The Hospital Universitario Ramón y Cajal is a public general hospital located in the Valverde neighborhood, in Madrid, Spain, part of the hospital network of the Servicio Madrileño de Salud.It is one of the healthcare institutions associated to the University of Alcalá for the purpose of clinical internship.
Lurbinectedin in combination with irinotecan showed synergistic antitumor activity in preclinical studies. A phase I/II trial (NCT02611024) evaluated this combination in patients with advanced solid tumors. The phase II stage evaluated the antitumor activity of the recommended dose (RD) (lurbinectedin 2.0 mg/m2 on Day (D)1 plus irinotecan 75 mg/m2 on D1 and D8 q3wk with primary granulocyte colony-stimulating factor prophylaxis) in five tumor-specific cohorts. This pooled analysis describes the safety profile of this combination from 233 patients with different advanced solid tumors treated at the RD. Adverse events (AEs) and laboratory abnormalities were graded using NCI-CTCAE v.4. The most frequent AEs (any grade) related to treatment were fatigue (71
Enzalutamide (ENZA), a next-generation non-steroidal androgen receptor (AR) inhibitor, plays a pivotal role in the management of both hormone-sensitive (HSPC) and androgen deprivation-resistant prostate cancer (ARPC). This paper presents real-world clinical outcomes of ENZA in a subgroup of metastatic HSPC (mHSPC) patients included in the ARON-3 study. Clinical information was extracted retrospectively from medical records at 29 cancer centres in 9 countries worldwide. Overall Survival (OS) was calculated from starting ENZA to death from any cause and the time on treatment (ToT) from ENZA initiation to discontinuation for any reason. The Kaplan–Meier method was used to estimate OS and ToT. PSA90 was defined as a ≥90% PSA reduction from baseline, and PSA0.2 as the achievement of an ultra-low PSA level ≤0.2 ng/ml. Adverse events (AEs) were categorised according to Common Terminology Criteria for Adverse Events v5.0. The study population comprised 424 patients treated with ENZA for mHSPC, of whom 80 (19%) had lymph node-only metastases, 265 (63%) bone-only metastases, and 50 (12%) visceral metastases. 273 patients (64%) had synchronous metastases and 151 (36%) had developed metachronous metastases. A total of 228 patients were diagnosed with low-volume disease, and 196 patients (46%) with high-volume disease. The median ToT was 31.8 months, and the median OS was not reached. The median time to PSA90 (achieved in 76% of patients) and PSA0.2 (59% of patients) was 6.0 months and 8.3 months, respectively. Statistically significant associations were identified between lymph node-only patterns, PSA90 and ultra-low PSA responses, and longer treatment duration and better overall survival. Grade 3–4 AEs were observed in 9% of patients <70 years and in 10% ≥70 years. Real-world clinical practice corroborates the findings from clinical trials, confirming the effectiveness and safety of ENZA in mHSPC patients.
Hyperprolactinemia is classically linked to reproductive dysfunction, but emerging evidence suggests an association with metabolic and cardiovascular (CV) risk. This study evaluated sex differences in CV risk factors (CVRFs) and cardiovascular disease (CVD) in patients with hyperprolactinemia. A multicenter, retrospective cross-sectional study was conducted in 449 adult patients (199 men, 250 women) with confirmed hyperprolactinemia from 19 tertiary referral centers in Spain. Clinical, biochemical, and hormonal data were collected and analyzed. The prevalence of CVRFs and CVD was compared between sexes. Associations between serum prolactin levels and CVRFs/CVD were assessed using nonparametric tests, correlation analyses, and multivariable logistic regression. Men had significantly higher serum prolactin levels than women (median 796 [IQR 250–1499] vs. 114 [74.5–224] ng/mL; p < 0.001) and a greater crude prevalence of all major CVRFs (p < 0.001 for all). After adjustment for age, male sex remained independently associated with smoking (OR 2.16; p = 0.007) and hyperlipidemia (OR 1.97; p = 0.031). Serum prolactin levels positively correlated with age, BMI, systolic blood pressure, glucose, total cholesterol, and triglycerides (all p < 0.001). In sex-stratified analyses, prolactin was associated with BMI and lipid profile in men, and with hypertension and hyperlipidemia in women. Prolactin levels were significantly elevated in patients with any form of CVD (p = 0.007), particularly arrhythmias (p = 0.013), while a trend was noted for ischemic heart disease (p = 0.050). Men with hyperprolactinemia exhibit a more adverse cardiometabolic profile, characterized by higher serum prolactin levels and a greater burden of classical CVRFs and CVD. Prolactin concentrations are positively associated with multiple metabolic and CV parameters, with sex-specific patterns suggesting distinct mechanisms of susceptibility and regulation. These findings underscore the importance of incorporating sex and hormonal context into CV risk assessment in patients with hyperprolactinemia.
Background HIV-exposed uninfected (HEU) children represent a little-studied growing population. We aimed to determine whether perinatal HIV exposure imparts long-term immune alterations. Methods A prospective cohort including 91 children (<13 years) from México was classified into four groups: HIV unexposed-uninfected (HUU, n=25), HEU (n=25), HIV exposed infected with undetectable (HEIundetVL, n=25) or detectable VL (HEIdetVL, n=16). Sixty-four immune biomarkers were measured in each child: 55 proteins in plasma and 9 mRNAs in paired-dried blood samples Results Principal Component Analysis revealed that HEU exhibited similarity to HEIundetVL and higher inter-individual variability than HUU. HEU children exhibited significantly higher levels of IL-17A, TIM-3, P-Selectin and CD14 mRNA along with lower levels in Serum amyloid A (SAA), IGFBP-4, Myeloperoxidase and tPA compared with HUU. Despite no differences in age at diagnosis, CD4 counts, or ART exposure time between the HIV-exposed and infected groups, active infection (HEIdetVL) was associated with significant alterations in 15 markers, indicating extensive immune dysregulation. These included higher levels of myeloid activation markers (sCD14, sCD163), chemokines (CXCL10), VEGF-A, immune-checkpoints (Galectin-9, PD-1 mRNA) and markers of vascular inflammation and coagulation (tPA, ICAM-1, Myeloperoxidase, N-GAL, or SAA), as well as lower levels of four immune-checkpoints (sCD86, sCD137, CTLA-4) and MMP-2, compared with HEIundetVL. Logistic regression models identified SAA, TIM-3 and IGFBP-4 as independently associated with HIV exposure, achieving an accuracy of 82% in classifying HEU vs. HUU children, whereas downregulated sCD86, combined with elevated Galectin-9 and VEGF-A levels, were independently associated with active HIV viremia, with a classification accuracy of 92.7%. Conclusions Perinatal HIV exposure induces persistent immune alterations, even in uninfected children, including elevated cytokines, immune-checkpoints, thrombosis and vascular inflammation markers. These findings suggest that, even without acquiring HIV, exposed children exhibit immunological imprints that may contribute to increased risk of adverse health outcomes.
BackgroundChitinase 3-like 1 (CHI3L1) is a prognostic biomarker in multiple sclerosis (MS). However, its clinical application is limited by a lack of standardized detection methods and concerns about preanalytical variability.ObjectivesThis study aims to evaluate the impact of preanalytical factors (delayed processing of blood and repeated thawing/freezing) on serum CHI3L1 levels. Additionally, we sought to correlate CHI3L1 blood and cerebrospinal fluid (CSF) levels and identified its cellular source in peripheral blood mononuclear cells (PBMCs) from MS patients.MethodsWe used an in-house Single Molecule Array (Simoa) assay to measure CHI3L1 levels in serum, plasma, and CSF from MS patients and controls. The source of CHI3L1 production in PBMCs was determined by flow cytometry.ResultsA strong correlation was found between serum, plasma, and CSF CHI3L1 levels. Serum CHI3L1 levels remained stable with delayed processing up to 6 hours and for up to three freeze-thaw cycles. Monocytes, particularly classical monocytes (CD14++CD16- cells), were identified as the main producers of CHI3L1 in PBMCs.ConclusionsThe study establishes preanalytical guidelines for sCHI3L1 assessment and confirms that blood levels can be as informative as CSF levels. This provides groundwork for the standardized use of CHI3L1 as a biomarker in managing MS patients.
