Incorporating immune checkpoint inhibitors in epithelial ovarian cancer.

Objective: Therapeutic interventions for epithelial ovarian cancer (EOC) have increased greatly over the last decade but improvements outside of biomarker selected therapies have been limited. There remains a pressing need for more effective treatment options that can prolong survival and enhance the quality of life of patients with EOC. In contrast to the significant benefits of immunotherapy with immune checkpoint inhibitors (CPI) seen in many solid tumors, initial experience in EOC suggests limited efficacy of CPIs monotherapy.

Targeted therapies and molecular targets in the therapeutic landscape of advanced urothelial carcinoma: state of the art and future perspectives.

Advanced urothelial carcinoma (aUC) has a dismal prognosis, with a 5-year survival rate of approximately 10%. Platinum-based chemotherapy has been the backbone of the first-line treatment of aUC for over 40 years. Only in the last decade, the treatment of aUC has evolved and been enriched with new classes of drugs that demonstrated pivotal improvements in terms of oncological responses and, ultimately, survival.

Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment.

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

Tax1bp1 enhances bacterial virulence and promotes inflammatory responses during infection of alveolar macrophages.

Crosstalk between autophagy, host cell death, and inflammatory host responses to bacterial pathogens enables effective innate immune responses that limit bacterial growth while minimizing coincidental host damage. () thwarts innate immune defense mechanisms in alveolar macrophages (AMs) during the initial stages of infection and in recruited bone marrow-derived cells during later stages of infection. However, how protective inflammatory responses are achieved during infection and the variation of the response in different macrophage subtypes remain obscure.

Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic form of heart failure that affects 1 in 5000 people globally and is caused by mutations in cardiac desmosomal proteins including , and . Individuals with ACM suffer from ventricular arrhythmias, sudden cardiac death, and heart failure. There are few effective treatments and heart transplantation remains the best option for many affected individuals.

Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state.

Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure-function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-mortem ocular tissue for basic research is rising in the glaucoma field, yet there are challenges in assessing disease stage and severity, since tissue donations with informed consent are often unaccompanied by detailed pre-mortem clinical information. Further, the interpretation of disease severity based solely on anatomical and morphological assessments by histology can be affected by differences in death-to-preservation time and tissue processing.

Basic Considerations for the Consistency Evaluation Based on ICH E17 Guideline.

In the International Council for Harmonisation (ICH) guidance on General Principles for Planning and Design of Multi-Regional Clinical Trials (E17), it is important to evaluate the consistency of treatment effect across regions in a multi-regional clinical trial (MRCT). In this paper, we elaborated on some basic considerations to evaluate consistency. We first list the design considerations, and then provide consistency evaluation and interpretation on pharmacokinetics, pharmacodynamics, efficacy, safety, and benefit-risk.

Fragment-to-Lead Medicinal Chemistry Publications in 2023.

This Perspective summarizes successful fragment-to-lead (F2L) studies that were published in 2023 and is the ninth installment in an annual series. A tabulated summary of the relevant articles published in 2023 is provided (17 entries from 16 articles), and a comparison of the target classes, screening methods, and overall fragment or lead property trends for 2023 examples and for the combined entries over the years 2015-2023 is discussed. In addition, we identify several trends and innovations in the 2023 literature that promise to further increase the success of fragment-based drug discovery (FBDD), particularly in the areas of NMR and virtual screening, fragment library design, and fragment linking.

Telomere-based risk models for the early diagnosis of lung cancer.

Background: The objective of this study was to evaluate the use of telomere length measurements as diagnostic biomarkers during early screening for lung cancer in high-risk patients.

Methods: This was a prospective study of patients undergoing lung cancer diagnosis at two Spanish hospitals between April 2017 and January 2020. Telomeres from peripheral blood lymphocytes were analysed by Telomere Analysis Technology, which is based in high-throughput quantitative fluorescent in situ hybridization.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.

Disparities in Utilization of Immune Checkpoint Inhibitor Therapy Among Older Patients With Advanced Non-Small Cell Lung Cancer: A SEER-Medicare Analysis.

Purpose: In the United States, there are disparities in access to care for patients with non-small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC).

Methods: This retrospective study used data from the SEER-Medicare-linked database.

Real-World Persistence and Effectiveness of Upadacitinib versus Other Janus Kinase Inhibitors and Tumor Necrosis Factor Inhibitors in Australian Patients with Rheumatoid Arthritis.

Introduction: This study sought to describe treatment patterns, persistence, and effectiveness of upadacitinib (UPA) alone and compared to other Janus kinase inhibitors (JAKis) or tumor necrosis factor inhibitors (TNFis) in patients with rheumatoid arthritis (RA).

Methods: This retrospective, non-interventional study used the OPAL dataset, derived from electronic medical records. Patients initiated UPA (N = 2624), other JAKis (baricitinib and tofacitinib [N = 925]), or TNFis (adalimumab, etanercept, certolizumab, golimumab, infliximab [N = 3540]) between May 2020 and March 2023.

Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression.

Introduction: Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Material And Methods: Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries.

Costs of Oral Corticosteroid Use in Patients with Severe Asthma With/Without Chronic Rhinosinusitis with Nasal Polyps: Data from the Italian SANI Registry.

Introduction: The burden of severe asthma on patients, especially on those with concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), is substantial. Treatment intensification with oral corticosteroids is a common strategy for managing severe asthma exacerbations; however, prolonged exposure to systemic corticosteroids is associated with multisystem toxicity. This study aimed to quantify the association between oral corticosteroid use and annual asthma-related costs in patients with severe asthma with or without CRSwNP.

Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.

Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

Detection of H3F3A K27M or BRAF V600E in liquid biopsies of brain tumor patients as diagnostic and monitoring biomarker: impact of tumor localization and sampling method.

Gliomas are the most common brain tumor type in children and adolescents. To date, diagnosis and therapy monitoring for these tumors rely on magnetic resonance imaging (MRI) and histopathological as well as molecular analyses of tumor tissue. Recently, liquid biopsies (LB) have emerged as promising tool for diagnosis and longitudinal tumor assessment potentially allowing for a more precise therapeutic management.

Effects of sex on imaging-based intravenous thrombolysis for ischaemic stroke with unknown onset time: a pooled analysis of clinical trials.

Introduction: The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex.

Patients And Methods: This study was a pooled analysis of individual patient-level data acquired from the Evaluation of unknown Onset Stroke thrombolysis trials.

Influence of next-generation artificial intelligence on headache research, diagnosis and treatment: the junior editorial board members' vision - part 2.

Part 2 explores the transformative potential of artificial intelligence (AI) in addressing the complexities of headache disorders through innovative approaches, including digital twin models, wearable healthcare technologies and biosensors, and AI-driven drug discovery. Digital twins, as dynamic digital representations of patients, offer opportunities for personalized headache management by integrating diverse datasets such as neuroimaging, multiomics, and wearable sensor data to advance headache research, optimize treatment, and enable virtual trials. In addition, AI-driven wearable devices equipped with next-generation biosensors combined with multi-agent chatbots could enable real-time physiological and biochemical monitoring, diagnosing, facilitating early headache attack forecasting and prevention, disease tracking, and personalized interventions.