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.

Ndegree39 - Fulminant life-threatening myopathy of the genetic origin

Objectives: Acute myopathy are seen in critically ill patients, in severe SARS-CoV2 pneumonia requiring mechanical ventilation, and other infection illness, toxin and drug-induced complications, or systemic inflammation. Periodic paralysis or carnitine disorders are known genetic causes of acute muscular weakness, besides genetically determined muscle diseases rarely have an acute clinical course. Content: Case presentation: 61-years old, healthy woman, after a one-time vaccination against Covid-19 about 2 weeks earlier, was admitted to the Neurological Department due to symptoms lasting for 2 days. On the first day of the disease she complained of vertigo and double vision, on the following day dysarthia and dysphagia appeared, she stopped walking. On the second day of hospitalization, the patient required mechanical ventilation. The initial diagnosis of Guillaine-Barre syndrome was not confirmed in the electrophysiological and laboratory (CSF) studies. Myopathic pattern with polyphasic potentials of short duration and low amplitude was observed in EMG, without spontaneous activity. In the electron microscope numerous fat drops between bundles of myofibrils in most muscle fibers were seen. She received intravenous immunoglobulins, and steroid therapy, together with high doses of vitamin B2 with very good motor improvement. Multiple acyl-CoA dehydrogenase deficiency (MADD) was suspected, and the Whole Exome Sequencing (WES) was performed. Conclusion(s): The authors note the possibility of acute, life-threatening myopathy, which may be caused by a genetic defect. MADD is a very rare genetic entity which can manifest for the first time very suddenly, especially in the presence of triggers, including but not limited to after vaccinations. Keywords: Acute myopathy;Multiple acyl-CoA dehydrogenase deficiency;Vitamin B2.Copyright © 2023

Enhanced fatty acid oxidation through Metformin and Baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023

The use of alanine, free carnitine and IGFBP-1 as potential biomarkers for glycogen storage disease type I

Background: Glycogen Storage Disease Ia (GSDIa) and Ib (GSDIb) are inborn errors of carbohydrate metabolism due to a deficiency of glucose-6-phosphatase (G6Pase) or glucose-6-phosphate translocase (G6PT), respectively. Consuming prescribed amounts of uncooked cornstarch (UCCS) to prevent hypoglycemia is the standard of care for GSDIa and GSDIb. Patients followed in our GSD Program are admitted to the hospital annually for evaluation of their metabolic control by measuring glucose and lactate levels and revising treatment regimens accordingly. Lack of bed space due to the COVID-19 pandemic has created a need for alternate markers of metabolic control as lactate measurements are unreliable in the outpatient setting. This research aims to identify alternative biomarkers to show degree of metabolic control in individuals with GSDI. Method(s): A retrospective chart review was conducted on 45 adults and children with GSDI using data from January 1, 2014 toMay 6, 2021. Plasma alanine and free carnitine levels were compared with laboratory reference ranges. Results from the three tests were not available on every subject. Plasma alanine was evaluated on 24 subjects (16-GSDIa, 8-GSDIb) and free carnitine was evaluated on 25 subjects (17-GSDIa, 8-GSDIb). Result(s): Alanine levels in subjects with GSDIa ranged from 378 to 786 umol/L, while alanine levels in subjects with GSDIb ranged from 254 to 506 umol/L (reference range = 103-528 umol/L). Free carnitine levels ranged from26 to 72 umol/L in subjects with GSDIa and from 44 to 90 umol/L in subjects with GSDIb (reference range = 19-55 umol/L). Conclusion(s): Our analysis showed that plasma alanine and free carnitine have potential to be used as biomarkers of metabolic control. For plasma alanine, there seemed to be differences between subjects with GSDIa and GSDIb, as the majority of subjects with GSDIa had elevations in plasma alanine, while subjects with GSDIb did not. Elevated plasma alanine levels indicate lactic acidosis. For GSDIb, we hypothesize that there may be some type of G6Pase enzyme activity that occurs outside of the endoplasmic reticulum. When looking at both groups, free carnitine levels were mostly elevated. This indicates that there could be inhibition of fatty acid oxidation.Copyright © 2022 Elsevier Inc. All rights reserved.

Post-COVID syndrome in children and adolescents: a literature review and clinical case

Post-COVID-19 syndrome is an important challenge for modern medicine, requiring the involvement of different health professionals. This multidisciplinary approach is underpinned by the variety of clinical manifestations and the need for comprehensive rehabilitation of patients, including children and adolescents. The review highlights clinical manifestations of post-COVID-19 syndrome. Currently, a symptom management approach has been established for improving post-COVID-19 conditions. Also, appropriate lifestyle changes, such as adequate rest and sleep hygiene, may be useful. Rehabilitation interventions for post-COVID-19 syndrome may include physiotherapy exercises and various psychotherapy techniques. Since mitochondrial dysfunction, energy supply deficit, oxidative stress, endothelial dysfunction, and immune dysregulation profoundly impact the pathogenesis of post-COVID-19 syndrome, the use of L-carnitine which plays a crucial role in energy production, is considered as a promising method in the management of such patients. L-carnitine may have cardioprotective, anabolic and neuroprotective effects. The authors present a case report of post-COVID-19 condition in their own patient, a 4-year-old boy who survived multisystem inflammatory syndrome. As a result of combination therapy, including L-carnitine, the patient's sense of well-being significantly improved: he had no complaints, the muscle weakness and asthenization became less pronounced, and his spirits rose. The described clinical case illustrated the effectiveness of using L-carnitine in the combined therapy of post-COVID-19 syndrome in children . © 2022, Meditsina-Inform LLC. All rights reserved.

Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases.

Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Modern possibilities of correction of postcovid disorders in the fetoplacental complex

The objective: to determine the peculiarities of hormonal support, liver enzymatic function and the state of the fetal-placental complex (FPC) in unvaccinated women with fetal growth retardation (FGR) and placental dysfunction (PD) who was ill with the coronavirus disease during the current pregnancy, on the background of the proposed correction scheme of the disorders and evaluation of its effectiveness. Materials and methods. The study included 22 pregnant women with FGR and PD who were being treated and delivered in the Department of Pregnancy and Childbirth Pathology of the State Institution «Institute of Pediatrics, Obstetrics and Gynecology named after Academician O.M. Lukyanova National Academy of Sciences of Ukraine» in 2021–2022 and suffered a coronavirus disease during the current pregnancy. All pregnant women had a general clinical examination and the following parameters were additionally determined: the level of placental lactogen (PL) in blood serum, indicators of liver enzyme activity (alanine aminotransferase – ALT, aspartate aminotransferase – AST, gamma-glutamyl transpeptidase – GHTP), the level of estriol in urine (after the 22d week of pregnancy). The examination was carried out before the start of treatment and preventive measures and 12–14 days after a 10-day course of therapy with simultaneous ultrasound (US) monitoring of the condition of the FPC. In the case of diagnosis of FGR and PD, a course of therapy was carried out, which included daily consecutive intravenous infusions of a balanced crystalloid infusion preparation with lactate and sorbitol in the amount of 200 ml and a solution of levocarnitine and arginine hydrochloride in the amount of 100 ml for 10 days, followed by ultrasound control of the condition of the fetus and FPC. The evaluation of the effectiveness of the treatment was carried out based on a combination of clinical, laboratory and instrumental indicators after 10 days of therapy. Results. All pregnant women had a moderate or mild course of the coronavirus disease at different terms of the current pregnancy. There were 9 (40.9 %) women who were infected with SARS-CoV-2 in the early terms of pregnancy (up to 12 weeks), and they were diagnosed the 2nd and 2nd-3rd degrees of FGR. The majority of pregnant women had gestational complications. Before treatment, 10 (45.5 %) women had oligohydramnios. FGR was diagnosed in 14 (63.6 %) pregnant women, among them: in 3 (13.6 %) persons – fetal growth retardation of the 2nd-3rd degree, in 6 (27.3 %) – of the 2nd degree, in 5 (22.7 %) – 1st degree. The analysis of laboratory indicators demonstrated the increase in the levels of ALT, AST and GHTP, and a decrease in the levels of estriol in urine. After the proposed course of treatment, oligohydramnios was found only in 2 (9.1 %) women. The average amniotic index before treatment was 10.1, after treatment – 15.3. 4 (18.2 %) women were diagnosed FGR after the treatment. As a result of the treatment, the improvement of all determined laboratory parameters and perinatal consequences were determined. Conclusions. The proposed scheme for correcting the identified disorders with the inclusion of balanced crystalloid infusion preparation with lactate and sorbitol and balanced crystalloid infusion preparation with lactate and sorbitol drugs made possible to improve microcirculation, metabolic processes, and to normalize the consequences of postcovid endotheliitis in the vascular system of pregnant women in general and in the FPC, in particular. This was manifested in the improvement of clinical, laboratory and instrumental indicators of conducted studies and had a positive effect on perinatal results. © The Author(s) 2022 This is an open access article under the Creative Commons CC BY license.

FETAL GROWTH RETARDATION AS A COMPLICATION OF POST-COVID ENDOTHELIITIS: CAUSES, CONSEQUENCES, WAYS OF PREVENTION.

The risk of fetal intrauterine growth retardation (IUGR) is increased in women who have experienced acute infections, as well as in pregnant women with gynecological pathology and endocrine diseases. A woman's lack of nutrition also makes a negative contribution to the development of IUGR. The frequency of IUGR in the population is very variable and depends on a number of reasons. In practically healthy pregnant women, IUGR is registered in 3-5% of cases, in case of complicated obstetric and gynecological diagnosis and complicated pregnancy - in 10-25%. Morphofunctional disorders in the chorion/placenta in pregnant women with COVID-19 on the background of post-covid endotheliitis are the main pathogenetic factor in the development of preeclampsia, ectopic pregnancy, antenatal fetal death, and impaired condition of the fetus and newborns. Sufficient saturation of the pregnant woman's body with the nitric oxide donor L-arginine and L-carnitine (main cofactor of fatty acid metabolism in cells) with the improvement of microcirculation and the correction of hypovolemic disorders in the fetoplacental complex can be considered one of the real ways to prevent IUGR in women in the post-covid period. A review of the scientific literature on pathogenesis, diagnosis, impact on the life and health of a newborn with IUGR in women after COVID-19, as well as the possibilities of medical correction of placental dysfunction during pregnancy was performed. This analysis and our own clinical experience allow us to state the fact that after a coronavirus infection during pregnancy, one of the frequent and threatening for the further development of the child is the formation of placental dysfunction and IUGR. One of the ways to prevent these conditions is to saturate the woman's body with the nitric oxide donor L-arginine from the stage of pre-gravid preparation, which will provide the opportunity for adequate angiogenesis and development of the embryo/fetus. In the case of additional risk factors, such as coronavirus disease, complex therapy blood (Rheosorbilact), in combination with a nitric oxide donor and L-carnitine as an endothelium-protective agent (Tivor-L).Copyright © 2022 Authors. All rights reserved.

Betaine- and L-Carnitine-Based Ionic Liquids as Solubilising and Stabilising Agents for the Formulation of Antimicrobial Eye Drops Containing Diacerein.

The therapeutic efficacy of topically administered drugs, however powerful, is largely affected by their bioavailability and, thus, ultimately, on their aqueous solubility and stability. The aim of this study was to evaluate the use of ionic liquids (ILs) as functional excipients to solubilise, stabilise, and prolong the ocular residence time of diacerein (DIA) in eye drop formulations. DIA is a poorly soluble and unstable anthraquinone prodrug, rapidly hydrolysed to rhein (Rhe), for the treatment of osteoarthritis. DIA has recently been evaluated as an antimicrobial agent for bacterial keratitis. Two ILs based on natural zwitterionic compounds were investigated: L-carnitine C6 alkyl ester bromide (Carn6), and betaine C6 alkyl ester bromide (Bet6). The stabilising, solubilising, and mucoadhesive properties of ILs were investigated, as well as their cytotoxicity to the murine fibroblast BALB/3T3 clone A31 cell line. Two IL-DIA-based eye drop formulations were prepared, and their efficacy against both Staphylococcus aureus and Pseudomonas aeruginosa was determined. Finally, the eye drops were administered in vivo on New Zealand albino rabbits, testing their tolerability as well as their elimination and degradation kinetics. Both Bet6 and Carn6 have good potential as functional excipients, showing solubilising, stabilising, mucoadhesive, and antimicrobial properties; their in vitro cytotoxicity and in vivo ocular tolerability pave the way for their future use in ophthalmic applications.

Cardiologic evaluation of Turkish mitochondrial fatty acid oxidation disorders.

