Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial.

Importance: Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor.

Objective: To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors.

Design, Setting, And Participants: The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017.

Dostarlimab, an anti-programmed death-1 monoclonal antibody, does not cause QT prolongation in patients with solid tumours: A concentration-QT analysis.

Aims: Patients with solid tumours were treated with the anti-PD-1 antibody dostarlimab in the Phase I GARNET trial. This study aimed to examine dostarlimab's effect on corrected QT (QTc) interval and the systemic concentration-QTc interval relationship.

Methods: In GARNET Part 2B, patients received 500 mg dostarlimab every 3 weeks (Q3W) for four cycles, then 1000 mg Q6W.

Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury.

Background And Purpose: Dysfunction of the blood-brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

Objective: Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB.

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial.

Background: Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284).

Materials And Methods: Here, we report an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1-4, then 1000 mg Q6W) until disease progression or unacceptable toxicity for > 2 years.

Six-Month Impairment in Cognition, Mental Health, and Physical Function Following COVID-19-Associated Respiratory Failure.

Unlabelled: To determine the prevalence and extent of impairments impacting health-related quality of life among survivors of COVID-19 who required mechanical ventilation, 6 months after hospital discharge.

Design: Multicenter, prospective cohort study, enrolling adults 18 years old or older with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received mechanical ventilation for 48 hours or more and survived to hospital discharge. Eligible patients were contacted 6 months after discharge for telephone-based interviews from March 2020 to December 2020.

Arterial Spin Labeling Reveals Elevated Cerebral Blood Flow with Distinct Clusters of Hypo- and Hyperperfusion after Traumatic Brain Injury.

Imaging detection of brain perfusion alterations after traumatic brain injury (TBI) may provide prognostic insights. In this study, we used arterial spin labeling (ASL) to quantify cross-sectional and longitudinal changes in cerebral blood flow (CBF) after TBI and correlated changes with clinical outcome. We analyzed magnetic resonance imaging scans from adult participants with TBI requiring hospitalization in the acute (2 weeks post-injury,  = 33) and chronic (6 months post-injury,  = 16) phases, with 13 participants scanned longitudinally at both time points.

Characteristics of Gun Advertisements on Social Media: Systematic Search and Content Analysis of Twitter and YouTube Posts.

Background: Although gun violence has been identified as a major public health concern, the scope and significance of internet gun advertising is not known.

Objective: This study aimed to quantify the characteristics of gun advertising on social media and to compare the reach of posts by manufacturers with those of influencers.

Methods: Using a systematic search, we created a database of recent and popular Twitter and YouTube posts made public by major firearm manufacturers and influencers.

Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial.

To evaluate, post hoc, the efficacy and safety of abaloparatide by degree of renal impairment. ACTIVE was a phase 3, 18-month, randomized, double-blind, active-comparator, placebo-controlled study of postmenopausal women with osteoporosis who received subcutaneous abaloparatide 80 µg, placebo, or open-label teriparatide 20 µg daily. Patients with serum creatinine >2.

Disc Degeneration in Unfused Caudal Motion Segments Ten Years Following Surgery for Adolescent Idiopathic Scoliosis.

Hypothesis: The frequency of disc degeneration (DD) in the distal mobile segments will increase over time following surgery for adolescent idiopathic scoliosis (AIS).

Design: Retrospective review of a prospective AIS registry.

Introduction: Durability of surgical outcomes is essential for maintenance of quality of life as well as for family decision making and for assessment of the value of a healthcare intervention.

Using realistic factors to simulate catastrophic congestion events in a network.

With the rapid growth of the Internet, there has been increased interest in the research literature in the use of computer models to study the dynamics of communication networks. An important example of this has been the study of dramatic, but relatively infrequent, events that result in abrupt, and often catastrophic, failures in the network due to congestion. These events are sometimes known as phase transitions.

Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms.

Aim: Pyrexia is a common adverse event (AE) on dabrafenib treatment (monotherapy or combination with trametinib). Since germline SNPs and HLA alleles are implicated in drug-induced AEs, this study investigated their association with pyrexia.

