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Background and Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes., Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included. The diagnostic performance of the Fibrosis-4 Index (FIB-4), enhanced liver fibrosis (ELF) and vibration-controlled transient elastography liver stiffness measurement (VCTE LSM) was evaluated. Performance was expressed as the area under the receiver operating characteristics curve (AUC). Thresholds for detecting advanced fibrosis (≥F3) were calculated for each NIT for fixed (high) sensitivity, specificity and predictive values., Results: Differences in AUC between all subgroups were small and statistically not significant, indicating comparable performance in detecting ≥F3, irrespective of these clinical factors. However, different thresholds were needed to achieve the same level of accuracy with each test. For example, for a fixed sensitivity and specificity, the thresholds for all three NITs were higher in patients with T2DM. Effects for sex, age and liver enzymes were less pronounced., Conclusions: Performance of the selected NITs in detecting advanced liver fibrosis does not vary substantially with clinical characteristics. However, different thresholds have to be selected to achieve the same sensitivity, specificity and predictive values in the respective subgroups. Large prospective studies are called for to study NIT accuracy considering multiple patient characteristics., (© 2025 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background: Due to the limited data from clinical trials and real-world settings in the realm of nusinersen, there is a need for further evidence. This study seeks to assess the impact of nusinersen, when combined with standard care, on bulbar function, respiratory function, and the necessity for respiratory support among pediatric patients with spinal muscular atrophy (SMA)., Methods: Prospective observational study, involving pediatric SMA patients (Types 1-3) undergoing nusinersen treatment at the Hospital Universitario Virgen del Rocío in Spain over at least 24 months. The cohort included 11 SMA type 1 patients, comprising 6 type 1b and 5 type 1c, 12 SMA type 2 patients, and 5 SMA type 3 patients., Results: Twenty-eight pediatric patients were enrolled with the majority being male ( n  = 20). Patients with type 1 were diagnosed and received treatment significantly earlier than those with types 2 and 3 ( p  < 0.001). Additionally, there was a longer period between diagnosis and the start of treatment in types 2 and 3 ( p  = 0.002). Follow-up revealed statistically improved functional and respiratory outcomes associated with earlier initiation of nusinersen treatment at 6, 12, and 24 months in all phenotypes. The ability to swallow and feed correctly remained unchanged throughout the study, with SMA type 1c patients maintaining oral feeding in contrast to patients with SMA type 1b. Notably, no deaths were recorded., Conclusions: This study provides important insights into the real-world clinical progress of pediatric SMA patients and their response to nusinersen treatment, highlighting the significance of early intervention for better functional and respiratory outcomes., Competing Interests: M.G., M.L.L., J.V.F., and M.M-G. received fees for ad hoc consultancy services to Biogen and conferences., (Thieme. All rights reserved.)

Background & Aims: Wilson disease (WD) is a copper metabolism disorder caused by mutations in ATP7B gene, with significant clinical variability. Several studies have analyzed the prevalence and penetrance of mutations. We evaluated both characteristics for our more frequent mutations., Methods: Evaluation of 260 patients from the National Registry: clinical, analytical and genetic data. Estimation of homozygotes and total cases according to Hardy-Weinberg equilibrium and comparison with Registry records., Results: The estimated number of homozygotes were higher than registered: p.Met645Arg (1949/6), p.His1069Gln (20/8), p.Leu708Pro (63/24) and p.Gly869Arg (147/0). p.Met645Arg homozygotes presented less cirrhosis at diagnosis, extrahepatic disease and Kayser-Fleischer ring (KFR) and more presymptomatic cases and diagnosis after 40 years of age than p.Leu708Pro and p.His1069Gln homozygotes. p.Met645Arg homozygotes presented more late diagnosis than p.Met645Arg compound heterozygotes. Compound heterozygotes carrying p.Met645Arg or p.Gly869Arg showed less cirrhosis at diagnosis, KFR and neurological symptoms and more hepatic and presymptomatic cases, despite clearly low ceruloplasmin levels. The estimated prevalence was 1:3.785, predicting more than 10.500 patients., Conclusions: The widespread mutations p.Met645Arg and p.Gly869Arg show low penetrance. WD might be underdiagnosed in Spain due to less severe phenotype of the most frequent mutations, a crucial fact to avoid misdiagnosis and to offer early therapy., Competing Interests: Conflict of interest Victor Vargas: Speaker fees, Alexion Pharma, Consultant (advisory board), Ipsen. Anna Miralpeix: speaker fees from Orphalan. Zoe Mariño: speaker fees from Orphalan and Gilead; advisory fees from Orphalan, Alexion and Deep Genomics; grants from Gilead. The others authors reported no conflict of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Inflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied., Methods: This retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term., Results: Overall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79-6.94, p < 0.0001), biologics (OR 5.45, 2.78-10.6, p < 0.0001) and surgeries (OR 2.65, 1.43-4.89, p < 0.001)., Conclusions: Chronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch., Competing Interests: Conflict of interest F. Mesonero has served as a speaker for and received consulting fees from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring Pharmaceuticals, Kern Pharma, Dr. Falk Pharma, Galapagos, Chiesi Farmaceutici and Faes Farma. - Y. Zabana has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte Therapeutics, Almirall, Amgen, Dr. Falk Pharma, Faes Farma, Ferring Pharmaceuticals, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda, Galapagos, Boehringer Ingelheim and Tillotts Pharma AG. - A. Fernández-Clotet has served as a speaker for and received educational funding from Dr. Falk Pharma, Janssen, Takeda, Chiesi Farmaceutici and Pfizer. - B. Caballol has served as a speaker for and received consulting fees from MSD, AbbVie, Janssen, Takeda, Ferring Pharmaceuticals, Shire Pharmaceuticals and Faes Pharma. - E. Leo-Carnerero has served as a speaker and consultant for and received educational funding from AbbVie, Janssen, Takeda, Ferring Pharmaceuticals, Gilead, Pfizer and Dr. Falk Pharma. - M. J. García has received financial support for travel and educational activities from Janssen, Pfizer, AbbVie, Takeda, Kern Pharma, Faes Farma and Ferring Pharmaceuticals. - R. Ferreiro-Iglesias has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte Therapeutics, Dr. Falk Pharma, Faes Farma, Ferring Pharmaceuticals, Janssen, MSD, Kern, Chiesi Farmaceutici, Gebro Pharma, Pfizer, Shire, Takeda and Tillotts Pharma AG. - M. Calafat has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte Therapeutics, Dr. Falk Pharma, Ferring Pharmaceuticals, Janssen, Pfizer, Takeda, Gilead, Chiesi Farmaceutici and Tillotts Pharma AG. - J. Miranda has received support for conference attendance, speaker fees and consulting and advisory fees from AbbVie, Adacyte Therapeutics, Dr. Falk Pharma, Faes Farma, Ferring Pharmaceuticals, Janssen, Pfizer, Takeda and Tillotts Pharma AG. - L. Torrealba has served as a speaker for and received educational funding from AbbVie, Janssen, Takeda, Ferring Pharmaceuticals, Gilead, Pfizer, Dr. Falk Pharma and Tillotts Pharma AG. - R. Sáiz-Chumillas has served as a speaker for and received consulting fees from Janssen, Ferring Pharmaceuticals and Faes Farma. - A. López has received support for conference attendance, educational funding and speaker fees from Chiesi Farmaceutici, AbbVie, Janssen, Ferring Pharmaceuticals, Takeda, Pfizer and Tillotts Pharma AG. - C. Rubín de Célix has received educational funding from Ferring Pharmaceuticals, Tillotts Pharma AG, AbbVie, Norgine, MSD, Pfizer, Takeda and Janssen and is supported by a grant from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III, Río Hortega CM21/00025) and co-financed by the European Social Fund Plus (ESF+) ‘Co-financed by the European Union’. - E. Brunet has served as a speaker and consultant for and received educational funding from Janssen, Takeda, Ferring Pharmaceuticals, Kern Pharma, AbbVie and Chiesi Farmaceutici. - A. Hernández has served as a speaker for and received educational funding from AbbVie, Takeda, Kern Pharma, Pfizer, Janssen, Adacyte Therapeutics, Chiesi Farmaceutici, Galapagos and Ferring Pharmaceuticals. - I. González-Partida has received support for conference attendance and speaker fees from AbbVie, Dr. Falk Pharma, Ferring Pharmaceuticals, Janssen, MSD, Kern, Pfizer, Shire, Takeda and Tillotts Pharma AG. - I. Rodríguez-Lago has received financial support for travel and educational activities from or has served as an advisory board member for AbbVie, Adacyte Therapeutics, Celltrion, Chiesi Farmaceutici, Danone, Ferring Pharmaceuticals, Faes Farma, Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda and Tillotts Pharma. I. R.-L. has also received financial support for research from Tillotts Pharma AG and is supported by research grants from Gobierno Vasco – Eusko Jaurlaritza (grant no. 2020111061) and Biobizkaia HRI (grant no. BCB/I/LIB/22/008). - M. C. Rodríguez-Grau has served as a speaker for Takeda, Shire Pharmaceutics and Dr. Falk Pharma and has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk Pharma, Shire Pharmaceutics, Mylan, Norgine, Chiesi Farmaceutici, Faes Farma, Ferring Pharmaceuticals and AbbVie. - A. Elosua has served as a speaker for or has received educational funding from AbbVie, Adacyte Therapeutics, Takeda, Faes Farma, Ferring Pharmaceuticals, Janssen and Tillotts Pharma AG. - J. Huguet has received fees for educational activities, research projects, scientific meetings and advisory boards sponsored by MSD, Ferring Pharmaceuticals, AbbVie, Janssen, Biogen, Sandoz, Kern Pharma, Faes Farma and Takeda. - M. Barreiro de Acosta has served as a speaker, consultant and advisory member for and has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gilead, Galapagos, BMS, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring Pharmaceuticals, Faes Farma, Dr. Falk Pharma, Chiesi Farmaceutici, Gebro Pharma, Adacyte Therapeutics and Vifor Pharma. Remaining authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Patch test results may be influenced by age-related factors. However, there is still discordant evidence between age and patch test results., Objectives: We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group., Methods: Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre-defined as children (0- to 11-years), adolescents (12- to 18-years), young adults (19- to 30-years), middle-aged adults (31- to 65-years) and older adults (≥66-years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression., Results: A total of 13 368 patients were patch-tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle-aged adults. Age-related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2-hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31-65 (OR: 1.41, 95% CI: 1.26-1.58) and above 66-years (OR: 1.15, 95% CI: 1.01-1.32) with a higher proportion of positive results, compared with young adults., Conclusions: Positive patch test results vary according to age, with the highest occurrence in middle-aged adults. Most haptens did not present age-related differences, reinforcing the use of baseline series regardless of age., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later-onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG, with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA. Clinical Trial Registration number: NCT06490510., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Objective: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA., Methods: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations., Results: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985) and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel GCA., Conclusion: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration and high ESR reduce the risk of visual involvement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson's disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD)., Methods: 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [ 18 F]FDG PET. We extracted grey matter volumes (sMRI), mean diffusivity (MD, dMRI), and standardized uptake value ratios ([ 18 F]FDG PET) for 52 cortical regions included in a neuroanatomical atlas. We assessed group differences using ANCOVA models and further applied a cross-validated machine learning approach to identify the modality-specific brain regions that are most indicative of dementia status and assessed their diagnostic accuracy for group separation using receiver operating characteristic analyses., Results: In sMRI, atrophy of temporal and posterior-parietal areas allowed separating PDD from PD-CN (AUC = 0.77 ± 0.07), but diagnostic accuracy was poor for separating PD-MCI from PD-CN (0.57 ± 0.10). dMRI showed most pronounced diffusivity changes in the medial temporal lobe, which provided excellent diagnostic performance for PDD (AUC = 0.87 ± 0.06), and a more modest but still significant performance for PD-MCI (AUC = 0.71 ± 0.09). Finally, [ 18 F]FDG PET revealed pronounced hypometabolism in posterior-occipital regions, which provided the highest diagnostic accuracies for both PDD (AUC = 0.89 ± 0.05) and PD-MCI (AUC = 0.78 ± 0.05). In statistical comparisons, both [ 18 F]FDG PET (p < 0.001) and dMRI (p < 0.031) outperformed sMRI for detecting PDD and PD-MCI., Conclusion: Among the tested modalities, [ 18 F]FDG PET was most accurate for detecting cortical changes associated with cognitive impairment in PD, especially at early stages. Diffusion measurements may represent a promising MRI-based alternative., Competing Interests: Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University hospital ‘Virgen del Rocío’ (Date: 08/01/2021, approval number: 2158-N-20). Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest.

Chest imaging in children presents unique challenges due to varying requirements across age groups. For chest radiographs, achieving optimal images often involves careful positioning and immobilisation techniques. Antero-posterior projections are easier to obtain in younger children, while lateral decubitus radiographs are sometimes used when expiratory images are difficult to obtain and for free air exclusion. Chest CT protocols should be age-dependent to minimise radiation exposure and motion artefacts. MRI is primarily used in specialised centres to reduce radiation exposure, requiring specific expertise and sedation in younger children. Respiratory distress syndrome is a leading cause of morbidity in preterm neonates, diagnosed through characteristic radiographic findings and a history of prematurity. Bronchopulmonary dysplasia is the most common complication of extreme preterm birth and chronic oxygen therapy; imaging is used for predicting outcomes for the assessment of severe cases. Transient tachypnoea of the newborn and meconium aspiration syndrome are common in term infants, with specific imaging characteristics aiding in their differentiation. Congenital lung malformations present diagnostic and management challenges, with imaging playing a crucial role in diagnosis and surgical planning. Finally, imaging is essential in detecting complications from pneumonia in children, such as empyema and necrotic pneumonia, or in identifying foreign object aspiration. CLINICAL RELEVANCE STATEMENT: This review summarises current radiology practice of paediatric chest pathologies, aiding in the accurate diagnosis and management of neonatal and congenital pulmonary conditions and pneumonia complications, ultimately improving patient outcomes through precise imaging interpretation and targeted clinical intervention. KEY POINTS: Chest radiographs should be systematically assessed for pathology. Ensure accurate differential diagnosis of neonatal lung diseases by collecting information on gestational age, method of delivery, presenting symptoms, ventilation type, and fetal ultrasound findings. Radiographs and ultrasound are initial diagnostic tools for paediatric pulmonary disease; CT should be reserved for complex cases. Referral to paediatric hospital should be considered when the use of chest MRI is indicated., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Pierluigi Ciet. Conflict of interest: The authors of this manuscript declare relationships with the following companies: Pierluigi Ciet receives speaker fees from Vertex Pharmaceutical, Chiesi Pharmaceutical, SIEMENS Healthineers. He has research grants from the Dutch Research Council (NWO), General Electric Healthcare, and Horizon AIC Pathfinder. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was not required. Ethical approval: Institutional Review Board approval was not required. Study subjects or cohorts overlap: Not applicable. Methodology: Practice recommendations, (© 2025. The Author(s).)

Introduction: The most frequent form of diabetes in pediatric patients is polygenic autoimmune diabetes (T1D), but single-gene variants responsible for autoimmune diabetes have also been described. Both disorders share clinical features, which can lead to monogenic forms being misdiagnosed as T1D. However, correct diagnosis is crucial for therapeutic choice, prognosis and genetic counseling. The aim of this study was to search for monogenic autoimmune diabetes in Spanish pediatric patients with early-onset T1D., Methods: Among 500 Spanish pediatric patients with T1D, those with disease onset between 9 and 30 months of age were selected for screening for monogenic autoimmune diabetes (n=44). Genetic testing was performed by NGS with a customized panel that included the major causative genes for monogenic autoimmune syndromes, including early-onset diabetes: AIRE, CTLA4, FOXP3, IL2RA, ITCH, LRBA, STAT1, STAT3, STAT5B. RT-PCR and cDNA sequencing of the RNA isolated from whole blood were used to analyze splicing variants., Results: Genetic screening identified, in two patients with diabetes onset under one year of age, two likely pathogenic novel variants affecting canonical splicing sites: c.286-12&#95;290del in STAT5B and c.-22-2delA in FOXP3. RNA analyses demonstrated that both variants modify mRNA splicing. The variant in STAT5B induced exon 4 skipping and the variant in FOXP3 caused a deletion of 16 nucleotides before the transcription start-site., Conclusions: T1D onset in the first year of life may indicate monogenic autoimmune diabetes and molecular testing may be recommended., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Background and Objectives: Primary objectives: to compare the rates of sustained clinical remission at 12 months in patients treated with antitumour necrosis factor (anti-TNF) and immunomodulators who withdraw anti-TNF treatment versus those who maintain it., Secondary Objectives: to evaluate the effect of anti-TNF withdrawal on relapse-free time, endoscopic and radiological activity, safety, quality of life and work productivity; and to identify predictive factors for relapse., Design: Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis or Crohn's disease in clinical remission for >6 months and absence of severe endoscopic (and radiological in Crohn's disease) lesions were randomised to maintain anti-TNF treatment (maintenance arm (MA)) or to withdraw it (withdrawal arm (WA)). All patients maintained immunomodulators. Patients were followed-up until month 12 or up to clinical relapse., Results: One-hundred forty patients were randomised: 70 were allocated to the MA and 70 to the WA. The proportion of patients with sustained clinical remission at 12 months was similar in the MA and WA: 59/70 (84%), 95% CI=74% to 92% versus 53/70 (76%), 95% CI=64% to 85%. The proportion of patients with significant endoscopic lesions at the end of follow-up was 8.5% in the MA and 19% in the WA (p=0.1); a higher proportion of patients had faecal calprotectin >250 µg/g at the end of follow-up in the WA (p=0.01). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar in both groups (4% in MA vs 7% in WA)., Conclusion: Anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic and radiological remission has no impact on sustained clinical remission at 1 year although objective markers of activity were higher in patients who withdrew treatment., Trial Registration Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-001410-10 https://clinicaltrials.gov/study/NCT02994836., Competing Interests: Competing interests: MBdA has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, GALAPAGOS, Pfizer, Sandoz, Biogen, Fresenius, Lilly, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. MCh has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly. ED has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.Marisa Iborra reports grants and personal fees from MSD, Janssen, Abbvie, Takeda, Kern and Chiesi, during the conduct of the study.Eduardo Leo has received grants or honoraria for scientific activities, presentations or as a scientific advisor for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Ferring, Dr. Falk Pharma, Adacyte and Otsuka Pharmaceutical. PNM reports grants and personal fees from MSD, grants from Otsuka, AbbVie; personal fees from Takeda, Kern, Biogen, Ferring. JP received financial support for research from AbbVie and Pfizer; consultancy fees/honorarium from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Morphic, Pandion, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Robarts, Sanofi, Takeda, Theravance and Wasserman; reports