Neighborhood-level Social Determinants of Health Improve Prediction of Preventable Hospitalization and Emergency Department Visits Beyond Claims History.

This study was conducted to assess if neighborhood-level social determinants of health improve model performance of predicting preventable hospitalization. Using medical and pharmacy claims and neighborhood-level social determinants and the split sample method (67% training with balanced sample and 33% validation), the authors developed prospective modeling for preventable hospital use, defined as hospitalization for ambulatory care sensitive conditions (Agency for Healthcare Research and Quality Prevention Quality Indicators 90 and 92) and preventable emergency department (ED) use (based on Billing's algorithm). Performance of age-gender only or age-gender with administrative claims models were compared to models with the addition of social determinants.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis.

Incorporating cytologic adequacy assessment into precision oncology workflow using telepathology: An institutional experience.

Background: Tumor sample quality and quantity determine the success of somatic mutation analysis. Thus, a rapid on-site evaluation (ROSE) tumor cytology adequacy assessment was incorporated into the workflow of precision oncology at Weill Cornell Medicine in New York City. Optimal samples were obtained from 68 patients with metastatic cancer.

Posterior lamellar keratoplasty: techniques, outcomes, and recent advances.

Over the past 2 decades, posterior lamellar keratoplasty (PLK) has emerged as an alternative to penetrating keratoplasty in the treatment of corneal endothelial disorders. The reasons for this trend include the search for a safer procedure to replace diseased endothelium that provides faster and better visual rehabilitation and reduces the need for postoperative care. Different surgical techniques, surgical instruments, devices, and lasers have been introduced to overcome technical difficulties, thus improving clinical outcomes.

Recovery in glioblastoma multiforme during inpatient rehabilitation is equivalent in first versus repeat resection: A 10-year retrospective analysis.

Background: Inpatient rehabilitation improves function in people with brain tumors, including glioblastoma multiforme (GBM) but there are limited data on the impact of multiple resections on outcomes. We hypothesize that outcomes will be more favorable for those patients with a single resection when compared to those with more than one resection.

Objective: To examine functional outcomes in inpatient rehabilitation for people with GBM who underwent one or more resections prior to admission.

Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification.

Neural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses.

Prior Oral Contraceptive Use and Longer Term Mortality Outcomes in Women with Suspected Ischemic Heart Disease.

Previous Women's Ischemia Syndrome Evaluation (WISE) work demonstrated prior oral contraceptive (OC) use was associated with lower coronary artery disease (CAD) in women with suspected ischemia. The association of prior OC use with longer term all-cause and cardiovascular disease (CVD) mortality is unclear. WISE women undergoing coronary angiography for suspected ischemia (enrolled 1996-2001) with prior OC use history and 10-year follow-up data were analyzed.

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.

Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle.

Vanucizumab mode of action: Serial biomarkers in plasma, tumor, and skin-wound-healing biopsies.

Vanucizumab is a novel bispecific antibody inhibiting vascular endothelial growth factor (VEGF-A) and angiopoietin-2 (Ang-2) that demonstrated safety and anti-tumor activity in part I of a phase I study of 42 patients with advanced solid tumors. Part II evaluated the pharmacodynamic effects of vanucizumab 30 or 15 mg/kg every 2 weeks in 32 patients. Serial plasma samples, paired tumor, and skin-wound-healing biopsies were taken over 29 days to evaluate angiogenic markers.

Safety and efficacy of navitoclax, a BCL-2 and BCL-X inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study.

Navitoclax, a novel BCL-2 and BCL-X inhibitor, demonstrated promising antitumor activity in the dose-escalation part of a phase 1/2a study (NCT00406809) in lymphoid tumors. Herein, we report the continued safety and efficacy results of the phase 2a portion. Twenty-six adult patients with relapsed/refractory follicular lymphoma ( = 11, Arm A) and other relapsed/refractory lymphoid malignancies ( = 15, Arm B) were enrolled.

PCORnet® 2020: current state, accomplishments, and future directions.

Objective: To describe PCORnet, a clinical research network developed for patient-centered outcomes research on a national scale.

Study Design And Setting: Descriptive study of the current state and future directions for PCORnet. We conducted cross-sectional analyses of the health systems and patient populations of the 9 Clinical Research Networks and 2 Health Plan Research Networks that are part of PCORnet.

Antifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic Stability.

The glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum dosing achievable in a neutropenic rabbit model.

Potential impact of dynamic automated CT aortic annular measurements on outcomes for transcatheter aortic valve replacement sizing.

To determine the potential impact of automated computed tomography (CT) software used for aortic annular sizing for transcatheter aortic valve replacement (TAVR) on paravalvular leak (PVL) and major adverse cardiovascular events (MACE) as compared to standard CT manual measurement. In 60 TAVR patients (84 ± 7 years, 60% male), we evaluated the preprocedural CT scans. For the standard manual measurement, we measured the perimeter and area from a single cardiac phase deemed to be of maximum systolic opening.

Even "WISE-R?"-an Update on the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation.

Purpose Of Review: For over 20 years, the Women's Ischemia Syndrome Evaluation (WISE), a program sponsored by the National Heart, Lung, and Blood Institute, has explored diverse and important aspects of ischemic heart disease in women.

Recent Findings: Women with symptoms and signs of ischemia but no significant epicardial obstructive coronary artery disease (INOCA) were documented to be at elevated risk for recurrent angina hospitalization, major adverse cardiac events, death, and health resource consumption rivaling those with obstructive coronary disease. WISE investigators have advanced our understanding of cardiovascular outcomes, systemic manifestations, psychological variables, socioeconomic factors, genetic contributions, hormonal status, advanced imaging, coronary functional findings, biomarkers, patient-reported outcomes, and treatments pertaining to women with this disease entity.

Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection.

The pathogenesis of viral infections involves an immune response by cytokines, causing a deleterious effect on organ function, in addition to tissue destruction due to viral replication. Clinical symptoms and laboratory findings of the human coronavirus disease COVID-19, caused by the novel coronavirus SARS CoV-2, indicate cytokine involvement. Our laboratory showed that an experimental murine coronavirus (MHV-A59) can be transmitted into the brain by intranasal or intracerebral exposure and that neurovirulence is mediated by cytokine secretion.

Adenomyoepithelial tumors of the breast: molecular underpinnings of a rare entity.

Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs.

Discovery and Structure-Activity Relationship Study of ()-5-Methylenethiazolidin-4-one Derivatives as Potent and Selective Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors.

Due to their role in many important signaling pathways, phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive targets for the development of experimental therapeutics for cancer, metabolic, and immunological disorders. Recent efforts to develop small molecule inhibitors for these lipid kinases resulted in compounds with low- to sub-micromolar potencies. Here, we report the identification of CVM-05-002 using a high-throughput screen of PI5P4Kα against our in-house kinase inhibitor library.

Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid.

The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells.

Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are important molecular players in a variety of diseases, such as cancer. Currently available PI5P4K inhibitors are reversible small molecules, which may lack selectivity and sufficient cellular on-target activity. In this study, we present a new class of covalent pan-PI5P4K inhibitors with potent biochemical and cellular activity.

Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors.

The PI5P4Ks have been demonstrated to be important for cancer cell proliferation and other diseases. However, the therapeutic potential of targeting these kinases is understudied due to a lack of potent, specific small molecules available. Here, we present the discovery and characterization of a pan-PI5P4K inhibitor, THZ-P1-2, that covalently targets cysteines on a disordered loop in PI5P4Kα/β/γ.

Accelerating the future of cardiac CT: Social media as sine qua non?

The vision for the Journal of Cardiovascular Computed Tomography's social media efforts is to amplify the impact of the Journal while driving engagement, increasing journal visibility and disseminating content to new audiences globally. Serving as "the front door" to the Journal, this digital evolution represents an important step forward for a field in which advancements in hardware, image processing and clinical evidence have evolved rapidly. However, is social media the panem et circenses of cardiovascular computed tomography (CT), that of superficial appeasement, or of sine qua non; an essential ingredient to the acceleration of the Journal and of the field of cardiovascular CT? This paper aims to present the initial impact of social media within a dedicated cardiovascular CT journal.

Tisagenlecleucel cellular kinetics, dose, and immunogenicity in relation to clinical factors in relapsed/refractory DLBCL.

The anti-CD19 chimeric antigen receptor (CAR)-T cell therapy tisagenlecleucel was evaluated in the global, phase 2 JULIET study in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We correlated tisagenlecleucel cellular kinetics with clinical/product parameters in 111 patients treated in JULIET. Tisagenlecleucel persistence in responders and nonresponders, respectively, was demonstrated for 554 and 400 days maximum by flow cytometry and for 693 and 374 days maximum by quantitative polymerase chain reaction (qPCR).

Breakthrough Bloodstream Infections Caused by Echinocandin-Resistant : An Emerging Threat to Immunocompromised Patients with Hematological Malignancies.

Background: is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of carries potentially ominous therapeutic implications.

Methods: We describe herein two patients with breakthrough fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant bloodstream infections (BSIs) and other diseases.