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Real-world evaluation of the effectiveness and safety of dupilumab in bullous pemphigoid: an ambispective multicentre case series.
No full text20.500.12530/87910Bullous pemphigoid (BP) affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. Evaluate the effectiveness and safety of dupilumab in the treatment of BP. A multicentre ambispective cohort study was conducted across 34 hospitals. Patients with BP treated with dupilumab were included. Most of the patients (97.1%) received an initial 600-mg dose followed by 300 mg every 2 weeks. The primary outcome was the proportion of patients achieving complete remission (CR) within 4 weeks, defined as an Investigator's Global Assessment score of 0 or 1. CR at weeks 16, 24 and 52, adverse events (AEs), reductions in Peak Pruritus Numerical Rating Scale (PP-NRS) and systemic glucocorticoid use were also assessed. The study included 103 patients with a median age of 77.3 years; 58.3% were male. CR was achieved by 53.4% within 4 weeks and 95.7% by week 52. The PP-NRS score reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented with AEs, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated BP and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments. Dupilumab is effective, rapid and safe in managing BP, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes
Galectin 9 Levels as a Potential Predictor of Intact HIV Reservoir Decay.
No full text20.500.12530/87908During antiretroviral therapy (ART), the HIV reservoir shows variability, with cells carrying intact genomes decaying faster than those with defective genomes, particularly in the first years. The host factors influencing this decay remain unclear. Observational study of 74 PWH on ART, 70 (94.6%) of whom were male. Intact proviruses were measured using the intact proviral DNA assay, and 32 inflammatory cytokines were quantified using Luminex immunoassay. Linear spline models assessed the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over seven years. Baseline Gal-9 was the strongest predictor, with lower levels predicting faster decay. A 10-fold decrease in baseline Gal-9 correlated with a 45% (95% CI, 14%-84%) greater annual decay of intact HIV genomes. Higher baseline interferon-inducible T-cell α chemoattractant (ITAC), interleukin 17 (IL-17), and macrophage inflammatory protein 1α (MIP-1α) levels also predicted faster decay. Longitudinal increases in MIP-3α and decreases in IL-6 were linked to a 9.5% and 10% faster decay, respectively. The association between lower baseline Gal-9 and faster intact HIV decay suggests targeting Gal-9 could enhance reservoir reduction. The involvement of MIP-3α and IL-6 highlights a broader cytokine regulatory network, suggesting potential multi-targeted interventions
Evaluating the Benefit of Home Support Provider Services for Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea: Protocol for an Ambispective International Real-World Study.
No full text20.500.12530/87854Adherence and persistence to positive airway pressure (PAP) therapy are key factors for positive health outcomes. Home support providers participate in the home implementation and follow-up of PAP therapy for patients with obstructive sleep apnea (OSA). In Europe, home support provider service levels are country (or area) specific, resulting in differences in content and frequency of patient interactions. However, no robust evaluation of the impact of these differences on clinical and patient outcomes has been performed. The AWAIR study aims to evaluate and compare the impact of different home support provider service levels on PAP adherence and persistence in 4 European countries. This real-world, ambispective, cohort study-conducted in France, Belgium, Spain, and Portugal-will recruit adults with OSA who started PAP therapy between 2019 and 2023 and were followed by an Air Liquide Healthcare home support provider. Given the large number of eligible participants (around 150,000), the study will use a decentralized and digital approach. A patient video will present the study objectives and the participation process. A secure electronic solution will be used to manage patient information and consent, as well as to administer a web-based questionnaire. Retrospective data, collected during routine patient follow-up by home support providers, include the level of service and device data, notably PAP use. Prospective data collected using an electronic patient-reported outcome tool include health status, OSA-related factors, patient-reported outcomes including quality of life and symptoms, OSA and PAP literacy, patient-reported experience, and satisfaction with PAP therapy and service. Hierarchical models, adjusted for preidentified confounding factors, will be used to assess the net effect of home support provider services on PAP adherence and persistence while minimizing real-world study biases and considering the influence of country-level contextual factors. We hypothesize that higher levels of home support provider services will be positively associated with adherence and persistence to PAP therapy. As of December 2024, the study has received approval in France, Portugal, and 2 regions of Spain. The study began enrollment in France in October 2024. Results are expected in the second quarter of 2025. The AWAIR study has a unique design, leveraging an unprecedented number of eligible participants, decentralized technologies, and a real-world comparative methodology across multiple countries. This approach will highlight intercountry differences in terms of patient characteristics, PAP adherence, and persistence, as well as patient-reported outcomes, patient-reported experiences, and satisfaction with the home service provider. By assessing the added value of home support provider services, the results will support best practices for patient management and for decision-making by payers and authorities. PRR1-10.2196/65840
Can the dose of belimumab be reduced in patients with systemic lupus erythematosus?
