Functional pleiotropy of calcium binding protein Regucalcin in signaling and diseases.

Regucalcin (Mr ~ 33.38 kDa) is a calcium binding protein, discovered in rat liver. In humans, gene for regucalcin is located on chromosome-11 (p11.3-q11.2) consisting of seven exons and six introns. The protein differs from other calcium binding protein in the way that it lacks EF-hand motif of calcium binding domain. It is also called as Senescence Marker Protein-30 (SMP-30) as previously its weight assumes to be 30 kDa and expression of this protein decreases with aging in androgen independent manner. Among vertebrates, it is a highly conserved protein showing gene homology in Drosophila, Xenopus, fireflies and others too. It is primarily expressed in liver and kidney in addition to brain, lungs, and skeletal muscles. Regucalcin acts as a Ca2+ regulatory protein and controls various cellular functions in liver and other organs. It suppresses protein phosphatase, protein kinase, DNA and RNA synthesis. Published evidences suggest regucalcin to be a reliable biomarker in various disorders of liver, kidney, brain and ocular. In over expressed state, it subdues apoptosis in cloned rat hepatoma cells and also induces hyperlipidemia and osteoblastogenesis by regulating various factors. Owing to the multi-functionality of regucalcin this review is presented to elaborate its importance in order to understand its involvement in cellular signaling during various pathologies.

34th Annual Meeting of the Japanese Society for Neuroimmunology (JSNI)

The proceedings contain 14 papers. The topics discussed include: MOG-positive anti-NMDA receptor encephalitis with no demyelinating lesions: two case reports;safety and tolerability of rozanolixizumab in the randomized phase 3 MycarinG study;Outcomes from RAISE: A randomized, phase 3 trial of zilucoplan in generalized myasthenia gravis;efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial;distinct effects among calcium-binding proteins for microglia to produce chemokines associated with the clinical severity of ALS;astroglial connexin 43 is a novel therapeutic target for a chronic multiple sclerosis model;targeting lymphocytes in SPMS: Th cell populations as a biomarker to predict the efficacy of Siponimod;CSF lysophospholipids as a novel biomarker in relapsing-remitting multiple sclerosis;the immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis;patient characteristics of siponimod-treated SPMS patients in Japan: interim results from post-marketing surveillance;and efficacy of ravulizumab across sex and age subgroups of patients with generalized myasthenia gravis: a post hoc analysis of the CHAMPION MG study.

Treatment of Multisystem Inflammatory Syndrome in Children

PURPOSE OF STUDY: To summarize the evidence on treatments for multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children. STUDY POPULATION: Pediatric patients with suspected MIS-C or other inflammatory illness after SARS-CoV-2 infection between June 20th, 2020 and February 24th, 2021. METHODS: Pediatricians worldwide were invited to upload their data into a central database for any pediatric patient with suspected MIS-C or any inflammatory disease after SARS-CoV-2 infection. Deidentified data, including demographics, clinical features, laboratory results, treatments (including intravenous immunoglobulin [IVIG], glucocorticoid, and biologic medications), and hospital stay length were collected and analyzed. Three primary treatment groups were compared: IVIG alone, IVIG plus glucocorticoid, and glucocorticoid alone, with IVIG alone classified as primary treatment based upon prestudy acceptance of IVIG as a primary treatment. Day 0 was considered the first calendar day of treatment of each treatment modality. There were 2 primary outcomes: (1) inotropic or mechanical ventilation (invasive or noninvasive) by day 2 or later or death;(2) reduction in disease severity on a seven-point scale between day 0 and 2. A subgroup analysis of only those meeting World Health Organization (WHO) criteria for MIS-C were included. Secondary outcomes included trends in inflammatory markers, escalation of immunomodulators, time to decrease in disease severity by 1 point, left ventricular dysfunction on echocardiogram, coronary artery aneurysm after treatment and increase in cardiorespiratory support after day 0. RESULTS: A total of 614 patients, among 81 hospitals in 34 countries, had suspected MIS-C. Of these, 246 received primary treatment with IVIG, 208 with IVIG plus glucocorticoid, and 99 with glucocorticoid alone. An additional 22 patients received immunomodulators, and 39 patients received no immunomodulatory treatment. Troponin levels and percentage of patients on inotropic agents on day 0 were higher in the IVIG plus glucocorticoid group. The first primary outcome occurred in 56 patients with IVIG plus glucocorticoid (odds ratio [OR] 0.77 compared with IVIG alone;95% confidence interval [CI], 0.33 to 1.82) and in 17 patients on glucocorticoids alone (OR 0.54;95% CI, 0.22 to 1.33). In the subgroup analysis, 490 (80%) patients met WHO criteria for MIS-C and the first primary outcome occurred in 40 patients on IVIG and glucocorticoids (OR 0.95) and in 12 patients on glucocorticoids alone (OR 0.3). The second primary outcome occurred in 54 patients on IVIG plus glucocorticoids (OR 0.9) and in 20 patients on glucocorticoids alone (OR 0.93) among the entire group. In the subgroup that met MIS-C criteria, a second primary outcome event occurred in 52 patients on IVIG plus glucocorticoids (OR 1.09) and in 16 patients on glucocorticoids alone (OR 1.95). Regarding secondary outcomes, escalation of immunomodulatory treatment was less common in IVIG plus glucocorticoids (OR 0.18), though inconclusive in the glucocorticoid versus IVIG group (OR 1.31). There was no clear difference in inflammatory markers, inotropic support, or mechanical ventilation in groups who had escalation of care by day 2 versus those without escalation in care. CONCLUSIONS: There were no significant differences in the primary outcomes for patients receiving IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone. When restricted to only those who met WHO MIS-C criteria, there was modest evidence of benefit in use of glucocorticoids compared with IVIG alone. There were no major differences in secondary outcomes, with the exception of lower odds of immunomodulatory treatment escalation in patients in IVIG plus glucocorticoids.

