Borupbroch1065

th a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97).

DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.

DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.

Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. CI-1040 research buy However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified.

To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated.

This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysder the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity.

High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

The behavioral variant of Alzheimer disease (bvAD) is characterized by early and predominant behavioral deficits caused by AD pathology. This AD phenotype is insufficiently understood and lacks standardized clinical criteria, limiting reliability and reproducibility of diagnosis and scientific reporting.

To perform a systematic review and meta-analysis of the bvAD literature and use the outcomes to propose research criteria for this syndrome.

A systematic literature search in PubMed/MEDLINE and Web of Science databases (from inception through April 7, 2021) was performed in duplicate.

Studies reporting on behavioral, neuropsychological, or neuroimaging features in bvAD and, when available, providing comparisons with typical amnestic-predominant AD (tAD) or behavioral variant frontotemporal dementia (bvFTD).

This analysis involved random-effects meta-analyses on group-level study results of clinical data and systematic review of the neuroimaging literature. The study was performed following Preferredr to bvFTD, while it shares most pathophysiological features with tAD. Based on these insights, we propose research criteria for bvAD aimed at improving the consistency and reliability of future research and aiding the clinical assessment of this AD phenotype.

Whether recent changes in demographic characteristics and therapeutic technologies have altered stroke outcomes remains unknown.

To determine secular changes in initial neurological severity and short-term functional outcomes of patients with acute stroke by sex using a large population.

This nationwide, hospital-based, multicenter, prospective registry cohort study used the Japan Stroke Data Bank and included patients who developed acute stroke from January 2000 through December 2019. Patients with stroke, including ischemic and hemorrhagic strokes, who registered within 7 days after symptom onset were studied. Modified Rankin Scale scores were assessed at hospital discharge for all patients.

Time.

Initial severity was assessed by the National Institutes of Health Stroke Scale for ischemic stroke and intracerebral hemorrhage and by the World Federation of Neurological Surgeons grading for subarachnoid hemorrhage. Outcomes were judged as favorable if the modified Rankin Scale score was 0 to 2 and un sexes. In intracerebral hemorrhage, favorable outcomes decreased in both sexes, and unfavorable outcomes and deaths decreased only in women. In subarachnoid hemorrhage, the proportion of favorable outcomes was unchanged, and that of unfavorable outcomes and deaths decreased in both sexes.

In this study, functional outcomes improved in patients with ischemic stroke during the past 20 years in both sexes presumably partly owing to the development of acute reperfusion therapy. The outcomes of patients with hemorrhagic stroke did not clearly improve in the same period.

In this study, functional outcomes improved in patients with ischemic stroke during the past 20 years in both sexes presumably partly owing to the development of acute reperfusion therapy. The outcomes of patients with hemorrhagic stroke did not clearly improve in the same period.Mutations in mitofusin 2 (MFN2) that are associated with the pathology of the debilitating neuropathy Charcot-Marie-Tooth type 2A (CMT2A) are known to alter mitochondrial morphology. One such abundant MFN2 mutation, R364W, results in the generation of elongated, interconnected mitochondria. However, the mechanism leading to this mitochondrial aberration remains poorly understood. Here, we show that mitochondrial hyperfusion in the presence of R364W-MFN2 is due to increased degradation of DRP1 (also known as DNM1L). The E3 ubiquitin ligase MITOL (also known as MARCHF5) is known to ubiquitylate both MFN2 and DRP1. Interaction with and subsequent ubiquitylation by MITOL is stronger in the presence of wild-type MFN2 than with R364W-MFN2. This differential interaction of MITOL with MFN2 in the presence of R364W-MFN2 renders the ligase more available for DRP1 ubiquitylation. Multi-monoubiquitylation and proteasomal degradation of DRP1 in R364W-MFN2 cells in the presence of MITOL eventually leads to mitochondrial hyperfusion. Here, we provide a mechanistic insight into mitochondrial hyperfusion, while also reporting that MFN2 can indirectly modulate DRP1 - an effect not shown previously. This article has an associated First Person interview with the first author of the paper.

Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research.

To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC.

PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020.

From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04).

This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

Neurofibromatosis type 1 (NF1) affects hearing through disruption of central auditory processing. The mechanisms, functional severity, and management implications are unclear.

To investigate auditory neural dysfunction and its perceptual consequences in individuals with NF1.

This case-control study included children and adults with NF1 and control participants matched on age, sex, and hearing level. Patients were recruited through specialist neurofibromatosis and neurogenetic outpatient clinics between April and September 2019. An evaluation of auditory neural activity, monaural/binaural processing, and functional hearing was conducted. Diffusion-weighted magnetic resonance imaging (MRI) data were collected from a subset of participants (10 children with NF1 and 10 matched control participants) and evaluated using a fixel-based analysis of apparent fiber density.

Type and severity of auditory dysfunction evaluated via laboratory testing and questionnaire data.

A total of 44 participants (18 [41%] fe could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.

The findings of this case-control study could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.

Telehealth has been posited as a cost-effective means for improving access to care for persons with chronic conditions, including kidney disease. Perceptions of telehealth among older patients with chronic illness, their care partners, and clinicians are largely unknown but are critical to successful telehealth use and expansion efforts.

To identify patient, care partner, and nephrologists' perceptions of the patient-centeredness, benefits, drawbacks of telehealth compared to in-person visits.

This qualitative study used semistructured interviews conducted from August to December 2020 with purposively sampled patients (aged 70 years or older, chronic kidney disease stages 4 to 5), care partners, and clinicians in Boston, Massachusetts; Chicago, Illinois; Portland, Maine; and San Diego, California.

Participants described telehealth experiences, including factors contributing to and impeding engagement, satisfaction, and quality of care. Thematic analysis was used to analyze data.

Of 60 interviews, 19 (32%) were with clinicians, 30 (50%) with patients, and 11 (18%) with care partners; 16 clinicians (84%) were nephrologists; 17 patient participants (43%) were non-Hispanic Black, and 38 (67%) were women.