a rare but well-known complication of hematological malignancies. Here, we present the case of a 39-year-old male who had type B lactic acidosis and recurrent hypoglycemia secondary to newly diagnosed Burkitt lymphoma. This case highlights the importance of considering malignancy workup in any case of unexplained type B lactic acidosis with vague clinical presentation, which can aid in early diagnosis and management.

Clinical profile and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection: a single-center observational study from South India

Background: Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious sequelae of acute COVID-19 infection affecting children. This study was done over a period of 12 months from December 2020 to November 2021 to describe the clinical presentation, laboratory abnormalities, and outcome of children with MIS-C. Method(s): Seventy-eight children below 12 years of age who satisfied the WHO diagnostic criteria for MIS-C were included in the study. Clinical parameters were recorded at admission. Relevant laboratory investigations, radiological studies, and outcome were documented. Result(s): The most commonly affected age group was 6-12 years with a female predominance. COVID RTPCR was negative in all patients. Most cases presented 2-6 weeks after the onset of acute COVID-19 infection. Lethargy, poor feeding, vomiting, abdominal pain, loose stools, cough, and cold are common symptoms of MIS-C syndrome in children and the common signs were rash, conjunctival congestion, hypotension, tachycardia, tachypnea, and hypoxemia. Gastrointestinal system was the commonly affected followed by the hepatic, renal, and cardiovascular systems. Coronary artery abnormalities were seen in 20% of cases. IVIg was the mainstay of therapy used in 95% of patients. Mortality was 1.3%. Cases responded well to IVIg and steroids. Conclusion(s): Overall, the short-term outcome was favorable with low mortality in our study cohort. One-fifth of children had coronary artery abnormalities during acute phase underscoring the need for long-term follow-up. Copyright © 2022, The Author(s).

Preparation of the Monoclonal Antibody against the African Swine Fever Virus p54 Protein and Identification of the Antigenic Epitope.

The aim of this paper was to prepare specific monoclonal antibody (mAb) against African swine fever virus (ASFV) p54 protein. The p54 protein was expressed in Escherichia coli expression system and used as the antigen in mAb production. The spleen cells from the immunized BALB/c mice were fused with myeloma cells SP2/0. To screen the positive hybridoma cells, the purified p54 protein was used as envelope antigen for indirect ELISA. After four times' subcloning, the supernatant of hybridoma cells were used to identify mAb subtype, ascites were prepared via in vivo induction method in mice and then the mAb was purified. The titer of the mAb was detected by indirect ELISA, and the specificity of the mAb was identified by cross reactivity assay, IFA and Western blot. According to the predicted secondary structure of p54 protein, using the stepwise truncation method identified the epitope region of mAbs, and labeled the region in tertiary structure of p54 protein. Results were as follows: six hybridoma cells secreting p54 monoclonal antibody were successfully screened and named 28G12-1, 31G7-1, 31G7-2, 35F10-1, 35F10-2, 38D3-1, respectively. The heavy chains of 28G12-1, 31G7-1, and 31G7-2 were IgG2a type, the heavy chains of 35F10-1, 35F10-2, 38D3-1 were IgG1 type, light chains were all kappa chains. The lowest titer of mAb was 1:25 600, and having no cross reaction with PRRSV, PRV, PEDV, PPV, SADS-CoV, PCV2, the specificity was strong. All six monoclonal antibodies could recognize the 127-146 aa on carboxyl end. In this study, ASFV p54 protein and p54 monoclonal antibody were successfully obtained, and the epitopes of six mAbs were identified, these experimental data laid a foundation for the functional research of p54 protein and the study of ASFV epitope vaccine. Copyright © 2023 Editorial Board, Institute of Animal Science of the Chinese Academy of Agricultural Sciences. All rights reserved.

Protein losing enteropathy (PLE) secondary to norovirus infection in a 4 year old patient

