Hospital de Santa Maria

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

Cardiac organ damage (OD) is associated with increased risk of cardiovascular disease. However, limited knowledge exists on cardiac OD in young patients with cryptogenic ischaemic stroke (CIS). To explore prevalence and covariates of cardiac OD in patients with CIS compared to controls participating in the SECRETO study. We analysed data from 427 patients with CIS aged <50 years and 361 age- and sex-matched controls. OD was defined as presence of abnormal left ventricular (LV) geometry (LV hypertrophy or concentric remodelling) or left atrial enlargement (LAE) assessed by echocardiography, using sex-specific threshold values. Compared to controls, patients had higher prevalences of obesity and tobacco smoking, patent foramen ovale (PFO) (52% vs. 25%) and abnormal LV geometry (12% vs. 7%, all p < 0.01), while presence of LAE did not differ. In multivariable analyses, CIS was associated with presence of abnormal LV geometry (odds ratio 1.86 [95% confidence interval 1.09-3.20], p=0.024). In separate multivariable analyses in patients only, obesity was associated with both abnormal LV geometry and LAE (both p < 0.01), and higher systolic blood pressure only with presence of abnormal LV geometry (p < 0.001). No significant association with PFO was found. In young patients with CIS participating in the SECRETO study, abnormal LV geometry was more prevalent compared to age- and sex-matched controls and associated with presence of higher blood pressure and obesity. The results point to the importance of blood pressure and weight control in CIS to prevent progression of cardiac OD and recurrent cardiovascular events.

Abstract Introduction Some studies reported familial clustering of Peripartum Cardiomyopathy (PPCM), and also co-occurrence with Dilated Cardiomyopathy (DCM), a phenotypically similar disease. PPCM and DCM share a genetic predisposition, with truncating variants in the TTN gene accounting for 10% to 20% of cases in both conditions. Multifactorial etiopathogenesis is also described in both, and immunology may be part of it. History of the family A 65 year-old woman (index patient, fig.1A - III3) was admitted in 2022 with de novo severe heart failure (HF) and reduced LVEF-25% (fig.1B). She was previously healthy but due to a family history of PPCM in her two oldest sisters (who have died both with DCM and HF at 52 and 55 years (y)), she was regularly followed during the last 40 years. Eight months before admission, her ECG and echocardiogram were normal. Genetic testing identified a pathogenic heterozygous variant c.78009G&amp;gt;A, p.(Trp26003*) in the TTN gene. After 11 months of optimised therapy, LVEF was 50% (fig.1C) and remained stable thereafter. Her 42-year-old daughter (fig.1A, IV3), who had PPCM immediately after a normal pregnancy and delivery at 38y, developed acute HF (LVEF-32%) with cardiogenic shock, and the LVEF recovered slowly to 56% after 1 year (fig.1E). She is a carrier of the same TTNtvs identified in her mother. Going back 40 years, the oldest sister of the index patient (fig.1A, III1) developed severe HF at 32 years, 20 days after a normal pregnancy and delivery. She had severe LV dilation and diffuse hypocontractility (fig.1D). Without any benefit from symptomatic therapy, immunosuppression (prednisolone and azathioprine) was decided, and a rapid clinical improvement occurred, returning to everyday life. However, severely reduced LV function persisted (fig.1F, G). Her daughter, 39 years old (fig.1A, IV1), has a normal heart and had three uneventful pregnancies. She refused a genetic test. A similar clinical history had the second sister (fig.1A, II-2) who developed PPCM when she was 30y. She was also treated with immunosuppressive therapy with a good clinical response, but the reduced LV function also persisted throughout life. Her only daughter chose not to be a mother. She has a normal heart and also refused a genetic test. Conclusion PPCM and DCM may occur as individual entities, or pregnancy can act as a modifier to unmask the latent phenotype of familial TTNtvs DCM. This family illustrates the concept that the genetic predisposition to PPCM and DCM may be the same. However, different evolutive profiles can be observed throughout life in affected patients within the same family, making genotype-phenotype correlations particularly difficult in DCM and PPCM.

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Ocular syphilis in the Iberian Peninsula shows a wide clinical spectrum and frequent posterior segment involvement. Most patients achieved favourable serological and visual outcomes. These findings support the effectiveness of standard therapies and highlight the need for early diagnosis, especially in high-risk populations.

<h3>Background and Importance</h3> Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which impair chloride and sodium transport across epithelial cell membranes. The F508del mutation is the most common. Clinical manifestations are predominantly respiratory involvement, gastrointestinal, reproductive and sweat gland dysfunction. Therapeutic strategies have evolved from symptomatic management to targeted modulation of the defective CFTR protein, particularly with the combination elexacaftor/tezacaftor/ivacaftor (Kaftrio ) and ivacaftor (Kalydeco ). <h3>Aim and Objectives</h3> To assess whether treatment with Kaftrio and Kalydeco in adult CF patients is associated with improvement in respiratory function and reduction in the number of exacerbations, intravenous antibiotic courses and hospital admissions, as well as evaluate the safety of these therapies. <h3>Material and Methods</h3> A retrospective observational study was conducted including all patients aged 18 years or older who initiated Kaftrio and Kalydeco from their introduction until August 2025. Demographic, diagnostic and treatment data were collected. Sweat chloride concentration, faecal elastase, pulmonary function tests, the number of respiratory exacerbations, intravenous antibiotic cycles, and hospitalisations were compared between the 12 months before and after treatment initiation. Adverse reactions were also recorded. <h3>Results</h3> Fifty-seven adult CF patients carrying at least one F508del mutation were included, of whom 38 received Kaftrio and Kalydeco between August 2024 and 2025. Sweat chloride concentration showed a mean decrease of 32.2 mmol/L. Pulmonary function demonstrated significant improvement, with mean forced expiratory volume increasing from 55% to 72% of the predicted value and forced vital capacity from 80% to 90%. Supportive therapy remained stable, but inhaled antibiotic and corticosteroid use decreased. Only two patients required intravenous antibiotics and one was hospitalised during the last 12 months. The most frequent adverse events were headache, mood changes, mild gastrointestinal symptoms, and skin rash. <h3>Conclusion and Relevance</h3> Treatment with Kaftrio and Kalydeco showed significant clinical benefits, with improved respiratory function and reduced need for antibiotic therapy and hospital admissions. The safety profile was favourable, supporting the impact of these modulators as a major advancement in the management of adults with CF. <h3>Conflict of Interest</h3> No conflict of interest

LN.There was an overexpression of zonulin (p<0.01).sCD14 (p<0.005), and LBP (p<0.05) were also overexpressed.Finally, serum from SLE patients induced a significantly greater TLR4 response (p<0.05).Conclusions SLE patients exhibit dysbiosis, increased gut permeability, and endotoxemia.Interventions focused on gut microbiota and maintenance of gut barrier integrity may be promising therapeutic targets in this disease.