The Role of Renal Denervation in HFpEF

Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome characterized by signs and symptoms of heart failure despite normal or near-normal ejection fraction. It is a debilitating chronic disease that affects millions of people worldwide, and due to the paucity of evidence-based pharmacological treatments for HFpEF, nonpharmacological approaches as potential therapeutic alternatives are of growing interest. As a result, renal denervation (RDN), initially developed as a therapeutic tool for resistant hypertension, has become an area of active clinical interest. RDN is a catheter-based procedure that targets the renal sympathetic pathways, aiming to reduce neurohormonal activation and mitigate maladaptive cardiac remodeling. Preclinical studies in animal models have demonstrated that RDN can improve cardiac and vascular fibrosis, reduce renal inflammation, control hypertension, and alleviate endothelial dysfunction. Recent clinical studies have further highlighted the potential benefits of RDN in patients with HFpEF and uncontrolled hypertension. In this review, we aim to outline the pathophysiology of HFpEF and demonstrate the complex clinical interplay involved in how RDN impacts the heart. Moreover, we discuss the present status of clinical studies on RDN and explore its therapeutic potential as a viable treatment for HFpEF. Keywords: cardiac remodeling; heart failure with preserved ejection fraction; interventional cardiology approaches; renal denervation

Palliative Care Initiated in the Emergency Department: A Cluster Randomized Clinical Trial

Importance: The emergency department (ED) offers an opportunity to initiate palliative care for older adults with serious, life-limiting illness. Objective: To assess the effect of a multicomponent intervention to initiate palliative care in the ED on hospital admission, subsequent health care use, and survival in older adults with serious, life-limiting illness. Design, setting, and participants: Cluster randomized, stepped-wedge, clinical trial including patients aged 66 years or older who visited 1 of 29 EDs across the US between May 1, 2018, and December 31, 2022, had 12 months of prior Medicare enrollment, and a Gagne comorbidity score greater than 6, representing a risk of short-term mortality greater than 30%. Nursing home patients were excluded. Intervention: A multicomponent intervention (the Primary Palliative Care for Emergency Medicine intervention) included (1) evidence-based multidisciplinary education; (2) simulation-based workshops on serious illness communication; (3) clinical decision support; and (4) audit and feedback for ED clinical staff. Main outcome and measures: The primary outcome was hospital admission. The secondary outcomes included subsequent health care use and survival at 6 months. Results: There were 98 922 initial ED visits during the study period (median age, 77 years [IQR, 71-84 years]; 50% were female; 13% were Black and 78% were White; and the median Gagne comorbidity score was 8 [IQR, 7-10]). The rate of hospital admission was 64.4% during the preintervention period vs 61.3% during the postintervention period (absolute difference, -3.1% [95% CI, -3.7% to -2.5%]; adjusted odds ratio [OR], 1.03 [95% CI, 0.93 to 1.14]). There was no difference in the secondary outcomes before vs after the intervention. The rate of admission to an intensive care unit was 7.8% during the preintervention period vs 6.7% during the postintervention period (adjusted OR, 0.98 [95% CI, 0.83 to 1.15]). The rate of at least 1 revisit to the ED was 34.2% during the preintervention period vs 32.2% during the postintervention period (adjusted OR, 1.00 [95% CI, 0.91 to 1.09]). The rate of hospice use was 17.7% during the preintervention period vs 17.2% during the postintervention period (adjusted OR, 1.04 [95% CI, 0.93 to 1.16]). The rate of home health use was 42.0% during the preintervention period vs 38.1% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of at least 1 hospital readmission was 41.0% during the preintervention period vs 36.6% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of death was 28.1% during the preintervention period vs 28.7% during the postintervention period (adjusted OR, 1.07 [95% CI, 0.98 to 1.18]). Conclusions and relevance: This multicomponent intervention to initiate palliative care in the ED did not have an effect on hospital admission, subsequent health care use, or short-term mortality in older adults with serious, life-limiting illness. Trial registration: ClinicalTrials.gov Identifier: NCT03424109

Barriers to Universal Availability of Medications for Opioid Use Disorder in US Jails

Importance: Many of the approximately 2 million people being held in US correctional facilities are experiencing an opioid use disorder (OUD). Providing medications for OUD (MOUD) to this population is, therefore, essential to curb the opioid crisis. Objective: To examine the types of MOUD jails are making available, factors associated with availability, and additional supports needed for jails to address implementation challenges. Design, setting, and participants: This survey study used a cross-sectional survey of jails conducted between February 2 and July 1, 2023, to explore how they administer MOUD. Publicly available county-level data were connected with the survey responses to assess how variables in the surrounding community were associated with MOUD availability. The survey was administered to jails via mail, telephone, and online survey link. Participants included jails with MOUD available that completed the survey. Exposures: Urbanization, average daily population, availability of a health care professional to administer MOUD, whether the state expanded Medicaid, average drive time to MOUD in the county, county overdose rate, and county social vulnerability were assessed. Main outcomes and measures: The primary outcome was the type of MOUD available in the jail, including buprenorphine, methadone, or naltrexone, or all 3 medications. Binary logistic regressions were conducted to identify the characteristics of jails and county-level factors associated with offering the medications. Results: A total of 462 jails were invited to complete the survey based on responses to a previous nationally representative survey of jails, in which they indicated that MOUD was available to individuals in their facility. A total of 265 US jails with MOUD available were included in the analysis, representative of 1243 jails nationwide with MOUD available after weighting (812 jails [65.3%] provided buprenorphine, 646 jails [52.0%] provided naltrexone, 560 jails [45.0%] provided methadone, and 343 jails [27.6%] provided all 3 medications). Availability was associated with urbanicity, location in a Medicaid expansion state, county opioid overdose rate, and county social vulnerability. Common challenges included jail policies and procedures and the logistical accessibility of the medication. Conclusions and relevance: The findings of this survey study of US jails demonstrate that jails with MOUD available still experience challenges with making all 3 types of medication available to anyone held within their facility. Policy, regulatory, financing, staffing, and educational solutions are needed to ensure that all detainees with OUD have access to treatment while incarcerated

Safety of an Unconventional Vertical Transumbilical Incision for Pediatric Umbilical Hernia Repair

Introduction: Umbilical hernias are a common pediatric surgical problem, typically repaired at 4-5 y of age. Vertical transumbilical incision (VTUI) is a less common surgical approach associated with improved cosmetic outcomes. Our goal was to demonstrate the safety of this approach compared to the periumbilical incision (PUI). Methods: We retrospectively reviewed 402 pediatric patients who underwent an index open umbilical hernia repair for any indication at a single institution from 2013 to 2023. Patient demographics, operative outcomes, narcotic use, and complications were compared by incision type. Data were stratified by age and weight. Analysis was performed using student\u27s t-test. Results: We analyzed 402 patients. Three hundred thirty-seven (83.8%) had PUI and 65 (16.2%) had VTUI. Mean (standard deviation) age was 5 (3.18) y, ranging 0-18 y. Females represented 55%. There was no difference in age based on incision type. PUI and VTUI room time (79.2 v 83.3 min, P = 0.10) and anesthetic time (37.8 v 33.2, P = 0.31) were not significantly different. Mean intraoperative morphine milliequivalents per kilogram (MME/kg) were not different between incision types (P = 0.99). Average postanesthesia care unit MME/kg showed no difference between PUI and VTUI (3.7 v. 7.6, P = 0.06). There were 6 (1.5%) complications with no difference based on incision: 4 recurrences (3 PUI, 1 VTUI), 1 hospital readmission (PUI), and 1 patient with uncontrolled pain requiring admission (PUI). Stratified by weight, there were no significant differences in complication rates based on incision type. Conclusions: Our findings support VTUI as a safe alternative in the pediatric population without an increase in postoperative complications, anesthetic time, or MME/kg utilization. Keywords: Congenital hernia; Hernia; Incision; Narcotics; Open repair; Operative time; Pediatric surgery; Umbilical hernia

Blood Product Utilization in Thromboelastography-Aided Transfusion in Gastrointestinal Bleeding: A Single-Center Experience

Background: Gastrointestinal bleeding (GIB) is a common cause for intensive care unit (ICU) admissions and is associated with high mortality rates. Effective resuscitation is essential prior to definitive procedural intervention. Thromboelastography (TEG) assesses patients\u27 dynamic coagulation profiles and has been shown to reduce blood product usage and mortality in specific patient populations; however, its role in the management of GIB remains controversial. Methods: We performed a retrospective study of patients who had TEG performed during resuscitation of GIB in the ICU between January 1, 2017 and December 31, 2020 at a single center. Patients were identified through ICD-10 codes and blood bank\u27s database. Results: A cohort of 244 patients was identified, of which 18 were excluded. The cohort was mainly represented by White (72%, n = 162) males (65%, n = 147) with a mean age of 61 (standard deviation (SD) 14) years. Alcoholic liver disease (31%, n = 69) and esophageal varices (30%, n = 65) were the most common comorbidities. Mean nadir systolic blood pressure was 75 (SD 18) mm Hg. Mean nadir hemoglobin concentration was 6.5 (SD 1.7) g/dL. Patients received a median of 5 packed red blood cells (pRBC) (interquartile range (IQR) 5.8), 1 fresh frozen plasma (FFP) (IQR 2), and 0 platelets and cryoprecipitate units (IQR 1 and 0, respectively). The median ICU length of stay was 3 (IQR 3) days. The observed mortality rate was 39% (n = 88). Conclusion: Although TEG may help reduce unnecessary blood product transfusions, its overall clinical benefit remains uncertain given the high mortality observed among patients with hemorrhagic shock secondary to GIB. Further studies are warranted to better evaluate the efficacy and clinical utility of TEG-guided transfusion strategies in this patient population. Keywords: Gastrointestinal bleeding; Hemorrhagic shock; Mortality; Restrictive resuscitation; Thromboelastography

