IgG autoantibodies against ACE2 in SARS‐CoV‐2 infected patients

alexandrossfakianakis shared this article with you from Inoreader IgG autoantibodies against ACE2 in SARS‐CoV‐2 infected patients via Journal of Medical Virology Abstract How frequently autoantibodies against angiotensin-converting enzyme 2 (ACE2) occur in patients infected by SARS-CoV-2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long-lasting effects of COVID-19 observed in some individuals, particularly if IgG class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS-CoV-2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti-ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID-19, but some severe and asymptomatic cases were also observed. Patients with severe infection had 2-fold higher titers than mild and asymptomatic cases. Age, comorbidities and influenza vaccination status were not related to ant ibody prevalence. The prevalence of IgG anti-SARS-CoV-2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor-binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS-CoV-2 infection, particularly concerning long COVID-19. This article is protected by copyright. All rights reserved. View on Web

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The effect of changing to Bictegravir on lipids using real world data: A brief report

alexandrossfakianakis shared this article with you from Inoreader The effect of changing to Bictegravir on lipids using real world data: A brief report via Journal of Clinical Pharmacy and Therapeutics Analysis of variance for change in lipid subfractions in patients switching to bictegravir. Abstract What is known and objective Cardiovascular disease is of increasing concern in patients living with HIV. The significant advancement in antiretroviral treatment has ensured that patients are now succumbing to traditional diseases of ageing. First generation antiretroviral therapy caused multiple side effects including significant dyslipidaemia. Despite the advancement and improving safety profile of treatment concerns remain about antiretroviral induced dyslipidaemia. We sought to investigate the real-world effect on lipids in patients switching to a Bictegravir based regime. Methods We conducted a retrospective analysis in patients switching therapy to Biktarvy at the Royal Liverpool University Hospital. Data was collected from the HIV database that is established for clinical use, as an electronic patient record, and audit purposes. Lipid data was cross checked with the Trust electronic reporting system. Participants were included if they were HIV-positive, >18 years and had switched to Biktarvy Patients were also required to have a lipid profile available 52 weeks prior to switching and 100 weeks post switching. Summary statistic were calculated and multiple regressions models were constructed to assess the independent predictors of lipid change. We also performed one way analysis of covariance (ANCOVA) to assess the impact of switching therapy on each quartile of the baseline lipid panel. Results and discussion There were 135 patients included in the analysis with a mean age of 47. The majority of the population were male (80%). At a mean follow up of 42 weeks post switch there was no significant difference in total cholesterol (p = 0.64), triglyceride (p = 0.64) or high density lipoprotein (HDL) cholesterol (p = 0.08). In the regression analysis the highest quartile of baseline total cholesterol and triglyceride were independently associated with improvement in lipid markers. Switching from protease inhibitor therapy was also significantly associated with improvement in triglyceride. In addition, the ANCVOA demonstrated that the highest quartiles of total cholesterol, triglyceride and the lowest quartile of HDL were associated with significant improvement in lipid markers after switching to Bictegravir. What is new and conclusion We demonstrated that patients with the most adverse lipid profiles at baseline had significant improvements in lipid profiles. In addition, patient switching away from protease inhibitor therapy also had significant improvements in triglyceride. View on Web

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Impact of belatacept and tacrolimus on cytomegalovirus viral load control and relapse in moderate and high‐risk cytomegalovirus serostatus kidney transplant recipients

alexandrossfakianakis shared this article with you from Inoreader Impact of belatacept and tacrolimus on cytomegalovirus viral load control and relapse in moderate and high‐risk cytomegalovirus serostatus kidney transplant recipients via Transplant Infectious Disease ABSTRACT Background : Belatacept improves long-term graft survival, but control of some primary viral infections may be impaired. We evaluated the impact of belatacept and tacrolimus on Cytomegalovirus (CMV) viral control, remission and relapse in CMV high-risk and moderate-risk recipients. Methods : Using a multi-state Markov model, we evaluated viral load state transitions of 173 kidney transplant recipients with at least 1 episode of viremia within 1 year after transplant: state 1, undetectable/low viral load; state 2, moderate viremia; and state 3, severe viremia. Results : Among high-risk recipients, belatacept-treated recipients exhibited significantly higher probability of entering moderate viremia (0.36; 95% CI = 0.31, 0.41) than tacrolimus-treated recipients (0.20; 95% CI = 0.13, 0.29). The expected number of days in viremic states differed. High-risk belatacept-treated recipients persisted in moderate viremia for significantly longer (128 days, 95% CI = 110, 146) than did tacrolimus-treated recipients (70.0 days, 95% CI = 45.2, 100) and showed a trend of shorter duration in low/undetectable viral load state (172 days, 95% CI = 148, 195) than did tacrolimus-treated recipients (239 days, 95% CI = 195, 277). Moderate-risk recipients showed better viral load control and with no differences by immunosuppression. Conclusion : High-risk belatacept-treated recipients showed defects in sustaining viral control relative to tacrolimus-treated recipients. Avoidance of initial use belatacept in high-risk recipients or development of modified management protocols should be considered. This article is protected by copyright. All rights reserved View on Web

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CHCHD2 p.Thr61Ile knock‐in mice exhibit motor defects and neuropathological features of Parkinson's disease

alexandrossfakianakis shared this article with you from Inoreader CHCHD2 p.Thr61Ile knock‐in mice exhibit motor defects and neuropathological features of Parkinson's disease via Brain Pathology We set out to study the biological role of the CHCHD2 p.T61I mutation in Parkinson's disease in vivo by generating a knock-in mouse model harbouring the mutation. The mutant mice had accelerated mortality, progressive motor deficits, and the loss of dopaminergic neurons. α-synuclein and p-α-synuclein aggregations were observed in the brains of the mutant mice; these mice also exhibited an aberrant mitochondrial morphology and impaired mitochondrial function. Induced pluripotent stem cell-derived dopaminergic neurons carrying the CHCHD2 p.T61I mutation reproduced the impaired mitochondria. Proteomic and RNA sequencing analysis revealed that p.T61I mutation induced mitochondrial dysfunction in aged mice likely through repressed IDE expression, resulting in the degeneration of the nervous system. Abstract The p.Thr61Ile (p.T61I) mutation in coiled-coil-helix–coiled-coil-helix domain containing 2 (CHCHD2) was deemed a causative factor in Parkinson's disease (PD). However, the pathomechanism of the CHCHD2 p.T61I mutation in PD remains unclear. Few existing mouse models of CHCHD2-related PD completely reproduce the features of PD, and no transgenic or knock-in (KI) mouse models of CHCHD2 mutations have been reported. In the present study, we generated a novel CHCHD2 p.T61I KI mouse model, which exhibited accelerated mortality, progressive motor deficits, and dopaminergic (DA) neurons loss with age, accompanied by the accumulation and aggregation of α-synuclein and p-α-synuclein in the brains of the mutant mice. The mitochondria of mouse brains and induced pluripotent stem cells (iPSCs)-derived DA neurons carrying the CHCHD2 p.T61I mutation exhibited aberrant morphology and impaired function. Mechanistically, proteomic and RNA sequencing analysis revealed that p.T61I mutatio n induced mitochondrial dysfunction in aged mice likely through repressed insulin-degrading enzyme (IDE) expression, resulting in the degeneration of the nervous system. Overall, this CHCHD2 p.T61I KI mouse model recapitulated the crucial clinical and neuropathological aspects of patients with PD and provided a novel tool for understanding the pathogenic mechanism and therapeutic interventions of CHCHD2-related PD. View on Web

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International variations in germ cell tumours incidence in children and adolescents

alexandrossfakianakis shared this article with you from Inoreader International variations in germ cell tumours incidence in children and adolescents via Japanese Journal of Clinical Oncology - current issue In order to compare the subtype distribution of germ cell tumours in children and adolescents between Japan and other countries, we extracted information on cancer incidence in children and adolescents from the third volume of the International Incidence of Childhood Cancer series (IICC-3) (1). The IICC-3 reports the number or incidence rates of cancers diagnosed in childhood and adolescence, from cancer registries (regional or national) worldwide. We analysed germ cell tumours incidence in four countries in Asia (Japan, China, the Republic of Korea and Thailand), two countries in Africa (Egypt and Uganda), four countries in the Americas (North: USA and Canada, Latin and Caribbean: Brazil and Colombia), three countries in Europe (the UK, France and Germany) and two countries in Oceania (Australia and New Zealand). Information from the Republic of Korea, USA , UK, Australia and New Zealand was obtained at the national level, and that from the other countries was extracted from one or multiple regional cancer registries. The years of incidence included in the analyses varied from country to country, ranging from 1990 to 2014, with the shortest being 12 years (Egypt: 1999–2010, UK: 2000–11) and the longest being 24 years (Japan and China: both 1990–2013). In this study, we compared the incidence and proportional distribution of soft tissue sarcoma subtypes in children (0–14 years old) and adolescents (15–19 years old) between these countries. View on Web

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Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir

alexandrossfakianakis shared this article with you from Inoreader Successful treatment of prolonged, severe COVID-19 lower respiratory tract disease in a B-cell ALL patient with an extended course of remdesivir and nirmatrelvir/ritonavir via Clinical Infectious Diseases Advance Access Abstract A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, IV remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery. View on Web

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Tonsillectomy vs Modified Uvulopalatopharyngoplasty for Hypertrophy and Obstructive Sleep Apnea

alexandrossfakianakis shared this article with you from Inoreader Tonsillectomy vs Modified Uvulopalatopharyngoplasty for Hypertrophy and Obstructive Sleep Apnea via JAMA Otolaryngology–Head & Neck Surgery Online First This randomized clinical trial examines whether modified uvulo palatopharyngoplasty is more effective than tonsillectomy alone for treating adults with tonsillar hypertrophy and moderate to severe obstructive sleep apnea. View on Web

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Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness, United States, 2022

alexandrossfakianakis shared this article with you from Inoreader Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness, United States, 2022 via Clinical Infectious Diseases Advance Access Abstract Background The COVID-19 pandemic was associated with historically low influenza circulation during the 2020–2021 season, followed by increase in influenza circulation during the 2021–2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain. Methods To understand the effectiveness of the 2021–2022 vaccine against hospitalized influenza illness, a multi-state sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI) and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by includin g SARS-CoV-2 positive controls. Results A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2 negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2 positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95%CI: -14 to 52%) among adults aged 18-64 years, -3% (95%CI: -54 to 31%) among adults aged ≥65 years, and 50% (95%CI: 15 to 71%) among adults 18-64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2-positive controls. Conclusions During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted. View on Web

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Perioperative Anaphylaxie – alte Zöpfe und Neues zu den Auslösern

alexandrossfakianakis shared this article with you from Inoreader Perioperative Anaphylaxie – alte Zöpfe und Neues zu den Auslösern via Laryngo-Rhino-Otologie Laryngorhinootologie 2022; 101: 882-885 DOI: 10.1055/a-1861-7011 Perioperative Anaphylaxien werden mit mindestens 1:6000 angegeben. Neue Kenntnisse der Pathophysiologie der anaphylaktischen Reaktionen beziehen die Auslösung über das Mastzell-related G-Protein und die Komplementaktivierungs-abhängige Pseudoallergie mit ein. Neu beschriebene Auslöser sind das Chlorhexidin oder Gelatine-Produkte, eingesetzt zur Blutstillung oder blaue Farbstoffe zur intraoperativen Markierun g. Wachsamkeit ist in Hinblick auf biphasische Reaktionen geboten. Propofol darf mittlerweile bei Ei- und Sojaallergikern eingesetzt werden. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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BIOPASS-Hybrid-Navigation für die endoskopische Nasennebenhöhlenchirurgie – ein Assistenzsystem

alexandrossfakianakis shared this article with you from Inoreader BIOPASS-Hybrid-Navigation für die endoskopische Nasennebenhöhlenchirurgie – ein Assistenzsystem via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1940-9723 Bisherige Navigationssysteme können zwar im Rahmen der funktionellen endoskopischen Nasennebenhöhlenchirurgie (FESS) die Position des „getrackten" Operationsinstruments in radiologische Schnitt-Bilddaten bestimmen, geben aber keine Hilfestellung direkt im videoendoskopischen Bild des Operateurs. Diese direkte Hilfestellung zur intraoperativen Orientierung und Risikoreduzierung zu entwickeln, war Ziel des BIOPASS-Projekts (Bi ld Ontologie und prozessgestütztes Assistenzsystem). Das Projekt verfolgt die Entwicklung eines neuartigen, markerlosen Navigationssystems für die FESS. BIOPASS beschreibt ein Hybrid-System, das verschiedene Sensordaten integriert und dem Chirurgen zur Verfügung stellt. Ziel ist es, das Tracking zu verlassen und ausschließlich Navigationsinformation direkt im Videobild zur Verfügung zu stellen. Die vorliegende Arbeit beschreibt den ersten Schritt der Entwicklung, im Rahmen dessen die Operationsphasen (Workflows) untersucht, die videoendoskopischen Landmarken klassifiziert und eine erste klinische Evaluation der Modellversion durchgeführt wurden. Die Ergebnisse stellen eine wichtige Grundlage und Plattform für den nächsten Projektschritt dar. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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