No full text20.500.12530/87852The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyse treatment modalities, and determine impact on control of disease activity. Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in nine patients receiving subcutaneous BEL and in six patients receiving intravenous BEL. The dose per administration was reduced in 16 patients. Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively [not statistically significant (NS)]. As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable
Pericardial bioscaffold coated with ECM gels and urothelial cells for the repair of a rabbit urinary bladder defect.
No full textRepair of damaged or faulty complex modular organs such as the urinary bladder is a current clinical challenge. The design of constructs for reconstructive urological surgery can draw advantage from the bioactivity of natural extracellular matrix (ECM) bioscaffolds, as well as the activity provided by cells seeded into constructs. Considering these benefits, this work compares the performance of pericardial ECM bioscaffolds and constructs seeded with gel-supported urothelial cells in the repair of urinary bladder defects in rabbits. The bioscaffolds considered in this study are of porcine (pM) and bovine (bM) origin and exhibited a residual composition that confers bioactivity in mesh presentation. Coating an ECM gel on the bioscaffolds promoted the adhesion and viability of urothelial cells. Repairing a full-thickness urinary bladder defect in a rabbit model with the bioscaffolds and constructs resulted in the integration with the host bladder; meanwhile, bladder volumetric capacity was promoted using bM and constructs. Although no contribution of gel/cell seeding to the failure of mechanical properties of the urinary neobladder was observed, this seeding technique is suitable for integration with different strategies to engineer constructs for urinary bladder reconstructive surgery
The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.
No full text20.500.12530/87909ANCA-associated vasculitis (AAV) is a group of chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022 and September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. Twenty-nine patients treated with avacopan were analysed. Twelve patients (41.4%) were male, and median age was 56 years. Most patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean estimated glomerular filtration rate (eGFR) of 23.2 ml/min. Mean follow-up was 456.8 (±181.7) days with a remission rate of 86.2%. eGFR increased from 23.2 (11.2) to 38.38 (18.55) ml/min after 12 months of diagnosis. Two patients had adverse events related to avacopan (severe neutropenia and a gastrointestinal affectation), 13 infections were reported and one death. Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (P-values of 0.02 and The combination of avacopan with standard immunosuppressive therapy presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR and removal of steroids
Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study.
No full text20.500.12530/87913The 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. We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties. The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables. The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies
HIV Infection Is Associated With a Less Aggressive Phenotype of Inflammatory Bowel Disease: A Multicenter Study of the ENEIDA Registry
No full text20.500.12530/87908INTRODUCTION:The coexistence of HIV infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management are scarce. The aim of this study was to describe the IBD phenotype, therapeutic requirements, and prevalence of opportunistic infections (OIs) in IBD patients with a coexistent HIV infection. METHODS:Case-control, retrospective study includes all HIV-positive patients diagnosed with IBD in the Nationwide study on genetic and environmental determinants of inflammatory bowel disease registry. Patients with positive HIV serology (HIV-IBD) were compared with controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, sex, and type of IBD. RESULTS:A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis, 35% had Crohn's disease (CD), and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in ulcerative colitis and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, nonbiological therapies (37.4% vs 57.9%; P = 0.001) and biologicals (26.4% vs 42.1%; P = 0.007), were used less frequently among patients in the HIV-IBD group. Conversely, patients with HIV-IBD developed more OI than controls, regardless of nonbiological therapy use. In the multivariate analysis, HIV infection (odds ratio 4.765, 95% confidence interval (CI) 2.48-9.14; P = 1 comorbidity (OR 2.445, 95% CI 1.23-4.85; P = 0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95% CI 0.18-0.78; P = 0.009). DISCUSSION:HIV infection seems to be associated with a less aggressive phenotype of IBD and a lesser use of nonbiological therapies and biologicals but entails a greater risk of developing OI
Plasma Levels of Propionylcarnitine Improved Prediction of Heart Failure and All-Cause Mortality in Patients with Stable Coronary Artery Disease
No full text20.500.12530/87897Background: Plasma metabolites could be suitable as predictive biomarkers for cardiovascular pathologies or death, thereby improving the prediction of protein biomarkers. The release of acylcarnitines may be altered after coronary artery disease (CAD) in subjects with recurrent clinical outcomes, and this could be used as a prognosis tool. Methods: Patients with stable coronary artery disease (SCAD) who had suffered an acute coronary syndrome 6-9 months before were followed for up to 4.3 years for adverse events. Soluble pro-inflammatory/fibrotic proteins, and a panel of 13 amino acids and 13 acylcarnitines, were evaluated by ELISA and metabolomics analyses as potential predictors of a primary outcome [heart failure (HF) or death]. Results: Among 139 patients (67.0 years old, BMI = 28.6 kg/m(2), and 71.2% male), 25 developed the primary outcome after a mean follow-up of 2.2 years. These patients showed increased plasma levels of NT-proBNP (1300 vs. 250 pg/mL; p M, p = 0.007, and 3.22 vs. 6.49 x 10(-2) mu M,
Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.
No full textAcute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors. We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic PBGD gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue. Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP. This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment