Reddy, Swetha

Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248 .

Background: Sepsis survivors experience substantial long-term cardiovascular (CV) morbidity and mortality. The pooled-cohort atherosclerotic cardiovascular disease (ASCVD) score estimates 10-year risk in the general population, but its accuracy soon after sepsis is unknown. Objectives: (1) Describe the absolute five-year incidence of major adverse cardiovascular events (MACE) after sepsis hospitalization. (2) Evaluate the discrimination and calibration of the 10-year ASCVD score for predicting five-year MACE in this setting. Research Questions: The ASCVD score would underpredict five-year MACE in sepsis survivors, reflecting their heightened risk. Methods: We performed a retrospective closed-cohort study using electronic health records from Mayo Clinic hospitals (USA). Adults aged 40–75 years hospitalized for sepsis between 2018 and 2020 were eligible if follow-up was ≥5 years; the age criterion matched the derivation range of the ASCVD score. The primary outcome was five-year MACE—myocardial infarction (MI), ischemic or hemorrhagic stroke, or CV death. Secondly we evaluated the predictive performance of ASCVD score for five-year MACE. Discrimination was assessed with the area under the receiver-operating curve (AUROC); calibration with Calibration-in-the-Large (CITL, ideal = 0) and slope (ideal = 1). Performance metrics were calculated in patients with complete ASCVD variables. Results: A total of 6306 sepsis admissions were screened. 2424 patients were excluded for age outside 40–75 years and 879 for <5 year follow-up, leaving 2718 patients for incidence analyses. Median age was 65 years (IQR 56–70); 55 % were male, 38 % required ICU care, and 91 % were White. Median body-mass index was 28.2 kg/m2 (IQR 23.7-34.7). During follow-up, 125 patients (4.6 %) had MI, 219 (8.1 %) experienced stroke, and 303 (11.1 %) died of CV causes; overall, 1573 patients (57.9 %) met the composite MACE outcome. Complete ASCVD data were available for 409 patients. In this subset, discrimination was moderate (AUROC 0.65; 95 % CI 0.59–0.71). Calibration showed CITL +0.34 (95 % CI 0.09–0.59) and slope 0.50 (95 % CI 0.28–0.72), indicating systematic infra-prediction and over-fitting, respectively. Conclusion: Five-year MACE incidence after sepsis is high. The 10-year ASCVD score moderately discriminates but underestimates five-year CV risk in this population, highlighting the need for sepsis-specific predictive models or recalibration to guide targeted post-sepsis cardiovascular prevention.

Background: Procalcitonin (PCT) is recognized as an inflammatory biomarker, often elevated in COVID-19 pneumonia alongside other biomarkers. Understanding its association with severe outcomes and comparing its predictive ability with other biomarkers is crucial for clinical management. Objectives: This retrospective multicenter observational study aimed to investigate the association between PCT levels and adverse outcomes in hospitalized COVID-19 patients. Additionally, it sought to compare the predictive performance of various biomarkers. Design: The study analyzed data from the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry, comprising COVID-19 patients hospitalized across multiple Mayo Clinic sites between March 2020 and June 2022. Methods: A total of 7851 adult COVID-19 patients were included. Patients were categorized into 6 groups based on the worst WHO ordinal scale. Multivariate models were constructed using peak biomarker levels within 72 hours of admission, adjusted for confounders. Results: Elevated PCT levels were independently associated with increased odds of adverse outcomes, including ICU admission (adjusted odds ratio [aOR] 1.32, 95%CI 1.27-1.38), IMV requirement (aOR 1.35, 95%CI: 1.28-1.42), and in-hospital mortality (aOR 1.30, 95%CI: 1.22-1.37). A 3.48-fold increase in IMV requirement and 3.55 times increase in in-hospital mortality were noted with peak PCT ⩾ 0.25 ng/ml. Similar associations were observed with other biomarkers like NLR (AUC 0.730), CRP, IL-6, LDH (AUC 0.800), and D-dimer (AUC 0.719). Models incorporating NLR, LDH, D-dimer, and PCT demonstrated the highest predictive accuracy, with a combined model exhibiting an area under the curve (AUC) of 0.826 (95%CI 0.803-0.849). Conclusions: Higher PCT levels were significantly linked to worse outcomes in COVID-19 patients, emphasizing its potential as a prognostic marker. Biomarker-based predictive models, particularly those including PCT, showed promising utility for risk assessment and clinical decision-making. Further prospective studies are warranted to validate these findings on a larger scale.

Objective Extracorporeal cardiopulmonary resuscitation (ECPR) utilizes veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in cardiac arrest patients to reduce the risk of mortality and multiorgan dysfunction from systemic hypoperfusion. We aimed to compare clinical outcomes of patients receiving ECPR versus conventional cardiopulmonary resuscitation (CCPR) for refractory cardiac arrest. Data Sources This was a systematic review and meta-analysis. A librarian searched the main databases, Ovid MEDLINE (including epub ahead of print, in-process & other non-indexed citations), Ovid EMBASE and Ovid Cochrane Central Register of Controlled Trials from inception through July 2024. Study Selection We included randomized controlled trials and observational studies that compared the outcomes of ECPR to CCPR in cardiac arrest patients. Primary outcomes were neurological sequelae and survival. Data Extraction We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened articles, extracted data on selected articles and performed risk of bias assessments using ROBINS-I for non-randomized controlled trials and the revised Cochrane risk of bias tool for randomized controlled trials with disagreements settled by a third independent reviewer. Data Synthesis Out of 3458 studies identified and screened, 28 studies including 304,360 cardiac arrest patients met eligibility criteria and were included. Survival at hospital discharge was 20% for ECPR versus 3.3% for CCPR (OR 0.48 [CI 0.27, 0.84]). Favorable neurological outcome at hospital discharge was 11.8% for ECPR versus 1.9% for CCPR (OR 0.41 [CI 0.17, 1.01]). Complications from bleeding were ten times higher in the ECPR group (35.3% vs 3.7%; OR 0.08 [0.03, 0.24]). Conclusions ECPR appeared to be superior to CCPR for improved neurological outcome and survival in cardiac arrest patients, although bleeding was increased. There was large heterogeneity in the included studies and outcomes reported. Future prospective studies may improve the identification of subgroups of patients that will benefit most from ECPR. Systematic review and meta-analysis registration: PROSPERO - CRD42023394128.

OBJECTIVES: Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. DATA SOURCES: Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. DATA EXTRACTION: Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. DATA SYNTHESIS: Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18–0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71–2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24–6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19–1.8). However, the certainty of evidence for most outcomes was low to very low. CONCLUSIONS: While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

ABSTRACT Background: Septic shock is the leading cause of acute kidney injury (AKI) in critically ill patients. The foundation of early septic shock management includes early fluid resuscitation, but the association between fluid resuscitation rates and kidney outcomes remains unclear. This investigation examines the association between fluid resuscitation rate and AKI recovery. Methods: In the medical intensive care unit of Mayo Clinic Rochester, adult patients with AKI and septic shock were retrospectively studied from January 1, 2006 to May 31, 2018. The surviving sepsis campaign recommends an initial fluid bolus of 30 ml/kg for sepsis resuscitation. The cohort of patients was divided into three groups based on the average fluid resuscitation time (<1 h, 1.1–3 h, >3 h) and the corresponding fluid rate ≥0.5, 0.17–0.49, and <0.17 ml/kg/min, respectively. The primary outcome was the recovery of AKI on day 7. To account for potential confounders, multivariable regression analyses were conducted. Results: After meeting the eligibility, 597 patients were included in the analysis. The AKI recovery was considerably different among the groups ( P = 0.006). Patients in group 1 who received fluid resuscitation faster had a higher rate of AKI recovery (53%) compared to group 2 and group 3 (50% and 37.8%). Conclusion: In septic shock patients with AKI, a higher fluid resuscitation rate of 30 ml/kg IV fluids within the 1 st -h sepsis diagnosis (i.e., >0.50 ml/kg/min) lead to higher AKI recovery compared with slower infusion rates.

AbstractThe objective of this study was to compare the long‐term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single‐center study, conducted from 2003 to 2022, had a median follow‐up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5‐year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.