Patients & Methods: 1006 melanoma subjects from five dabrafenib-trametinib clinical studies underwent genotyping for genome-wide SNPs, which enabled imputation of 150 HLA alleles.

Bone mineral density changes following discontinuation of ronacaleret treatment: off-treatment extension of a randomized, dose-finding phase II trial.

Context: Parathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism.

Objective: The aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.

Ronacaleret, a calcium-sensing receptor antagonist, increases trabecular but not cortical bone in postmenopausal women.

Intermittent injections of parathyroid hormone have osteoanabolic effects that increase bone mineral density (BMD). Ronacaleret is an orally administered calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release from the parathyroid glands. Our objective was to compare the effects of ronacaleret and teriparatide on volumetric BMD (vBMD) measured by quantitative computed tomography (QCT).

Ronacaleret, a calcium-sensing receptor antagonist, has no significant effect on radial fracture healing time: results of a randomized, double-blinded, placebo-controlled Phase II clinical trial.

Background: Fractures cause significant morbidity, mortality, and use of health care resources. An oral agent that enhances fracture healing could reduce costs and prevent future disabilities. In Phase I studies, ronacaleret, a novel calcium-sensing receptor antagonist, stimulated parathyroid hormone (PTH) release and increased bone formation markers, suggesting that it may act as an effective oral anabolic agent to enhance fracture healing.

The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density.

Context: Ronacaleret, a calcium-sensing receptor antagonist that stimulates PTH release from the parathyroid glands, was evaluated as an oral osteoanabolic agent for the treatment of osteoporosis.

Objective: Our objective was to compare the effects of ronacaleret, teriparatide, and alendronate on bone mineral density (BMD) and markers of bone turnover.

Design And Setting: In this randomized, placebo-controlled, dose-ranging trial, spine and hip BMD were assessed by dual-energy x-ray absorptiometry and bone turnover markers were measured.

Comparison of radiographic joint space width with magnetic resonance imaging cartilage morphometry: analysis of longitudinal data from the Osteoarthritis Initiative.

Objective: Magnetic resonance imaging (MRI) and radiography are established imaging modalities for the assessment of knee osteoarthritis (OA). The objective of our study was to compare the responsiveness of radiographic joint space width (JSW) with MRI-derived measures of cartilage morphometry for OA progression in participants from the Osteoarthritis Initiative (OAI).

Methods: This study examined the baseline and 12-month visits of a subset of 150 subjects from the OAI.

Bone marrow lesions and joint effusion are strongly and independently associated with weight-bearing pain in knee osteoarthritis: data from the osteoarthritis initiative.

Objective: It is widely believed that there are multiple sources of pain at a tissue level in osteoarthritis (OA). Magnetic Resonance Images (MRIs) provide a wealth of anatomic information and may allow identification of specific features associated with pain. We hypothesized that in knees with OA, bone marrow lesions (BMLs), synovitis, and effusion would be associated with weight-bearing and (less so with) non-weight-bearing pain independently.

Solution structure of the bb' domains of human protein disulfide isomerase.

Protein disulfide isomerase is the most abundant and best studied of the disulfide isomerases that catalyze disulfide bond formation in the endoplasmic reticulum, yet the specifics of how it binds substrate have been elusive. Protein disulfide isomerase is composed of four thioredoxin-like domains (abb'a'). Cross-linking studies with radiolabeled peptides and unfolded proteins have shown that it binds incompletely folded proteins primarily via its third domain, b'.

Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative.

Objective: The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI).

Methods: Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study.

Longitudinal study of magnetic resonance imaging and standard X-rays to assess disease progression in osteoarthritis.

Objective: To investigate, over 1-year, the relationship between X-ray and magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis (OA).

Methods: Sixty-two osteoarthritic patients (46 women) were followed for 1 year. At baseline and after 1 year, volume and thickness of cartilage of the medial tibia, the lateral tibia and the femur were assessed by MRI.

Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study.

Objective: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis.

Methods: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed.