Multivalent GCase Enhancers: Synthesis and Evaluation of Glyco-Gold Nanoparticles Decorated with Trihydroxypiperidine Iminosugars.

The present study reports the preparation of the first multivalent iminosugars built onto a glyco-gold nanoparticle core (glyco-AuNPs) capable of stabilizing or enhancing the activity of the lysosomal enzyme GCase, which is defective in Gaucher disease. An -nonyltrihydroxypiperidine was selected as the bioactive iminosugar unit and further functionalized, via copper-catalyzed alkyne-azide cycloaddition, with a thiol-ending linker that allowed the conjugation to the gold core. These bioactive ligands were obtained with either a linear monomeric or dendritic trimeric arrangement of the iminosugar.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress.

Thermal Liquid Biopsy: A Promising Tool for the Differential Diagnosis of Pancreatic Cystic Lesions and Malignancy Detection.

Pancreatic cystic lesions (PCLs) are a heterogeneous group of lesions with increasing incidence, usually identified incidentally on imaging studies (multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS)) [...

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis.

Background And Objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

Resilience and emergence of pneumococcal serotypes and lineages in adults post-PCV13 in Spain: A multicentre study.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain.

Cholangiocarcinoma in Latin America: a multicentre observational study alerts on ethnic disparities in tumour presentation and outcomes.

Background: Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America.

Methods: This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at five referral centres across Latin America.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

Productivity and aseptic process evaluation during batch production simulation of intravenous medications using a semi-automated compounding device.

Introduction: Intravenous (IV) medications can be prepared using compounding devices to increase productivity, and reduce risks associated with aseptic compounding. This study evaluated the productivity and quality outcomes of the aseptic process for simulated batches of IV medications used in clinical practice produced using a semi-automated compounding device (Gri-fill; Grifols).

Methods: Simulated batches from 50 to 600 preparations were completed representing hazardous and non-hazardous drugs, including one-step single component (atropine sulfate, cisplatin) and multistep, multiple component (mitomycin C, piperacillin/tazobactam, trastuzumab, 5-fluorouracil and gemcitabine).

Executive summary: Clinical practice guidelines on the management of resistant tuberculosis of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) have developed together Clinical Practice Guidelines (GPC) on the management of people affected by tuberculosis (TB) resistant to drugs with activity against Mycobacterium tuberculosis. These clinical practice guidelines include the latest updates of the SEPAR regulations for the diagnosis and treatment of drug-resistant TB from 2017 to 2020 as the starting point. The methodology included asking relevant clinical questions based on PICO methodology, a literature search focusing on each question, and a systematic and comprehensive evaluation of the evidence, with a summary of this evidence for each question.

Temporo-spatial analysis of amyotrophic lateral sclerosis in Spain: Altitude and land use as new determinants of the disease.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Currently, ALS is conceived as the result of the interaction between genetics, environmental factors, and aging. This study analyzed the spatial and temporal patterns of ALS in Spain, delving into the potential relationships between altitude, land cover, and this disease.

Should We Offer Universal Germline Genetic Testing to All Patients with Pancreatic Cancer? A Multicenter Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC.

Persistence, Effectiveness, and Safety of Upadacitinib in Crohn's Disease and Ulcerative Colitis in Real Life: Results From a Spanish Nationwide Study (Ureal Study).

Introduction: Real-world data on the effectiveness of upadacitinib for inflammatory bowel disease (IBD) are limited. To assess upadacitinib persistence, effectiveness, and safety in a real-world scenario.

Methods: Retrospective multicenter study of patients with IBD who received upadacitinib before 31st December 2022 and at least 12 weeks before the recruitment date.

Failure rate of the pulmonary embolism rule-out criteria rule for adults 35 years or younger: Findings from the RIETE Registry.

Background: The use of a computed tomography pulmonary angiogram to diagnose pulmonary embolism (PE) has increased, leading not only to higher PE diagnoses but also to overdiagnosis and unnecessary radiation exposure, even in young patients despite a lower PE incidence. The aim of this study was to assess the failure rate of the pulmonary embolism rule-out criteria 35 (PERC-35) rule developed to reduce unnecessary testing in individuals aged ≤35 years among patients included in the Registro Informatizado de la Enfermedad TromboEmbolica Venosa (RIETE) Registry.

Methods: This retrospective cohort study used data from the RIETE Registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism.

A simplified four-tier classification for thyroid core needle biopsy.

Purpose: To propose a simplified histological classification for core-needle biopsy (CNB) of thyroid nodules with four diagnostic categories (DC) and provide the risk of malignancy (ROM) and the expected incidence for each DC. There is no uniform scheme for categorizing CNB specimens, except for a Korean diagnostic classification similar to the Bethesda system for FNAC.

Methods: Data from a single institution using CNB as a routine diagnostic tool for thyroid nodules.

Screening for SCA27B, CANVAS and other repeat expansion disorders in Greek patients with late-onset cerebellar ataxia suggests a need to update current diagnostic algorithms.

Objective: Late-onset cerebellar ataxia (LOCA) is a slowly progressive cerebellar disorder with symptom onset ≥30years of age. Intronic tandem repeat expansions (TREs) in RFC1 and FGF14 have recently emerged as common causes of LOCA. The relative contribution of classic vs.

Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed.

Objectives: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP.

Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study.

Introduction: The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience.

Methods: We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020.

Oncological safety of fertility preservation treatment in ovarian cancer: A Spanish multicenter study.

Objective: To assess the safety of fertility-sparing treatments for early-stage ovarian cancer in women younger than 40 years old.

Methods: We performed a retrospective multicenter study including women aged 18-40 years diagnosed with early-stage (FIGO I-II) ovarian cancer in 55 Spanish hospitals, from January 2010 to December 2019. Benign and borderline tumors were excluded, as well as advanced stages (FIGO III-IV).