Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway.

Purpose: Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options.

Clinical control in COPD and therapeutic implications: The EPOCONSUL audit.

Objective: This study aimed to evaluate clinical control in chronic obstructive pulmonary disease (COPD), the consequences in terms of treatment decisions, and their potentially associated factors during follow-up of patients in real-life clinical practice.

Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of COPD in respiratory clinics in Spain and multivariable logistic regression models to assess the relationships between clinical control and clinical inertia.

Results: 4225 patients from 45 hospitals in Spain were audited.

Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: an open-label, randomized controlled trial.

Small fetuses, with estimated fetal weight (EFW) below the tenth percentile, are classified as fetal growth restriction (FGR) or small for gestational age (SGA) based on prenatal ultrasound. FGR fetuses have a greater risk of stillbirth and perinatal complications and may benefit from serial ultrasound scans to guide early delivery. Abnormal serum angiogenic factors, such as the soluble fms-like tyrosine kinase-1 (sFlt-1):placental growth factor (PlGF) ratio, have shown potential to more accurately distinguish FGR from SGA, with fewer false positives.

Long-Term Effectiveness and Safety of Proactive Therapeutic Drug Monitoring of Infliximab in Paediatric Inflammatory Bowel Disease: A Real-World Study.

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD).

Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21).

Practical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease.

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications.

Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis.

Purpose: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity given the involvement of DNA repair.

Methods: Primary analysis was performed on 1494 prostate cancer, 483 lung cancer and 1820 breast cancer patients assessed for development of RT toxicity in the REQUITE study.

Challenges in assessing national radiotherapy costs: application of the ESTRO-HERO model in Spain.

Background And Purpose: The aim was to estimate the cost of the external beam radiotherapy (EBRT) in public health care centers in Catalonia (Spain), according to the ESTRO-HERO costing model for 2018.

Materials And Methods: Personnel, equipment, and activity data from 2018 from the 11 RT centers were used, incorporating European mean values adapted to the Catalan context. Secondly, EBRT costs were estimated, incorporating 2023 fractionation technique and scheme usage percentages.

Immune-inflammatory effects of the multicomponent intervention FIBROWALK in outdoor and online formats for patients with fibromyalgia.

The multicomponent intervention FIBROWALK integrates pain science education (PSE), therapeutic exercise, cognitive behavioral therapy (CBT), and mindfulness training for treating fibromyalgia (FM). This study investigated the effects of the FIBROWALK in online (FIBRO-On) and outdoor (FIBRO-Out) formats compared to treatment-as-usual (TAU) on core clinical variables along with serum immune-inflammatory biomarkers and brain-derived neurotrophic factor (BDNF). Furthermore, the predictive value of these biomarkers on clinical response to FIBROWALK was also evaluated.

Generation of three human induced pluripotent stem cell lines from retinitis pigmentosa 25 patient and two carriers but asymptomatic daughters.

Retinitis Pigmentosa type 25 (RP25) is a form of inherited retinal dystrophy characterized by a progressive loss of rod photoreceptors, subsequent degeneration of cone photoreceptors, and eventually, the retinal pigment epithelium. Caused by mutations in the EYS gene, it is believed to be critical for the structural and functional integrity of the retina. Using a non-integrative RNA reprogramming method, we have generated human induced pluripotent stem cell (hiPSC) lines from RP25 patient and from carriers but asymptomatic daughters.

Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

Untangling areas of improvement in secondary prevention of ischemic stroke in patients with atrial fibrillation.

Improvement of post-stroke outcomes relies on patient adherence and appropriate therapy maintenance by physicians. However, comprehensive evaluation of these factors is often overlooked. This study assesses secondary stroke prevention by differentiating patient adherence to antithrombotic treatments (ATT) from physician-initiated interruptions or switches.

Use of non-specific immunoglobulins in Catalonia in three third-level hospitals: a descriptive analysis of a hospital-prescribed medication registry.

Background: The increasing use of non-specific immunoglobulins (NSIGs) and their current shortage show a need for NSIGs' use prioritization. Data from a clinical perspective are necessary, mainly for pediatric patients.

Objectives: The aim of the study was to assess the level of clinical evidence (LoE) of the indications that NSIGs are used for, the reasons for discontinuation, and the costs invested.

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.