Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Axial spondyloarthritis.

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints).

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study.

Background: Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Phase-specific changes in hip joint loading during gait following sacroiliac joint fusion: Findings from a finite element analysis.

Background: Low back pain affects over 80 % of adults, with sacroiliac joint dysfunction accounting for 15-30 % of these cases. Sacroiliac fusion is a surgical procedure for refractory joint pain. While the biomechanics of the joint and its fusion relative to the spinal column are well-known, the hip-spine relationship post-fusion remains unclear.

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Accelerative Effects of Transcutaneous Electrical Acustimulation on Postoperative Recovery After Thoracolumbar Vertebral Fracture Associated With Suppressed Sympathetic Activity and Interleukin-6.

Objectives: Gastrointestinal (GI) disturbance is a frequent complication in patients with thoracolumbar vertebral fracture (TVF). Transcutaneous electrical acustimulation (TEA) has been reported to effectively accelerate postoperative GI function recovery after abdominal surgery. This study aimed to investigate the effects of TEA on postoperative recovery and the associated mechanisms.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Variations in Revascularization Strategies for Chronic Limb-Threatening Ischemia: A Nationwide Analysis of Medicare Beneficiaries.

Background: Recent data support both surgical-first and endovascular-first revascularization approaches for chronic limb-threatening ischemia (CLTI), but hospital-based practices are poorly described.

Objectives: This aim of this study was to characterize contemporary variations and outcomes associated with each strategy among U.S.

The Role of Exosomes in Medical Dermatology: Literature Review and Update.

Background: Exosomes are extracellular vesicles, composed of a phospholipid bilayer, that are primarily derived from stem cells. The contents of exosomes can be incorporated into the tissue in which they are introduced, which presents a unique therapeutic option.

Aims: Exosomes have been investigated as a treatment for a number of medical ailments, but the literature supporting these indications is inconclusive.

Learning from Other Tumors: Pathways for Progress and Overcoming Challenges in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a group of complex and heterogeneous tumors originating from the epithelial cells of bile ducts that can occur in intrahepatic, perihilar, or distal localizations [...

Preclinical Models for Functional Precision Lung Cancer Research.

Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody-drug conjugates, and emerging investigational treatments.

S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.

S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer.

Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.

Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms.

Three monoclonal antibodies directed against specific forms of the amyloid-β (Aβ) peptide have been granted accelerated or traditional approval by the FDA as treatments for Alzheimer disease, representing the first step towards bringing disease-modifying treatments for this disease into clinical practice. Here, we review the detection, underlying pathophysiological mechanisms and clinical implications of amyloid-related imaging abnormalities (ARIA), the most impactful adverse effect of anti-Aβ immunotherapy. ARIA appears as regions of oedema or effusions (ARIA-E) in brain parenchyma or sulci or as haemorrhagic lesions (ARIA-H) in the form of cerebral microbleeds, convexity subarachnoid haemorrhage, cortical superficial siderosis or intracerebral haemorrhage.

Presentation and Management of Silicone Lymphadenopathy: A Single Institutional Retrospective Cohort Study.

Introduction: Silicone Lymphadenopathy (SL) is a complication of breast implants that involves migration of silicone to nearby soft tissue/lymph nodes. Data on its clinical features and management is scarce. We aimed to identify the clinical presentation and management of SL.

The genomic architecture of circulating cytokine levels points to drug targets for immune-related diseases.

Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals.

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial.

We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics.

BK Polyomavirus-associated nephropathy - diagnostic and treatment standard.

BK polyomavirus (BKPyV) is recognised as a significant viral complication of kidney transplantation. Prompt immunosuppression reduction reduces early graft failure rates due to BK polyomavirus-associated nephropathy (BKPyVAN), however modulation of immunosuppression can lead to acute rejection. Medium-to-long term graft outcomes are negatively impacted by BKPyVAN, likely due to a combination of virus-induced graft damage and host immune responses against graft alloantigens potentiated by immunosuppression reduction.

The genetic architecture of differentiating behavioral and emotional problems in early life.

Background: Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.

Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background And Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected.