Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Pharmacokinetic and Exposure-Response Modeling Support Body Surface Area-Based Dosing of Farletuzumab Ecteribulin in Japanese Patients with Solid Tumors.

The first-in-human, Phase 1 Study 101 showed antitumor activity and a tolerable safety profile of farletuzumab ecteribulin in Japanese patients with platinum-resistant ovarian and non-small cell lung cancer. A pharmacometric assessment evaluated farletuzumab ecteribulin pharmacokinetics and exposure-response (E-R) relationships for efficacy and safety to support dose optimization. Patients received 0.

Treatment Patterns and Economic Burden of Ulcerative Colitis in Japan: A Retrospective Claims Analysis.

Introduction: This retrospective claims analysis characterized contemporary ulcerative colitis (UC) treatment patterns and investigated the economic burden of UC in Japan.

Methods: This study used anonymized claims data in the Medical Data Vision database. Patients were included if they had a confirmed UC diagnosis and ≥ 1 claim of systemic treatment for UC (index date) between June 2018 and December 2022, in addition to continuous enrollment for ≥ 6 months before and ≥ 12 months after the index date.

Treatment Utilisation and Satisfaction With Management in Individuals With Osteoarthritis and Metabolic Multimorbidity: A Cross-Sectional Multi-Country Study.

Purpose: To compare treatment utilisation for osteoarthritis (OA) and satisfaction with OA management between individuals with and without comorbid metabolic conditions (e.g., diabetes, obesity, dyslipidaemia, hypertension).

Capecitabine and temozolomide or temozolomide alone in patients with atypical carcinoids.

Background: Lung neuroendocrine neoplasms (NENs) represent about 20% of all lung cancers. Few therapeutic options are available for atypical carcinoids (ACs). Single-agent temozolomide (TEM) is active in lung NENs, but whether the addition of capecitabine (CAPTEM) is associated with improved outcomes, is unknown.

Patients with antiphospholipid antibodies preferentially seek health information from physicians: a cross-sectional online patient quantitative survey.

Little is known about how patients with antiphospholipid syndrome (APS) or antiphospholipid antibodies (aPL) access and trust health information. This research aimed to: describe the sources of information most frequently accessed/trusted by patients with APS/aPL; identify if individuals with APS/aPL perceived their health had been negatively impacted by various sources and document obstacles to accessing health information. Patients meeting Revised Sapporo Criteria for APS or with ≥1 positive aPL on ≥2 occasions were recruited to an online survey regarding their health information use at diagnosis and within 6 months preceding survey completion.

Favorable long-term cognitive outcomes following recurrent ARIA linked to amyloid-lowering therapies: two cases.

Introduction: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).

Methods: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT.

Background/objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology.

In Situ TEM Study of Electrical Property and Mechanical Deformation in MoS/Graphene Heterostructures.

We present a versatile method for synthesizing high-quality molybdenum disulfide (MoS) crystals on graphite foil edges via chemical vapor deposition (CVD). This results in MoS/graphene heterostructures with precise epitaxial layers and no rotational misalignment, eliminating the need for transfer processes and reducing contamination. Utilizing in situ transmission electron microscopy (TEM) equipped with a nano-manipulator and tungsten probe, we mechanically induce the folding, wrinkling, and tearing of freestanding MoS crystals, enabling the real-time observation of structural changes at high temporal and spatial resolutions.

A Canadian Perspective on Systemic Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma.

Although the majority of patients with nasopharyngeal carcinoma (NPC) present with early-stage or locoregional disease that can be treated with definitive radiotherapy, approximately 20% of patients experience disease recurrence, and 15% present with metastatic disease that is not amenable to curative therapy. Management of patients with recurrent or metastatic (r/m) NPC who are not candidates for local salvage therapy is challenging in Canada, as there is uncertainty in extrapolating evidence that is largely generated from Southeast China to non-endemic regions such as Canada. Currently, treatment options in Canada are limited to chemotherapy regimens that can only achieve short-term response and prolongation of survival.

IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies.

Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation.

The Immune Landscape and Its Potential for Immunotherapy in Advanced Biliary Tract Cancer.

Biliary tract cancers (BTC) are a highly heterogeneous group of cancers at the genomic, epigenetic and molecular levels. The vast majority of patients initially present at an advanced (unresectable) disease stage due to a lack of symptoms and an aggressive tumour biology. Chemotherapy has been the mainstay of treatment in patients with advanced BTC but the survival outcomes and prognosis remain poor.

Real-World Characterization of Toxicities and Medication Management in Recipients of CAR T-Cell Therapy for Relapsed or Refractory Large B-Cell Lymphoma in Nova Scotia, Canada.

Nova Scotia (NS) began offering CAR T-cell therapy as a third-line standard of care for eligible patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) in 2022. Recipients of CAR T-cell therapy often experience acute toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require close monitoring and prompt management. This retrospective review aimed to describe the characteristics of adult patients with r/r LBCL deemed eligible to receive CAR T-cell therapy with axicabtagene ciloleucel in NS between January 2022 and June 2024, the toxicities experienced and toxicity management, hospital visits and intensive care unit (ICU) admissions, the utilization of toxicity management guidelines, and general efficacy outcomes.

Fully automated coronary artery calcium score and risk categorization from chest CT using deep learning and multiorgan segmentation: A validation study from National Lung Screening Trial (NLST).

Background: The National Lung Screening Trial (NLST) has shown that screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. These patients are also at high risk of coronary artery disease, and we used deep learning model to automatically detect, quantify and perform risk categorisation of coronary artery calcification score (CACS) from non-ECG gated Chest CT scans.

Materials And Methods: Automated calcium quantification was performed using a neural network based on Mask regions with convolutional neural networks (R-CNN) for multiorgan segmentation.

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Dominant Occipital Sinus: A Rare Anatomical Variant With Potentially Catastrophic Consequences if Unrecognized Preoperatively.

The occipital sinus is often thought of as a redundant vestigial structure in adults. However, in rare cases, it can form the dominant route of intracerebral venous drainage, with a risk of significant surgical morbidity if unrecognised. We present an illustrative case describing this anatomical variant and tailoring of a midline suboccipital craniotomy to allow resection of a fourth ventricular epidermoid tumour with preservation of a dominant occipital sinus, and a review of the published literature.

Trochlear Morphological Changes in Skeletally Immature Patients Across Consecutive MRI Studies.

Background: Trochlear dysplasia is a consistent risk factor for recurrent patellofemoral instability (PFI), but there is limited understanding of how the trochlea develops during growth. The aim of this study was to evaluate serial magnetic resonance imaging (MRI) studies performed in skeletally immature patients with and without PFI to characterize changes in trochlear anatomy over time.

Hypothesis: PFI leads to progressive worsening of trochlear dysplasia over time.

Real-world use of tafasitamab preceding CD19-directed chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma.

Potential CD19 antigen loss following CD19-directed therapy has raised concerns over sequential use of these therapies. Tafasitamab, a CD19-targeting immunotherapy, combined with lenalidomide, is approved for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in adults ineligible for autologous stem cell transplantation. This retrospective analysis examined characteristics and outcomes of adults with R/R DLBCL who received tafasitamab preceding CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in a real-world setting.

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.

Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation.

Enhancing trauma triage in low-resource settings using machine learning: a performance comparison with the Kampala Trauma Score.

Background: Traumatic injuries are a leading cause of morbidity and mortality globally, with a disproportionate impact on populations in low- and middle-income countries (LMICs). The Kampala Trauma Score (KTS) is frequently used for triage in these settings, though its predictive accuracy remains under debate. This study evaluates the effectiveness of machine learning (ML) models in predicting triage decisions and compares their performance to the KTS.

Heart failure with preserved ejection fraction and atrial fibrillation: epidemiology, pathophysiology, and diagnosis interplay.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are increasingly prevalent cardiovascular conditions, particularly among the elderly population. These two conditions share common risk factors and often coexist, leading to a complex interplay that alters the clinical course of each other. The pathophysiology of HFpEF is multifaceted and intricately linked, with atrial disease serving as a common pathophysiological pathway.

Glucose Lowering through Weight management (GLoW): a randomised controlled trial of the clinical and cost effectiveness of a diabetes education and behavioural weight management programme vs a diabetes education programme in adults with a recent diagnosis of type 2 diabetes.

Aims/hypothesis: UK standard care for type 2 diabetes is structured diabetes education, with no effects on HbA, small, short-term effects on weight and low uptake. We evaluated whether remotely delivered tailored diabetes education combined with commercial behavioural weight management is cost-effective compared with current standard care in helping people with type 2 diabetes to lower their blood glucose, lose weight, achieve remission and improve cardiovascular risk factors.

Methods: We conducted a pragmatic, randomised, parallel two-group trial.