PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

ECMO in acute fulminant myocarditis in pediatrics

Objectives: To describe our experience in ECMO for acute myocarditis Methods: Descriptive, retrospective study (2018-2022) of a cohort of 8 patients < 16 years with acute myocarditis who were assisted on ECMO. Result(s): 8 patients were collected, (6 females), with a mean age 7;8 years [range 0;1-13;8]. In 7/8, the reason for cannulation was hemodynamic instability refractory to medical treatment, with a mean inotropic score of 70 [range 10-122]. Sixty-two percent presented cardiorespiratory arrest prior to cannulation and 2 of them needed ECRP. The mean precannulation troponin level was 1498 ng/ml [range 89-6212]. Primary transport was performed in 4 patients. ECMO was peripheral veno-arterial in 100%, jugulo-carotid in 2/8 and femoro-femoral in 6/8. All patients underwent atrioseptostomy. They received treatment with levosimendan, immunoglobulins, corticoids and carnitine. In 4 acute infectious etiology was confirmed (parvovirus, influenza and SARSCoV2), another one was due to PIMS-TS and in 3 no etiology was found. Six patients underwent myocardial biopsy and 5 of them showed inflammatory infiltrates. The mean time on ECMO was 8 days [range 3-14], 2 of them requiring 2 ECMO courses. The mean length of PICU stay was 21 days [range 10-50]. Two were transferred to a heart transplant center. The main complications were arterial hypertension (88%), bleeding (63%), neurological (50%), arrhythmias (38%), coagulopathy (38%) and infectious (38%). One patient required renal replacement therapy. 1 patient died, 2 had moderate neurological sequels. Conclusion(s): ECMO is a therapeutic option in patients with fulminant myocarditis refractory to medical treatment and may help improve their prognosis.

ECMO for the immunocompromised pediatric patient: Our experience

Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.

Anaphylaxis to Cyclophosphamide Metabolites during Lymphodepletion for CAR-T Therapy

Background: Cyclophosphamide (Cy) is used in hematopoietic stem cell transplant (HSCT) preparative regimens and lymphodepletion for chimeric antigen receptor T-cell (CAR-T) therapy. We describe a case of cyclophosphamide hypersensitivity in a pediatric patient during CAR-T therapy. Case description: A 13 year old boy was diagnosed with very high risk ALL in 2015 and had 2 isolated CNS relapses treated with intensified chemotherapy (chemo) and cranial radiation (1st relapse) and Blinatumomab with intrathecal (IT) chemo followed by sibling donor HSCT (2nd relapse). At age 19, and 18 months after HSCT, he had a 3rd CNS relapse treated with IT chemo and referral for CAR-T therapy. At our center, leukapheresis and CAR-T production (Novartis) were performed. Later, during lymphodepletion with fludarabine (Flu) and Cy, physiologic replacement hydrocortisone (HC) was briefly held to prevent interference with CAR-T function. After 3 days of Flu/Cy, he developed fever and hypotension requiring inotropic support. Hypotension and fever resolved with stress dose HC and antibiotics and was attributed to culture-negative sepsis and adrenal crisis. CAR-T infusion was subsequently delayed by skin GVHD requiring glucocorticoids and COVID-19 infection treated with convalescent plasma and nirmatrelvir/ritonavir. Physiologic HC replacement was continued when he was re-admitted for CAR-T therapy, but he again developed fever, diffuse erythema and shock in hours following the first dose of Cy necessitating stress dose HC, antibiotics, inotropes, and mechanical ventilation. Negative blood cultures and ongoing physiologic HC replacement suggested an alternative explanation for shock. Case reports of anaphylaxis to Cy metabolites implicated Cy as the causative agent so it was discontinued. After recovery, CAR-T cells were infused without complications. In the following weeks, he had no evidence of recurrent leukemia but was persistently pancytopenic. A sibling donor stem cell boost was proposed but the patient accepted only palliative care. He had several opportunistic infections before succumbing to E. coli sepsis. Discussion(s): The first episode of shock was initially attributed to adrenal crisis and sepsis, although no organism was identified. The second episode appeared anaphylactic in timing and clinical presentation with adequate HC replacement and negative cultures, suggesting Type I hypersensitivity. The patient previously received Cy uneventfully before HSCT, suggesting that the donor-derived immune system was the source of new Cy hypersensitivity. Onset of anaphylaxis within hours rather than minutes after Cy administration supports hypersensitivity to Cy metabolites rather than to the drug itself. This case highlights the importance of consideration of sensitivity to Cy metabolites as well as acquired donor-specific allergy even when alternative explanations are likely.Copyright © 2023 American Society for Transplantation and Cellular Therapy

A Rare Case Of Eosinophilic Myocarditis Due To Subacute Sars-cov-2 Illness

Background: Eosinophilic myocarditis is a rare inflammatory cardiomyopathy with a poor prognosis. SARS-CoV-2 (COVID-19) illness has been associated with myocarditis, particularly of lymphocytic etiology. Although there have been cases of eosinophilic myocarditis associated with COVID-19 vaccination, there have been few reported cases secondary to COVID-19 illness, with the majority being diagnosed via post-mortem autopsy. Case: A 44-year-old woman with no significant medical history other than recent COVID-19 illness 6 weeks prior presented with progressive dyspnea. Patient developed acute dyspnea and diffuse pruritic rash after taking hydroxyzine. Labs were significant for mild eosinophilia. Echocardiography showed biventricular systolic dysfunction with left ventricular ejection fraction of 40%, and a moderate pericardial effusion that was drained percutaneously. She underwent left heart and right heart catheterization showing elevated biventricular filling pressures, Fick cardiac index of 1.6 L/min/m2, and no coronary disease. She was started on intravenous diuretics and transferred to our facility for further management. Her course was complicated by cardiogenic shock requiring intra-aortic balloon pump (IABP) support. Mixed venous saturations continued to decline and the patient was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The patient underwent endomyocardial biopsy (EMB) showing marked interstitial infiltration of eosinophils and macrophages with myocyte injury (see image). She was intubated with mechanical ventilation as well due to worsening pulmonary edema and hypoxemia. She was started on intravenous steroids with improvement of hemodynamics and myocardial function and eventually VA- ECMO was decannulated to low-dose inotropic support which in turn was ultimately weaned after 3 days of mechanical support. Conclusion(s): Eosinophilic myocarditis is a rare and under-recognized sequela of acute COVID-19 infection associated with high mortality rates. It requires prompt diagnosis and aggressive supportive care, including temporary mechanical circulatory support. There are few literature-reported cases of COVID-19 myocarditis requiring use of both IABP and VA-ECMO, none of which were used in biopsy-proven eosinophilic myocarditis, with most of these cases resulting in either fatal or unreported outcomes. Most cases of covid myocarditis required IV glucocorticoids therapy in conjunction with IVIG or interferon therapy. Here, we present a rare case of cardiogenic shock secondary to biopsy-proven eosinophilic myocarditis associated with recent COVID-19 illness with a survival outcome after temporary use of IABP and VA-ECMO support, as well as aggressive immunosuppressive therapy.Copyright © 2022

An Unusual Case of Cardiogenic Shock in a Cardio-Oncologic Patient

Background Graft versus host disease (GVHD) most often occurs 100-365 days after hematopoietic stem cell transplant (HSCT). Manifestations most often are dermatologic, hepatic or pulmonic, and are rarely cardiac. We present a unique case of GVHD inducing cardiogenic shock necessitating advanced heart failure therapies. Case This is a 34 year-old male with a history of acute lymphoblastic leukemia who completed chemoradiation and HSCT from an HLA perfect sibling in 1992. In May 2020, he presented with dyspnea for 6 weeks. An echocardiogram at that time showed an EF of 10% and severe biventricular dilatation. He was originally hospitalized at an outside institution for hypoxia where a left heart catheterization showed normal coronaries and goal directed therapy was initiated. After 2 negative COVID tests, he was discharged with a LifeVest. One month later, despite medication compliance, he returned in cardiogenic shock after his LifeVest was activated for ventricular tachycardia (VT). Decision-making He was started on inotropic therapy and an intra-aortic balloon pump (IABP) was placed 1:1 prior to transfer to our tertiary center. After support was started, a right heart catheterization showed a right atrial pressure of 13 mmHg, a wedge of 17, and a cardiac index of 2.6. His course was complicated by VT storm. Differentials for his non-ischemic cardiomyopathy (NICMO) included myocarditis (viral vs. giant cell) with a possible component of chemotherapy/radiation induced NICMO. Immediate AHFT work-up was started. He was unable to be weaned off his IABP or inotropic support. The decision was made to pursue emergent left ventricular assist device placement (LVAD) and achieve a definitive diagnosis with a core biopsy. Pathology resulted with myocyte hypertrophy, chronic inflammation with eosinophils concerning for chronic GVHD. Conclusion There have only been a handful of case reports describing cardiac manifestations of GVHD, and none with NICMO and cardiogenic shock requiring an LVAD. Despite this, suspicion should remain present for GVHD in HSCT patients regardless of time frame from oncologic therapies or specificity of HLA match when presenting in cardiogenic shock.Copyright © 2023 American College of Cardiology Foundation

Fulminant Myocarditis (Fm) Requiring Heart Transplantation: A Rare Sequela of Sars-Cov-2 Infection

