Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN.

The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease.

Positive Fecal Immunochemical Test Strongly Predicts Adenomas in Younger Adults With Fatty Liver and Metabolic Syndrome.

Introduction: The incidence of early-onset colorectal cancer is increasing. This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults.

Methods: This single-center study included 6,457 participants who underwent health examination from 2013 to 2016 including index colonoscopy (3,307 individuals aged 30-49 years as the younger adult group and 3,150 aged ≥50 years as the average-risk group).

Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death.

Objective: To evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).

Methods: We used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017.

Direct control of CAR T cells through small molecule-regulated antibodies.

Antibody-based therapeutics have experienced a rapid growth in recent years and are now utilized in various modalities spanning from conventional antibodies, antibody-drug conjugates, bispecific antibodies to chimeric antigen receptor (CAR) T cells. Many next generation antibody therapeutics achieve enhanced potency but often increase the risk of adverse events. Antibody scaffolds capable of exhibiting inducible affinities could reduce the risk of adverse events by enabling a transient suspension of antibody activity.

In vivo cytidine base editing of hepatocytes without detectable off-target mutations in RNA and DNA.

Base editors are RNA-programmable deaminases that enable precise single-base conversions in genomic DNA. However, off-target activity is a concern in the potential use of base editors to treat genetic diseases. Here, we report unbiased analyses of transcriptome-wide and genome-wide off-target modifications effected by cytidine base editors in the liver of mice with phenylketonuria.

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.

Search for dark matter produced in association with a leptonically decaying boson in proton-proton collisions at .

A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 . The search uses the decay channels and .

Search for top squark pair production using dilepton final states in collision data collected at .

A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from quarks, and missing transverse momentum. The search uses data from proton-proton collisions at collected with the CMS detector, corresponding to an integrated luminosity of 137 . Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables.

Measurement of single-diffractive dijet production in proton-proton collisions at with the CMS and TOTEM experiments.

Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss and the four-momentum transfer squared . Both processes and , i.e.

Automated feature quantification of Lipiodol as imaging biomarker to predict therapeutic efficacy of conventional transarterial chemoembolization of liver cancer.

Conventional transarterial chemoembolization (cTACE) is a guideline-approved image-guided therapy option for liver cancer using the radiopaque drug-carrier and micro-embolic agent Lipiodol, which has been previously established as an imaging biomarker for tumor response. To establish automated quantitative and pattern-based image analysis techniques of Lipiodol deposition on 24 h post-cTACE CT as biomarker for treatment response. The density of Lipiodol deposits in 65 liver lesions was automatically quantified using Hounsfield Unit thresholds.

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients.

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome).

In Vitro Characterization of Ertugliflozin Metabolism by UDP-Glucuronosyltransferase and Cytochrome P450 Enzymes.

Ertugliflozin is primarily cleared through UDP-glucurosyltransferase (UGT)-mediated metabolism (86%) with minor oxidative clearance (12%). In vitro phenotyping involved enzyme kinetic characterization of UGTs or cytochrome P450 enzymes catalyzing formation of the major 3---glucuronide (M5c) and minor 2---glucuronide (M5a), monohydroxylated ertugliflozin (M1 and M3), and des-ethyl ertugliflozin (M2) metabolites in human liver microsomes (HLMs). Fractional clearance (f) from HLM intrinsic clearance (CL) indicated a major role for glucuronidation (f 0.

Phytochemical Investigation and Anti-Inflammatory Activity of the Leaves of var. .

In a series of anti-inflammatory screenings of lauraceous plants, the methanolic extract of the leaves of var. (Hayata) J.C.

Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy.

Objective: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI.

Methods: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified.

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters.

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters and nonhuman primates have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals.

National trends in incidence, mortality, hospitalizations, and expenditures for pemphigus in Taiwan.

Background: Data on trends in epidemiological characteristics and economic burden of pemphigus are scarce.

Objective: To describe national trends in pemphigus' incidence, mortality, hospitalizations, and expenditures between 2003 and 2015 in Taiwan.

Methods: This nationwide study used the Taiwan National Health Insurance Research Database to identify pemphigus patients from 2003 to 2015.

Search for physics beyond the standard model in events with jets and two same-sign or at least three charged leptons in proton-proton collisions at .

A data sample of events from proton-proton collisions with at least two jets, and two isolated same-sign or three or more charged leptons, is studied in a search for signatures of new physics phenomena. The data correspond to an integrated luminosity of at a center-of-mass energy of , collected in 2016-2018 by the CMS experiment at the LHC. The search is performed using a total of 168 signal regions defined using several kinematic variables.

Study of central exclusive production in proton-proton collisions at and 13TeV.

Central exclusive and semiexclusive production of pairs is measured with the CMS detector in proton-proton collisions at the LHC at center-of-mass energies of 5.02 and 13TeV. The theoretical description of these nonperturbative processes, which have not yet been measured in detail at the LHC, poses a significant challenge to models.

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice.

Predicting Incomplete Resection in Non-Small Cell Lung Cancer Preoperatively: A Validated Nomogram.

Background: Patients who are surgically treated for stage I to III non-small cell lung cancer (NSCLC) have dismal prognosis after incomplete (R1-R2) resection. Our study aimed to develop a prediction model to estimate the chance of incomplete resection based on preoperative patient-, tumor-, and treatment-related factors.

Methods: From a Dutch national cancer database, NSCLC patients who had surgical treatment without neoadjuvant therapy were selected.

Contemporary management of chronic indwelling inferior vena cava filters.

Objective: Despite increasing retrieval rates of the inferior vena cava (IVC) filter, less than one-third are removed within the recommended timeline. Prolonged filter dwell times may increase the technical difficulty of retrieval and filter-related complications. We sought to evaluate the contemporary outcomes of patients with chronic indwelling IVC filters at a tertiary care center.