Plasma Aβ42/Aβ40 ratios are not reduced in older people living with HIV

alexandrossfakianakis shared this article with you from Inoreader Plasma Aβ42/Aβ40 ratios are not reduced in older people living with HIV via Clinical Infectious Diseases Advance Access Abstract Background As people with HIV (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders, e.g., Alzheimer disease (AD), and if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically-available blood biomarker test for AD (plasma Aβ42/Aβ40 ratio), in cognitively-normal (CN) or cognitively-impaired (CI) PWH and people without HIV (PWoH) who were CN or with symptomatic AD. Methods 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, magnetic resonance imaging (MRI), and completed a neuropsychological battery or Clinical Dementia Rating scale (CDR). Participants were categorized by impairment (PWH_CN n = 43; PWH_CI n = 23; PWoH_CN n = 138; PWoH_AD n = 57). Plasma Aβ42 and Aβ40 concentrations were obtained using a liquid chromatography-tandem mass spectrometry method to calculate the PrecivityAD® Amyloid Probability Score (APS). The APS incorporates age and apolipoprotein E proteotype into a risk score for brain amyloidosis. Plasma Aβ42/Aβ40 and APS were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only). Results The plasma Aβ42/Aβ40 ratio was significantly lower, and APS higher, in PWoH_AD compared to other groups. A lower Aβ42/Aβ40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The Aβ42/Aβ40 ratio and APS were not associated with cognition or HIV clinical measures for PWH. Conclusions The plasma Aβ42/Aβ40 ratio can serve as a screening tool for AD and may help differentiate effects of HIV from AD within PWH, but larger studies with older PWH are needed. View on Web

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ACE2 PET to Reveal the Dynamic Patterns of ACE2 Recovery in an Infection Model with Pseudo Corona Virus

alexandrossfakianakis shared this article with you from Inoreader ACE2 PET to Reveal the Dynamic Patterns of ACE2 Recovery in an Infection Model with Pseudo Corona Virus via Journal of Medical Virology Abstract Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potentials to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virus-host interaction, 68Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation, and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period were visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time period-dependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in heart, liver, kidneys, lungs and so on, but liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days P.I., with brain and genitals still of a decreased SUVACE2, meanwhile, kidneys were of an increased SUVACE2. These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was of the superiority on earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUVACE2 and the ACE2 specificity were further confirmed. In conclusion, 68Ga-cyc-DX600 was developed as an ACE2-specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference an d approach to explore the ACE2-related pathological basis of sequelae in long COVID. This article is protected by copyright. All rights reserved. View on Web

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Analysis of long noncoding RNAs and mRNAs expression profiles in the hearts of mice with acute viral myocarditis

alexandrossfakianakis shared this article with you from Inoreader Analysis of long noncoding RNAs and mRNAs expression profiles in the hearts of mice with acute viral myocarditis via Journal of Medical Virology Abstract Acute viral myocarditis (AVMC) is a common acute myocardial inflammation caused by viral infections, which can lead to severe cardiac dysfunction. Several long noncoding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of AVMC. However, the expression profiles and functions of lncRNAs in AVMC have not been fully elucidated. In the present study, we constructed AVMC mouse models by intraperitoneal injection of coxsackievirus B3 (CVB3) and performed RNA sequencing (RNA-seq) on heart tissues to investigate the differences in lncRNAs and mRNAs expression profiles. Based on the cutoff criteria of adjusted p-values (padj) < 0.05 and |log2FoldChange| > 1, a total of 1,122 differentially expressed lncRNAs (DElncRNAs) and 3,186 differentially expressed mRNAs (DEmRNAs) were screened, including 734 upregulated and 388 downregulated lncRNAs, 1,821 upregulated and 1,365 downregulated mRNAs. RT-qPCR analysis validated that the expression patte rns of 12 randomly selected genes (6 DElncRNAs and 6 DEmRNAs) were highly consistent with those in RNA-seq, proving the reliability of the RNA-seq data. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that differentially expressed genes (DEGs) were mainly involved in metabolic and immune-related processes. Furthermore, co-expression networks between DElncRNAs and DEmRNAs in cytokine-cytokine receptor interaction, MAPK signaling pathway, and PI3K-Akt signaling pathway were constructed to study the molecular interactions of these molecules. Our study, for the first time, reveals the expression profiles of lncRNAs and mRNAs associated with AVMC, which may shed light on the roles of lncRNAs in disease pathogenesis and aid in discovering new therapeutic targets. This article is protected by copyright. All rights reserved. View on Web

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Nirmatrelvir‐ritonavir for the treatment of COVID‐19 patients: a systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Nirmatrelvir‐ritonavir for the treatment of COVID‐19 patients: a systematic review and meta‐analysis via Journal of Medical Virology Abstract Nirmatrelvir-ritonavir (Paxlovid™) is an oral antiviral that has been approved for the treatment of mild-to-moderate COVID-19. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of nirmatrelvir-ritonavir in COVID-19 patients. Various databases including PubMed, the Cochrane Library, medRxiv and Embase were searched from inception till 10 October 2022 and results from 12 studies (two randomized controlled trials (RCTs) and 10 observational studies) were pooled using a random-effects model with risk ratio (RR) as the effect measure. Nirmatrelvir-ritonavir reduced the risk of mortality (RR 0.24; 95% CI:0.15–0.37, I2=48%; moderate certainty) and hospitalization (RR 0.41; 95% CI:0.29–0.59, I2=90%; low certainty) in both patients with or without previous immunity to SARS-CoV-2 without an increased risk of adverse events. Our study provides encouraging evidence for nirmatrelvir-ritonavir as a safe and efficacious agent for COVID-19 but lar ge-scale RCTs are needed to confirm these findings. This article is protected by copyright. All rights reserved. View on Web

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Outcomes of KTP Laser Ablation in Glottic Neoplasms: A Systematic Review and Meta‐Analysis

alexandrossfakianakis shared this article with you from Inoreader Outcomes of KTP Laser Ablation in Glottic Neoplasms: A Systematic Review and Meta‐Analysis via The Laryngoscope The aim of our review is to evaluate the safety and efficiency of transoral laser microsurgery (TLM) with potassium-titanyl-phosphate (KTP) laser ablation for glottic neoplasms. Eight studies were included. After an average follow-up of 3.3 years, the overall survival and disease-free survival for patients who underwent KTP. KTP is a safe and effective method for treating patients with early glottic neoplasms. Objectives To evaluate the safety and clinical effectiveness of transoral laser microsurgery (TLM) with potassium-titanyl-phosphate (KTP) laser ablation for glottic neoplasms. Data Source MEDLINE via PubMed, SCOPUS, Web of Science, and Cochrane Library. Review Methods A systematic review and meta-analysis of studies assessing the safety and efficacy of KTP laser therapy in patients with early-stage glottic neoplasms. Results Eight studies were included. After an average follow-up of 3.3 years, the overall survival and disease-free survival for patients who underwent KTP were 90.7% (95% CI 85%–96.5%) and 98.5% (95% CI 97.3%–99.8%), respectively. In the single-arm meta-analysis, the pooled estimate of recurrence was 7.7% (95% CI 3.4%–12%). The overall voice handicap index (VHI) estimate attributed to KTP in the single-arm meta-analysis was 6.76 (95% CI [3.05, 10.48]) and 5.21 (95% CI [2.86, 7.56]) within 6 months and after a one-year follow-up, respectively. Conclusion KTP laser ablation is a safe and effective method for treating patients with early glottic neoplasms. Laryngoscope, 2023 View on Web

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Drug‐induced radiation recall reactions and non‐anticancer drugs: A descriptive analysis from VigiBase®

alexandrossfakianakis shared this article with you from Inoreader Drug‐induced radiation recall reactions and non‐anticancer drugs: A descriptive analysis from VigiBase® via Fundamental & Clinical Pharmacology Abstract Background Radiation recall reactions are inflammatory reactions confined to previously irradiated tissues, often of drug-induced etiology, particularly with anticancer therapies. Other drugs, in particular COVID-19 vaccines, may also be involved. Objective To describe radiation recall reactions under non-anticancer drugs more precisely. Material and method We extracted the cases of radiation recall reactions associated with non-anticancer drugs from WHO pharmacovigilance database VigiBase®. We performed two analyses from this extraction: a global analysis and an analysis focusing on vaccination-related issues. Results We extracted 120 cases corresponding to 269 drugs, of which 130 were non-anticancer (22 vaccines). Among the non-anticancer drugs, tozinameran was the most reported treatment (4.46% of cases), followed by levofloxacin (2.97%) and folinic acid (2.60%), dexamethasone (2.23), ChAdOx1 nCoV-19 vaccine and prednisone (1.86% each). Among vaccines, tozinameran (54.55% of cases) was the most reported, followed by ChAdOx1 nCoV-19 (22.73%), HPV & inactivated influenza vaccine (9.09% each), and elasomeran (4.55%). Conclusion Our study first describes the occurrence of radiation recall reactions during non-anticancer treatment. It also highlights a potential safety signal with COVID-19 vaccines. View on Web

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Temporal trends in the incidence of malignant and non-malignant primary brain and central nervous system tumors by method of diagnosis in England, 1993-2017

alexandrossfakianakis shared this article with you from Inoreader Temporal trends in the incidence of malignant and non-malignant primary brain and central nervous system tumors by method of diagnosis in England, 1993-2017 via Neuro-Oncology Advance Access Abstract Background Several studies report increasing incidence of primary CNS tumors. The reasons for this are unclear. Methods Data on all 188,340 individuals diagnosed with a primary CNS tumor in England (1993-2017) were obtained from the National Cancer Registry. Data on all CT head and MRI brain scans in England (2013-2017) were obtained from NHS Digital. Age-sex-standardized annual incidence rates per 100,000 population (ASR) were calculated by calendar year, tumor behavior, tumor location and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC). Results The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: 1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: -0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically c onfirmed, the ASR increased modestly (AAPC: 1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those aged 65+. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013-2017, with especially large increases in 65-84 and 85+ year olds (AAPCs: 18.4% and 22.5%). Conclusion Increases in CNS tumor incidence in England are largely attributable to greater detection of benign tumors. This could be the result of increasing use of neuroimaging, particularly CT head scans in A&E in people aged 65+. View on Web

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