Barriers to and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters.

Introduction: Exacerbations of COPD decrease physical activity. Physical activity interventions after these events are desirable but have had mixed results. Understanding the barriers to and enablers of physical activity may help to improve the results of these interventions.

Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy.

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.

Impact of hyper- and hypothermia on cellular and whole-body physiology.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes.

Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.

Background: Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.

Methods: A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.

Balloon atrioseptostomy for transposition of the great arteries in Europe: characteristics and outcomes.

Introduction And Objectives: Balloon atrial septostomy (BAS) improves oxygenation in neonates with transposition of the great arteries (TGA) and restrictive foramen ovale. Currently, there is a global shortage of dedicated BAS catheters, while new unmarked catheters have recently become available at some European centers. This study aimed to characterize BAS outcomes using the currently available BAS catheters in Europe.

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.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Dent disease: Clinical Practice Recommendations.

Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay.

Nutritional Status in Locally Advanced or Metastatic Solid Cancer Patients Treated With Chemotherapy, Radiotherapy, and Immunotherapy in Spanish Outpatient Oncology Units.

Objectives: Malnutrition is a prevalent condition in cancer patients that significantly impacts patients' clinical outcomes and health-related quality of life (HR-QoL). The outcome was to characterize the nutritional status by describing the prevalence of malnutrition (mild, moderate, or severe) and its risk in outpatient cancer patients.

Methods: Multicenter, prospective, cross-sectional, descriptive, two-cohort study conducted on consecutive adult patients with locally advanced or metastatic solid tumors (stages III-IV).

Unsupervised clustering of intraventricular hemodynamic forces for the phenotyping of left-ventricular function in non-ischemic left ventricular cardiomyopathy.

Background: Cardiac magnetic resonance (CMR) is essential for diagnosing cardiomyopathy, serving as the gold standard for assessing heart chamber volumes and tissue characterization. Hemodynamic forces (HDF) analysis, a novel approach using standard cine CMR images, estimates energy exchange between the left ventricular (LV) wall and blood. While prior research has focused on peak or mean longitudinal HDF values, this study aims to investigate whether unsupervised clustering of HDF curves can identify clinically significant patterns and stratify cardiovascular risk in non-ischemic LV cardiomyopathy (NILVC).

Comorbidities Associated With Different Degrees of Severity in Children and Young People Hospitalized With Acute COVID-19.

In this prospective cohort study with 2326 hospitalized children and young people with coronavirus disease 2019 in Spain and Colombia, 36.4% had comorbidities. Asthma, recurrent wheezing, chronic neurological, cardiac and pulmonary diseases significantly increased the risk of severe outcomes such as death, mechanical ventilation and intensive care unit admission.

Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis.

Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients.

Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics.

Prospective evaluation of opioid cessation in patients with suspected Opioid-induced esophageal dysfunction (OIED).

Introduction: The causal relationship between chronic opioid use and esophageal motor dysfunction in symptomatic patients has not been established.

Methods: A prospective before-and-after multicenter study, including chronic active opioid patients referred for esophageal motility tests due to non-obstructive dysphagia.

Results: 37 patients were evaluated, 27 (73%) had criteria of opioid-induced esophageal dysfunction (OIED).

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

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.

Mechanism of syncope: role of ambulatory blood pressure monitoring and cardiovascular autonomic function assessment.

Background And Aims: Identifying the haemodynamic mechanism of autonomic syncope is the essential pre-requisite for effective and personalized therapy aimed at preventing recurrences. The present study assessed the diagnostic efficacy of a two-step assessment.

Methods: Multicentre prospective, cross-sectional, observational study.

Machine Learning Algorithms in Controlled Donation After Circulatory Death Under Normothermic Regional Perfusion: A Graft Survival Prediction Model.

Background: Several scores have been developed to stratify the risk of graft loss in controlled donation after circulatory death (cDCD). However, their performance is unsatisfactory in the Spanish population, where most cDCD livers are recovered using normothermic regional perfusion (NRP). Consequently, we explored the role of different machine learning-based classifiers as predictive models for graft survival.

Disease activity in patients with idiopathic inflammatory myopathy according to time since diagnosis and positivity to antisynthetase autoantibodies: data from the Myo-Spain registry.

Objective: To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs).

Methods: Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent.

Decreased impulsiveness and MEG normalization after AI-digital therapy in ADHD children: a RCT.

Attention-deficit/hyperactivity disorder (ADHD) presents with symptoms like impulsiveness, inattention, and hyperactivity, often affecting children's academic and social functioning. Non-pharmacological interventions, such as digital cognitive therapy, are emerging as complementary treatments for ADHD. The randomized controlled trial explored the impact of an AI-driven digital cognitive program on impulsiveness, inattentiveness, and neurophysiological markers in 41 children aged 8-12 with ADHD.

Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.

Purpose: Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non-small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.

Methods: Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery.

EBV-specific T-cell immunity: relevance for multiple sclerosis.

Genetic and environmental factors jointly determine the susceptibility to develop multiple sclerosis (MS). Improvements in the design of epidemiological studies have helped to identify consistent environmental risk associations such as the increased susceptibility for MS following Epstein-Barr virus (EBV) infection, while biological mechanisms that drive the association between EBV and MS remain incompletely understood. An increased and broadened repertoire of antibody and T-cell immune responses to EBV-encoded antigens, especially to the dominant CD4 T-cell EBV nuclear antigen 1 (EBNA1), is consistently observed in patients with MS, indicating that protective EBV-specific immune responses are deregulated in MS and potentially contribute to disease development.

Sperm recovery from urine in men with retrograde ejaculation.

Introduction: Retrograde ejaculation (RE) consists of the reflux backwards, towards the bladder, of the ejaculate, during the emission phase of ejaculation, causing a total or partial absence of sperm emission, with the consequent diversion of semen into the bladder during the emission phase of ejaculation. Evaluating the ejaculate may not be sufficient for identifying RE in some patients. Hence, the management of infertility may involve the use of invasive methods such as epididymal fluid retrieval or testicular biopsy.

Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol.

Osteosarcoma is a rare disease, but it is the most frequent malignant bone tumor. Primary treatment consists of preoperative MAP (methotrexate (MTX), doxorubicin and cisplatin) chemotherapy followed by surgery and adjuvant chemotherapy. Pathological response to preoperative chemotherapy is one of the most important prognostic factors, but molecular biomarkers are lacking.