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.
Inflammation is a biological phenomenon beneficial for homeostasis, but it is unfavorable if dysregulated. Although major progress has been made in characterizing inflammation in specific diseases, a global, holistic understanding is still elusive. This is particularly intriguing, considering its function for human health and the potential for modern medicine if fully deciphered. In this study, we leveraged advances in single-cell transcriptomics to delineate inflammatory processes of circulating immune cells during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of more than 6.5 million peripheral blood mononuclear cells from 1,047 patients (56% female, 43% male) and 19 diseases allowed us to learn a comprehensive model of inflammation in circulating immune cells. The atlas expands current knowledge of the biology of inflammation of immune-mediated diseases, acute and chronic inflammatory diseases, infections and solid tumors and lays the foundation to develop a disease classification framework using unsupervised as well as explainable machine learning. Beyond a disease-centered analysis, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting discriminative inflammation-related genes to further understand mechanisms of inflammation. We present a rich resource for the community and lay the groundwork for learning a classifier for inflammatory diseases, presenting cells in circulation as living biomarkers.
Chronic infection by hepatitis B virus (HBV) and hepatitis D virus (HDV) continues to pose a major public health challenge in Spain due to its high morbidity and mortality and the risk of progression to cirrhosis and hepatocellular carcinoma. Although effective tools exist for the control of hepatitis B and recent therapeutic advances have been made for hepatitis D, significant inequalities persist in early diagnosis, access to treatment, and appropriate patient follow‑up. This consensus document has been jointly developed by the Spanish Association for the Study of the Liver (AEEH), the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)—through its Viral Hepatitis Study Group (GEHEP)—the Spanish Society of Digestive Pathology (SEPD), the Spanish Society of Family and Community Medicine (semFYC), the Spanish Society of Hospital Pharmacy (SEFH), the Alliance for the Elimination of Viral Hepatitis in Spain (AEHVE), and the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition (SEGHNP). The objective is to provide updated and consensus‑based recommendations on the diagnosis, management, and treatment of chronic HBV and HDV infection, from a multidisciplinary perspective and adapted to real‑world clinical practice. The document addresses screening and diagnostic strategies, criteria for assessing liver fibrosis, indications for antiviral treatment, specific management of hepatitis D, and the role of coordination between primary care and hospital care. Likewise, it emphasizes the need to implement strategies to advance toward the goals of viral hepatitis elimination.
OBJECTIVES:To analyze the current situation of Healthcare Ethics Committees (HECs) in Spain, their composition and functions, as well as the implementation of Clinical Ethics Consultancy (CEC). Finally, to assess the involvement of internists in HECs. MATERIALS AND METHODS:A cross-sectional descriptive study conducted through a self-administered online survey distributed between February and May 2025 to all identified HECs in the country. RESULTS:A total of 112 HECs (47.66%) out of the 235 accredited nationwide participated. The average number of members per committee was 16 (range: 6-29). The most represented professional profiles were nursing and medicine. In 99.1% of the committees, at least one member had postgraduate training in Bioethics. The most frequent range of meetings per year was between 7 and 12 (46.8%). Most HECs (91.1%) were involved in educational activities, and 58% had produced ethical documents. The majority reviewed between 1 and 5 cases annually (69.6%). The CEC role was established in 40.2% of HECs and in the process of implementation in 18.8%. Internists were present in 54% of HECs. In 65% of cases, the internist is part of the CEC. CONCLUSIONS:HECs in Spain demonstrate significant involvement in educational activities and the development of ethical documents; however, they receive a relatively low number of annual consultations. Clinical Ethics Consultancy is gradually being integrated into the structure of HECs, which may enhance the management of ethical inquiries. Internists are members of more than half of the HECs and play a very active role in their operations.
Background: Frailty has emerged as a critical factor to predict postoperative outcomes in elderly surgical patients. This study aimed to evaluate the prevalence of frailty and its association with morbidity and mortality after elective and emergency general surgery in older adults across Spain, using two validated screening tools: the Clinical Frailty Scale (CFS) and PRISMA-7. Methods: We conducted a prospective, multicenter observational study including 32 Spanish hospitals. Patients aged >70 years undergoing general surgery between October and December 2022 were consecutively enrolled. Frailty was assessed preoperatively using CFS and PRISMA-7. The primary endpoint was 30-day mortality; secondary outcomes included overall postoperative complications, severity of complications, and hospital readmissions. Surgical complexity was categorized using the Operative Severity Score. Predictive performance was assessed using ROC curves. Results: A total of 2051 patients were included (median age 77). Frailty prevalence was 39.5% using CFS and 40.8% according to PRISMA-7. Overall, 30-day mortality was 6.2%, and 34% experienced at least one postoperative complication. Both scales showed good predictive value for mortality (AUROC 0.77 for CFS and 0.75 for PRISMA-7) but limited capacity for predicting complications or hospital readmissions (AUROC < 0.65). Frailty was independently associated with increased mortality, especially in procedures of higher complexity. Conclusions: Frailty is highly prevalent in elderly surgical patients and is a strong predictor of 30-day mortality. The systematic screening of frailty using validated tools such as the CFS and PRISMA-7 should be incorporated into perioperative care pathways to enhance risk stratification and support clinical decision-making.
