The venous excess ultrasound score (VExUS) is a promising method to assess venous congestion in adults, but evidence in children is scarce. This study aimed to evaluate the feasibility, reproducibility, and clinical usefulness of VExUS in pediatric patients. We also explored whether portal venous Doppler (PVD) alone could serve as a faster alternative and assessed the role of inferior vena cava (IVC) measurements. In this prospective single-center study, 35 pediatric patients were enrolled between 2022 and 2024. Associations between clinical variables and VExUS grades at admission (VExUS-0), 24 h (VExUS-24 h), and 48 h (VExUS-48 h), as well as PVD at corresponding time points, were analyzed. The relationship between IVC diameter and VExUS was also evaluated. VExUS demonstrated perfect reproducibility (κ coefficient and intraclass correlation coefficient = 1). Patients with VExUS-0 or VExUS-24 h grades 2–3 had longer aortic cross-clamp times (p = 0.03; 0.04) and higher vasoactive–inotropic scores (p = 0.01) than those graded 0–1. A higher incidence of acute kidney injury was observed in VExUS-24 h grades 2–3 (p = 0.04). Similar associations were found with PVD. Most patients with VExUS grades 2–3 had non-dilated IVCs according to pediatric reference values. Conclusion: VExUS is a feasible, reproducible, and clinically relevant bedside tool for detecting venous congestion in children. Its association with morbidity markers suggests prognostic potential, with optimal performance 24 h after PICU admission. PVD may provide comparable information in less time, while IVC diameter appears unreliable for this purpose.
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.
Infections are the most common adverse events associated with systemic treatment for psoriasis. Using data from the BIOBADADERM registry, we analyzed incidence rates of overall, serious, and special-interest infections associated with biologics and oral small molecules. Adjusted incidence rate ratios were calculated using propensity score analysis, with adalimumab as the comparator. The study included 4820 patients (8826 treatment cycles; 20,829 patient years of follow-up). The overall incidence of serious infections was low across all treatments (5.33%), with infliximab showing the highest incidence rate. The most frequent serious infections were pneumonia, followed by COVID-19 pneumonia and cellulitis. Among nonserious infections, respiratory tract infections were most common, followed by COVID-19 and urinary tract infections. Risankizumab and ustekinumab were associated with significantly lower risk of overall infections than adalimumab (P < .002). The risk of Candida infections was significantly higher with bimekizumab, brodalumab, secukinumab, and ixekizumab. Guselkumab, secukinumab, ixekizumab, and ustekinumab were linked to reduced incidence of respiratory infections. Ixekizumab was associated with a lower risk of COVID-19 infection, whereas dimethyl fumarate showed an increased risk compared with adalimumab. Overall, our findings support the favorable safety profile of biologics and small molecules in psoriasis, particularly regarding serious infections.
BACKGROUND AND AIMS:Conduction system pacing has emerged as an alternative to biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). The left-bundle CRT trial evaluated whether left-bundle branch area pacing (LBBAP) is non-inferior to BiVP in patients eligible for CRT. METHODS:The left-bundle CRT trial was a multi-centre, randomized, investigator-initiated, and non-inferiority study. Patients with guideline-based CRT indications and left-bundle branch block per Strauss criteria were randomized to BiVP-CRT or LBBAP-CRT. The primary endpoint was the proportion of patients with a positive CRT response at 6-months, defined as either an improved clinical composite score (CCS) or a ≥15% reduction in left ventricular end-systolic volume. The non-inferiority margin was the lower bound of the 95% confidence interval (CI) and was set at 10%. Patients were followed for 12-months; secondary endpoints included echocardiographic, clinical, and quality-of-life outcomes. RESULTS:The baseline characteristics of the 176 patients randomized to BiVP-CRT (n=84) or LBBAP-CRT (n=92) were similar, except for a wider intrinsic QRS in the LBBAP group: median 172 ms [IQR 158-184] vs. 165 ms [152-180]; P=0.04. Crossovers occurred in 26 patients (14.9%). In the intention-to-treat analysis, the primary endpoint was achieved in 94.6% of BiVP-CRT and 89.7% of LBBAP-CRT patients (RR 0.95; 95% CI 0.88-1.02), not meeting non-inferiority. CCS improved in 77% and 68% of patients randomized to BiVP-CRT and LBBAP-CRT, respectively and 85% and 79% had a ≥15% reduction in left ventricular end-systolic volume. Rates of adverse events and heart failure hospitalization were similar between groups. CONCLUSIONS:In CRT candidates with typical LBBB, LBBAP-CRT was not shown to be non-inferior to BiVP-CRT. Both strategies yielded high response rates and similar clinical outcomes.
Background:Systemic lupus erythematosus (SLE) is characterized by fluctuating activity and unpredictable flares that contribute to cumulative organ damage. Biomarkers capable of identifying patients at risk of near-term disease reactivation are needed. Interleukin-6 (IL-6) has been associated with SLE activity, but its prospective predictive value remains uncertain. Methods:We conducted a prospective, longitudinal, single-center study (2017-2023) including 188 adult with SLE. Serum IL-6 levels were measured at routine and unscheduled visits. Patients were categorized using a prespecified cutoff of 5 pg/mL. Disease activity was assessed using SLEDAI-2K (with values >4 suggesting active disease) and organ-specific manifestations. Prospective (lagged) associations were analyzed using the log-rank test. Discriminative performance was evaluated using ROC analyses and multivariable models adjusted for clinical confounders. IL-6 was compared with anti-double-stranded DNA antibodies and complement components C3 and C4. Results:During follow-up, 48% of patients had IL-6 levels >5 pg/mL. IL-6 >5 pg/mL was associated with a shorter time to subsequent flare, with a median time to SLEDAI-2K >4 that was 10 months shorter. Elevated IL-6 also predicted arthritis, nephritis, serositis, and hematologic manifestations. Concurrently, IL-6 demonstrated greater discriminative performance than anti-dsDNA, C3, and C4. Conclusions:Elevated circulating IL-6 levels are associated with short-term disease reactivation in SLE and may complement established biomarkers in longitudinal disease assessment.
