Progressive systemic inflammation precedes decompensation in compensated cirrhosis.

Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation.

Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg).

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis.

Background And Objective: Selection of patients harboring mutations in homologous recombination repair (HRR) genes for treatment with a PARP inhibitor (PARPi) is challenging in metastatic castration-resistant prostate cancer (mCRPC). To gain further insight, we quantitatively assessed the differential efficacy of PARPi therapy among patients with mCRPC and different HRR gene mutations.

Methods: This living meta-analysis (LMA) was conducted using the Living Interactive Evidence synthesis framework.

How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes.

Staged thoracoscopic internal traction approach for early repair of long-gap esophageal atresia (LGEA) with distal tracheoesophageal fistula (TEF).

Background: Long-gap esophageal atresia (LGEA) can complicate the management of esophageal atresia (EA) with or without a tracheoesophageal fistula (TEF). This series describes a short interval, staged, thoracoscopic internal traction approach for LGEA with distal TEF to manage complex anastomotic tension or an anatomically impossible esophageal anastomosis.

Methods: A retrospective review (2018-2024) was performed across four tertiary centers to identify patients with LGEA and distal TEF, managed with a staged, thoracoscopic internal traction approach.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

Background And Aims: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking.

Explaining cognitive function in multiple sclerosis through networks of grey and white matter features: a joint independent component analysis.

Cognitive impairment (CI) in multiple sclerosis (MS) is only partially explained by whole-brain volume measures, but independent component analysis (ICA) can extract regional patterns of damage in grey matter (GM) or white matter (WM) that have proven more closely associated with CI. Pathology in GM and WM occurs in parallel, and so patterns can span both. This study assessed whether joint-ICA of GM and WM features better explained cognitive function compared to single-tissue ICA.

Expert Clinical Management of Inflammatory Immune-Related Arthritis in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Introduction: Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices.

Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial.

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. Interim results demonstrated strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 post-dosing.

INSIGHT: A Tool for Fit-for-Purpose Evaluation and Quality Assessment of Standardized Observational Data Sources for Real World Evidence on Medicine and Vaccine Safety.

Purpose: To describe the development of INSIGHT, a real-world data quality tool to assess completeness, consistency, and fitness-for-purpose of observational health data sources.

Methods: We designed a three-level pipeline with data quality assessments (DQAs) to be performed in ConcePTION Common Data Model (CDM) instances. The pipeline has been coded using R.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

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).