Case Report: Protein losing enteropathy (PLE) occurs when proteins leak from the gastrointestinal (GI) system more rapidly than they are produced. Inflammation of the GI tract facilitates increased membrane permeability of gastric mucosa, leading to excess protein leakage. 1 PLE in children has been associated with CMV, rotavirus, COVID-19, HIV, C. difficile, and autoimmune diseases like Crohn's Disease. 2-6 Norovirus is a known cause of PLE in immunocompromised pediatric patients. 7-8 However, to our knowledge, there are no case reports about PLE precipitated by norovirus in immunocompetent pediatric patients. The purpose of this case report is to present a case of PLE precipitated by a norovirus infection in a 4- year-old previously healthy child. While the above gastrointestinal viruses have been proposed as precipitators for this disease, PLE precipitated by norovirus infection has not been well described. This case also highlights the importance of early diagnosis and management to avoid complications. Method(s): Our patient initially presented with two days of abdominal pain, diarrhea, emesis, reduced urine output, and swelling of the lower extremities. He was exposed to several sick family members-his sister had upper respiratory symptoms and his grandmother had gastrointestinal symptoms. Physical exam was notable for diminished breath sounds in the right lower lobe, abdominal distension with diffuse tenderness and dullness to percussion, significant scrotal and penile edema, and bilateral lower extremity pitting edema. Laboratory results revealed leukocytosis, hypoalbuminemia, hyponatremia, elevated aspartate aminotransferase (AST), and elevated serum alpha-1-antitrypsin, as well as low Immunoglobulins G and M. CD3 and CD4 levels were low reflecting cellular immune dysregulation seen in patients with PLE. IgA and Tissue Transglutaminase (TTF) were within normal limits. Ebstein Barr Virus and cytomegalovirus IgM antibodies were negative. COVID IgG was negative as well. His Polymerase chain reaction (PCR) gastrointestinal panel was positive for norovirus. A chest X-ray showed a large right pleural effusion. Abdominal CT revealed large ascites slightly more predominant in the upper abdomen, mesenteric lymphadenitis, and bilateral pleural effusions. Echocardiogram showed small anterior and apical pericardial effusions. Result(s): Based on the patient's elevated serum alpha-1 antitrypsin levels, hypoalbuminemia, low levels of immunoglobulins and lymphocytes, and clinical manifestations of ascites, bilateral pleural effusions, pericardial effusion, and dependent edema, along with a positive PCR for norovirus, the diagnosis of PLE secondary to Norovirus was made. Conclusion(s): This case demonstrates the importance of recognizing viruses like Norovirus as potential causes of PLE to avoid a delay in diagnosis and initiation of therapy, and to avoid unnecessary additional testing. Copyright © 2023 Southern Society for Clinical Investigation.

The Gastrointestinal Presentation of Pims-Ts/ Mis-C in a Cohort at a Tertiary Centre Paediatric Centre

Introduction/Background Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition with poorly understood pathophysiology. Acute presentation varies, with some children acutely unwell in systemic shock, whereas others may have features of Kawasaki disease. This study reports on the presence of gastrointestinal (GI) symptoms and subsequent investigations in children with PIMS-TS at presentation and follow-up, in a large cohort from a tertiary/quaternary paediatric centre. Aim The aim of this prospective observational cohort study is to characterise the gastrointestinal impact of children with PIMS-TS at presentation and at first follow-up. Subjects and Methods Patients from one paediatric centre within the multidisciplinary PIMS-TS service were identified, meeting the following inclusion criteria: under 18 years old, satisfying RCPCH criteria for PIMS-TS, admitted during their acute presentation between 25/4/20-01/12/20. Clinical presentation, symptom profile and initial management were recorded. Investigations including biochemical and inflammatory profiles, stool calprotectin and abdominal imaging (US-Small bowel and CT- Abdomen) were documented. On discharge, GI symptoms and investigations were monitored on subsequent assessments using a standardised template. Results 54 children were identified (35 male), with a median age of 10.3 years (x = 10.0, range 0.75-17.2y). 48/54 (94%) of children had GI symptoms on presentation to admitting hospital (abdominal pain 76%, vomiting 59%, diarrhoea 57%, nausea 35% and ascites 22%). See figure 1. Faecal calprotectin was not a recommended investigation in the UK National PIMS-TS consensus (Delphi process), as such was only performed on 3/54 children at presentation. All of which were within normal range Elevated ALT, AST and/or GGT were seen in 63% of children. Abdominal imaging was performed in 36/54 (67%) of total cohort. On CT abdomen 22/36 (61%) had abnormal abdominal findings (ileocolitis [5/8, 63%], hepatobiliary abnormalities [2/8, 26%]). On abdominal ultrasound (ascites [13/32, 40%], hepatobiliary abnormalities [10/32, 31%], ileocolitis [10/32, 31%], mesenteric adenitis [4/32, 13%], appendicitis [2/32, 6%]) were seen. All patients were reviewed following discharge. On first review (mean: 54 days from discharge), there was resolution of GI symptoms in 96% of the total cohort, however 19% continued to have abnormal abdominal imaging (predominately hepatobiliary abnormalities) and 15% had persistently raised transaminases. 23/54 (43%) children had a faecal calprotectin analysed during the follow-up period - 48% (11/23) had an elevated calprotectin >50mug/g (range 55-399). Summary and Conclusion PIMS-TS has predominately been characterised as a rare condition that effects the cardiovascular system and/or is signified by symptoms of fever and circulatory shock. This study demonstrates the high incidence of GI symptoms at presentation. Abnormalities in transaminases and abdominal imaging and are seen in significant numbers, notably inflammation in the distal ileum and proximal colon and hepatobiliary abnormalities which persist in 19% at their first review. Increased faecal calprotectin levels seen at follow-up, suggest utility at testing at admission. The prevalence of abdominal symptoms may aid the differentiation between Kawasaki disease and PIMS-TS. The persistence of abdominal symptoms, abnormal abdominal imaging and biochemical markers indicate follow-up is required to better understand the long-term GI implications and prognosis of this condition.

A More Unique Than Rare Myopericarditis - a Case Report

A 33yo man, ex-convict, with a history of IV substance abuse, without previous cardiological history, was admitted at our emergency department in the clinical context of an acute pericarditis, intermittent fever in the last 10 days and non-itchy maculo-papular erythema of palms and thorax. EKG documented a diffuse ST-segment elevation, chest X-rays revealed a bilateral pleural effusion and echocardiography documented a normal biventricular morphology and function, normal valvular function, and a circumferential pericardial effusion (14mm). The patient was admitted at our Cardiology Unit after a negative PCR SARS-CoV-2 test. Blood chemistry showed elevated WBC count with an important neutrophilia (24.000/mm3;90% neutrophils), elevated TnI-HS (236 ng/L;n.v. <18 ng/L), elevated C-reactive protein (340 mg/L;n.v. < 5mg/L). A classic anti-inflammatory therapy was set up with indomethacin + colchicine with little clinical benefit. Blood cultures, bacterial serology (i.e., Tubercolosis, T.gondii, Syphilis, Leptospirosis) and viral serology (i.e., HIV, HCV, HBV, EBV, HSV) resulted negative. However, an empirical antibiotic coverage was set up: sequentially with Piperacillin/Tazobactam, Vancomycin, Linezolid and Ceftriaxone. None of the antibiotics improved patient's clinical status. On the contrary, the patient developed an allergic reaction to Vancomycin and Linezolid. All autoantibodies tested resulted negative. After 10 days of hospitalization, the patient's clinical status continued to deteriorate. The intermittent fever (max 41degreeC) was not responsive to any treatment. The evanescent skin rash had spread to the whole body and was concomitant with the fever peaks. The indexes of inflammation were rising (C-reactive protein 400 mg/ L) and so were the WBC count (36.000/mm3). The patient lost weight (-8kg), developed hand and feet arthralgia, diffuse myalgia, painful retronucal lymph nodes, pharyngodynia and abdominal pain. An abdominal echography and CT were performed with evidence of mild abdominal effusion and splenomegaly. Hepatic cytolysis indices began to rise (AST 100 U/L;ALT 150 U/L;LDH 385 U/L). At that point, on the basis of Yamaguchi's Criteria, we suspected our patient could be affected by Adult-onset Still's disease (AOSD) with an initial stage of hemophagocytic lymphohistiocytosis (HLH). Prednisone (IV 2 mg/kg/die) was administered for 72h with an incomplete clinical and biochemical response (C-reactive Protein 180 mg/L). Subsequently, Anakinra (SC 100 mg/die) was administered with a complete clinical response in less than 72h. AOSD is very uncommon. The annual incidence is 0.16/100.000 with an equal distribution between sexes. HLH have been observed in 15% of patients, meanwhile myopericarditis is a rare complication. Although rare, it is fair to know and consider AOSD in the complicated and tricky diagnostic process of myopericarditis. A noteworthy point of this case report is the extreme efficacy of Anakinra in contexts of systemic inflammation and myopericarditis. A point still to be clarified concerns the duration of the treatment and the down-titration of Anakinra in these complicated contexts..