Background SARS-CoV-2 infection, the cause of COVID-19, has been associated with myocarditis. Fulminant myocarditis (FM) is rare. Case A 30-year-old male with a past medical history of SARS-CoV-2 infection 7 months prior, presented with a 2-week history of malaise, cough, dyspnea, and signs of cardiogenic shock. He was fully vaccinated 9 months prior. Respiratory viral PCR testing, including SARSCoV-2, was negative. HS-troponin was >20,000 ng/L (NR: 0-53 ng/L). An echocardiogram revealed a dilated cardiomyopathy with an EF of 15-20%. Cardiac catheterization revealed no CAD. Workup for an autoimmune etiology was unrevealing. His condition worsened and he required inotropic support, eventual placement of an LVAD, and initiation of ECMO. He was not able to tolerate cardiac MRI or endomyocardial biopsy. Ultimately, he underwent orthotopic heart transplantation. Pathologic examination of the explanted heart confirmed lymphocytic myocarditis. Decision-making Myocardial injury due to the cardiotropic nature of SARS CoV-2 has been increasingly reported. There has been a 42% increase in viral myocarditis, and the risk is 16 times greater with a history of COVID-19. Symptomatic myocarditis typically manifests within weeks of infection. Such a delayed presentation has not been described. Data from autopsies of deceased COVID-19 patients revealed a 25% to 50% detection rate of SARS-CoV-2 mRNA in the myocardium. One case report described a deceased FM patient with multiple negative SARS-CoV-2 PCR tests, including bronchial lavage samples, having confirmed SARS-CoV-2 within the myocardium postmortem. Hence SARS-Cov-2 can persist in the heart after the resolution of respiratory infection, possibly leading to ongoing inflammation and myocardial damage. This may explain why our patient presented 7 months after a resolved infection. Conclusion SARS-CoV-2 is cardiotropic and can cause fulminant myocarditis even in the absence of a detectable respiratory infection. Hence closer monitoring of post-COVID-19 patients, including screening for subclinical myocarditis, may be prudent. Further research on monitoring and an evaluation of the clinical utility of medical therapy, is also warranted.Copyright © 2023 American College of Cardiology Foundation

Effect of Hemoperfusion on the Clinical Outcome of Severe and Critical Covid-19 Patients Admitted at the University of Santo Tomas Hospital: An Analytical Cohort Study

Introduction: Severe sepsis is a life-threatening end organ dysfunction resulting from dysregulated host response to infection and poses a significant burden to healthcare systems worldwide. Since the advent of CoVID-19, cytokine release syndrome has also been attributed to clinical deterioration presenting as acute respiratory distress syndrome and acute kidney injury of infected individuals. Objective(s): To determine the clinical outcome of Severe and Critical COVID-19 patients who underwent hemoperfusion compared with patients who did not undergo hemoperfusion. Method(s): This study entailed a retrospective cohort analysis of patients aged >= 18 and < 90 years old admitted at University of Santo Tomas Hospital who were diagnosed with Severe or Critical COVID-19. Subjects were grouped between those who underwent hemoperfusion (HP group) using HA 330 cartridge and those who did not undergo the procedure (non-HP). Demographic and clinical data collected for both groups included age, sex, comorbidities present, time to initiation of hemoperfusion, total hemoperfusion time, use of other medications specifically: immunomodulator and anti-viral drugs, antibiotics and steroid, length of hospital stay and in-hospital mortality. Mean arterial pressure, cardiac rate, oxygen saturation, arterial blood gas, complete blood count, oxygen requirement, inotropic score, serum creatinine, urine output, lactate dehydrogenase (LDH), ferritin, high sensitivity C-reactive protein (HsCRP), Interleukin-6 values and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared from baseline and after 4 sessions of hemoperfusion for the HP group. The clinical outcomes: length of hospital stay, in-hospital mortality and time to off high flow nasal cannula (HFNC) between two groups were also compared. Result(s): A total of 98 cases were included, 49 subjects underwent hemoperfusion using HA 330 and 49 patients did not undergo hemoperfusion. Demographic data is similar between both groups. Baseline clinical data between Hemoperfusion and non-Hemoperfusion group did not show statistical difference. However, Baseline LDH, HsCRP, Ferritin, IL-6, PF ratio and APACHE II score were statistically different between two groups. Effect on Disease Severity Length of hospital stay and time to off HFNC was shorter in the non-HP group vs the HP group, median of 13 days vs 18 days (p-value 0.003) and 107 hours vs 222 hours (p- value <0.001), respectively. There is also no significant difference in in-hospital mortality between two groups. [Formula presented] [Formula presented] [Formula presented] Conclusion(s): This retrospective study did not show survival benefit with the use of hemoperfusion. Undergoing hemoperfusion did not show a significant effect on changes in disease severity as represented by no significant difference seen in APACHE II score, PF ratio, acute kidney injury, length of hospital stay and in-hospital mortality. Hemoperfusion also has no significant effect in terms of decreasing the values of inflammatory markers LDH, ferritin, and IL-6. A large, multi-center, randomized clinical trial is warranted to truly determine the clinical benefit of hemoperfusion not only in severe to critical COVID-19 but also in severe sepsis and conditions that trigger systemic inflammatory response and cytokine storm. *This abstract was also submitted for the ISN Frontiers:Infections and the Kidneys congress. No conflict of interestCopyright © 2023

Clinical Profile and Outcomes of Covid-19 in Renal Transplant Recipients - a Single Centre Experience

Introduction: The COVID-19 infection amongst the renal transplant recipients (RTR) has a varied presentation and severity of illness. The overall mortality amongst RTR was found to be 11.6%- 27% compared to the mortality rate of 2-3% amongst the COVID-19 infected general population. The incidence of acute kidney injury(AKI) in RTR was also found to be higher compared to general population with Covid 19 (27.5% versus 13.3%). We assessed the clinical outcomes of COVID 19 infection among RTR and its impact on the graft function along with predictors of poor clinical outcomes. Method(s): Ours is a single centre observational cohort study of 83 RTR with Covid 19 infection with a follow up period of 6 months. The data pertaining to demographics, renal transplantation, maintenance immunosuppression, baseline allograft function prior to Covid 19 infection and comorbidities was recorded in both hospitalised and outpatient RTR. Lab investigations including renal function tests and inflammatory markers were noted. Renal allograft function was assessed by estimated glomerular filtration rate(eGFR) using CKD-EPI equation prior to admission, hospital stay and 6 months follow up. The need for oxygenation, invasive ventilation;presence of hypotension, acute kidney injury(AKI),acute respiratory distress syndrome(ARDS) and need for renal replacement therapy(RRT) was noted. Modification of immunosuppressant medications with respect to dose reductions and withdrawal was recorded. The primary endpoint was mortality and presence of acute kidney injury during Covid 19 infection. Result(s): The mean age was 47.67+/-13.7 years and 75.91 % were males. Around 81.9%(68/83) RTR were hospitalised & 18.9%(15/83)were managed as outpatients. Out of 83 patients,43 (51.8%), 23(27.7%),17(20.5%) had mild, moderate and severe COVID 19 illness respectively. The mortality rate amongst COVID 19 infected RTR was 19.3%(16/83). Out of 83 RTR,17 required inotropic support owing to hypotension. The baseline eGFR(ml/min) prior to Covid 19 infection was 66.3 +/- 30.66. The eGFR(ml/min) during Covid 19 was 44.27 +/- 31.53.Acute kidney injury(AKI) was seen in 72.3%(60/83) of RTR.19.28%(16/83) required RRT.The percentage change in eGFR from baseline during COVID-19 was found to be statistically significant(p=0.003)and correlated with mortality(p=0.003).At 6 months of follow up,55/83 RTR had stable allograft function with mean eGFR(ml/min) of 51.74 +/- 29.92 and 8/83 patients(9.6%) patients were on maintenance haemodialysis. In contrast to the survivors, the non survivors had a higher mean age(67+/-13 vs 57+/-12 years), number of years of hypertension(15+/-9 vs 8.5 +/-7 years),body mass index(27.05+/-4.7 vs 23.11+/- 7.8), percentage change in eGFR from baseline(114.1 +/-81.7% vs 58.8 +/-61.4%), serum Interleukin levels (120.7 vs 10 pg/ml) and D dimer(145 vs 21.3 mcg/ml) levels (p<0.05).Other risk factors which correlated significantly with outcome of mortality and reduced renal recovery include presence of hypoxia at presentation and ARDS(87.5 Vs 28.1%),presence of hypotension requiring inotropes(81.3% vs 6%) and AKI and the need for RRT(56.7% vs 10.4%). [Formula presented] [Formula presented] Conclusion(s): The mortality rate amongst the RTR with COVID 19 infection was found to be 19.3%.AKI was found in 72% of patients during the illness and about 9.6% developed graft loss by 6 months. RTR needs a close supervision and follow up as they are prone to acute kidney injury and may develop allograft failure. No conflict of interestCopyright © 2023

A case of multisystem inflammatory syndrome in children (MIS-C)