payment for lectures including service on speaker bureau from Abbott, Ferring, Janssen, Pfizer and Takeda; and reports payment for development of educational presentations from Abbott, Janssen, Pfizer Roche and Takeda. MR has served as a speaker or advisory member from TaKeda, Janssen, Galapagos, Ferring and Pfizer. MV has received educational funding from Janssen, Kern Pharma and Takeda. Rest of authors have nothing to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Low cardiac output syndrome (LCOS) is the most common complication after cardiac surgery in children with congenital heart disease (CHD). The aim of this study was to assess the predictive value of serum inorganic phosphorus (SIPL) as an indicator of LCOS in the postoperative period., Materials and Methods: From June 2018 to December 2019, a single-center prospective study was conducted in patients with CHD undergoing surgery who required extracorporeal circulation (ECC). In the postoperative period, patients were divided into group 1 with LCOS and group 2 without LCOS. Blood samples were extracted in pre and postoperative periods. Serial measurements of SIPL, NT-proBNP, troponin T and creatinine were collected and compared between both groups. Multivariate analyses were conducted to identify the risk factors of SBGC., Results: A total of 97 patients were included, with 31 in group 1 and 66 in group 2. There was an increment of SIPL which peaked at the 8-h postsurgery (5.3 mg/dL, 4.6-5.8). Postoperative median SIPL in the group 1 were significantly higher than in the group 2. All consecutive SIPL measurements also were significantly higher in group 1. Changes in SIPL over time approached statistical significance (p < 0.001). Logistic regression analyses indicated that ECC (OR: 1.01; 95% CI: 0,9-1.01), SIPL (OR: 1.02; 95% CI: 1-1.04), NT-ProBNP (OR: 1; 95% CI; 1-1.0) were the independent risk factors of LCOS., Conclusions: The increase in SIPL was more pronounced in LCOS group 1. SIPL emerged as a new predictive risk factors of LCOS., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) dysfunction and wall motion abnormalities without culprit coronary artery disease. LV thrombus (LVT) formation during the acute phase is a fearsome complication., Objectives: To identify factors associated with LVT and its prognostic impact in TTS patients., Methods: Data from the nationwide REgistry on TAKOtsubo syndrome (RETAKO), which combines retrospective (2002-2012) and prospective (2012 onwards) recruitment with prospective follow-up, were reviewed to assess patient characteristics, imaging findings, and clinical outcomes according to the presence of LVT., Results: Of 1478 TTS consecutive patients (median age 72 years, 13.5 % men), 42 patients (2.8 %) presented with LVT. Presentation with syncope, a typical "apical ballooning" pattern, the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging, and elevated high sensitivity-C reactive protein (hs-CRP), were associated with LVT. On multivariable analysis, elevated hs-CRP at admission and LGE persisted as independent predictors of LV thrombus. Patients with LVT had higher rates of in-hospital major bleeding (9.5 % vs. 3.1 %, p = 0.023) and major adverse cardiovascular events (26.8 % vs. 15.2 %, p = 0.035), mainly driven by stroke (14.6 % vs. 2.5 %, p < 0.001) and systemic embolism (19 % vs. 1.3 %, p < 0.001). At a median follow-up of 18 months, there were no differences in mortality, cardiac readmissions, or TTS recurrence between groups., Conclusions: In TTS patients, elevated hs-CRP and LGE are associated with a higher risk of LVT. Although LVT is rare, it is associated with increased in-hospital thromboembolic events and bleeding, while long-term outcomes are comparable to those without LVT., Competing Interests: Declaration of competing interest No relevant conflicts of interest, (Copyright © 2024. Published by Elsevier B.V.)

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model. Our objective was to assess the safety and efficacy of tamoxifen over 48 weeks in non-ambulant DMD patients. In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at six European centres boys aged 10-16 years with genetically diagnosed DMD, non-ambulant and off corticosteroid treatment for ≥6 months, randomly assigned (1:1) to either 20 mg/day tamoxifen orally or placebo were included. The primary outcome was change in D2 motor function measure from baseline to week 48. Of 15 non-ambulant male patients with DMD screened, 14 were enrolled from January 24th, 2019, to January 6th, 2021. Eight patients were randomised to the treatment and six to the placebo group. The primary efficacy outcome did not differ significantly between tamoxifen and placebo (7.8 percentage points, 95 % CI, -26.82 to 11.22, p=0.359) with a trend not favouring tamoxifen. No deaths or life-threatening serious AEs occurred. Tamoxifen was safe but due to insufficient clinical evidence, it cannot be recommended as a treatment option for DMD. Trial registration: ClinicalTrials.gov (NCT03354039)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abstract: Mutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2, and NPM1, are rarely found in chronic myelomonocytic leukemia (CMML), and their prognostic significance in CMML has not been clearly identified. In 127 patients with CMML, we have retrospectively analyzed next-generation sequencing and polymerase chain reaction data from bone marrow samples collected at the time of CMML diagnosis. Seven patients harbored CEBPA mutations, 8 FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations, and 11 NPM1 mutations. Patients with CMML harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN) more frequently had the myeloproliferative subtype, a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CMML Prognostic Scoring System molecular classification, mutCFN patients with CMML had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN patients with CMML closely resembled that of patients with AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible. Furthermore, certain targeted therapies approved for use in AML should be considered., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background/objectives: Anaplastic large cell lymphomas (ALCLs) present unique challenges due to their clinical and genetic heterogeneity. This study investigated the clinical characteristics of children diagnosed with systemic ALCL., Methods: Retrospective data from 14 pediatric patients diagnosed with systemic ALCL at Valme University Hospital were studied. Demographic, clinical, and treatment data were collected and statistically analyzed., Results: The mean age at diagnosis was 8.5 years, with a male predominance (78.6%). Cutaneous presentation occurred in 35.7% of cases, with characteristic rapidly growing subcutaneous nodules. B symptoms were present in 57.1% of patients, while 100% exhibited nodal involvement. Visceral and bone marrow involvement was observed in 71.4% and 7.1% of patients, respectively. Central nervous system (CNS) involvement was absent. Anaplastic lymphoma kinase (ALK) rearrangement was positive in all cases. Anthracycline-based chemotherapy resulted in 100% 5- and 10-year overall survival rates., Conclusions: Systemic ALCL in children often presents with advanced-stage disease, with cutaneous involvement in a significant proportion of cases. Prompt recognition of skin lesions is vital to expedite diagnosis and treatment initiation, ultimately improving patient outcomes. This study underscores the importance of vigilance and early intervention in managing pediatric ALCL., (© 2024 Wiley Periodicals LLC.)

Background: Leptomeningeal disease (LMD) is associated with poor survival and diminished quality of life. Trastuzumab deruxtecan (T-DXd) has shown remarkable intracranial and extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). The DEBBRAH trial was designed to evaluate its efficacy and safety in patients with HER2-positive and HER2-low ABC with a history of brain metastases (BMs) and/or LMD. Here, we report results from cohort 5, which specifically included patients with pathologically confirmed LMD., Methods: This single-arm, open-label, five-cohort, phase 2 trial enrolled seven patients in cohort 5 who received 5.4 mg/kg T-DXd intravenously every 21 days until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and safety profile., Findings: At data cutoff (April 4, 2023), the median duration of follow-up was 12.0 months (range, 2.5-18.6). The median OS was 13.3 months (95% confidence interval [CI], 5.7-NA, p < 0.001), meeting the primary endpoint. The median PFS was 8.9 months (95% CI, 2.1-NA). Two (28.6%) of seven patients remained on treatment after 18.6 and 11.9 months, respectively. Of the five patients who progressed and died, none had intracranial progression or clinical worsening of leptomeningeal symptoms. Notably, 71.4% (95% CI, 29.0-96.3) achieved prolonged stabilization (≥24 weeks) by response evaluation criteria in solid tumors (RECIST) v.1.1. No unexpected safety signals and no treatment-related deaths were observed., Conclusions: T-DXd showed promising antitumor activity in patients with HER2-positive and HER2-low ABC with previously untreated, pathologically confirmed LMD. These encouraging data warrant further investigation to address the unmet need in this difficult-to-treat condition., Funding: This work was funded by Daiichi Sankyo/AstraZeneca. This trial is registered with ClinicalTrials.gov: NCT04420598., Competing Interests: Declaration of interests M.V.B. reports participating in a consulting/advisory board for AstraZeneca; participating as an invited speaker for Daiichi Sankyo and Nutricia; and receiving travel fees from AstraZeneca, Daiichi Sankyo, Pfizer, and GSK. J.M.P.-G. reports having a consulting or advisory role for Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, and Seattle Genetics; receiving travel compensation from Roche; and employment at MEDSIR. J.A.G.-S. declares consultative and advisory services for Seagen, AstraZeneca, Daiichi Sankyo, Novaris, Gilead, and Menarini; consultancy/speaker fees from Celgene, Eli Lilly, EISAI, MSD, Exact Sciences, Tecnofarma, Nolver (Adium), Asofarma, and Roche; institution and research funding from AstraZeneca; and travel support from Gilead, AstraZeneca, and Daiichi Sankyo. M.R.-B. reports serving as a consultant to Roche and Puma and receiving honoraria from Roche/Genentech, Pfizer, and Novartis. M.F.-A. reports participating in an advisory board for Seagen and Daiichi Sankyo-AstraZeneca and speakers’ bureau from Novartis and Lilly. M.G. reports receiving honoraria from Roche, Novartis, Gilead, and Daiichi Sankyo and travel compensation from Roche, Pfizer, and Daiichi Sankyo. G.M. is a full-time employee at MEDSIR. D.A.-L. is a full-time employee at MEDSIR. J.P.-E. is a full-time employee at MEDSIR. M.S.-C. reports participating in an advisory board for Optimapharm, Ability Pharma, and MD Anderson and is a full-time employee at MEDSIR. A.L.-C. reports receiving research support from Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Gilead, and Daiichi Sanyo; consulting or advisory roles for Lilly, Roche, Pfizer, and Novartis; speakers’ bureaus from Lilly, AstraZeneca, and Merck Sharp & Dohme; travel support from Roche, Pfizer, and AstraZeneca; and stock or other ownership of MEDSIR and Initia-Research. S.B. reports participating in a consulting/advisory board for Daiichi Sankyo, AstraZeneca, Novartis, and Roche; participating as an invited speaker for Daiichi Sankyo, AstraZeneca, Novartis, and Roche; and receiving travel fees from Daiichi Sankyo, AstraZeneca, Novartis, and Roche. J.C. reports serving as a consultant/advisor to Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, and Expres2ion Biotechnologies; receiving honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; research funding to the Institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, and Queen Mary University of London; stock of MEDSIR, Nektar Pharmaceuticals, and Leuko (relative); travel, accommodations, and expenses from Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, and Gilead; and the following patents: (1) “Pharmaceutical Combinations of A Pi3k Inhibitor And A Microtubule Destabilizing Agent,” Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde, WO 2014/199294 A, ISSUED; and (2) “Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy,” Aleix Prat, Antonio Llombart, Javier Cortés, US 2019/0338368 A1, LICENSED., (Copyright © 2024. Published by Elsevier Inc.)

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. A risk stratification score integrated with the model of end-stage liver disease score in a donor-recipient (D-R) matching system was developed., Methods: This retrospective multicenter cohort study used 539 D-R pairs of cDCD livers recovered with NRP, including 20 donor, recipient, and NRP variables. The following machine learning-based classifiers were evaluated: logistic regression, ridge classifier, support vector classifier, multilayer perceptron, and random forest. The endpoints were the 3- and 12-mo graft survival rates. A 3- and 12-mo risk score was developed using the best model obtained., Results: Logistic regression yielded the best performance at 3 mo (area under the receiver operating characteristic curve = 0.82) and 12 mo (area under the receiver operating characteristic curve = 0.83). A D-R matching system was proposed on the basis of the current model of end-stage liver disease score and cDCD-NRP risk score., Conclusions: The satisfactory performance of the proposed score within the study population suggests a significant potential to support liver allocation in cDCD-NRP grafts. External validation is challenging, but this methodology may be explored in other regions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

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. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model., Results: A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p < 0.05)., Conclusions: The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs., Competing Interests: Declaration. Ethics approval and consent to participate: The study was approved by the reference Clinical Investigation Ethics Committee (Hospital La Paz, Madrid) and by the local ethics committees. All the patients gave their written informed consent before being included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The application of personalized medicine in patients with first-episode psychosis (FEP) requires tools for classifying patients according to their response to treatment, considering both treatment efficacy and toxicity. However, several limitations have hindered its translation into clinical practice. Here, we describe the rationale, aims and methodology of Applied Pharmacogenetics to Predict Response to Treatment of First Psychotic Episode (the FarmaPRED-PEP project), which aims to develop and validate predictive algorithms to classify FEP patients according to their response to antipsychotics, thereby allowing the most appropriate treatment strategy to be selected. These predictors will integrate, through machine learning techniques, pharmacogenetic (measured as polygenic risk scores) and epigenetic data together with clinical, sociodemographic, environmental, and neuroanatomical data. To do this, the FarmaPRED-PEP project will use data from two already recruited cohorts: the PEPS cohort from the "Genotype-Phenotype Interaction and Environment. Application to a Predictive Model in First Psychotic Episodes" study (the PEPs study from the Spanish abbreviation) (N=335) and the PAFIP cohort from "Clinical Program on Early Phases of Psychosis" (PAFIP from the Spanish abbreviation) (N = 350). These cohorts will be used to create the predictor, which will then be validated in a new cohort, the FarmaPRED cohort (N = 300). The FarmaPRED-PEP project has been designed to overcome several of the limitations identified in pharmacogenetic studies in psychiatry: (1) the sample size; (2) the phenotype heterogeneity and its definition; (3) the complexity of the phenotype and (4) the gender perspective. The global reach of the FarmaPRED-PEP project is to facilitate the effective deployment of precision medicine in national health systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Mas, Julià, Cuesta, Crespo-Facorro, Vázquez-Bourgon, Spuch, Gonzalez-Pinto, Ibañez, Usall, Romero-López-Alberca, Catalan, Mané and Bernardo.)

Background: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT., Methods: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis., Results: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression., Conclusions: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles., Methods: A longitudinal retrospective multicenter cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed., Results: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. A total of 27.2% of patients were in DORIS ≥50% of the visits and 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC., Conclusion: Our study not only demonstrates belimumab's efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective, Study Design, Setting, Methods: To improve our knowledge about head and neck paragangliomas (HN-PGL), the clinical characteristics of all the patients with HN-PGL included in the Spanish Registry were analyzed, as well as the treatment modalities and their outcomes., Results: A total of 202 patients, 67.8% women, aged 53.1 ± 17.4, with 264 HN-PGL, from 16 Spanish hospitals, were included. Tumors were located in the carotid body in 61%, jugular bulb in 20.5%, tympanic area in 10.2%, and along the vagal nerve in 6.4%. Multiple tumors developed in 20.8% and metastatic disease in 4%. A genetic study was done in 64.4% and showed a pathogenic variant in SDHx in 50%. These patients were younger, with no sex predominance, and had more multiple and metastatic tumors. Tumors were treated by surgery in 134 patients, radiotherapy in 33, and other treatments in 20, and were observed without active treatment in 41 patients, who were older, more often asymptomatic, and had smaller tumors. Tumors treated with radiotherapy were larger and more often in locations other than the carotid body. After a median follow-up of 80 months (interquartile range: 41-136), 6.9% had died; among the survivors, 48.4% were disease-free, 42.1% stable, and 9.4% had progressed. The rate of sequelae was similar among patients submitted to surgery, radiotherapy, or observation. We could not identify any prognostic factor for progression., Conclusion: Most HN-PGL are localized slow-growing tumors. Long-term survival is high, even in case of metastasis. Although surgery is the most common treatment, radiotherapy and active surveillance are safe approaches., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves., Methods: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD., Results: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21)., Conclusions: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The transition of adolescents from pediatric to adult hospitals is a planned and guided process that involves changes in the focus, style, and location of care. During this period, complications are common in those with type 1 diabetes mellitus (T1DM). The objective of this study was to understand the influence of a nurse-led structured therapeutic education program on maintaining glycemic control and emotional wellbeing in these adolescents., Materials and Methods: Monocentric quasi-experimental clinical trial of a single group. SPSS and R-Commander were used for statistical analysis, including Student's t-test, Wilcoxon test, Cohen's d, Rosenthal's r, and multivariate linear regression analysis., Results: A total of 15 adolescents with a 5-to-17-year history of the disease participated in the study. They had a BMI of 18-26.3kg/m 2 and were on basal-bolus therapy. No significant differences were found in glycemic control and emotional wellbeing between baseline values and at 3 months. A significant difference in self-care was observed at 12 months. Family function and eating disorders were positively associated at baseline, 3 months, and 12 months., Conclusions: The structured therapeutic education program for adolescents with T1DM transitioning from pediatric to adult care maintains glycemic control and emotional wellbeing., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported .CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

Phenylketonuria is a rare inherited disorder that disrupts the metabolism of phenylalanine (Phe) to tyrosine by phenylalanine hydroxylase (PAH). Sapropterin dihydrochloride (Kuvan®) is approved for use in Europe to reduce blood Phe levels and improve Phe tolerance in sapropterin-responsive individuals. KAMPER (NCT01016392) is an observational, multinational registry assessing long-term safety and efficacy of sapropterin. Five hundred and seventy-six participants with PAH deficiency were enrolled from nine European countries (69 sites; December 2009-May 2016). Participants were aged <4 years (n = 11), 4 to <12 years (n = 329), 12 to <18 years (n = 141), and ≥18 years (n = 95) at enrolment. Overall, 401 (69.6%) participants experienced a total of 1960 adverse events; 61 events in 42 participants were serious, and two were considered sapropterin-related by the investigator. Mean (standard deviation) actual dietary Phe intake increased from baseline across all age groups: 957 (799) mg/day to a maximum of 1959 (1121) mg/day over a total study period of 11 years. Most participants exhibited an increase in Phe tolerance while blood Phe levels remained in the target range for their age (120-360 μmol/L for <12 years; 120-600 μmol/L for ≥12 years). Most participants exhibited normal growth for height, weight, and body mass index. No additional safety concerns were identified. As an observational study, limitations include variability in routine care practices and inconsistent availability of data. Long-term sapropterin use demonstrates a favourable safety profile in real-world settings and increases Phe tolerance in participants with PAH deficiency while maintaining blood Phe levels in the target ranges., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: Antiaggregant and anticoagulant therapy complicate the management of patients with osteoporotic hip fracture., Objective: To homogenize and improve daily clinical practice with simple recommendations., Methods: The haemostasis section of SEDAR established a working group to define an action plan for the management of antiaggregated or anticoagulated patients with an osteoporotic hip fracture. The suggested recommendations are based on evidence of best practices, and have been validated by a multidisciplinary group formed by 6 specialties., Results: Early surgery reduces complications and mortality and improves patient comfort and functional recovery, with no difference in mortality between intradural and general anaesthesia., Conclusion: Although uncertainties remain, it is recommended to perform surgery within 24-48 h of admission, adapting peripheral nerve blocks and type of anaesthesia (neuraxial or general) an to the haemostatic conditions. A multimodal management of antithrombotics, and the optimisation of haemostasis, haemoglobin and venous thromboprophylaxis since admission are suggested., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Parenteral nutrition (PN) composition could play a role in the management of systemic inflammatory response and intestinal barrier disruption. We aimed to evaluate changes in biomarkers of inflammation, oxidative status and intestinal permeability in patients with type 2 diabetes mellitus (T2DM) who received different PN lipid formulas., Methods: This was a prospective study, including 94 patients with T2DM who received omega (n)-3 polyunsaturated fatty acids (PUFA)-enriched PN, a mixture of medium and long chain triglycerides (MCT/LCT) PN, or an olive oil-based PN. Serum levels of biomarkers of oxidative status, intestinal permeability and inflammation biomarkers were determined at day 1 and day 5 after PN initiation. Registered under ClinicalTrials.gov Identifier no. NCT02706119., Results: At day 5 after the onset of PN, the MCT/LCT group had a significant reduction of 2 proinflammatory cytokines [interleukin (IL)-15, IL-17A], elevation of the anti-inflammatory cytokine IL-13 and increase of zonulin and indoxylsulfate. The olive oil group showed a statistically significant reduction of 5 proinflammatory cytokines [IL-1β, IL-17A, IL-6, cytokine-leukemia inhibitory factor (LIF) and tumor necrosis factor alpha (TNF-α)] and reduced concentrations of the anti-inflammatory cytokine IL-1RA, while the n-3 PUFA-enriched group presented a statistically significant reduction of 8 proinflammatory cytokines (interferon-gamma, IL-1β, IL-15, IL-17A, IL-6, LIF, monocyte chemoattractant protein 1, and TNF-α). In the between-group comparisons, indoxylsulfate significantly increased in the MCT/LCT group compared to the n-3 PUFA-enriched group, while 8-isoprostane and indoxylsulfate significantly increased in the MCT/LCT group compared to the other groups and superoxide dismutase significantly decreased in the MCT/LCT group compared to the other groups., Conclusion: In patients with T2DM, PN lipid composition exerts a profound impact on proinflammatory, prooxidative and intestinal permeability biomarkers., Competing Interests: Conflict of interest The authors have declared that no competing interests exist., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To understand the impact of the niraparib individualized starting dose (ISD), compared with fixed starting dose (FSD), on the cost of hematologic adverse event (AE) management from a US payer perspective. Methods: The frequencies of grade ≥3 hematologic AEs that occurred in >1% of patients treated with niraparib were obtained from the primary analysis results of the phase III PRIMA/ENGOT-OV26/GOG-3012 trial. US unit costs for each grade ≥3 AE in the base case were obtained from the 2017 Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project database; unit costs were adjusted to 2020 US dollars. AE management costs per patient were calculated by multiplying AE unit cost by the frequency of each AE by niraparib starting dose. Because AEs were assumed to occur independently of one another, costs were added to derive the total cost. Results: For niraparib, the estimated AE management cost per patient was lower for the ISD than the FSD for all hematologic AEs (FSD vs ISD: thrombocytopenia, $4701.87 vs $1921.89; anemia, $2784.00 vs $1760.59; platelet count decreased, $2103.47 vs $922.51; neutropenia, $2112.50 vs $1369.56; neutrophil count decreased, $1285.87 vs $770.38). The total mean calculated AE management cost per patient was $12,987.71 with the FSD and $6744.93 with the ISD. Conclusion: For niraparib, the cost of managing hematologic AEs in the US was reduced by almost half with the ISD compared with the FSD. The cost reduction and improvements in safety associated with the niraparib ISD support its use in clinical practice.

Objective: To analyze the reliability and validity of the SERVPERF questionnaire for assessing the quality of care from the patient's perspective in emergency departments for abdominal pain patients undergoing clinical ultrasound, as well as the influence of sex., Design: Prospective study from March 2023 to April 2024 involving patients treated for abdominal pain who underwent clinical ultrasound., Setting: Emergency department., Participants: Adults over 18 years old with abdominal pain., Interventions: Conducting clinical ultrasound and collecting the adapted SERVPERF questionnaire., Main Measurements: Overall score of the questionnaire, sex, age, length of stay in the emergency department, referral origin, discharge destination, ultrasound results., Results: A total of 115 patients were included, with a mean age of 58.2 years (SD: 19.4) and 66.1% being women. To validate the questionnaire, the Bartlett's test of sphericity yielded a value of 0.000 (P<.05) and the KMO (Kaiser-Meyer-Olkin) test resulted in a value of 0.855 (>0.5). The reliability of the questionnaire was assessed using Cronbach's alpha: 0.928 (95% CI: 0.908-0.946). The mean score on the scale was 124.57±9.30. Men showed a higher overall mean score than women, approaching statistical significance (P=.05). Using multiple linear regression, no variable was independently associated with a higher perception of quality in care, although sex was marginally significant., Conclusions: The SERVPERF questionnaire is shown to be reliable and valid for determining the perceived quality of service. Additionally, the perceived quality of care using clinical ultrasound in the emergency department was very high. No differences based on sex were observed., Competing Interests: Conflicto de intereses Los autores no refieren ningún conflicto de intereses., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Eosinophilic esophagitis (EoE) is a chronic allergic condition affecting the esophagus and driven by food antigens. Many individuals diagnosed with EoE have other allergic conditions, such as food allergy, asthma, allergic rhinitis, and atopic dermatitis. The clinical goals of therapy in EoE include symptomatic, histologic, and endoscopic remission. The current paradigm for the treatment of EoE in Spain includes proton pump inhibitors, swallowed topical corticosteroids, and food elimination diets. These treatments have proven very effective in clinical studies. In April 2024, the Spanish Agency for Medicines and Medical Products approved dupilumab as the second drug for the treatment of EoE, thus adding this biologic to the therapeutic arsenal in EoE. The present review includes a positioning statement by the authors, all of whom are members of the Spanish Society of Allergy and Clinical Immunology Food-EoE Working Group.

The evolution of blood saving programs to Patient Blood Management (PBM) represents a broader and more comprehensive approach to optimize the use of the patient's own blood, thus improving clinical outcomes and minimizing the risks associated with allogeneic blood transfusion with a holistic view of socio-economic sustainability. Implementing the strategies of the three PBM pillars in any hospital center involves a transversal change throughout the organization in which it can be very useful to apply the strategy defined by Kotter at the business level for change management. The support of renowned institutions such as the World Health Organization and the European Commission demonstrates the importance and urgency of implementing PBM programs, setting guidelines at an international level and supporting the adoption of effective strategies in the management of blood transfusion at a national and institutional level. In Spain, we need to have health managers at both the Hospital Management level and the Regional Health Services and/or Ministry of Health that provide the necessary resources for its proper implementation in the health system from primary care to hospital care and also the resources for the timely evaluation of the results., (Copyright © 2024 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: It is a priority to find surgical techniques that guarantee acceptable healing rates without sequelae in the treatment of complex anal fistula. The concept of the deep intersphincteric space as the origin of perianal sepsis has provided a new perspective, allowing the emergence of techniques such as TROPIS (Transanal Opening of Intersphincteric Space), with few published series to date. The aim of this study is to evaluate the healing rate and complications one year after the TROPIS technique as a treatment for complex anal fistula without hospitalization., Method: Prospective, observational study from January 2021 to January 2023. Patients with complex anal fistulas who met the inclusion criteria were treated using the TROPIS technique. A one-year follow up review was conducted, assessing healing rates, recurrence, continence, and complications., Results: A total of 23 patients with cryptoglandular complex perianal fistula were included (87% male, mean age 54.7 ± 9.6 years). 78.3% were treated for recurrent fistulas with an average of 3.3 ± 3.2 previous interventions. At one month, 82.6% of the patients had complete healing. At three, six, and twelve months, complete healing occurred in 63.6%, 61.9%, and 55.6%, respectively. One patient developed an abscess at one month. Continence was altered in 8.7%., Conclusions: The treatment of cryptoglandular complex anal fistula with this procedure was safe and showed acceptable healing rates. [[es]]Resumen INTRODUCCIóN: Es prioritario encontrar técnicas quirúrgicas que garanticen tasas de curación aceptables sin secuelas en el tratamiento de la fístula anal compleja. El concepto de espacio interesfintérico profundo como origen de la sepsis perianal ha dado una nueva perspectiva, permitiendo la aparición de técnicas como, TROPIS (Transanal Opening of Intersphincteric Space), con escasas series publicada hasta el momento. El objetivo de este estudio es valorar la tasa de curación y las complicaciones al año de la técnica TROPIS, como tratamiento de la fistula anal compleja sin ingreso. MéTODO: Estudio ambispectivo, observacional, desde enero del 2021 a enero del 2023. Se trató mediante técnica TROPIS a pacientes con fístula anal compleja que cumplían criterios de inclusión. Se realizó una evaluación al año, valorando tasas de curación, recurrencia, de continencia y complicaciones., Resultados: Se han incluido un total de 23 pacientes con fistula anal compleja criptoglandular (87% varones, edad media 54,7 +/- 9,6 años). El 78,3% fueron fistulas recidivadas con una media de 3,3+/- 3,2 intervenciones previas. Al mes, un 82,6% de las pacientes tuvieron una curación completa. A los tres, seis y doce meses la curación completa se dio en un 63,6%, 61,9% y 55,6% respectivamente. Un paciente tuvo un absceso al mes. La continencia se modificó en un 8.7%., Conclusiones: El tratamiento de la fístula anal compleja criptoglandular con este procedimiento fue seguro y mostró aceptables tasas de curación., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [ 18 F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [ 18 F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated proportion: 43%, p < 0.001). In combined models, posterior cBF atrophy explained more variance in cortical hypometabolism (R 2  = 0.26, p < 0.001) than local atrophy in the cortical areas themselves (R 2  = 0.16, p = 0.01). Topographic correspondence analysis with the [ 18 F]FEOBV-PET pattern revealed that cortical areas showing most pronounced cBF-associated hypometabolism correspond to those showing most severe cholinergic denervation in PD (Spearman's ρ = 0.57, p < 0.001). In conclusion, posterior cBF atrophy in PD is selectively associated with hypometabolism in denervated cortical target areas, which mediates the effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University Hospital ‘Virgen del Rocío’ (approval number: 2158-N-20). Consent for publication: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Information on the prognostic value of immunoparesis (IP) recovery in multiple myeloma (MM) patients has been only generated in some observational and retrospective studies. We have evaluated the prognostic impact of IP recovery and its association with minimal residual disease (MRD) in a series of 113 newly diagnosed transplant-ineligible (NDTI) patients, that received fix duration treatment (18 cycles of VMP/lenalidomide-dexamethasone) within the PETHEMA/GEM2010MAS65 trial and who achieved CR or VGPR. Immunoglobulin levels were measured at diagnosis, at the end of treatment (after cycle 18th) and during subsequent follow up whereas MRD was analyzed only at the end of the treatment (after cycle 18th). We found that patients who had IP at diagnosis and recovered it during or after treatment had longer progression free survival (PFS) [p < 0.001; HR 0.32 (0.19-0.52)] and longer overall survival (OS) [p = 0.007; HR 0.40 (0.20-0.80)] compared to those who failed to recover it. When we analyzed IP recovery in MRD negative patients, we found that those cases with IP recovery had longer PFS [p = 0.007; HR 0.31 (0.13-0.76)] and longer OS [p = 0.012; HR 0.21 (0.06-0.80)] as compared to MRD negative patients but without IP recovery. In conclusion, IP recovery confers better prognosis in NDTI-MM patients with fixed duration treatment who achieve CR or VGPR and the prognostic value of MRD can be complemented when combined with IP recovery., Competing Interests: Declarations. Ethical approval: The review board or independent ethics committee of each participating center approved the study. This trial was registered at www.clinicaltrials.gov with the number #NCT01237249. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC., Patients and Methods: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis., Results: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient., Conclusion: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug., (Copyright © 2024 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression., Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/β-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350)., Results: R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased β2-microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNγ/IL-2 secretion. However, comparing N ≤ 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern., Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Familial chylomicronemia syndrome (FCS) is a very rare, underdiagnosed disorder that can cause abdominal pain and recurrent pancreatitis from childhood -potentially life-threatening- and chronic complications such as diabetes mellitus and exocrine pancreatic insufficiency. FCS affects the quality of life and mental health of those who suffer from it, aspects that must be taken into account in its treatment, based on a strict low-fat diet, which is difficult to adhere to and persist. People with FCS lack the lipolytic capacity to hydrolyze triglycerides (TG) and have a minimal or null response to conventional lipid-lowering treatments. ApoCIII antagonists, specifically volanesorsen, olezarsen and ARO-APOC3, are the most promising drugs to reduce TG concentrations in patients with FCS. Anti-ANGPTL3 therapies appear to be less effective. More clinical trials and new pharmacological treatments are needed to improve the quality of life and prognosis of people with FCS., (Copyright © 2024 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)