The Natural History of Renal Function in Patients with Cirrhosis and Ascites Who Require Regular Large Volume Paracentesis

Background: Patients with decompensated cirrhosis and ascites are at risk for developing acute kidney injury (AKI), occurring in 20-49% of patients. Those with recurrent or refractory ascites requiring regular large volume paracentesis (LVPs) are at greater risk for AKI because of their advanced cirrhosis, abnormal hemodynamics and frequent fluid shifts from the LVPs. Aim(s): To assess the natural history of renal function in ascitic cirrhotic patients who require regular LVPs. Method(s): A single centre retrospective study including all ascitic cirrhotic patients who attended for outpatient regular LVPs from April 2020 to March 2021, excluding those with COVID infection, hepatocellular carcinoma exceeding Milan's criteria, or extensive non-liver malignancy. Data collected included demographics, paracentesis details, albumin infusions, renal function at baseline and during 3-month (M) follow-up, especially any AKI details, hospital admissions and survival. Result(s): 87 (M:57, F:30;62.0+/-11.3 yrs;MELD-Na: 17.6+/-4.8) mostly alcoholic (47%) and NASH (25%) patients who attended for regular LVPs were included. 14 patients had history of variceal bleed, 26 had a history of encephalopathy (HE). Ascites had been present for 17+/-24M at enrolment, and 12 patients had prior spontaneous bacterial peritonitis. LVP had started 9+/-11M earlier. The mean # of LVPs was 4.2+/-2.6/M with 7.3+/-2.6L of ascites removed/LVP, receiving 90.5+/-38gm/M albumin with the LVPs. The mean serum creatinine (sCr) at enrolment was 100.9+/-50.3mumol/L, with 12 patients fulfilling the KDIGO's criteria for chronic kidney disease (CKD), due to diabetes or hypertension or both. 23 patients were diagnosed to have AKI at enrolment, 3 with background CKD. 5 patients required hospital admission. Table shows the details of AKI at enrolment. During 3M follow-up, 15 episodes of AKI (stage 1: n=9, stage 2: n=6) recurred in 11 patients, with the final sCr at 3M at 113+/-90mumol/L. 17 patients had 26 admissions in 3M, mostly related to cirrhosis complications (AKI/ HRS: n=4, HE: n=4;ascites related: n=4, GI bleed: n=4;infection (n=6). There was 1 liver transplant and 7 liver related deaths. Conclusion(s): CKD is becoming common among ascitic cirrhotic patients requiring LVPs. Irrespective of CKD presence, such patients frequently develop AKI, although mostly stage 1, but recur often, leading to gradual worsening of renal function within 3 M. This subset of patients needs close monitoring and future strategies to prevent AKIs.

Differences in Mortality Rates in Inpatients with Cirrhosis Depends on the Low, Middle or High Income Country Location: Multi-National Cleared Consortium Experience

Background: Although cirrhosis is a major cause of mortality worldwide, there could be disparities in outcomes. This needs a global consortium to study disparities in inpatient cirrhosis care Aim: Define the impact of location in prediction of outcomes in inpts with cirrhosis. Method(s): CLEARED prospectively enrolled non-electively admitted cirrhosis pts without COVID from all continents. To ensure equity, we allowed only 50 pts/site. Admission details, cirrhosis history, inpatient & 30-day course were recorded. World bank classification of low/low middle income (LMI), upper middle (UMI) & High income (HI) were used. Cirrhosis details, inpatient & 30-day outcomes were compared between groups. Multi-variable regression was performed using inpatient & 30-day mortality as outcomes. Result(s): 2758 pts from 21 countries from all continents, including Africa & Australia, were included.727 were L/LMI, 1050 UMI & 981 pts were from HICs. More men & younger pts were in LMI. Cirrhosis details: More pts in HI gp had 6M hospitalizations & infections, HE & ascites while prior variceal bleeding was higher in LMI . Prior HCC & transplant listings were lower in LMI but similar in UMI/HI. Alcohol & NASH was highest in HI. Viral hepatitis & cryptogenic were highest in UMI.Admissions: Admission MELD was highest in LMI. LMI pts were admitted more for GI Bleed, HE, & DILI, while anasarca & HBV flares were higher in UMI. Higher SBP (36% vs 24% vs 21% p<0.0001) & lowest skin/soft-tissue infections were in LMI (5% vs 5% vs 10% p=0.008);rest were similar. Nosocomial infections, driven by UTI were highest in LMI & HI pts (15% vs 14% vs 11% UMI, p=0.03). Admission diuretics, PPIs, Lactulose & statins were highest & antivirals lower in HI. SBP prophylaxis & rifaximin were highest in LMI pts. Outcome(s): More LMI pts needed ICU & had more organ failures (Fig B). Discharge MELD was highest in LMI. In-hospital mortality was highest & transplant lowest in LMI. This extended to 30-day mortality & transplant in LMI patients vs HI pts.Regression: In-hospital mortality was linked with age, infections, MELD & being in a LMI/UMI vs HIC while being on a transplant list, diabetes, & SBP prophylaxis were protective (Fig C). 30-day mortality predicted by age, ascites, HCC, discharge MELD, organ failures, LMI/UMI vs HIC but rifaximin was protective(Fig D). In-hospital transplant was higher with high MELD, admission rifaximin & listed pts &lower in LMI (OR 0.26) & UMI (OR 0.22) & age. 30-day transplant was higher in those with hyponatremia, ascites & HRS, on the list & on rifaximin and lower in LMI (OR 0.24) & UMI (OR 0.59) vs HI. Conclusion(s): In a global study of inpatients with cirrhosis, there were major differences in outcomes. Not being in a high-income country significantly increased the risk of inpatient and 30-day mortality independent of demographics, medications, in-hospital course, and cirrhosis severity likely due to disparities in access to transplant, which should be accounted for in global models. (Figure Presented).

