Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain.

Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA).

Integrated single-cell chromatin and transcriptomic analyses of human scalp identify gene-regulatory programs and critical cell types for hair and skin diseases.

Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of gene-regulatory networks in relevant cell types. We generated matched single-cell chromatin profiles and transcriptomes from scalp tissue from healthy controls and patients with alopecia areata, identifying diverse cell types of the hair follicle niche. By interrogating these datasets at multiple levels of cellular resolution, we infer 50-100% more enhancer-gene links than previous approaches and show that aggregate enhancer accessibility for highly regulated genes predicts expression.

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial.

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.

Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation.

Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab.

Quantitative Analysis of Translatory Movements in Patients With Horizontal Strabismus.

Purpose: To investigate translatory movement during the lateral gaze in patients with horizontal strabismus using magnetic resonance imaging.

Methods: Patients with esotropia or exotropia and normal controls underwent orbital magnetic resonance imaging during the central gaze and lateral gaze at 40°. The position of the static tissues was superimposed three-dimensionally for all gazes using a self-developed software, allowing the analysis of the net eyeball movement.

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.

Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS.

Investigation of MicroRNA Expression in Anterior Lens Capsules of Senile Cataract Patients and MicroRNA Differences According to the Cataract Type.

Purpose: We investigated the microRNAs (miRNAs) expression in the anterior lens capsules of patients with senile cataract and compared it to that in the anterior lens capsules of healthy controls. Moreover, we compared the differences in miRNAs expression according to the types of cataracts.

Methods: Individual lens epithelium samples were collected from 33 senile patients and 10 controls.

Functional compensation precedes recovery of tissue mass following acute liver injury.

The liver plays a central role in metabolism, protein synthesis and detoxification. It possesses unique regenerative capacity upon injury. While many factors regulating cellular proliferation during liver repair have been identified, the mechanisms by which the injured liver maintains vital functions prior to tissue recovery are unknown.

Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees.

Background: Targeted muscle reinnervation is an emerging surgical technique to treat neuroma pain whereby sensory and mixed motor nerves are transferred to nearby redundant motor nerve branches. In a recent randomized controlled trial, targeted muscle reinnervation was recently shown to reduce postamputation pain relative to conventional neuroma excision and muscle burying.

Questions/purposes: (1) Does targeted muscle reinnervation improve residual limb pain and phantom limb pain in the period before surgery to 1 year after surgery? (2) Does targeted muscle reinnervation improve Patient-reported Outcome Measurement System (PROMIS) pain intensity and pain interference scores at 1 year after surgery? (3) After 1 year, does targeted muscle reinnervation improve functional outcome scores (Orthotics Prosthetics User Survey [OPUS] with Rasch conversion and Neuro-Quality of Life [Neuro-QOL])?

Methods: Data on patients who were ineligible for randomization or declined to be randomized and underwent targeted muscle reinnervation for pain were gathered for the present analysis.

Profiling Hospital Performance Based on Mortality After Transcatheter Aortic Valve Replacement in Ontario, Canada.

Background: Public reporting of hospital-level outcomes is increasingly common as a means to target quality improvement strategies to ensure the delivery of optimal care. Despite the rapid dissemination of transcatheter aortic valve replacement (TAVR), there is a paucity of reliable case-mix adjustment models for hospital profiling in TAVR. Our objective was to develop and evaluate different models for calculating risk-standardized all-cause mortality rates (RSMRs) post-TAVR.

Inhibition of Advanced Glycation End Products Formation Attenuates Cardiac Electrical and Mechanical Remodeling and Vulnerability to Tachyarrhythmias in Diabetic Rats.

Diabetic patients with cardiomyopathy show a higher incidence of arrhythmias and sudden death. Chronic hyperglycemia induces the formation of advanced glycation end products (AGEs), which contribute to the pathogenesis of diabetic cardiomyopathy. This study investigated whether inhibition of AGEs formation by aminoguanidine (AG) could prevent cardiac electromechanical and arrhythmogenic remodeling in diabetes mellitus.

Clinical Outcomes of Posterior Versus Anterior Circulation Infarction With Low National Institutes of Health Stroke Scale Scores.

Background And Purpose: We compared baseline characteristics and outcomes at 3 months between patients with minor anterior circulation infarction (ACI) versus minor posterior circulation infarction (PCI), including the influence of large vessel disease on outcomes.