Background/Purpose: MIS-C is uncommon and yet potentially life threatening disorder associated with COVID-19 infection. MIS-C Malaysia Study Group had reported 174 cases, mostly affecting children < 12 years old (93.7%). The fatality rate was 4%. Hereby, we report a case of MIS-C at our adult rheumatology centre. Method(s): Patient's admission note and electrical medical information were reviewed. Result(s): This is a 17 year-old adolescent with underlying obesity (BMI 42 kg/m2). He completed COVID-19 vaccination (Pfizer-BioNTech x 2 doses) in October 2021. In end-February 2022, he presented acutely with recurrent seizures associated with fever (40.3degreeC) and headache. The COVID-19 RTK antigen and PCR tests were positive, and COVID-19 IgM & IgG were negative. At emergency room, he developed haemodynamic instability, needing ventilatory support for respiratory failure and inotropic therapy on Day 1 of illness. The initial diagnosis was severe COVID-19 infection with encephalitis and secondary bacterial infection. Subsequent investigations showed evidence of systemic inflammation with organ dysfunction involving neurological (seizures, CNS vasculitis), cardiac (myocarditis), renal (acute kidney injury) and gastrointestinal (acute livery injury) systems. MIS-C was then diagnosed with early initiation of immunomodulatory treatment (IVIg 2 g/kg and IV methylprednisolone 1-2 mg/kg/day) according to ACR recommendation. Low dose aspirin and high intensity prophylactic SC enoxaparin were prescribed but were discontinued soon due to bleeding tendency. Antimicrobial therapy was continued until microbiological study was proven sterile. With the immunomodulatory treatment, he had rapid clinical and laboratory improvement within first week and was transferred out from ICU on Day 10 of illness. The organ dysfunction was mostly resolved with no sequelae except for high blood pressure requiring antihypertensive. Inflammatory markers were markedly reduced;Serum ferritin reduced from 22,339 to 565.8 mug/L, procalcitonin decreased from 26.7 ng/ml to 1.5 ng/ml and CRP normalised (<5 mg/L). Home discharge was made on Day 16 of illness with oral prednisolone 60 mg daily without antiplatelet. During clinic visit after D30 of illness, he remained asymptomatic with good effort tolerance and normal blood pressure readings. He subsequently completed the high school examination in April 2022 and even enrolled at college later. Oral prednisolone was eventually tapered off at 3rd month of illness with appointments for MRI cardiac and brain scheduled for further assessment. Conclusion(s): MIS-C is a hyperinflammatory syndrome which requires high clinical suspicion as many patients response well to early immunodulatory treatment without sequelae. Long term follow up maybe needed for those with cardiac involvement. (Table Presented).

Mortality Risk Factors in Geriatric Patients Infected with Covid-19 in the Intensive Care Ward at Dr. Soetomo Hospital Surabaya

Background: With the COVID-19 pandemic since December 2019, many people around the world have been infected and affected, one of them is Indonesia. The increasing number of deaths due to COVID-19 infection that occurs in the adult to geriatric age group, especially in geriatrics who often have comorbidities. This study aims to describe the analysis of risk factors for mortality in geriatric patients infected with COVID-19 in the intensive care unit. Method(s): This study is a retrospective observational analytic Single Center study, the study was conducted by taking medical record data from geriatric patients with COVID-19 who were treated in the ICU during the period from February 1 to May 31, 2021. Result(s): Of the 52 patient medical record data, 27 patients died. In this study the mean age, weight, height, BMI and SOFA score;66 years, 70 kg, 160 cm2, 26 kg/m2, and 6. From the results of medical record data, the highest mortality was found in the group with risk factors, namely SOFA score, PaO2/FiO2 ratio, ventilator use, inotropic use, and vasopressor use. Conclusion(s): Mortality in our study was 51.9%. Risk factors that affect mortality in geriatric patients infected with COVID-19 are high SOFA scores, low PaO2/FiO2 ratios, use of ventilators, inotropes, and vasopressors. Copyright © 2022, Anka Publishers. All rights reserved.

Systematic Review and Meta-Analysis on the Incidence of Shock and the Usage of Vasopressor Support in Severe Covid-19 and Multisystem Inflammatory Syndrome in Children

BACKGROUND AND AIM: The clinical manifestations of COVID-19 in children varies largely from asymptomatic to multi-organ damage. Shock became one of the most common manifestation in severe COVID-19 and MISC needing prompt therapy, where vasopressors/inotropics plays important therapeutic support in intensive care. This study analyzes current reports of shock incidence in children with MISC and severe COVID-19 and the usage of vasopressor support. METHOD(S): PubMed, Medline, Google Scholar and Cochrane database search for research articles published from December 2019 to January 2022. Keywords used term MISC, Severe COVID-19, Shock, vasoactive, inotropic. We performed systematic review describing their characteristic, and 9 studies were used for metanalysis pooling the incidence of shock and comparing the use of vasoactive support in COVID-19 or MISC patients. RESULT(S): Database search resulted in 99 articles describing characteristics of MISC and severe acute covid-19 children, and 9 studies were included in Metaanalysis. The studies reported 279 MISC and 523 Severe Acute Covid-19 children, with 58.7% pooled incidence of shock in MISC patients compared to 13% in severe acute covid-19. The incidence was more likely to appear in MISC group with OR 12.02(95% CI7.73-18.67%, I2=68%). Further analysis showed usage of vasopressor support being more likely used in patients with MISC, with OR 9.01(95% CI 5.69-14.25%, I2=71%). CONCLUSION(S): Incidence of shock and usage of vasopressor support in MISC is greater than in Severe Acute Covid-19. Further research is needed to analyze the outcome of vasopressor usage, as well as types and doses of vasopressors being used.

Severe Dengue with Multisystem Inflammatory Syndrome in Children Due to Covid-19: A Coinfection Case Series from a Tertiary Care Centre Hyderabad India

BACKGROUND AND AIM: India is currently facing a double burden of severe dengue and SARS-CoV-2 infection. Co-infection with these viruses can result in severe morbidity. We present five cases of severe dengue with MIS-C due to SARS-CoV-2 infection in children. METHOD(S): All the children presented with shock with variable degrees of plasma leakage. They were treated initially as Dengue cases only but due to refractory symptoms like persistent fever, inotropic requirements an alternate diagnosis was suspected. RESULT(S): They were successfully managed according to WHO dengue shock syndrome and COVID-19 MISC guidelines with IV fluids, Methylprednisolone, Aspirin and IVIG. CONCLUSION(S): Severe dengue in endemic regions coexisting with COVID-19 makes it hard to diagnose which can be fatal without early, appropriate management.

Prevalence of Bacterial Infection in Multisystem Inflammatory Syndrome in Children (Mis-C)

INTRODUCTION: Clinical presentation of MIS-C resembles bacterial infections and patients often receive empiric antibiotics. Bacterial infection prevalence has not been studied in MIS-C patients and data are limited to studies of MIS-C association with non-SARS-CoV-2 infections. We aim to study prevalence of bacterial infection in MIS-C patients to better understand this association and to limit unnecessary use of antibiotics. METHOD(S): Data from hospitalized patients with a diagnosis of MIS-C at Advocate Children's Hospital were retrospectively collected and analyzed. Primary objective was the prevalence of bacterial infection in MISC patients. Secondary objective was the pattern of antibiotics use. RESULT(S): Forty six patients were included. Most patients were male (63%), and majority were non-Hispanic (45%). Most patients received antibiotics for 2 days, and most frequently used antibiotic was ceftriaxone. Blood culture was positive in three cases (7.9%), and identified species was Staphylococcus (2) and E. coli (1). Urine culture was positive in seven cases and mostly identified as E. coli. All patients except one received IVIG and majority (92%) were treated with steroids. one third of our patients received inotropic or vasopressor supports during their hospitalizations. However, all patients had favorable outcomes and were discharged home in a stable condition. CONCLUSION(S): Children with MIS-C are less likely to have a bacterial infection. Our data suggest that antibiotics were used in the setting of pending blood and urine cultures and were discontinued when preliminary culture results became available. Further large-scale studies are needed to establish guidelines regarding antibiotics use in MIS-C patients.

Impact of Paediatric Multisystem Inflammatory Syndrome Temporally Associated with Covid-19 (Pims-Ts) on Critical Care - an Hdu Experience

Aims Background Alder Hey is a tertiary children's hospital in North-West England with co-located Intensive Care and High Dependency units, covering North West England, North Wales and Isle of Man. PIMS-TS is a new multisystem inflammatory condition which has led to an increased demand on critical care beds. Some children presenting with PIMS-TS need haemodynamic support in the form of inotropes, which would traditionally need an PICU bed. Aim Review of all patients managed on Critical Care with PIMS-TS. Methods All patients in the region were discussed in a PIMSTS multidisciplinary meeting attended by Paediatrics, Infectious Diseases, Rheumatology, Cardiology and Critical Care daily. Patients across the region needing haemodynamic support or cardiology evaluation were highlighted as, in need of either HDU or PICU bed and transferred by the North West & Wales Paediatric Transport Service (NWTS). This is a retrospective analysis of all children admitted to HDU or PICU with a diagnosis of PIMS-TS, from October 2020-December 2021. Results Thirty (10%) patients were admitted to HDU from the 300 patients discussed over the 15month period. 16 (53%) of patients were female. Mean age was 10 years (range 3-17). Median length of stay (LOS) on HDU was 2 days (range 1-8) with a median hospital LOS of 6 days (range 2- 10). All patients admitted were monitored appropriately and had full echocardiography assessment. Twenty nine (97%) patients admitted to HDU required inotropic support, twelve (40%) patients required a single agent and seventeen (57%) required double agents with a combination of adrenaline, noradrenaline and milrinone. Median fluid resuscitation was 40mls/kg (range 20-70mls/ kg). Eight patients (27%) were escalated to PICU for either invasive ventilation (4) or higher inotropic requirements of 0.2micrograms/kg/minute. There were no adverse events. Conclusion Most children with PIMS-TS have low to moderate haemodynamic instability that can be safely managed on HDU with appropriate monitoring and agreed limits to vasopressor therapy. Our experience in managing with these patients successfully and safely in a high dependency setting has helped in the use of a critical care bed efficiently, thus reducing dependency on the availability of a PICU bed.

Anakinra: A Successful Anti-Inflammatory Rescue Medicine in Acute Onset Multisystem Inflammation

Aims Anakinra is an Interleukin-1 receptor (IL-1) antagonist;a biologic drug that has historically been used as part of longerterm management in methotrexate-resistant rheumatoid arthritis, cryopyrin-associated periodic syndromes and systemic juvenile idiopathic arthritis. We describe its successful use in acute multisystem inflammation in a cohort of recently treated children in a Tertiary Children's Hospital. Methods We reviewed the details of 6 acutely unwell inpatients admitted over the last 6 months, with acute multisystem inflammation, who had been treated with Anakinra as a rescue medication, following resistance to first-line anti-inflammatory medications. Five of these patients had been diagnosed with Paediatric Multisystem Inflammatory Syndrome temporarily associated with COVID-19 (PIMS). One of these patients had been diagnosed with Hemophagocytic Lymphohistiocytosis (HLH). Results The average length of initial treatment was 3.5 days before commencing Anakinra. All patients on Anakinra also received contemporaneous intravenous methylprednisolone treatment (IVMP), and 5/6 patients had received intravenous immunoglobulin therapy (IVIG). Common indications for commencing Anakinra were: persisting fevers despite at least 3 days of IVMP, and increasing inflammatory markers despite first line treatment. The average C-reactive Protein (CRP) at initiation of Anakinra was 82 (range 32 to 132) and the average Ferritin at initiation was 1500 (range 129 to 4640), with the average treatment duration of 6.7 days until CRP normalised, and all with normal CRP two weeks after treatment. All patients were started on an initial 2mg/kg dose of Anakinra, rounded up to nearest 100mg dose in most. Five patients were prescribed a subcutaneous route whilst one patient was started on an IV route. Half of patients were commenced on a once daily regime, two patients were started on a twice daily regime, and one patient was started on a QDS regime. One patient required a dose increase due to ongoing fevers after initiation. Average treatment length for the patients diagnosed with PIMS was 8.6 days, whereas treatment length was 25 days in the patient with HLH. We also describe the need for inotropic support (1/5), significant echocardiography findings at presentation (3/5) and at 2 weeks post-discharge (1/5) in this cohort of patients with PIMS. Conclusion Anakinra was successfully used as an acute treatment for our 6 described patients with multisystem inflammation. With more recent waves of PIMS, Anakinra has increasingly been used as a second-line treatment. Its introduction ceased ongoing fevers in all patients;5 of 6 with immediate effect. There are some clear advantages of Anakinra as a rescue drug over other potential biological alternatives, namely;choice of preparation, tolerability and few described side effects with short-term use. We highlight the experiential effectiveness of the acute use of Anakinra in our cohort of children with hyperinflammation, and recommend its accessibility as an emergency drug.

A Case Report of a Neonate with Severe Covid Pneumonitis

Aims Literature describes that most neonates with SARS-CoV-2 infection are asymptomatic or present with mild symptoWe describe an ex-preterm twin infant, born at 31+5 with birthweight 1600g, who deteriorated with COVID pneumonitis at 34 weeks corrected gestational age. They were an inpatient in a level 3 neonatal centre, with an uncomplicated stay prior to becoming unwell and had never been ventilated in their early neonatal course. Methods They acquired postnatal covid on day 24 of life, and deteriorated over the next 72 hours, escalating from high flow to CPAP then BiPAP, and finally requiring intubation. They were empirically commenced on antibiotics and required sedation and muscle relaxation to manage their worsening respiratory failure. Given their acute respiratory decompensation in the context of COVID, and with negative extended virology and bacterial testing otherwise, they were managed on a presumptive diagnosis of COVID pneumonitis. CXRs were consistent with this diagnosis. Despite further escalation in their ventilation strategies, including high frequency oscillatory ventilation and inhaled nitric oxide, they continued to deteriorate with severe hypoxic respiratory failure. Inotropic support was required to maintain cardiac stability. There was extensive MDT discussion between NICU, PICU and the Infectious Diseases teaDue to the severity of their condition, Remdesivir was commenced and the parents were fully informed of the trial nature of the drug and the guarded prognosis. Hydrocortisone was also commenced. Results Due to ongoing deterioration, the patient was transferred to PICU for ongoing care and consideration of ECMO. However, the infant stabilised and the hydrocortisone that had been commenced was switched to methylprednisolone. The Remdesivir was discontinued after 2 doses due to a worsening in LFTs. The situation was further complicated by COVID isolation guidelines while keeping family centred care at the heart of our approach, working within infection control policies and managing a relatively unfamiliar pathology in the neonatal population. Conclusion The infant progressed well and was extubated onto nasal cannula oxygen on day 40 of life and repatriated to our neonatal unit on day 41 at 37+4 corrected gestational age. They had an uneventful stay in our SCBU, establishing feeding, until discharge with home oxygen at 41+1 weeks corrected gestational age.

