Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Patients With Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

Objective: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (JAK inhibitor) and elsubrutinib (BTK inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE).

Methods: Patients were randomized 1:1:1:1:1 to elsubrutinib 60 mg and upadacitinib 30 mg once daily (ABBV-599 high dose), elsubrutinib 60 mg and upadacitinib 15 mg once daily (ABBV-599 low dose), elsubrutinib 60 mg once daily (QD), upadacitinib 30 mg QD, or placebo QD. The primary endpoint was the proportion of patients achieving both Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and glucocorticoid dose ≤10 mg QD at week 24.

A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.

Purpose: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737.

Patients And Methods: Patients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16, and 17, and intravenous gemcitabine on days 1, 8, and 15.

A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance.

Thrombomodulin-expressing monocytes are associated with low-risk features in myelodysplastic syndromes and dampen excessive immune activation.

The bone marrow of patients with low-risk myelodysplastic syndromes (MDS) is often an inflammatory environment and associated with an active cellular immune response. An active immune response generally contributes to antitumor responses and may prevent disease progression. However, chronic immune stimulation can also induce cell stress, DNA damage and contribute to the pathogenesis of MDS.

Medium- to long-term outcomes of botulinum toxin A for idiopathic overactive bladder.

Botulinum toxin A (BoNT-A) has become an important therapeutic tool in the management of refractory overactive bladder (OAB). Over the last decade, there have been growing numbers of patients receiving repeat injections and these outcomes have begun to be reported in large, high-quality cohorts. This article reviews the current evidence for the medium- to long-term use of BoNT-A in adults with idiopathic detrusor overactivity (IDO) receiving repeat injections.

The B3 conundrum-the radiologists' perspective.

The management of B3 lesions is both controversial and complicated. There have been recent publications regarding how best to manage this heterogeneous group particularly in light of the Marmot Review and with the advent of vacuum-assisted biopsy technique. It is recognized that B3 lesions on core biopsy can be upgraded to malignancy in up to one-third of cases, but this is predominantly to ductal carcinoma in situ or low-grade invasive tumours.

Optimising Translational Research Opportunities: A Systematic Review and Narrative Synthesis of Basic and Clinician Scientists' Perspectives of Factors Which Enable or Hinder Translational Research.

Introduction: Translational research is central to international health policy, research and funding initiatives. Despite increasing use of the term, the translation of basic science discoveries into clinical practice is not straightforward. This systematic search and narrative synthesis aimed to examine factors enabling or hindering translational research from the perspective of basic and clinician scientists, a key stakeholder group in translational research, and to draw policy-relevant implications for organisations seeking to optimise translational research opportunities.

Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry.

Objective: Genome-wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci.

BiP, a putative autoantigen in rheumatoid arthritis, stimulates IL-10-producing CD8-positive T cells from normal individuals.

Objectives: We have reported that synovial fluid T cells from patients with rheumatoid arthritis (RA) proliferate in response to the endoplasmic reticulum molecular chaperone immunoglobulin binding protein (BiP). The aim of the present work was to clone and define T cells responding to this protein.

Methods: T-cell clones were generated from the peripheral blood of an individual known to respond to BiP by limiting dilution of BiP-stimulated peripheral blood mononuclear cells.