Methods: This study is an analysis of a prospective multicenter registry database in South Korea. Eligibility criteria were patients with ischemic stroke admitted within 7 days of stroke onset, lesions in either anterior or posterior circulation, and National Institutes of Health Stroke Scale score of ≤4 at baseline.

Different Antiplatelet Strategies in Patients With New Ischemic Stroke While Taking Aspirin.

Background And Purpose: Selecting among different antiplatelet strategies when patients experience a new ischemic stroke while taking aspirin is a common clinical challenge, currently addressed by a paucity of data.

Methods: This study is an analysis of a prospective multicenter stroke registry database from 14 hospitals in South Korea. Patients with acute noncardioembolic stroke, who were taking aspirin for prevention of ischemic events at the time of onset of stroke, were enrolled.

Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study.

Background And Purpose: The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment.

Reperfusion Times for Radial Versus Femoral Access in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Observations From the Cardiac Care Network Provincial Primary PCI Registry.

Background: Radial access is associated with less bleeding and vascular complications. However, it may delay reperfusion during primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.

Methods And Results: A provincial database prospectively collected clinical and procedural characteristics for all urgent percutaneous coronary intervention procedures performed between June 2010 and September 2011 in Ontario for ST-segment-elevation myocardial infarction, including time of arrival in the catheterization laboratory and time of first balloon inflation.

Clinical outcomes of treatment by percutaneous coronary intervention versus coronary artery bypass graft surgery in patients with chronic kidney disease undergoing index revascularization in Ontario.

Background: There is a paucity of data on the comparative effectiveness of percutaneous coronary intervention using contemporary drug-eluting stent (DES) compared with coronary artery bypass graft (CABG) surgery in patients with chronic kidney disease.

Methods And Results: A population-based study was performed using the Cardiac Care Network, a provincial registry of all patients undergoing cardiac catheterization in Ontario, to evaluate patients treated with either percutaneous coronary intervention using DES or CABG between October 1, 2008, and September 30, 2011. Chronic kidney disease was defined as creatinine clearance <60 mL/min.

Grading and interpretation of white matter hyperintensities using statistical maps.

Background And Purpose: We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke.

Methods: We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.

Gallic acid regulates body weight and glucose homeostasis through AMPK activation.

Gallic acid [3,4,5-trihydroxybenzoic acid (GA)], a natural phytochemical, is known to have a variety of cellular functions including beneficial effects on metabolic syndromes. However, the molecular mechanism by which GA exerts its beneficial effects is not known. Here we report that GA plays its role through the activation of AMP-activated protein kinase (AMPK) and by regulating mitochondrial function via the activation of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α).

Impact of system and physician factors on the detection of obstructive coronary disease with diagnostic angiography in stable ischemic heart disease.

Background: Wide variation exists in the detection rate of obstructive coronary artery disease (CAD) with elective coronary angiography for suspected stable ischemic heart disease. We sought to understand the incremental impact of nonclinical factors on this variation.

Methods And Results: We included all patients who underwent coronary angiography for possible suspected stable ischemic heart disease, from October 1, 2008, to September 30, 2011, in Ontario, Canada.

Practice patterns and trends in the use of medical therapy in patients undergoing percutaneous coronary intervention in Ontario.

Background: Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). However, the extent to which medical therapy is applied before and after percutaneous coronary intervention (PCI) in contemporary clinical practice is uncertain. We evaluated medication use for patients with stable CAD undergoing PCI, and assessed whether the COURAGE study altered medication use in the Canadian healthcare system.

Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification and vascular territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging.

Background: The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion-weighted imaging study may help resolve this lack of clarity.

Methods And Results: We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion-weighted imaging and who underwent a thorough etiological investigation.

The impact of acute kidney injury on the long-term risk of stroke.

Background: The incidence of acute kidney injury (AKI) requiring dialysis in hospitalized patients is increasing; however, information on the long-term incidence of stroke in patients surviving to discharge after recovering from AKI after dialysis has not been reported.

Methods And Results: Patients that survived after recovery from dialysis-requiring AKI during index hospitalizations from 1999 to 2008 were identified in nationwide administrative registries. The risk of de novo stroke and death were analyzed with time-varying Cox proportional hazard models.