Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.

In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

Background: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.

Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

Background: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot.

Shift Volume Directly Impacts Neuroradiology Error Rate at a Large Academic Medical Center: The Case for Volume Limits.

Background And Purpose: Unlike in Europe and Japan, guidelines or recommendations from specialized radiological societies on workflow management and adaptive intervention to reduce error rates are currently lacking in the United States. This study of neuroradiologic reads at a large US academic medical center, which may hopefully contribute to this discussion, found a direct relationship between error rate and shift volume.

Materials And Methods: CT and MR imaging reports from our institution's Neuroradiology Quality Assurance database (years 2014-2020) were searched for attending physician errors.

A family of oxychloride amorphous solid electrolytes for long-cycling all-solid-state lithium batteries.

Solid electrolyte is vital to ensure all-solid-state batteries with improved safety, long cyclability, and feasibility at different temperatures. Herein, we report a new family of amorphous solid electrolytes, xLiO-MCl (M = Ta or Hf, 0.8 ≤ x ≤ 2, y = 5 or 4).

High-Entropy Spinel Ferrites with Broadband Wave Absorption Synthesized by Simple Solid-Phase Reaction.

In this work, high-entropy (HE) spinel ferrites of (FeCoNiCrM)O (M = Zn, Cu, and Mn) (named as HEO-Zn, HEO-Cu, and HEO-Mn, respectively) were synthesized by a simple solid-phase reaction. The as-prepared ferrite powders possess a uniform distribution of chemical components and homogeneous three-dimensional (3D) porous structures, which have a pore size ranging from tens to hundreds of nanometers. All three HE spinel ferrites exhibited ultrahigh structural thermostability at high temperatures even up to 800 °C.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer.

Background: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study.

Methods: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles.

Survival with Cemiplimab in Recurrent Cervical Cancer.

Background: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population.

Methods: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status.

A population-specific reference panel for improved genotype imputation in African Americans.

There is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME).

GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease.

Biochemical, pathogenic, and human genetic data confirm that GSAP (γ-secretase activating protein), a selective γ-secretase modulatory protein, plays important roles in Alzheimer's disease (AD) and Down's syndrome. However, the molecular mechanism(s) underlying GSAP-dependent pathogenesis remains largely elusive. Here, through unbiased proteomics and single-nuclei RNAseq, we identified that GSAP regulates multiple biological pathways, including protein phosphorylation, trafficking, lipid metabolism, and mitochondrial function.

Yet Another Automated Gleason Grading System (YAAGGS) by weakly supervised deep learning.

The Gleason score contributes significantly in predicting prostate cancer outcomes and selecting the appropriate treatment option, which is affected by well-known inter-observer variations. We present a novel deep learning-based automated Gleason grading system that does not require extensive region-level manual annotations by experts and/or complex algorithms for the automatic generation of region-level annotations. A total of 6664 and 936 prostate needle biopsy single-core slides (689 and 99 cases) from two institutions were used for system discovery and validation, respectively.

Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants.

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.

Newly Diagnosed Leptospirosis and Subsequent Hemorrhagic Stroke: A Nationwide Population-Based Cohort Study.

Background And Purpose: Preceding infection as an important risk factor for ischemic stroke has been reported but neglected for hemorrhagic stroke, especially in young and middle-aged patients. This study investigates whether newly diagnosed leptospirosis is associated with an increased risk of stroke.

Methods: We identified 3699 in-patients who were aged ≥18 years and newly diagnosed with leptospirosis.

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease.

Background: Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate-restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats.

Objectives: To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate-restricted diet and to explore its role in CKD-mineral and bone disorder (CKD-MBD) in cats.

Exercise Capacity and Ventricular Remodeling After Transcatheter Ventricular Septal Defect Closure in Asymptomatic or Minimally Symptomatic Adolescents and Adults.

Background: Transcatheter ventricular septal defect (VSD) closure is a safe and efficacious alternative to surgery. However, its benefits in asymptomatic or minimally symptomatic patients remain unknown.

Methods: Sixty patients with VSD aged 12 to 60 years underwent cardiopulmonary exercise test and echocardiography 1 day before transcatheter VSD closure and 6 months after intervention (closure group).

Tepotinib in Non-Small-Cell Lung Cancer with Exon 14 Skipping Mutations.

Background: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.

Methods: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed exon 14 skipping mutation.

Major Radiologic and Clinical Outcomes of Total Spine MRI Performed in the Emergency Department at a Major Academic Medical Center.

Background And Purpose: Total spine MRIs are requested by the emergency department when focused imaging can not be ordered on the basis of history or clinical findings. However, their efficacy is not known. We assessed the following: 1) major radiologic and clinical outcomes of total spine MR imaging performed by the emergency department, and 2) whether the presence of a high-risk clinical profile and/or neurologic findings impacts the clinical outcomes.

Automated Gleason Scoring and Tumor Quantification in Prostate Core Needle Biopsy Images Using Deep Neural Networks and Its Comparison with Pathologist-Based Assessment.

The Gleason grading system, currently the most powerful prognostic predictor of prostate cancer, is based solely on the tumor's histological architecture and has high inter-observer variability. We propose an automated Gleason scoring system based on deep neural networks for diagnosis of prostate core needle biopsy samples. To verify its efficacy, the system was trained using 1133 cases of prostate core needle biopsy samples and validated on 700 cases.