The exponential growth of cancer survivors represents a major healthcare challenge, with more than 23 million people in Europe and 2.2 million in Spain requiring long-term specialized follow-up. Five-year survival has reached 60
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.
ABSTRACT:Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially fatal multisystem complication of hematopoietic cell transplantation for which there is no approved treatment. In a single-arm study (NCT02222545), narsoplimab treatment for TA-TMA demonstrated a median overall survival (OS) of 274 days from date of diagnosis. Here, we compare OS observed in 2 cohorts treated with narsoplimab to OS in a well-matched external control to test survival benefit in patients with high-risk TA-TMA. OS in patients (aged ≥16 years) with high-risk TA-TMA treated with narsoplimab in a single-arm, open-label study (NCT02222545) or in the narsoplimab expanded access program (EAP; NCT04247906) was compared with OS in a control group with high-risk TA-TMA from the Kyoto Stem Cell Transplantation Group (KSCTG) registry. Narsoplimab-treated patients in the single-arm study (N = 28) had a fourfold reduction in risk of mortality compared with patients from the KSCTG registry (N = 111; hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.19, 0.34; P < .0001). Similarly, in high-risk patients treated with narsoplimab in the EAP (N = 49), mortality risk was significantly lower than among high-risk patients from the KSCTG registry (N = 121; HR 0.38; 95% CI 0.28, 0.51; P < .0001). When narsoplimab-treated patients from the single-arm study and the EAP (N = 77) were compared with KSCTG patients, the HR for mortality was 0.28 (95% CI, 0.22, 0.37; P < .0001). In conclusion, in patients with high-risk TA-TMA, narsoplimab treatment significantly reduced mortality relative to a well-matched external control group who did not receive narsoplimab. These results support narsoplimab as a potential therapeutic option for TA-TMA.
BACKGROUND:Dual antiretroviral therapy (ART) with dolutegravir/lamivudine (DTG/3TC) is widely used in virologically suppressed individuals. However, data remain limited on potential differential effects of ART regimens on mid-term systemic inflammation and metabolic health. We evaluated whether switching from DTG/3TC to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) modifies systemic inflammation or metabolic parameters. METHODS:INSTINCT was a phase IV, multicenter, open-label, randomized trial enrolling adults with HIV-1 on stable DTG/3TC and sustained viral suppression. Participants were randomized (1:1) to continue DTG/3TC or switch to BIC/FTC/TAF and followed for 96 weeks. Plasma biomarkers (sCD14, IL-6, sCD163, hsCRP, D-dimer, and kynurenine/tryptophan ratio) were measured at baseline, week 48, and week 96. Secondary outcomes included CD4⁺ and CD4/CD8 ratio, virological suppression, weight, lipid profile, and renal function. Longitudinal changes were analyzed using linear mixed-effects models. RESULTS:A total of 141 participants were randomized. Over 96 weeks, no significant between-group differences were observed in inflammatory biomarkers. CD4⁺ T-cell counts and CD4/CD8 ratio remained stable and comparable across arms. Weight changes were modest and similar; the proportion with ≥5% weight gain did not differ. No relevant differences were found in lipids, glucose, or eGFR. Virological suppression was maintained in >95% of participants. Adverse events were mild and balanced between groups. CONCLUSIONS:In virologically suppressed individuals, maintaining DTG/3TC or switching to BIC/FTC/TAF demonstrated equivalent profiles with respect to systemic inflammation, metabolic outcomes, and immunologic markers over 96 weeks.
ABSTRACT:The therapeutic landscape for systemic immunoglobulin light chain (AL) amyloidosis has been revolutionized by daratumumab-based regimens, achieving 76% 5-year overall survival in the landmark ANDROMEDA trial. However, the current prognostic models were developed using patient populations treated with now-suboptimal therapies, creating a critical gap between risk stratification models and contemporary outcomes. This comprehensive review analyzes prognostic factors and progression biomarkers in AL, categorizing them into disease-specific (clone-related and organ-related) and patient-specific factors. Notably, traditional baseline biomarkers including difference between involved and uninvolved free light chains and bone marrow plasma cell burden are losing prognostic significance with effective clone-directed therapies. Emerging approaches show promise, including dynamic markers such as minimal residual disease by free light chain mass spectrometry, cardiac imaging parameters such as global longitudinal strain, and functional measures. There is an urgent need for validation studies and prognostic model refinement to identify patients at high risk who may benefit from interventions beyond anti-plasma cell therapy.
