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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Die Schnittstelle der Logopädie im Prozess der Geschlechtsangleichung von Mann zu Frau

alexandrossfakianakis shared this article with you from Inoreader Die Schnittstelle der Logopädie im Prozess der Geschlechtsangleichung von Mann zu Frau via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1940-9794 Hintergrund Die Stimme ist für die Geschlechtsidentifikation während des Transitionsprozesses entscheidend, da die Stimmfeminisierung einen bedeutenden Anteil zum Gelingen des Passing hat. Um die Rolle der Logopädie während des interdisziplinären Geschlechtsangleichungsprozesses von MzF-Trans* einordnen zu können, bedarf es möglicher Handlungsempfehlungen für die Zusammenarbeit mit den beteiligten Ärzten. Material und Methoden Vier Experteninterviews aus den Bereichen der Phonochirurgie, Phoniatrie, Endokrinologie sowie plastischen Chirurgie wurden durchgeführt. Auf Grundlage dieser Interviews wurde ein potenzieller Leitlinienkonsens zur Einordnung der Rolle der Logopädie im Prozess der Geschlechtsangleichung von MzF-Trans* erstellt. Ergebnisse Anhand der Expertengespräche wird einheitlich empfohlen, die logopädische Stimmtherapie schon zu Beginn der Transition zu berücksichtigen. Primär sollte eine konservative Therapie berücksichtigt werden, um z.B. irreversible Operationen des Larynx zu vermeiden. Der Fokus logopädischer Stimmtherapie bei Stimmfeminisierung obliegt zentral bei der Anpassung der mittleren Sprechstimmlage. In postoperativen Fällen sollte die logopädische Stimmtherapie das Sprechverhalten an die neue Anatomie anpassen und Komplikationen, wie z.B. eine unökonomische Stimm- und Sprechgebung, vorbeugen. Schlussfolgerung Die aktuellen Interviews stellen einen ersten Einblick in die Kooperation von Logopäden und den medizinischen Fachbereichen zur Behandlung von MzF-Trans* dar. Um die Empfehlungen aus den Experteninterviews für einen potenziellen Leitlinienkonsens implementieren zu können, bedarf es Rücksprachen mit den hierzu beteiligten Fachgesellschaften sowie mehr randomisierter Studien zu spezifischen logopädischen Stimmtherapien. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.