OBJECTIVES:Gonorrhoea, caused by Neisseria gonorrhoeae, is a significant public health challenge due to the rising incidence of antimicrobial resistant (AMR) strains. The Valencian Region, one of the top tourist destinations in Eastern Spain, has witnessed an increase of over 200% in the number of cases in recent years. Here, we aimed to investigate the impact of imported AMR lineages in shaping the local gonococcal population and generating sustained transmission events. METHODS:We analysed 1647 N. gonorrhoeae isolates collected in the Valencian Region between 2012 and 2024 with accompanying phenotypic antimicrobial susceptibility and epidemiological data. Genomic data was obtained through high-throughput sequencing and combined with 5894 genomes from national and international isolates. From these, information on typing and genetic AMR determinants was derived. Phylogenomic and statistical inference were used to investigate the local dynamics of this pathogen. RESULTS:Results revealed high levels of AMR, including 63.6% (n = 449/706) ciprofloxacin resistance, 17.7% (n = 195/1102) azithromycin resistance, and 8.4% (n = 66/783) reduced susceptibility or resistance to ceftriaxone. The two main circulating lineages were NG-STAR CC1615 and CC63, carrying 55.0% (n = 121/220) and 26.5% (n = 45/170) isolates with a mosaic mtr (mosaic mtrD and mtrR promoter), respectively. Phylodynamic analyses identified multiple introductions of AMR lineages into the region leading to sustained transmissions since the 1990s. These lineages significantly carried more isolates with mtr mosaics (OR = 4.17 [3.27-5.34]; p 1.26E-33) and phenotypic resistance to azithromycin (OR = 2.22 [1.60-3.06]; p 1.14E-06), among other antimicrobials. CONCLUSIONS:This study highlights the dynamic evolution and dissemination of AMR N. gonorrhoeae at the local level, highlighting the role of international mobility, sexual networks, and antibiotic usage in shaping resistance patterns. Enhanced genomic surveillance, with special monitoring of mosaic mtr-carrying lineages, together with targeted public health interventions, will be key to curb local and regional spread of resistant gonococcal strains.
Minimal disease activity (MDA) is an emerging therapeutic goal in atopic dermatitis (AD), providing a multidimensional assessment of disease control. We conducted a retrospective multicenter study of adults with moderate-to-severe AD receiving biologics or JAK inhibitors. MDA was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Pruritus Numerical Rating Scale (NRS) ≤ 1. Univariate analyses were performed to identify baseline predictors of sustained MDA at week 52 among patients who had previously achieved MDA at week 16. Among 197 patients with week 16 data, 107 (54.3
BACKGROUND:In previous studies, we identified a deficiency of γδ T cells and an increased prevalence of anti-Anisakis simplex antibodies in patients with Crohn's disease (CD). Additionally, decreased gene expression of the interleukin 2 (IL-2) receptor γ subunit (CD132) was observed in tissues from CD patients. OBJECTIVE:To analyse the gene expression of IL-7 and its receptors in tissues from CD patients and to explore its relationship with anti-A. simplex antibodies. METHODS:52 patients diagnosed with CD were compared with a control group of 52 healthy individuals. Peripheral blood samples were analysed to assess levels of anti-A. simplex antibodies and IL-7. In addition, intestinal tissue samples from 20 subjects in each group were examined to evaluate IL-7 gene expression, IL-7 protein levels, the IL-2 receptor γ subunit (CD132), the IL-7 receptor α subunit (CD127), and caspase-3 expression. FINDINGS:Anti-A. simplex antibody levels were elevated in patients with CD. Caspase-3 expression was significantly reduced in the tissues of CD patients with anti-A. simplex IgA, and this reduction extended to IgG and IgE in healthy individuals. A negative correlation was observed between caspase-3 levels and serum anti-A. simplex IgA, as well as IL-7 levels in the tissues of CD patients. In healthy subjects, tissue IL-7 levels were lower in those positive for anti-A. simplex IgA, while serum IL-7 levels were higher in individuals positive for anti-A. simplex IgG. MAIN CONCLUSIONS:This study revealed the interplay between IL-7 signalling, γδ T cell deficiency, and immune responses to A. simplex in CD. Our findings underscored a cause-effect relationship between CD132 deficiency, γδ T cell depletion, and defective mucosal immunity, which may drive both CD inflammation and susceptibility to parasitic infections like A. simplex.
In a large multicenter real-world cohort, we aimed to evaluate outcomes of FLAG-Ida salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) and validated the SALFLAGE prognostic score. We analyzed 1079 adults with R/R AML treated across 112 PETHEMA institutions over 26 years (1998-2024), including patients with primary refractory disease (36.9%) and first relapse episode (63.1%), with a median age of 52 years. Complete remission composite (CRc) was achieved 56.8%, including complete remission (CR) in 51.0%, CR with incomplete recovery in 4.0%, and morphological-free-state in 1.8%, enabling 35.2% of patients and 62% of responders to proceed to allogeneic transplantation without morphological disease. With median follow-up of 50.9 months, median overall survival (OS) was 10.2 months, with 5-year OS rate of 21.6%. Prior allogeneic transplantation (HR 0.54; p < 0.001) and relapse-free interval ≥ 1 year (HR 0.75; p = 0.024) independently predicted improved OS, whereas modified high-risk cytogenetics including t(8; 21) (HR 3.58; p < 0.001), FLT3-ITD mutation at primary diagnosis (HR 1.61; p < 0.001), and age ≥ 60 (HR 1.43; p < 0.001) conferred inferior OS. Validation of the SALFLAGE score demonstrated moderate discrimination (C-index 0.67), with 5-year survival of 38.4%, 27.2%, and 12.7% across risk categories (p < 0.001). Outcomes improved over periods (1998-2005 vs. 2006-2016 vs. 2017-2024): 30-day mortality was 6.9% vs. 9.3% vs. 5.0%, respectively (p = 0.030), and median OS was 7.8 versus 9.4 versus 11.1 months, respectively (p = 0.16). We confirm FLAG-Ida as a reference salvage regimen in fit R/R AML and validate the SALFLAGE score in this setting.
