Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU.

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. 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. 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. 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). 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. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-001410-10 https://clinicaltrials.gov/study/NCT02994836

Anthracycline-induced cardiovascular toxicity: validation of the Heart Failure Association and International Cardio-Oncology Society risk score.

20.500.12530/87912Baseline cardiovascular toxicity risk stratification is critical in cardio-oncology. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score aims to assess this risk but lacks real-life validation. This study validates the HFA-ICOS score for anthracycline-induced cardiovascular toxicity. Anthracycline-treated patients in the CARDIOTOX registry (NCT02039622) were stratified by the HFA-ICOS score. The primary endpoint was symptomatic or moderate to severe asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), with all-cause mortality and cardiovascular mortality as secondary endpoints. The analysis included 1066 patients (mean age 54 ± 14 years; 81.9% women; 24.5% ≥65 years). According to the HFA-ICOS criteria, 571 patients (53.6%) were classified as low risk, 333 (31.2%) as moderate risk, 152 (14.3%) as high risk, and 10 (0.9%) as very high risk. Median follow-up was 54.8 months (interquartile range 24.6-81.8). A total of 197 patients (18.4%) died, and 718 (67.3%) developed CTRCD (symptomatic: n = 45; moderate to severe asymptomatic: n = 24; and mild asymptomatic: n = 649). Incidence rates of symptomatic or moderate to severe symptomatic CTRCD and all-cause mortality significantly increased with HFA-ICOS score [hazard ratio 28.74, 95% confidence interval (CI) 9.33-88.5; P The HFA-ICOS score effectively categorizes patients by cardiovascular toxicity risk and demonstrates strong predictive ability for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality

"Short" Versus "Long" Duration of Untreated Psychosis in People with First-Episode Psychosis: A Systematic Review and Meta-Analysis of Baseline Status and Follow-Up Outcomes.

20.500.12530/87858Duration of untreated psychosis (DUP) has been linked to worse mental health outcomes in psychotic disorders. We meta-analytically studied the relationship between "long" vs. "short" DUP and mental health outcomes. This PRISMA/MOOSE-compliant meta-analysis searched for nonoverlapping individual studies from database inception until November 01, 2023, reporting data from author-defined "short"/"long" DUP (according to author's definition) in patients with first-episode psychosis (FEP). We compared differences between "short"/"long" DUP groups at baseline and/or follow-up in continuous and binary outcomes. We conducted random-effects meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO: CRD42023479321). From 16,055 citations, 34 studies were included (n = 6,425, age = 27.5 ± 7.1 years, males = 60.4%, white = 70.2%, DUP: mean = 60.8 ± 43.8 weeks, median = 52.5, interquartile range = 31.3, 68.0 weeks, follow-up = 19.2 ± 35.0 months). The definition of "short"/"long" varies significantly between the studies. Compared to "short" DUP (mean = 10.2 ± 11.2 weeks), "long" DUP (mean = 58.8 ± 76.4 weeks) was associated with higher baseline Positive and Negative Syndrome Scale (PANSS) negative (k = 14, ES = 0.45, 95%CI = 0.16, 0.74) and Scale for the Assessment of Negative Symptoms (k = 7, ES = 0.29, 95%CI = 0.11, 0.47) scores, lower remission (k = 7, OR = 0.40, 95%CI = 0.24, 0.67) and more suicide attempts (k = 4, OR = 2.01, 95%CI = 1.36, 2.96). At follow-up, compared to "short" DUP, "long" DUP was associated with lower Global Assessment of Functioning (k = 4, ES = -0.63, 95%CI = -0.83, -0.43) and higher PANSS negative subscale scores (k = 5, ES = 0.66, 95%CI = 0.05, 1.27). In FEP, longer DUP is related to greater baseline negative symptoms, less remission, and more suicide attempts, as well as greater postbaseline negative symptom severity and functional disability. To what degree longer DUP contributes to poorer outcomes or whether DUP only correlates with these outcomes requires further study. A greater consensus on the definition of long DUP is needed to make comparisons between studies more feasible

Trichophyton indotineae extensive tinea: successful posaconazole treatment in four cases from Spain.

20.500.12530/8790

Response to: 'Correspondence on 'Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases'' by Aydin <i>et al</i>

20.500.12530/8785

Benefit-Risk Trade-offs and Patient Preferences for Therapy Selection in Ulcerative Colitis: a Multicountry Preference Study.

To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment. Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used. Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo. Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

20.500.12530/87908Limited 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. 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. 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. 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

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

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. 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. 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. 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

Ketone Bodies Are Potential Prognostic Biomarkers in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results from the R2-GDP-GOTEL Trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for high-dose chemotherapy have limited treatment options and poor life expectancy. The purpose of this study is to identify a serum metabolomic profile that may be predictive of outcome in patients with R/R-DLBCL. This study included 69 R/R DLBCL patients from the R2-GDP-GOTEL trial (EudraCT 2014-001620-299). Serum samples were collected at baseline, and the mean length of follow-up was 41 months. Serum metabolites were analyzed by nuclear magnetic resonance (NMR). Metabolites were correlated with treatment response, progression-free survival (PFS), and overall survival (OS). Serum levels of 3-hydroxybutyrate (3OHB) and acetone were significantly ( 141 μM) were specific to the ABC subtype of DLBCL, while acetone levels were elevated in both types of DLCBL but more pronounced in ABC cases. In a multivariate survival analysis, including the International Prognostic Index (IPI) score and refractoriness status (R/R), 3OHB and acetone remained significant. To aid oncologists employing the R2-GDP regime, we constructed PFS and OS nomograms for R/R-DLBCL risk stratification, incorporating 3OHB levels or acetone levels, IPI score, and refractoriness status. The nomogram with 3OHB and refractoriness status showed a time-dependent AUC of 0.86 for 6-month PFS and 0.84 for 12-month OS. These nomograms provide a comprehensive tool for individualized risk assessment and treatment optimization. The ketone bodies 3OHB and acetone are potential prognostic biomarkers of poor outcome in R/R DLBCL patients treated with the R2-GDP regimen, independently of IPI score and chemorefractoriness status

Long-term effectiveness and tolerability of dolutegravir/lamivudine in treatment-naive people with HIV: an analysis of a multicentre cohort at 96 weeks.

20.500.12530/87852To evaluate the long-term effectiveness, persistence and tolerability of dolutegravir (DTG)/lamivudine (3TC), compared with the most frequently prescribed first-line treatment regimens, among antiretroviral-naive people with HIV from CoRIS, a multicentre cohort in Spain, in 2018-23. We used multivariable regression models to compare viral suppression (VS) (HIV RNA viral load Of 2359 participants, DTG/3TC was prescribed in 472 (20.0%), bictegravir/tenofovir alafenamide (TAF)/emtricitabine (FTC) in 1134 (48.1%), DTG + tenofovir disoproxil fumarate/FTC in 300 (12.7%), DTG/abacavir/3TC in 273 (11.6%) and darunavir/cobicistat/TAF/FTC in 180 (7.6%). At 96 weeks from treatment initiation, 94.0% of participants initiating with DTG/3TC achieved VS, and the mean increase in CD4 cell counts was 295.5 cells/μL (95% CI: 269.9-321.1). During the first 96 weeks after DTG/3TC initiation, 9.8% and 1.3% discontinued their initial regimen, overall and due to AEs, respectively. In multivariable analyses, we did not find significant differences in VS or increase in CD4 cell counts among participants initiating with DTG/3TC compared with other regimens. Initiating ART with a regimen other than DTG/3TC was associated with a higher risk of treatment discontinuation, overall and due to AEs. Among treatment-naive people with HIV from this large multicentre cohort, DTG/3TC had similar effectiveness and better persistence and tolerability than those of the most frequently prescribed first-line regimens at 96 weeks