Hospital General Universitari de Castelló

In kidney transplantation, it remains unclear whether mammalian target of rapamycin inhibitors (mTORi) improve cardiovascular outcomes-through plaque stabilization and attenuation of left ventricular remodeling-or worsen them by deranging glucose and lipid metabolism. We aimed to assess the true impact of this drug class on major cardiovascular outcomes in a deeply phenotyped cohort with long-term follow-up. All patients transplanted at our center between 1st June 2013 and 31st December 2019 (n=845) were screened for inclusion. A total of 492 patients were selected through 1:1 propensity score matching (PSM) based on 18 key donor and recipient variables. All patients received tacrolimus (TAC), steroids, and either mTORi (n=246) or mycophenolic acid (MPA) (n=246). The primary outcome was major adverse cardiovascular events (MACE), defined as non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. Baseline variables were adequately balanced after PSM (absolute standardized difference<0.10). Over a mean follow-up of 4.81±2.49 years, MACE occurred in 78 patients (15.9%), with no significant difference between the mTORi and MPA groups (HR[95% CI] 0.84[0.54-1.30], P=0.443). Subgroup analyses-including patients with diabetes, prior MACE, stable immunosuppression, or pre-transplant ischemia testing-also showed no differences. Independent predictors of MACE were age (HR[95% CI] for upper tertile 2.17[1.38-3.42], P<0.001), dialysis vintage (HR[95% CI] for upper tertile 1.91[1.22-3.01], P=0.005), prior myocardial infarction (HR[95% CI] 2.12[1.19-3.78], P=0.011), and deceased vs. living donor graft (HR[95% CI] 3.42[1.47-7.92], P=0.004). Cardiovascular disease after kidney transplantation occurs due to non-modifiable risk factors and does not appear to be related to baseline immunosuppression.

For thousands of years, humans have been plagued by the deadly disease malaria, affecting millions of people and harming their physical, social, and economic well-being. Despite significant progress over the past two decades in reducing malaria-related morbidity and mortality, malaria remains a major public health threat, particularly in Ethiopia. It is important to assess the treatment outcome of severe malaria and the factors influencing them due to the high prevalence and epidemic nature of the disease in the Gambella region of Ethiopia. An institution-based retrospective study was conducted atGambella General Hospitalamong 417 children aged from one month to fourteen years who were admitted with severe malaria between May 2022 to May 2024. Data were collected using pre-tested data collection forms. The collected data were cleaned and entered into EPIData, which was again exported into statistical software for analysis. Bivariate and multivariable logistic regression analyses were used to determine associations between determinants and the outcome variable. A significance level was set at p < 0.25 and p < 0.05 for bivariate and multivariable logistic regression, respectively. Of 417 children enrolled in the study, the mean age was4.03years (SD of ± 2.11years). The overall case fatality rate for severe malaria was 9.11%. High case fatality rates were also observed among children presenting with severe anemia 31.8%, convulsions 27%, pulmonary edema 19.7%, Coma 18.5%, acute kidney injury 18.4%, and comorbid illnesses 16.9%. The majority of the children (91.7%) admitted to the hospital hadPlasmodium falciparum,which accounted for 34 (89.5%) of the deaths. Among the predictor variables assessed, convulsion, severe anemia, and comorbid illnesses were significantly associated with the outcome. In this study, the overall case fatality rate of severe malaria in children was notably high. This underscores the pressing necessity of prioritizing intervention packages that include preventive strategies, early detection, and the prompt identification of features that indicate severity.

Subcutaneous (SC) infliximab biosimilar CT-P13 has shown comparable efficacy and safety to the intravenous (IV) formulation in inflammatory bowel disease (IBD). However, long-term real-world data remain limited. This study assessed the three-year effectiveness, safety, and pharmacokinetics profile of SC CT-P13 in IBD patients switched from IV infliximab. Prospective, observational, multicenter study conducted in eight hospitals (Valencian Community, Spain). Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) receiving IV infliximab were switched to SC CT-P13 and followed for up to 3 years. Clinical activity, inflammatory biomarkers, adverse events, treatment persistence, and infliximab trough levels were assessed, including analyses according to immunomodulatory therapy (IM) use and dosing intensities. Seventy-four patients were included (43% UC, 57% CD). Mean SC CT-P13 trough levels increased significantly from baseline to 3 years (8.15 ± 5.93 to 15.89 ± 7.99 µg/mL, p<0.001), with consistent results across disease type, intensified dosing, and perianal CD subgroups. Inflammatory markers (CRP, calprotectin) remained stable throughout follow-up. Concomitant IM use decreased from 51% at baseline to 26.3% at study end, without changes in pharmacokinetics, clinical outcomes, or biomarkers. Treatment persistence at 3 years was 80% overall and 88% when considering only discontinuations due to loss of efficacy or adverse events. Fourteen patients (19%) experienced adverse events, predominantly mild. Switching from intravenous to subcutaneous infliximab biosimilar CT-P13 was associated with sustained treatment persistence, stable disease control, favorable pharmacokinetics, and good tolerability over 3 years. These real-world findings support SC CT-P13 as a convenient long-term maintenance option in routine clinical practice.

PURPOSEQuizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type (WT) FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3-ITD–negative AML. The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3-ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3-ITD–negative AML.METHODSThe phase II, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients age 18-70 years with ND FLT3-ITD–negative (mutant-to-WT allelic ratio <0.03) AML. Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety.RESULTSOverall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively (P = .046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P = .012); 3-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis.CONCLUSIONThe addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3-ITD–negative AML.