Myocarditis Following SARS-CoV-2 Vaccines: A Series of Six Cases: An International Journal of Medical Toxicology and Drug Experience

Introduction: Myocarditis was observed after the commercialization of mRNA vaccines and was not initially described in the safety data of these vaccines [1,2]. Lately, it was considered an adverse effect of mRNA vaccines and mentioned in the summary of product characteristics. Objective: In this work, we aim to present the cases of myocarditis after SARS-CoV-2 vaccination reported during the vaccination campaign. Methods: We present the cases of myocarditis reported to the pharmacovigilance national center after the SARS-CoV-2 vaccination. Data were collected retrospectively. All cases were defined according to Brighton's case definition of myocarditis. The vaccine causality assessment was estimated by the French imputability updated method of Begaud et al. [3]. Results: A total of six patients were included in this study. The sex ratio (M/F) was 0.5. The mean age was 31 years ranging from 18 to 41 years. All patients had no notable cardiovascular history and did not report any significant past medical history. The mean onset delay was 10 days post-vaccination. The predominant reported symptoms are chest pain and dyspnea in the six cases. Five patients have received an mRNA vaccine and one patient a viral vector vaccine. Cardiac magnetic resonance imaging confirmed the myocarditis diagnosis in five patients (not performed for one patient). All patients presented a troponin serum level elevation. The ejection fraction was reduced for five patients and conserved for one patient. All cases were classified as definitive cases according to the Brighton case definition of myocarditis. One patient required hospitalization in a cardiac intensive care unit. All the patients have recovered from acute myocarditis within a few days. Five cases were scored I2 and one case I1 according to the French updated imputability method. Conclusion: Reported cases of myocarditis post-SARS-CoV-2 vaccination are rare, generally not severe, and have a quick favorable outcome. Currently, causal relationships have been demonstrated with mRNA vaccines only.

EHRA 2022 Abstract

The proceedings contain 629 papers. The topics discussed include: digitalized ECG measure of p-wave duration predicts incident heart failure;diagnostic value of Peguero Lo Presti Electrocardiografic index for diagnosis of left ventricle hypertrophy in correlation with cardiovascular magnetic resonance;electrocardiography: an useful tool for prediction of the diagnosis and severity of pulmonary embolism;association between excessive supraventricular ectopic activity and future diagnosis of atrial fibrillation in patients with cryptogenic stroke;low-level vagus nerve stimulation during cardiac surgery: smart neuromodulation;a polymorphism in histidine-rich calcium binding protein as second hit in phospholamban cardiomyopathy;genetic predisposition according to the age at the onset of atrial fibrillation;familial clustering of unexplained heart failure - a Danish nationwide cohort study;and fever following covid-19 vaccination in subjects with Brugada syndrome: incidence and management.

Clinical features, laboratory characteristics and risk factors for mortality of COVID-19 patients in a secondary hospital in Oman during the first wave of the SARS-CoV-2 pandemic

BackgroundThe changing epidemiological profile of the COVID-19 pandemic and the uncertain clinical picture of patients characterise this ongoing and most challenging health event.ObjectivesTo report clinical features, laboratory characteristics, and mortality risk factors among COVID-19 patients admitted to a secondary hospital in Oman.MethodsA retrospective study for the first 455 patients admitted with COVID-19 to Rustaq hospital from 12th April, 2020 to 27th September, 2020. A predesigned questionnaire collected data from the hospital medical electronic system.ResultsThe mean age was 42.84 (SD = 19.86) years, and the majority of patients were aged 30 to 59 and 60 or above;207 (45.5%) and 189 (41.5%), respectively. Male patients constituted approximately two-thirds of the subjects. Fever, dyspnea and cough were the most common presenting symptoms (69%, 66%, and 62%, respectively), while comorbidities with diabetes mellitus and hypertension were 47% and 44%, respectively. Bacterial growth was identified at approximately 10%. Bivariate analysis turned out to be significant with a number of factors. However, multivariate analysis showed significance with patients aged over 60 (OR = 7.15, 95% CI 1.99–25.63), dyspnea (OR = 2.83, 95% CI 1.5–5.33), dyslipidemia (OR = 1.93, 95% CI 1.02–3.66) and being bed-ridden (OR = 5.01, 95% CI 1.73–14.44). Durations from onset of symptoms to admission and respiratory distress were lower among patients who died;p = 0.024 and p = 0.001, respectively. Urea, Troponin and LDH may act as potential diagnostic biomarkers for severity or mortality.ConclusionsThis study identified groups of patients with a higher risk of mortality, with severe disturbance in the laboratory markers while some could act as potential diagnostic biomarkers.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.