BACKGROUND: Mitochondrial fatty acid oxidation disorders (FAODs) cause impairment in energy metabolism and can lead to a spectrum of cardiac pathologies including cardiomyopathy and arrhythmias. The frequency of underlying cardiac pathologies and the response to recommended treatment in FAODs was investigated. METHODS: Sixty-eight children (35 males, 33 females) with the diagnosis of a FAOD were included in the study. Cardiac function was evaluated with 12-lead standard electrocardiography, echocardiography, and 24 h Holter monitoring. RESULTS: Forty-five patients (66%) were diagnosed after disease symptoms developed and 23 patients (34%) were diagnosed in the pre-symptomatic period. Among symptomatic patients (n: 45), cardiovascular findings were detected in 18 (40%) patients, including cardiomyopathy in 14 (31.1%) and conduction abnormalities in 4 (8.8%) patients. Cardiac symptoms were more frequently detected in primary systemic carnitine deficiency (57.1%). Patients with multiple acyl-CoA dehydrogenase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and mitochondrial trifunctional protein deficiencies also had an increased frequency of cardiac symptoms. Patients with medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and carnitine palmitoyltransferase I deficiencies had a lower prevalence of cardiac symptoms both during admission and during clinical follow up. Cardiomyopathy resolved completely in 8/14 (57%) patients and partially in 2/14 (14.3%) patients with treatment. Two patients with cardiomyopathy died in the newborn period; cardiomyopathy persisted in 1 (7.1%) patient with very long-chain acyl-CoA dehydrogenase deficiency. CONCLUSION: Early diagnosis, treatment and follow up made a significant contribution to the improvement of cardiac symptoms of patients with FAODs.

The effect of l-carnitine supplementation on mortality and clinical outcomes in ventilator-dependent critically ill patients with obesity and COVID-19: Protocol for a randomized double-blind placebo-controlled trial.

Background: Coronavirus disease 2019 (COVID-19) still remains a pandemic accounting for at least 15% of intensive care unit (ICU) admissions. Recently, it has been observed that l-carnitine levels, which play an important role in fatty acid metabolism, have an inverse association with the severity of COVID-19 and its complications, hence a potential role for supplementing with this nutraceutical has been suggested. The current protocol describes a trial aiming to an evaluation of the effect of l-carnitine intervention on mortality and clinical outcomes in ICU-admitted patients with COVID-19. Methods: This parallel-group, randomized, placebo-controlled, and double-blind clinical trial involves 50 participants and will be performed at the ICU of Artesh (AJA) Hospital, Mashhad, IRAN. Eligible participants will be randomized into two groups: 1) the intervention group will receive 1000 mg l-carnitine capsules 3 times a day, and 2) the placebo group will receive 1000 mg placebo capsules 3 times a day. Assessments will be performed at baseline, 7 and 28 days after study initiation. The primary outcome includes changes in serum levels of C-reactive protein (CRP). Secondary outcomes include the length of stay in the ICU, ICU mortality, hospital mortality, 28-day mortality, duration of mechanical ventilation (MV), and the neutrophil-lymphocyte ratio (NLR). Conclusion: Based on previous evidence, l-carnitine may reduce inflammation and oxidation stress and improve respiratory function. However, the effects of l-carnitine on ventilator-dependent COVID-19 critically ill patients have not been assessed yet, justifying the necessity to conduct a clinical study in this field. c.

The effects of adjunctive treatment with L-carnitine on monitoring laboratory variables in ICU patients: a double-blinded randomized controlled clinical trial.

BACKGROUND: Critically ill patients must be monitored constantly in intensive care units (ICUs). Among many laboratory variables, nutritional status indicators are a key role in the prognosis of diseases. We investigated the effects of L-carnitine adjunctive therapy on monitoring variables in critical illness. METHOD: A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 g L-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. RESULT: Of 54 patients randomly assigned, 51 completed the trial. Serum albumin (Alb) (P-value: 0.001), total protein (P-value: 0.003), and calcium (Ca) (0.044) significantly increased in the intervention vs. control group. Alanine transaminase (ALT) (0.022), lactate (<0.001), creatinine (Cr) (0.005), and international normalized ratio (INR) (0.049) decreased meaningfully in the intervention vs. control group. CONCLUSION: L-Carnitine supplementation in critically ill patients can improve several parameters including INR, Cr, ALT, lactate, Ca, Alb, and total protein. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT 20151108024938N2. This trial was approved by the Research Ethics Committee of Mashhad University of Medical Sciences (registration code: IR.MUMS.fm.REC.1396.671) (available at https://en.irct.ir/trial/30748 , May 2018).

Rhabdomyolysis Associated with Recent SARS-COV-2 Infection in a Patient with Carnitine Palmitoyltransferase II Deficiency.

Carnitine palmitoyltransferase II deficiency (CPT II) is an autosomal recessive inherited disorder of long-chain fatty acid oxidation in the mitochondrial matrix, resulting in an inability to utilize fat for energy in cells. The most frequent myopathic form occurs in young adults and is associated with recurrent episodes of exercise-induced rhabdomyolysis. The myopathic form is caused by the Ser113Leu mutation of the CPT II gene. Rarely, massive rhabdomyolysis could be complicated by acute kidney injury (AKI), cardiomyopathy, and respiratory insufficiency. We present a case of an 18-year old male with myalgia, muscular weakness, and dark-colored urine after prolonged exercise and a recent mildSARS-CoV-2infection. Massive rhabdomyolysis was diagnosed with markedly increased serum concentrations of myoglobin and creatine kinase, with normal kidney function. The patient experienced two similar episodes in the years 2017 and 2018, with rhabdomyolysis and AKI treated with hemodialysis. After excluding autoimmune and infectious diseases as causes of recurrent rhabdomyolysis, the patient was genetically tested and Ser113Leu mutation of the CPT II gene was confirmed. When a patient presents with myalgia and dark-colored urine triggered by minor physical activities, genetic testing for possible CPT II deficiency should be initiated. TheSARS-CoV-2infection could be a factor that triggers the occurrence of rhabdomyolysis and aggravates the severity of the attack in patients with CPT II deficiency.

B Cells Fit for Germinal Center Activity Predict Response to a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs. Method(s): Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series. Result(s): Notably, even in the absence anti-spike antibody after two doses, spikespecific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased classswitched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells. Conclusion(s): This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation. (Figure Presented).

HYPERAMMONEMIA POSTLUNG TRANSPLANTATION: AN UNCOMMON BUT LIFE-THREATENING COMPLICATION

SESSION TITLE: Lung Transplantation Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Hyperammonemia is an uncommon yet serious complication that has been described in patients after solid organ transplantation, most commonly after lung transplantation. It has an incidence of about 2-4 % and a high fatality rate. Given the myriad of etiologies that can lead to encephalopathy post lung transplantation, hyperammonemia can easily be missed unless we have a high index of suspicion. Unlike in hepatic cirrhosis, non cirrhotic hyperammonemia can result in rapidly rising high levels of ammonia which can result in cerebral edema, seizures and long term neurological deficits. Hence, quick diagnosis and a multi faceted treatment approach is required for a favorable outcome CASE PRESENTATION: 37 year old man with COVID pneumonia and respiratory failure on ECMO support underwent bilateral orthotopic lung transplant. He had no significant past medical history. ECMO was decannulated on post op day 4 and by day 6 he was progressing well and working with physical therapy. On post op day 11 he had an abrupt decline in mental status and had an episode of seizure. Initial ammonia level was 181 uMol/L (Normal < 45 uMol/L) with a peak level of 248 uMol/L. Bronchial wash was positive for Ureaplasma species by PCR. CT head did not reveal any signs of cerebral edema. Management included daily hemodialysis, Sodium phenyl butyrate, Levocarnitine, Rifaximin, Lactulose and Doxycycline. Mental status started improving and ammonia levels normalized in the next 4 days. He was subsequently discharged home from the hospital without any neurological deficits. DISCUSSION: The etiology of post lung transplant hyperammonemia is not very clear. The etiology with the most evidence is an infection with urease producing bacteria as in our patient. Based on this, obtaining a PCR screening for these organisms in the Donor/recipient has been proposed. Obtaining a screening ammonia level at around day 7 post transplant has also been suggested. Given the high mortality and morbidity associated with this condition an aggressive multimodal treatment approach is required that includes renal replacement therapy, Nitrogen scavengers, bowel decontamination and empiric antibiotics. Hemodialysis has been shown to be more effective than continuous veno-venous hemodialysis for ammonia clearance. Antibiotics such as Azithromycin and Doxycycline that would be effective against urease producing organisms should be administered. In patients with signs of raised intracranial pressure, prompt neuroimaging and also measures to reduce cerebral edema must be instituted. CONCLUSIONS: Clinical signs of hyperammonemia should be promptly recognized in post lung transplant patients and managed aggressively given high mortality rates without treatment. A multi-pronged treatment approach with Intermittent high flux hemodialysis, bowel decontamination and agents targeting the urea cycle should be used to rapidly decrease the ammonia levels. Reference #1: Krutsinger D, Pezzulo A, Blevins AE, Reed RM, Voigt MD, Eberlein M. Idiopathic hyperammonemia after solid organ transplantation: Primarily a lung problem? A single-center experience and systematic review. Clin Transplant. 2017 May;31(5). doi: 10.1111/ctr.12957. Epub 2017 Apr 7. PMID: 28295601. Reference #2: Leger RF, Silverman MS, Hauck ES, Guvakova KD. Hyperammonemia Post Lung Transplantation: A Review. Clin Med Insights Circ Respir Pulm Med. 2020 Oct 26;14:1179548420966234. doi: 10.1177/1179548420966234. PMID: 33192115;PMCID: PMC7594252. Reference #3: Anwar S, Gupta D, Ashraf MA, Khalid SA, Rizvi SM, Miller BW, Brennan DC. Symptomatic hyperammonemia after lung transplantation: lessons learnt. Hemodial Int. 2014 Jan;18(1):185-91. doi: 10.1111/hdi.12088. Epub 2013 Sep 2. PMID: 23998793. DISCLOSURES: Research Grant relationship with Alung Please note: $1001 - $5000 by Bindu Akkanti, value=Grant/Research Support No relevant relationships by Soma Jyothula no disclosure on file for Manish Patel;No relevant relationships by Sandeep Patri

Effects of L-carnitine supplementation in patients with mild-to-moderate COVID-19 disease: a pilot study.

BACKGROUND: The present single-center clinical trial was designed to evaluate the potential benefits of L-carnitine supplementation in patients with COVID-19 disease. METHODS AND PATIENTS: The study was conducted on 75 patients with mild-to-moderate COVID-19 hospitalized in Shahid Beheshti Hospital-Hamadan, IRAN. The participants were randomly divided into intervention (n = 32) and control groups (n = 43). The control group received their standard hospital treatment only. In addition to standard medications, the intervention group received 3000 mg oral L-carnitine daily in three divided doses for five days. The blood samples were collected and para-clinical parameters were measured at the beginning and end of the treatment. Clinical outcomes were also recorded, and data were analyzed using χ2 and t-tests. RESULTS: Higher means of O2 saturation were observed in the intervention rather than in the control group. Mean erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly lower in the intervention group. Furthermore, mean alkaline phosphatase (ALP) activity and lactate dehydrogenase (LDH) were lower in the intervention group. Also, lower mean serum creatine phosphokinase (CPK) was observed in the intervention group. No significant differences were observed in terms of clinical symptoms; however, six patients (14%) in the control group died due to the complications of COVID-19, while all patients in the intervention group survived. CONCLUSION: Taken together, L-carnitine can be considered as a drug supplement in patients with COVID-19.

A 51-YEAR-OLD MAN WITH WEIGHT LOSS AND CARDIOGENIC SHOCK

CASE: A 51-year-old man without significant past medical history presented to our hospital with dyspnea on exertion. SARS-CoV-2 was detected on routine occupational screening 2 months prior to admission. He subsequently reported a 100lb weight loss, during which time he experienced dysgeusia and ate primarily cereal, sandwiches, and potatoes and consumed nearly no fruits or vegetables. Three weeks prior to admission he developed postprandial nausea and vomiting and anorexia. A week later he developed progressive epigastric pain, lower extremity edema, and dyspnea while walking around the college campus where he worked as a security guard, and sought medical attention. He did not have fever, chills, night sweats, cough, orthopnea, paroxysmal nocturnal dyspnea, rash, or diarrhea. He had not seen a doctor in 20 years and took no medications. He did not drink alcohol, smoke cigarettes, or use illicit substances. Vital signs were T 36.6°F HR 104 BP 149/111 RR 20 and SpO2 97%. Physical examination revealed a cachectic man with bitemporal wasting, sunken orbits, poor dentition, and severe periodontal disease. JVP was 14cm of H2O at 45°. An S3 was present. The abdomen was tender to palpation in the mid epigastrium. The extremities were cool with 3+ pitting edema. Pancreatitis was diagnosed after discovery of markedly elevated lipase levels and peripancreatic fat stranding on abdominal CT. TTE showed biventricular systolic dysfunction with LVEF 15%. He developed cardiogenic shock complicated by oliguric renal failure, congestive hepatopathy and obtundation, requiring ICU transfer for diuresis and inotropic support. Further workup revealed deficiencies of thiamine, zinc, and vitamins A, C, and D. A regadenoson myocardial perfusion PET/CT showed no flow-limiting coronary artery disease, and workup for inflammatory, infectious, and toxic-metabolic causes of heart failure was unrevealing. While COVID myocarditis and multisystem inflammatory syndrome in adults (MIS-A) were considered, ultimately, a diagnosis of wet beriberi was made. After 5 months of aggressive nutritional supplementation via percutaneous gastrostomy tube and initiation of guideline-directed medical therapy, LVEF improved to 53% and weight increased by 35lbs. IMPACT/DISCUSSION: Wet beriberi is a potentially underrecognized cause of dilated cardiomyopathy in resource-rich areas. Within 3 months, thiamine deficiency can cause high-output heart failure due to impaired myocardial energy metabolism and dysautonomia. Risk factors include alcohol use disorder, prolonged vomiting, and history of bariatric surgery. CONCLUSION: The laboratory evaluation of non-ischemic dilated cardiomyopathy should include measurement of serum thiamine, carnitine, and selenium levels in select patients, alongside iron studies, ANA, screening for HIV, Chagas disease, and viral myocarditis, and genetic testing in patients with a suggestive family history. Empiric thiamine repletion should be considered in all critically ill patients with evidence of malnutrition.

COVID VACCINE-INDUCED RHABDOMYOLYSIS. A CASE OF RECURRENT RHABDOMYOLYSIS

CASE: A 46-year-old African-American female was evaluated for generalized body aches five days after receiving second dose of COVID mRNA-1273 (Moderna) vaccine. Six months prior, she received her first dose of Ad26 (Johnson & Johnson) vaccine without sequelae, Family history includes maternal systemic lupus erythematous. Patient has a history of cystic acne and, most notably, frequent episodes of muscle aches and weakness. In 2006 and 2016, patient was hospitalized for episodes of rhabdomyolysis after receiving influenza vaccine. Autoimmune myositis was ruled out. She has never received statin medication. In late 2017, she was admitted for rhabdomyolysis after upper respiratory tract infection. She reported dark urine but no rash or arthralgia. Patient had elevated CK 107,737 U/L, AST 379 U/L, and ALT 115 U/L. Her renal function, sed rate, TSH, HIV, influenza, direct Coombs, protein electrophoresis, and antinuclear antibodies were negative or within normal limits. She was treated with IV fluids, pain medication, and discharged. In her current admission for rhabdomyolysis, she presented with dark urine, CK 130,702 U/L, AST 692 U/L, ALT 208 U/L, and D-dimer 1,544 ng/mL. No acute renal injury was noted. Patient was treated with intravenous crystalloids and pain medication. CK and transaminases steadily trended down. Patient was discharged as she was asymptomatic and CK had dropped significantly. IMPACT/DISCUSSION: Rhabdomyolysis can be an adverse event to vaccine administration, most commonly influenza vaccination. Detection of SARS-CoV-2 inside skeletal muscle has not been documented. Reports on COVID- 19 vaccine-induced rhabdomyolysis focus on the type of vaccine the patient received, the number of doses that triggered the event, CK level, and presence of risk factors for developing rhabdomyolysis. Although no pathophysiologic mechanism has been established, several hypotheses exist to explain muscle damage including genetic factors, autoimmune reactions to the virus nucleic material, or external adjuvant. This has been described as autoimmune/inflammatory syndrome induced by adjuvants. Our patient had a history of recurrent episodes of rhabdomyolysis after receiving influenza and COVID immunizations, as well as viral infection. CONCLUSION: The mechanism of our patients' reaction is unknown. Reported cases support autoimmunity as the major risk factor for vaccinerelated rhabdomyolysis. This patient had elevated CK level on subsequent episodes of rhabdomyolysis fitting the pattern where a more exaggerated response of the immune system is observed every time patient is re-exposed to known insult. Genetic predisposition may also play a role. AfricanAmericans have higher prevalence of slow acetylation and carnitine palmitoyltransferase II deficiency, a disorder of fatty acid. The myopathic form presents with high CK values. Therefore, patients should be counseled to seek medical attention when symptoms occur and physicians should consider vaccination as a possible cause.

Alterations in the Covid-19 - Associated Proteome Relative to Length of Hospital Stay

RATIONALE: The proteomic responses of hospitalized patients with SARS Co-V-2 infection may provide insight into risk, time course, and mechanisms associated with this infection. We used a high throughput proteomic platform to examine proteins that were differentially expressed relative to the length of hospital stay (LOS). METHOD:26 patients, hospitalized with SARS CoV-2 infection (mean age 48 yrs, 44% women) had blood samples obtained within 72 hours of admission. Initial plasma samples were analyzed from patients who were hospitalized for < 3 days (n=6), < 7days (n=12) and > 7 days (n=8) of LOS and compared to healthy controls (HC, n=8). Samples were analyzed with the modified aptamer-based array (SomaScan) that measures more than 7,000 human proteins representing different molecular pathways and gene families. Differentially regulated proteins with > 1.5 fold change and a false discovery rate of 5% were analyzed using the Ingenuity Pathway Analysis (IPA). Unique protein categories associated with LOS were assessed. RESULT: Compared to HC, differentially expressed proteins were detected among the 3 groups: 461 at < 3 days, 1,635 proteins at < 7 days and 1,738 proteins in >7 days. 407 proteins were common among all hospitalized COVID 19 individuals independent of LOS and 12, 250 and 361 proteins were uniquely present at < 3 days, < 7 days and > 7 days respectively compared to HC. The table below demonstrates the top highly enriched canonical pathway, molecular function and upstream regulator of differentially expressed proteins. The temporal sequence of these protein networks varied with LOS. Representative examples include early responses;platelet membrane glycoprotein GP6 signaling pathway that involves the FcR gamma-chain and the Src kinases linked to platelet aggregation, signaling involved in T cell receptor-mediated IL-2 production (TEC kinase). Less than 7 days include diacylglycerol associated with T cell activation, carnitine palmitoyltransferase associated with mitochondrial beta-oxidation of long chain fatty acids. CXCR4 a receptor for stromal -cell derived factor 1 and associated with COVID-19 prognosis. Late responses after 7 days include pathways involved in remodeling of epithelial adherens junctions. CONCLUSIONS : A high throughput proteomic approach provides insight into the dynamic regulation of protein pathways associated with the progression of SARS-Co-V2 infection. This may provide additional insight into risk and mechanisms associated with outcomes in COVID. (Table Presented).

1-YEAR FOLLOW-UP DATA OF ARTERIAL ABNORMALITIES IDENTIFIED IN KIDNEYS TRANSPLANTED INTO CHILDREN DURING THE FIRST COVID-19 PANDEMIC WAVE

BACKGROUND AND AIMS: Graft artery stenosis can have a significant shortand long-term negative impact on kidney graft function. We previously reported an unusual number of graft-arterial anomalies following kidney transplantation (KTx) in children during the first coronavirus disease (COVID-19) pandemic wave (Berteloot et al.) [1]. We report herein the 1-year follow-up of these patients. METHOD: In this retrospective study, we included all children who received a KTx at our centre from February to July 2020. We compared their outcome to that of paediatric recipients who were transplanted at our centre from 2015 to 2019 and presented an allograft vascular complication ('Historic' group) by querying our local data warehouse. RESULTS: Among the 9 children who received a KTx at our centre between February and July 2020 [8 boys, median age 10 years (3-17)], 8 presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern (Figure 1) after a median delay of 13 days (8-113). For comparison, persistent spectral Doppler arterial anomalies were observed in only 5% of children following KTx at our centre over the previous 5-year period and were all focal anastomotic stenoses. In addition, five children had lymphoceles, which required surgical management as compared to only one patient in the 5 previous years (1%). We retrospectively diagnosed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-20 infection in 6/8 children with arterial stenosis on serologies performed at D0, including one boy with a history of positive real time reverse transcription-polymerase chain reaction (RT-PCR) 120 days before KTx. None of the patients had reported any symptom suggestive of COVID-19. The remaining two patients had received a graft from an asymptomatic deceased adolescent donor with a positive serology at D0. These data led us to suspect immune post-viral graft vasculitis, triggered by SARS-CoV-2. At 1-year post-transplantation, the outcome was favourable in the 8 isolated KTx recipients. A total of 4/8 children had normal blood pressure and 4 had controlled high blood pressure on mono or bi-therapy. Doppler anomalies had resolved in 5/8 and persisted in 3/8 with a trend for improvement of peak systolic velocities and no severe consequences on kidney function and histology. Indeed, the median glomerular filtration rate (GFR) was 91 mL/min/1.73 m2 (65-129), with unspecific and mild lesions on 4/8 protocol kidney biopsies (IFTA 1 or Cpt 1). One liver-kidney graft recipient had persistent hypertension and diffuse irregular inflammatory parietal thickening of the whole vascular graft associated with a parietal thrombus upstream of the birth of the two hepatic arteries (Figure 2);treated with anti-aggregation and prednisone 10 mg/d. CONCLUSION: Our case series suggests a risk of post-viral kidney graft vasculitis in children with recent SARS-CoV-2 infection in the recipient or donor. Pre-transplant vaccination against COVID-19 is mandatory in children > 5 years and their kidney donor candidates at our centre. We also strongly recommend vaccination of all people aged > 5 years in the household. (Figure Presented).