Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort.

Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC.

Blood Pressure After Endovascular Thrombectomy and Outcomes in Patients With Acute Ischemic Stroke: An Individual Patient Data Meta-analysis.

Background And Objectives: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).

Methods: A study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model.

Novel Bruton's Tyrosine Kinase inhibitor remibrutinib: Drug-drug interaction potential as a victim of CYP3A4 inhibitors based on clinical data and PBPK modeling.

Remibrutinib, a novel oral Bruton's Tyrosine Kinase inhibitor (BTKi) is highly selective for BTK, potentially mitigating the side effects of other BTKis. Enzyme phenotyping identified CYP3A4 to be the predominant elimination pathway of remibrutinib. The impact of concomitant treatment with CYP3A4 inhibitors, grapefruit juice and ritonavir (RTV), was investigated in this study in combination with an intravenous microtracer approach.

Phenotypic characterization of two novel cell line models of castration-resistant prostate cancer.

Background: Resistance to androgen deprivation therapies is a major driver of mortality in advanced prostate cancer. Therefore, there is a need to develop new preclinical models that allow the investigation of resistance mechanisms and the assessment of drugs for the treatment of castration-resistant prostate cancer.

Methods: We generated two novel cell line models (LAPC4-CR and VCaP-CR) which were derived by passaging LAPC4 and VCaP cells in vivo and in vitro under castrate conditions.

Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others.

Background And Purpose: Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce.

Methods: Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders.

Patterns and Predictors of First-Line Taxane Use in Patients with Metastatic Triple-Negative Breast Cancer in US Clinical Practice.

We investigated first-line (1L) treatment patterns and predictors of taxane use to better understand the evolving metastatic triple-negative breast cancer (mTNBC) treatment landscape. This retrospective analysis of the Truven Health MarketScan® (Somers, NY, USA) Database included women with mTNBC who received 1L therapy within six months of diagnosis (January 2005-June 2015). Multivariate logistic regression models identified predictors of taxane use, adjusting for prognostic factors.

Comparison of Clinical and Biomechanical Outcomes of Small Incision Lenticule Extraction With 120- and 140-µm Cap Thickness.

Purpose: The purpose of this study was to compare the clinical outcomes and corneal biomechanical changes between 120-µm and 140-µm cap thickness after small incision lenticule extraction (SMILE).

Methods: This prospective study included 150 eyes (150 patients: 91 eyes in the 120-µm group, and 59 eyes in the 140-µm group) who underwent SMILE. Enhanced correction nomograms were applied for patients according to cap thickness.

Shifting landscapes of human MTHFR missense-variant effects.

Most rare clinical missense variants cannot currently be classified as pathogenic or benign. Deficiency in human 5,10-methylenetetrahydrofolate reductase (MTHFR), the most common inherited disorder of folate metabolism, is caused primarily by rare missense variants. Further complicating variant interpretation, variant impacts often depend on environment.

Impact of Anti-HER2 Treatments Combined With Atezolizumab on the Tumor Immune Microenvironment in Early or Metastatic Breast Cancer: Results From a Phase Ib Study.

Background: Despite advances, there continues to be unmet need in breast cancer. Combining anti-programmed death-ligand 1 (PD-L1) cancer immunotherapy atezolizumab with other targeted therapies may enhance T-cell-dependent cytolytic antitumor activity.

Methods: This open-label, phase Ib study evaluated the safety of atezolizumab-based combinations with antibody-dependent cellular cytotoxicity or antibody-drug conjugate (ADC) agents.

Age-Dependent Patient and Trauma Characteristics and Hospital Resource Requirements-Can Improvement Be Made? An Analysis from the German Trauma Registry.

The burden of geriatric trauma patients continues to rise in Western society. Injury patterns and outcomes differ from those seen in younger adults. Getting a better understanding of these differences helps medical staff to provide a better care for the elderly.

Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration.

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression.

Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. , , and mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD).

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Asymmetric opening of the homopentameric 5-HT serotonin receptor in lipid bilayers.

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout the nervous system. They have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. We report three structures of the Cys-loop 5-HT serotonin receptor (5HTR) reconstituted into saposin-based lipid bilayer discs: a symmetric and an asymmetric apo state, and an asymmetric agonist-bound state.

A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles.

Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults.

sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients.

Considerations for Antiplatelet Management of Carotid Stenting in the Setting of Mechanical Thrombectomy: A Delphi Consensus Statement.

Background And Purpose: There are only few data and lack of consensus regarding antiplatelet management for carotid stent placement in the setting of endovascular stroke treatment. We aimed to develop a consensus-based algorithm for antiplatelet management in acute ischemic stroke patients undergoing endovascular treatment and simultaneous emergent carotid stent placement.

Materials And Methods: We performed a literature search and a modified Delphi approach used Web-based questionnaires that were sent in several iterations to an international multidisciplinary panel of 19 neurointerventionalists from 7 countries.

Venetoclax-rituximab with or without bendamustine vs bendamustine-rituximab in relapsed/refractory follicular lymphoma.

This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C).

Use of Chest Imaging in the Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide.

The World Health Organization (WHO) undertook the development of a rapid guide on the use of chest imaging in the diagnosis and management of coronavirus disease 2019 (COVID-19). The rapid guide was developed over 2 months by using standard WHO processes, except for the use of "rapid reviews" and online meetings of the panel. The evidence review was supplemented by a survey of stakeholders regarding their views on the acceptability, feasibility, impact on equity, and resource use of the relevant chest imaging modalities (chest radiography, chest CT, and lung US).

Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using /-Deficient Mice.

Peroxisome proliferator-activated receptor (PPAR)β/δ is a member of the nuclear receptor superfamily of transcription factors, which plays fundamental roles in cell proliferation and differentiation, inflammation, adipogenesis, and energy homeostasis. Previous studies demonstrated a reduced choroidal neovascularization (CNV) in /-deficient mice. However, PPARβ/δ's role in physiological blood vessel formation and vessel remodeling in the retina has yet to be established.

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.

Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used.

The COMPASS Trial: Net Clinical Benefit of Low-Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients With Chronic Vascular Disease.

Background: Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome.