26-A-17807-ACC CORRELATION OF SOCIAL DETERMINANTS OF HEALTH AND CLINICAL COMPLEXITY AMONG PATIENTS ADMITTED WITH ACUTE HEART FAILURE

Journal of the American College of Cardiology · 2026-03-27

Mitochondrial Transplantation as a Therapeutic Strategy for Inherited Mitochondrial Diseases

Advanced Science · 2026-01-22 · 1 citations

Mitochondria are essential organelles responsible for cellular energy production and diverse metabolic processes. Mitochondrial dysfunction is implicated in a wide range of diseases. Specifically, genetic mitochondrial diseases, arising from mutations in mitochondrial or nuclear DNA, lead to significant mitochondrial deficits, which result in debilitating and often life-threatening symptoms. Conventional treatments frequently fail to address these underlying mitochondrial defects, leaving few therapeutic options. Mitochondrial transplantation (MTx), an emerging therapeutic approach involving the delivery of healthy exogenous mitochondria to target cells, has demonstrated beneficial effects in various mitochondria-mediated diseases in both preclinical and early clinical studies. However, its application to inherited mitochondrial disorders remains largely unexplored and raises important questions about the need for repeated or continuous administration to sustain therapeutic effects. This review systematically examines the potential of MTx for inherited mitochondrial disorders by classifying these diseases by mitochondrial and nuclear DNA origin, critically assessing MTx evidence and mechanisms, and identifying unique translational requirements for chronic inherited disorders. While significant challenges remain, MTx represents a promising approach to directly address mitochondrial dysfunction in these life-threatening conditions with limited therapeutic alternatives.

Optimizing infection management after cardiac arrest: addressing diagnostic uncertainty and therapeutic dilemmas—a narrative review

Journal of Intensive Care · 2026-01-28

Infections are frequent after cardiac arrest and materially affect post-ICU care and outcomes. Diagnostic uncertainty is heightened by post-cardiac arrest syndrome (PCAS)-hypoxic-ischemic brain injury, myocardial dysfunction, systemic ischemia-reperfusion injury, and immune dysregulation-and by sedation and targeted temperature management (TTM), which can mask clinical signs and modulate host defenses. Pneumonia predominates; bloodstream infection and intra-abdominal or hepatobiliary infections are under-recognized, especially in device-dependent or extracorporeal membrane oxygenation (ECMO)-treated patients. Conventional biomarkers such as C-reactive protein and procalcitonin show reduced infection specificity early after return of spontaneous circulation; therefore, single timepoint cutoffs are unreliable, and serial trajectories interpreted with clinical examination, microbiology, and imaging are preferred. Risk scores (e.g., Sequential Organ Failure Assessment [SOFA], Clinical Pulmonary Infection Score [CPIS]) may support stratification but are insufficient for definitive diagnosis. Observational cohorts report higher pneumonia rates with TTM, and temperature control can blunt fever and leukocytosis and alter cytokine and biomarker kinetics, complicating timely recognition. Prevention should emphasize protocolized bundles, including hand hygiene and asepsis, head-of-bed elevation, structured oral care per local policy, minimization of sedation with spontaneous breathing trials, and early removal of unnecessary devices, within an antimicrobial stewardship framework that supports early de-escalation once cultures and trajectories clarify etiology. Procalcitonin-guided early discontinuation reduces antibiotic exposure in general critical-care populations; in PCAS, use should prioritize serial trends integrated with clinical context rather than single thresholds. No fixed algorithm is prescribed; instead, practical considerations are presented to guide diagnostic practice, emphasizing early microbiological sampling and imaging, integration of serial biomarker trajectories with clinical assessment, and timely de-escalation as the clinical picture clarifies, without endorsing single-test cutoffs. Priorities include quantifying infection-attributable morbidity and mortality; developing and validating PCAS-specific biomarkers and composite decision tools, including electronic health record-based early warning models; evaluating short post-intubation prophylaxis in selected high-risk patients; optimizing TTM parameters (target temperature, duration, rewarming rate); and systematically characterizing under-recognized infections. A protocol-driven, multimodal program that integrates prevention, standardized diagnostics, and stewardship is required to deliver timely, appropriate therapy and improve outcomes after cardiac arrest.

Abstract 4366118: Assessing Social and Clinical Determinants of Hospital Length of Stay Among Emergency Department Patients with Acute Heart Failure

Circulation · 2025-11-03

Introduction: Acute Heart Failure (AHF) is the leading cause of hospitalization in adults over 65. Prolonged hospital stays increase morbidity and costs. While clinical severity is a known contributor to length of stay (LOS), the influence of social factors is less understood. This study aims to identify clinical and social determinants associated with hospital LOS in AHF patients presenting to the emergency department (ED), with a focus on the predictive value of the Emergency Heart Failure Mortality Risk Grade (EHMRG) score. Research Questions: How does the EHMRG score correlate with extended LOS in AHF patients admitted through the ED? What social determinants of health are most strongly associated with extended hospital LOS in AHF patients? Methods: The study presents a pilot analysis of a larger multicenter retrospective study of 15,000 AHF patients admitted via nine EDs in 2019. A stratified random sample of 2,400 admissions underwent manual chart review. Data from electronic health records included demographics, medical history, vital signs, labs, and social risk factors. Prior-year ED notes were reviewed for visit frequency, and EHMRG scores were calculated. Patients were grouped by LOS: <5 days, 5–10 days, or >10 days. Primary outcomes included risk scores, labs, healthcare utilization, and discharge plans. Descriptive statistics, chi-square, and ANOVA were used (p<0.05). Results: A total of 592 AHF patients were analyzed (mean age 77.3; 51.9% male); 309 had LOS <5 days and 109 had LOS >10 days. The >10 day group had significantly higher EHMRG scores (p<0.001) and elevated creatinine levels (p=0.0052) compared to the <5 days group. Social determinants were also strongly associated with extended LOS. Patients with financial concerns at discharge had longer LOS (p=0.01), and patients discharged to short-term skilled nursing facilities were significantly more likely to have LOS >10 days compared to <5 days (p<0.00001). Conclusion: Higher EHMRG scores and elevated creatinine levels were significant clinical predictors of extended LOS. Social factors such as financial concerns and discharge to skilled nursing facilities were also independently associated with prolonged hospitalization. These findings underscore the value of integrating social determinants into risk stratification and discharge planning. Future efforts should develop integrated clinical-social predictive models to improve outcomes and reduce avoidable hospital utilization.

Feasibility of Xenogeneic Mitochondrial Transplantation in Neuronal Systems: An Exploratory Study

Life · 2025-06-23 · 1 citations

Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post–xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability.

2022 Interim Guidance to Health Care Providers for Basic and Advanced Cardiac Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration With the American Academy of Pediatrics, American Association for Respiratory Care, the Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists

UNC Libraries · 2025-04-17

The American Heart Association, along with its collaborating organizations American Academy of Pediatrics, American Association for Respiratory Care, American Society of Anesthesiologists, and the Society of Critical Care Anesthesiologists, is committed to providing the most up-to-date evidence-based guidelines on resuscitation and supporting the health care providers that provide these interventions. At times, there is a need for an interim statement based on new data or, in the case of this pandemic, a rapidly changing environment. Interim guidance may arise from a scientific review of a single topic, or the need for a best-practice statement because of new or urgent public health initiatives. Based on evolving epidemiological reports, emergence of new and more transmissible strains of the coronavirus, declining vaccine effectiveness, as well as recent feedback from the health care provider community, it became clear that the guidance developed in the spring of 2021 and published in October 2021 needed to be updated to emphasize fully protecting health care providers who perform resuscitation. Our overall guiding principles and goals in providing this interim guidance are to achieve the best possible resuscitation outcomes and simultaneously ensure optimal protection for health care providers. Language has been clarified in this updated interim guidance to adhere to this guiding principle. Interim guidance will continue to evolve as the pandemic continues to ensure our guidance reflects the best, most up-to-date science and available evidence to guide best practices.

The Promise of Biostasis: A New Frontier in Medicine

Proceedings of the American Philosophical Society held at Philadelphia for promoting useful knowledge · 2025-06-01

Abstract: Biostasis sits at the center of a rapidly evolving field that challenges our understanding of life, death, and the processes in between. As a physician and researcher who has spent forty years studying how to bring the seemingly dead back to life, I have witnessed firsthand the limitations of traditional resuscitation methods and the immense potential of emerging biostasis techniques. These advancements, ranging from artificial circulation and temperature control to novel pharmacological interventions, offer new possibilities for extending the window of survival and improving outcomes in critical care, surgery, and even space travel. The potential applications of biostasis are vast, with implications for everything from emergency medicine to organ transplantation, and even long-duration space missions, on which metabolic suspension could be invaluable.

Abstract Sat303: Association of Metformin Use with Survival from Cardiac Arrest in the Emergency Department

Circulation · 2025-11-03

Background: Metformin, an anti-diabetic oral medication with anti-inflammatory properties, has been shown in animal models to protect against ischemia-reperfusion injury post Cardiac Arrest (CA). There is a paucity of data on the survival outcomes of Emergency Department (ED) patients with metformin use. Research Question: Our objective was to investigate the association of CA outcomes in ED patients with reported history of metformin use prior to CA. Aims: We sought to determine the association of history of metformin use prior to CA in the ED with survival to admission, hospital discharge, and neurological function. Hypothesis: Metformin use prior to ED CA is associated with increased odds of survival to admission, hospital discharge, and improved neurological function. Methods: This is a single-center, registry-based, retrospective cohort study of adult, non-traumatic CA patients seen in our quaternary care ED from 1/3/2017 to 8/25/2024. Patients with existing do not resuscitate orders were excluded. Outside hospital cardiac arrest (OHCA) as well as in ED CA patients were included. Patient demographics, history of diabetes mellitus (DM) and metformin use, pre-hospital and/or ED initial rhythms, survival to admission and hospital discharge, and neurologic function on modified Rankin Scale (mRS) were collected and entered into the registry. Descriptive statistics, bivariate tests and multivariable regression analysis were used. Results: 744 CA patients were included. Median age was 76 years (IQR: 63-86), 59.3% male, 55.1% White, and 75.5% OHCA. Initial prehospital shockable rhythm in OHCA was 16.6%. ED shockable rhythm was 13.9%. Overall, 34.4% had DM history and 68 (9.1%) had history of metformin use, which was associated with increased survival to admission (54% vs 41%, p=0.03) and survival to discharge (23% vs 12%, p=0.01) compared to no metformin use (table 1). When controlling for age and initial rhythm, there was no significant difference in survival to hospital admission; however, survival to hospital discharge was higher with metformin use (OR 2.68; 95% CI 1.13-6.34; table 2). mRS were comparable. Conclusion: Metformin use prior to OHCA and ED CA is associated with higher odds of survival to hospital discharge, but no difference in survival to hospital admission when controlling for age and initial rhythm.

Beneficial effects of mitochondria-targeted S-nitrosothiol on outcomes after cardiac arrest and resuscitation in rats

Free Radical Biology and Medicine · 2025-08-12 · 3 citations

The role of homogenization cycles and Poloxamer 188 on the quality of mitochondria isolated for use in mitochondrial transplantation therapy

Scientific Reports · 2025-01-27 · 2 citations

Mitochondrial transplantation (MTx) offers a promising therapeutic approach to mitigate mitochondrial dysfunction in conditions such as ischemia-reperfusion (IR) injury. The quality and viability of donor mitochondria are critical to MTx success, necessitating the optimization of isolation protocols. This study aimed to assess a rapid mitochondrial isolation method, examine the relationship between mitochondrial size and membrane potential, and evaluate the potential benefits of Poloxamer 188 (P-188) in improving mitochondrial quality during the isolation process. Mitochondria were isolated from pectoral muscle biopsies of adult male Sprague-Dawley rats using an automated homogenizer. MitoTracker Deep Red (MTDR) staining and flow cytometry were used to assess mitochondrial purity, while the JC-1 assay evaluated membrane potential. Mitochondrial size groups were compared for membrane potential differences. Homogenization frequency and P-188 supplementation (1 mM) were assessed for their effects on mitochondrial membrane potential and particle size, and particle counts. The rapid isolation method yielded mitochondria that retained sufficient membrane potential to be effectively inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a disruptor of mitochondrial membrane potential. Larger mitochondria exhibited significantly higher JC-1 ratios, indicating greater membrane potential. Excessive homogenization (10 cycles) reduced membrane potential compared to 3 cycles homogenization (P = 0.026). P-188 significantly increased the JC-1 ratio from 10.26 ± 2.57 to 33.78 ± 17.78 (P = 0.023). Particle size and count analysis revealed that 10 cycles homogenization significantly increased particle count compared to 3 cycles homogenization (P = 0.0001), but was associated with smaller particle sizes (P = 0.0031). The rapid mitochondrial isolation method produced viable mitochondria, with larger mitochondria exhibiting superior membrane potential. Reducing homogenization frequency and incorporating P-188 improved mitochondrial quality and preserved particle size. These strategies offer promising strategies for optimizing MTx protocols. Further refinement of these techniques is necessary for their clinical application in MTx therapy.