Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Homologous recombination deficiency in ovarian cancer: Global expert consensus on testing and a comparison of companion diagnostics.

Background: Poly (ADP ribose) polymerase inhibitors (PARPis) are a treatment option for patients with advanced high-grade serous or endometrioid ovarian carcinoma (OC). Recent guidelines have clarified how homologous recombination deficiency (HRD) may influence treatment decision-making in this setting. As a result, numerous companion diagnostic assays (CDx) have been developed to identify HRD.

Hydrogel-antimicrobial peptide association: A novel and promising strategy to combat resistant infections.

Infections from multi-drug resistant bacteria (MDRB) have raised a worldwide concern, with projections indicating that fatalities from these infections could surpass those from cancer by 2050. This troubling trend is influenced by several factors, including the scarcity of new antibiotics to tackle challenging infections, the prohibitive costs of last-resort antibiotics, the inappropriate use of antimicrobial agents in agriculture and aquaculture, and the over-prescription of antibiotics in community settings. One promising alternative treatment is the application of antimicrobial peptides (AMPs) against MDRB.

Recommendations for Transitioning Young People with Primary Immunodeficiency Disorders and Autoinflammatory Diseases to Adult Care.

Purpose: Significant improvements in the prognosis for young patients with Primary Immunodeficiency Diseases (PID) and Autoinflammatory Disorders (AID), which together make up the majority of Inborn Errors of Immunity (IEI), have resulted in the need for optimisation of transition and transfer of care to adult services. Effective transition is crucial to improve health outcomes and treatment compliance among patients. Evaluations of existing transition programmes in European health centres identified the absence of disease-specific transition guidelines for PID and AID, as a challenge to the transition process.

Demographic and Clinical Characteristics of Mild, Young and Early COPD: A Cross-Sectional Analysis of 5468 Patients.

Early, mild and young COPD concepts are not clearly defined and are often used interchangeably to refer to the onset of the disease. : To describe and compare the characteristics of mild, young and early COPD in a large sample of COPD from primary and secondary care. : Pooled analysis of individual data from four multicenter observational studies of patients with stable COPD (≥40 years, FEV/FVC < 0.

Is Disease Stability an Attainable COPD Treatment Goal?

Chronic obstructive pulmonary disease (COPD) is a heterogenous lung condition characterized by progressive airflow obstruction. Despite advancements in diagnosis and treatment, the disease burden remains high; although clinical trials have shown improvements in outcomes such as exacerbations, quality of life, and lung function, improvement may not be attainable for many patients. For patients who do experience improvement, it is challenging to set management goals given the progressive nature of COPD.

Influence of agarose in semi-IPN hydrogels for sustained Polymyxin B release.

Hydrogels (HGs) are 3-D polymeric networks with high water content, making them appropriate for biomedical applications such as drug delivery systems. This study examines the impact of agarose in semi-interpenetrating polymer networks (Semi-IPNs) based on poly(acrylic acid) (p(AA)), N, N' Methylenebis(acrylamide) (MBA) and agarose (AGA) on the sustained release of Polymyxin B (PolB). Agarose incorporation improved the mechanical strength, swelling behavior and drug retention capacity of the HG.

Systematic Coronary Risk Evaluation 2 for Older Persons (SCORE2-OP): 10 years risk validation, clinical utility and potential improvement.

Aims: European Systematic Coronary Risk Assessment 2 for Older Persons (SCORE2-OP) model has shown modest performance when externally validated in selected cohorts. We aim to investigate its predictive performance and clinical utility for 10-years cardiovascular (CV) risk in an unbiased and representative cohort of older people of a low CV risk country. Furthermore, we explore whether other clinical or echocardiographic features could improve its performance.

Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease.

The central nervous system represents a major target tissue for therapeutic approach of numerous lysosomal storage disorders. Fabry disease arises from the lack or dysfunction of the lysosomal alpha-galactosidase A (GLA) enzyme, resulting in substrate accumulation and multisystemic clinical manifestations. Current enzyme replacement therapies (ERTs) face limited effectiveness due to poor enzyme biodistribution in target tissues and inability to reach the brain.

Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome.

The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration.

Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta.

Background And Aim: Serum HBV RNA and HBcrAg levels have been proposed as useful biomarkers in the management of HBV patients, however their role in chronic hepatitis Delta (CHD) is currently unknown.

Methods: Consecutive untreated CHD patients were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected.

Complement Activation Profiles Predict Clinical Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background And Objectives: The role of the complement system in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is not completely understood, and studies exploring its potential utility for diagnosis and prognosis are lacking. We aimed to investigate the value of complement factors (CFs) as diagnostic and prognostic biomarkers in patients with MOGAD.

Methods: Multicentric retrospective cohort study including patients with MOGAD, multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD) with available paired serum and CSF samples.

Role of routine uterine artery Doppler at 18-22 and 24-28 weeks' gestation following routine first-trimester screening for pre-eclampsia.

Objectives: To assess the performance of mean uterine artery pulsatility index (UtA-PI) at 18-22 and 24-28 weeks of gestation in the prediction of pre-eclampsia (PE) and small-for-gestational age (SGA), and its role in reassessing the risk of PE and SGA in pregnancies screened for PE in the first trimester.

Methods: This was a retrospective observational cohort study of 4464 women with singleton pregnancy screened routinely for PE in the first trimester, using the Gaussian algorithm, from March 2019 to May 2021, and who underwent UtA-PI assessment at 18-22 gestational weeks. Women were categorized as low risk or high risk based on the risk index obtained after first-trimester screening for PE.

Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer.

Background And Objective: Advanced prostate cancer (PCa) is enriched for alterations in DNA damage repair genes; poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of drugs that have demonstrated effectiveness in PCa, particularly in tumors with alterations in BRCA1/2 and other homologous recombination repair (HRR) genes, acting through a synthetic lethal mechanism. To prevent or delay drug resistance, and to expand the patient population that can benefit from this class of drug, combination treatment strategies have been developed in preclinical and clinical studies.

Methods: This review examines the latest developments in clinical trials testing PARPi for advanced PCa and their emerging role in earlier disease settings.

Reirradiation Practice in Gynecological Cancer: Insights from a National Survey in Spain.

Purpose: Given the lack of standardisation in gynecological cancer reirradiation, the Gyneacologial Radiation Oncology (GINECOR) working group on behalf of the Spanish Society of Radiation Oncology (SEOR), works towards to inquire the current state of reirradiation practices among the radiation oncology departments in Spain.

Methods: An online 37-question survey was sent to all GINECOR members, representing most Spanish centers. The survey addressed general aspects of reirradiation, including experience, reirradiation sites, and techniques used.

Socioeconomic inequalities in COVID-19 infection and vaccine uptake among children and adolescents in Catalonia, Spain: a population-based cohort study.

Introduction: This study aims to investigate the relationship between deprivation, as measured by a socioeconomic deprivation index (SDI) score for census tract urban areas, and COVID-19 infections and vaccine uptake among children and adolescents before and after the vaccination rollout in Catalonia, Spain.

Methods: We conducted a population-based cohort study using primary care records. Individuals were followed 3 months before the start of the vaccination campaign in Spain and 3 months after.

Genetic immune escape in cancer: timing and implications for treatment.

Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate.

Clinical and non-clinical aspects of reimbursement policy for orphan drugs in selected European countries.

Objectives: The aim of the study was to assess the reimbursement policy for orphan drugs (ODs) in selected European countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedures and reimbursement decision-making.

Materials And Methods: A list of authorized ODs was extracted from a web-based registry of the European Medicines Agency, including information on active substance, Anatomical Therapeutic Chemical (ATC) classification code, and therapeutic area. A country-based questionnaire survey was conducted between September 2022 and September 2023 among selected experts from 12 European countries.

A phase I dose-escalation study of LRP5/6 antagonist BI 905677 in patients with advanced solid tumors.

Background: Aberrant Wnt pathway signaling has been implicated in the development of many cancers. Targeting of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptors inhibits Wnt signaling and may be a novel therapy. BI 905677 is an LRP5/6 antagonist that has demonstrated preclinical antitumor activity.

The Efficacy and Safety of Mirvetuximab Soravtansine in FRα-Positive, Third-Line and Later, Recurrent Platinum-Sensitive Ovarian Cancer: The Single-Arm Phase 2 PICCOLO Trial.

Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with US Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase 2, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC).

Patients And Methods: Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.