Hospice ultrasound availability enabling out of hospital paracentesis during the first COVID lockdown. A review of paracentesis achieved and their sonographic appearances

BackgroundLike many other hospitals in the UK, the NHS trust local to Saint Francis Hospice (SFH) became overwhelmed with COVID patients during the first lockdown (April to June 2020). The Trust struggled to access a hospital bed for people with advanced disease requiring paracentesis, and getting a permanent drain was difficult. The use of ultrasound in hospices has grown in recent years;its usefulness in hospice paracentesis is well documented. Knowing that SFH had access to ultrasound gave oncology and cardiac colleagues’ confidence to offer the hospice as an alternative.AimsTo identify by retrospective notes review whether the first lockdown affected frequency of paracentesis procedures carried out by the hospice, to identify any obstacles to smooth admission/procedure, and to identify outcomes.MethodsRetrospective review of hospice notes, search term ‘paracentesis’, ‘ascites’.ResultsEighteen drainages were carried out on 8 patients during the 9 month period 08/10/2019 – 30/06/2020. Five had advanced cancer and three had heart failure. 11 were carried out pre-lockdown and 7 during it, a rate increase during lockdown. No permanent drains were achieved during lockdown. 16/18 were planned admissions for paracentesis (2 were crisis admissions for other reasons). All had ultrasounds pre- procedure. Average wait from referral to admission 5.9 days;Average time drain in situ 53 hours;Average volume drained 9.4L. Positive feedback from patients, and no adverse events attributable to the procedure. The audit identified need for adjustment of the admission process to avoid delays from blood tests awaited or sonographer unavailability.ConclusionAvailability of ultrasound allowed safe paracentesis in the hospice and contributed to timely patient care/protection of hospital beds. This poster will provide an overview of typical sonographic appearances of ascites and highlight scenarios that may influence the suitability of drainage.

Paediatric inflammatory multisystem syndrome presenting as acute appendicitis: A case report and literature review

Aims: Paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2 (PIMS-TS) is a novel hyperinflammatory condition that most commonly presents with an acute abdomen. Here we present a case of PIMS-TS mimicking appendicitis and a review of The literature with a proposed protocol for managing abdominal pain in patients with recent SARS-CoV-2 infection. Result(s): An 8-year old girl presented with suspected appendicitis. She underwent a day case open appendicectomy with normal appendix confirmed on histology. Unfortunately, she re-presented The following day with persistently high fever and was investigated for post-appendicectomy complication. She was started on intravenous antibiotics. MRI of abdomen and pelvis showed no collection but evidence of lymphadenopathy. on post-operative day four she was transferred to The tertiary centre PICU for specialist management of suspected severe PIMS-TS. Common abdominal radiological findings in PIMS-TS include ascites, bowel wall thickening and mesenteric inflammation. In addition, CRp and ferritin have been found to be significantly higher in PIMS-TS. White cells may be raised with neutrophilia and lymphopaenia. In addition, highly deranged inflammatory markers in The context of a normal abdominal imaging are more consistent with PIMS-TS than appendicitis. We propose anyone with these findings is considered as having PIMS-TS and requires urgent imaging including combined senior surgical and paediatrician review. Conclusion(s): PIMS-TS may present mimicking acute appendicitis and given The severe cardiac compromise that can develop in patients with PIMS-TS is it important to avoid unnecessary General anaesthetic and abdominal Surgery where possible. Our proposed protocol could help reduce unnecessary abdominal Surgery in these patients.