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Novel perspectives on extracellular vesicles in autoimmune diseases: immunogenicity, inflammation, and immune surveillance
No full textCells release extracellular vesicles (EVs) with cargo that originates from distinct subcellular compartments, including the nucleus, cytoplasm, and plasma membrane. Given their diverse cargo, EVs play multiple roles in physiology and pathology, including in immune dysregulation and autoimmune pathogenesis. For example, EVs can act as autoantigens by transporting immunogenic molecules from the nucleus or cytoplasm, whereas EVs carrying membrane-bound MHCs from antigen-presenting cells can activate adaptive immunity by presenting self-antigens to T cells. EV-associated cytoplasmic peptidases or proteasomes contribute to immune regulation by modulating antigen processing and presentation. Moreover, EVs also drive inflammatory responses by shuttling a variety of proinflammatory molecules that sustain autoimmune responses. Intriguingly, emerging evidence indicates that EVs might contribute to autoimmune surveillance by activating cytosolic surveillance sensors, modulating immune checkpoints, regulating NK/T cell cytotoxicity, and altering macrophage and DC phagocytosis, representing an exciting and underexplored frontier in autoimmune research. By tackling critical knowledge gaps, this Review explores the emerging roles of EVs and their diverse cargo in driving autoimmune diseases, suggesting new perspectives on their potential as innovative therapeutic targets
Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: Pathophysiology, diagnosis, and emerging therapeutic strategies
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD), the updated terminology for fatty liver disease linked to metabolic dysfunction, is highly prevalent among individuals with type 2 diabetes mellitus (T2DM). MASLD affects a majority of patients with T2DM and markedly increases the risk of fibrosis, cirrhosis, hepatocellular carcinoma, and cardiovascular mortality. The pathogenesis in diabetic populations reflects a convergence of insulin resistance, dyslipidemia, mitochondrial dysfunction, chronic inflammation, and genetic predisposition. Advances in non-invasive diagnostics, including elastography and serum biomarkers, enable earlier identification and staging of disease, though limitations remain in diabetic cohorts. Lifestyle modification is the cornerstone of therapy, yet emerging pharmacotherapies are reshaping the therapeutic landscape. Antidiabetic agents such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and pioglitazone show hepatic benefits beyond glycemic control, while novel agents and combination regimens are under active evaluation. This narrative review synthesizes current evidence on epidemiology, mechanisms, diagnostics, and therapeutics of MASLD in T2DM, and highlights future directions in precision medicine. Integration of multidisciplinary care is essential to address this converging epidemic.
Keywords: Fatty liver; Glucagon-like peptide-1 receptor agonists; Hepatic fibrosis; Insulin resistance; Metabolic associated steatohepatitis; Metabolic dysfunction-associated steatotic liver disease; Non-invasive diagnostics; Personalized medicine; Sodium-glucose cotransporter-2 inhibitors; Type 2 diabetes mellitus
Muscle strength, neuromuscular function, and functional measures across stages of chronic kidney disease
No full textBackground
Individuals with chronic kidney disease (CKD) exhibit impairments to skeletal muscle function when compared to age-matched healthy controls. The current study was designed to compare muscle strength, functional measures, and the levels of some biomarkers across the stages of CKD compared to age-matched healthy controls (HC). Methods
Thirty-nine individuals with either CKD stage 3 (n = 10, age = 69.7 ± 9.95), stage 4 (n = 10, age = 66.5 ± 6.95), or stage 5 (n = 9, age = 58.7 ± 13.01) or age-matched HC (n = 10, age = 62.3 ± 10.4) were recruited to participate in this study. After obtaining approval from a physician, participants came to the lab on two occasions. The first lab visit consisted of the completion of an informed consent form, a health screening form, and a medical history questionnaire. Anthropometric measurements were then taken, as well as a blood sample via venipuncture. Next, a familiarization trial with maximum voluntary isometric contractions (MVIC) was performed, in addition to the six-minute walk test (6MWT), and the short physical performance battery test (SPPB). Participants visited the lab for the second time after a minimum of 72 h had passed. During this visit, three MVICs were performed. Force was recorded using a load cell. Concentrations of uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS), along with inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-⍺) were analyzed using commercially available enzyme-linked immunosorbent assays per the manufacturer’s instructions. Results
Uremic toxins IS and pCS, as well as the inflammatory marker IL-6 all increased significantly from HC to CKD stage 3, to CKD stage 4, and to CKD stage 5. TNF-⍺ increased significantly from HC to CKD stage 3, but not between the CKD groups. SPPB, MVIC, and 6MWT performance decreased significantly between HC to CKD stage 3, to CKD stage 4. No significant change was found in SPPB, MVIC, and 6MWT from CKD stage 4 to CKD stage 5. Conclusion
As CKD progresses, indices of muscular strength and functional measures decline compared to HC but the biomarkers, uremic toxins and markers of inflammation increase. These changes in biomarkers are associated with worsened skeletal muscle function
Impact of frailty on outcomes following percutaneous coronary intervention for acute myocardial infarction: A propensity-score matched analysis of 45,362 pairs
No full textAcute myocardial infarction; Frailty; Outcomes; Percutaneous coronary intervention; Risk stratification
Incarceration history and HIV testing among people who inject drugs in the Boston metro area: a pooled cross-sectional study
No full textBackground
The persistent incidence of HIV among people who inject drugs (PWID) underscores the urgency for HIV prevention efforts to end the HIV epidemic. Little is known about the role carceral settings play as touchpoints for HIV testing in this population. The objectives of this study were to characterize patterns and sources of HIV testing among PWID and to understand how carceral facilities fit into this population’s HIV testing landscape. Methods
Secondary analysis of cross-sectional survey data of PWID in the Boston metro area from the 2015 and 2018 cycles of the National HIV Behavioral Surveillance (NHBS). Among self-reported HIV-negative participants, we examined incarceration and HIV testing histories and used a multivariable modified Poisson regression model to evaluate the association between incarceration history (main exposure) and past-year HIV testing (primary outcome). Results
Among 957 participants, average age was 38.9 (SD 11.1) years, 70.1% were male, 15.2% were Hispanic (of any race), 8.4% were non-Hispanic Black, and 68.1% were non-Hispanic White. Regarding incarceration experiences, 43.5% of participants reported past-year incarceration, and 41.8% reported a history of incarceration but only prior to the past year. Among those with past-year incarceration, 23.4% said their last HIV test was done at a jail or prison. Adjusting for other characteristics, compared to no incarceration history, past-year incarceration (PR 1.39; 95% CI: 1.29, 1.49) and incarceration prior to the past year (PR 1.19; 95%CI: 1.02, 1.38) were both associated with a greater prevalence of past-year HIV testing. Conclusions
Among PWID, incarceration was very common and was a substantial source of HIV testing. However, more testing is still needed—in both community and carceral settings—to reach optimal testing rates in this key population. Data availability
The data analyzed in this study (National HIV Behavioral Surveillance data collected at the Boston site) are restricted and managed by the Massachusetts Department of Public Health. Inquiries about the Boston area NHBS data should be directed to [email protected]. The code used in this analysis is available from the authors upon reasonable request
Protocol for a randomized trial of a scalable, interactive tool to support surrogate decision-makers of critically ill patients
No full textBackground: Patients, particularly those at the end of their lives, frequently receive goal-discordant care, and their surrogate decision-makers suffer long-term psychological injury. Contributors to these issues may include infrequent communication between clinicians and surrogates, failure to discuss prognosis, values, and treatment options that include comfort-focused care, and surrogates facing high-stakes decision-making while underprepared and overwhelmed psychologically and emotionally.
Design: This is a multicenter, patient-randomized efficacy trial of a multi-component intervention, versus usual care, for 370 incapacitated, critically ill adults at high risk of death or severe disability, and their surrogate decision-makers, from 7 hospitals across the United States.
Intervention: The intervention combines surrogate utilization of a digital Family Support Tool (FST) in real-time during their loved one\u27s hospitalization with proactively scheduled family meetings, for which both surrogates and clinicians receive additional preparation, at set intervals during the ICU hospitalization. Those in the control arm will receive usual ICU care.
Outcomes: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care (PPPC) scale. Secondary outcomes include surrogates\u27 psychological symptom burden, communication and decision quality, and patients\u27 health resource utilization and clinical outcomes.
Conclusion: This trial will provide robust evidence about the impact of combining the FST with increased and intentional communication, on patient, family, and health system outcomes for those hospitalized in the ICU.
Keywords: Clinical trial; Intensive care; Palliative care; Patient-centered care; Quality of communication; Surrogate decision-making
Effect of Age on Restrictive and Liberal Transfusion Outcomes in Patients with Anemia and Myocardial Infarction
No full textFor patients with anemia and myocardial infarction, the randomized, 3504-patient MINT trial found that a liberal transfusion threshold (10 g/dL) may be preferable to a restrictive threshold (8 g/dL) in terms of death or myocardial infarction. The relative effects of liberal versus restrictive transfusion in younger and older patients are unknown. The present prespecified MINT sub-study found no significant interaction between age and transfusion strategy for death or myocardial infarction, heart failure, revascularization procedures, cardiac death, pulmonary embolism or deep vein thrombosis, and bacteremia or pneumonia and death at 30 and 180 days. A liberal transfusion approach appears to be safe and may be the preferred transfusion strategy in anemic patients with myocardial infarction, regardless of age. MINT Trial, ClinicalTrials.gov Number NCT02981407, https://www.minttrial.org/.
Keywords: Anemia; myocardial infarction; transfusion