Life-threatening rhythm and conduction disorders by a child with MIS-C

Background and Aim: Cardiac involvement is seen in the majority of cases with multisystem inflammatory syndrome in children (MIS-C). Various rhythm and conduction disturbances, as well as repolarization abnormalities, have been described by more than 50% of the patients, while there are few cases with complete heart block or with asystole. Method(s): Case report Results: 8-year old girl presented with a 5-day history of fever, cough, headache, and abdominal pain. Because of the critical con-dition, with respiratory insufficiency and heart failure symptoms, the child was intubated and started on inotropic support. ECG showed complete AV-block with a ventricular rate of 75/min and with ST-T changes;echocardiography revealed dilated left ventricle with reduced contractility, CT-scan of the lungs showed bilateral pneumonia, the inflammatory markers were elevated, in combination with high troponin levels, and positive SARS-CoV2-IgG antibodies. The diagnosis MIS-C was made and treatment with immunoglobulins, antibiotics, corticosteroids, and anticoagulants was initiated. During the next 2 days, the cardiac function deteriorated further, and while still on mechanical ventilation and inotropic support, extreme bradycardia with a ventricular rate of 35/min was regis-tered, and the patient was indicated for temporary emergency pac-ing. Upon induction of anesthesia, the child became asystolic, requiring extensive resuscitation. After circulation recovery, the ECG showed nodal tachycardia with a heart rate of 140-170/min. A temporary transvenous pacemaker (PM) was inserted, and the patient was started on intravenous amiodarone which resulted in a slower ventricular rate of 70/min. 3 days later sinus rhythm was restored, with first-degree AV-block, which allowed removal of the PM 5 days after its insertion. Left ventricular dimensions were normalized and contractility remained low-normal (EF 56%). During the 6-month follow-up, the ECG and the Holter-monitoring showed sinus rhythm with first-degree AV-block. Magnetic resonance imaging (MRI) on day 15 of the hospital stay demonstrated scattered areas of myocarditis and ischemia predominantly in the left ventricle, as well as thickening of the basal septum. Six months later the MRI changes were reduced but still persistent. Conclusion(s): MIS-C can present with serious and life-threatening rhythm and conduction disturbances in children;this is why extensive cardiac monitoring is obligatory by all patients.

Successful resolution of left ventricular thrombuses in a patient with MIS-C

Background and Aim: A 15 year old young man with symptoms and signs consistent with MIS-C was admitted to the Intensive Care Unit for inotropic support as he was exhibiting signs of cardiogenic shock. He was previously fit and healthy and he had been exposed to Covid 19 confirmed cases 6-8 weeks prior to becoming unwell. Method(s): The patient received IVIG and steroids as an immuno-modulating regime. On the admission echocardiogram there was a structurally normal heart with large LV thrombuses. The D-Dimers were extremely elevated on admission and the patient received therapeutic heparin infusion. Other prothrombotic causes were excluded. Result(s): The surveillance echocardiogram 24h post admission showed resolution of the thrombuses. The patient never exhibited any signs or symptoms of cardiac ischaemia on the electrocardio-gram or regional wall motion abnormality on the echocardiogram or neurologic impairment and the brain MRI-MRA one week post admission was normal. The patient was discharged home 5 days post admission and on follow ups up to a year after the acute phase remains very well physically and clinically. Conclusion(s): Thromboembolic events are frequently described in COVID-19 patients and in some patients with MIS-C and are the consequence of a hyperinflammatory response and endothelial dysfunction. There might be a potential role of an antiphospholi-pid syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as has been proposed. An increase in D-dimer level has been shown to be associated with thromboembolic events, including arterial thrombosis especially in the older population and should be investigated promptly. With the appropriate immunomodulation and antithrombotic treat-ment adverse events are prevented. More studies to assess endothelial function and its role in the MIS-C prothrombotic state are necessary.

Single-centre study: MIS-C impact on blood pressure, coronary arteries and left ventricular function

Background and Aim: MIS-C is a hyperinflammatory syndrome caused by Sars-CoV-2 virus. Cardiovascular system impairment is observed up to 100 % of all MIS-C patients with a wide spectrum and severity of symptoms. It is important to identify the course of the disease and its outcome, which could significantly improve public health. Method(s): A single-centre study, prospective cohort study, con-ducted in the Children's Clinical University hospital in Latvia from January to December 2021. Patients between the ages of one to seventeen years who met the MIS-C criteria were included in the study. We evaluated blood pressure, left ventricular heart func-tion, size of coronary arteries and hospital course. Result(s): Thirty-one patients were included who met the MIS-C criteria. The median age was 8.0 years, 52% were boys. Of all patients 77% initially presented with hypotension of whom 42% required inotropic support. Treatment in PICU was required in 58% of all patients. Reduced left ventricular ejection fraction was observed in 35% of all patients. Mildly decreased ventricular ejection fraction (lt;55%) was observed in 19% of cases but mod-erate dysfunction (ejection fraction lt;45%) was observed in 16% of patients. Twelve percent of patients received milrinone to improve left heart function. Left heart function significantly improved in all patients during the hospitalisation. In 6 % of all patients coronary artery dilations was observed. All patients had dilations resolution at the time of discharge. Median length of hospitalisation was twelve days and median length of PICU stay was three days. Conclusion(s): All patients cardiovascular symptoms had resolved at the time of discharge. Whether patients will have chronic cardiac impairment is unknown therefore it is crucial to perform long-term follow-up.