Timing of mechanical ventilation and its association with in-hospital outcomes in patients with cardiogenic shock following ST-elevation myocardial infarction: a multicentre observational study

Objective: To evaluate the association between the timing of invasive mechanical ventilation (MV) initiation and clinical outcomes in patients with cardiogenic shock (CS) secondary to ST-elevation myocardial infarction (STEMI). Design: Retrospective analysis of a multicentre registry. Setting: Data were obtained from the Gulf-Cardiogenic Shock registry, which includes hospitals across six countries in the Middle East. Participants: 1117 patients diagnosed with STEMI and CS. Of these, 672 (60%) required MV and were included in this analysis. Primary and secondary outcome measures: The primary outcome was in-hospital mortality. Secondary outcomes included comparisons of baseline characteristics, Society of Coronary Angiogram and Intervention (SCAI) shock stage, and clinical parameters among groups based on time to MV. Results: Participants were categorised by time from shock diagnosis to MV: early (≤15 min), intermediate (30 min) and late (≥60 min). Median times were 15 min (IQR 10-20), 30 min (IQR 25-35) and 60 min (IQR 45-70), respectively. Baseline characteristics were comparable across groups. Increased delay in MV was associated with a higher mortality risk during the first 60 min post-diagnosis, beyond which the risk plateaued. Delayed MV was an independent predictor of in-hospital mortality (OR 2.14, 95% CI 1.36 to 3.38, p\u3c 0.001). Conclusions: Early initiation of MV in patients with STEMI complicated by CS was associated with lower in-hospital mortality. These findings highlight the importance of timely respiratory support, warranting further investigation in prospective or randomised controlled studies. Keywords: Coronary intervention; Ischaemic heart disease; Mortality; Myocardial infarction; Ventilators, Mechanical

Sexual identity, sexual behavior, and drug use behaviors among people who use drugs in the rural U.S

Introduction: People who use drugs (PWUD) are at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within rural communities is not well understood. Further, while interventions designed to more explicitly affirm individuals\u27 sexual orientation and behaviors may be more effective, descriptions of behavior variability by orientation are lacking. We sought to describe how disease transmission behaviors and overdose risk vary by sexual orientation and activity among rural PWUD. Methods: From 01/2018-03/2020, rural PWUD participating in the Rural Opioid Initiative were surveyed across 8 sites. Collected data included: demographics; experiences with drug use, overdose, and healthcare; stigma; gender identity; and sexual orientation and partners. Participants were categorized as: monosexual by orientation and behavior (Mono-only), monosexual by orientation but behaviorally bisexual (Mono/Bi), and bisexual by orientation (Bi+). Analyses included descriptive summaries, bivariate examination (chi-square), and logistic regression (relative risk [RR] and 95 % confidence interval [CI]). Results: The 1455 participants were 84.8 % Mono-only, 3.2 % Mono/Bi, and 12.0 % Bi+. Compared to Mono-only men, Mono/Bi and Bi+ men had greater risk of transactional sex (RR = 9.71, CI = 6.66-14.2 and RR = 5.09, CI = 2.79-9.27, respectively) and sharing syringes for injection (RR = 1.58, CI = 1.06-2.35 and RR = 1.85, CI = 1.38-2.47). Compared to Mono-only women, Mono-Bi and Bi+ women had greater risk of transactional sex (RR = 4.47, CI = 2.68-7.47 and RR = 2.63, CI = 1.81-3.81); and Bi+ women had greater risk of sharing syringes for injection (RR = 1.49, CI = 1.23-1.81), sharing syringes to mix drugs (RR = 1.44, CI = 1.23-1.69), and experiencing an overdose (RR = 1.32, CI = 1.12-1.56). Bi+ men and women both more frequently reported selling sex as a source of income (versus Mono-only, both p \u3c 0.050) and measures of perceived stigma (all p \u3c 0.050). Conclusions: Rural PWUD who are bisexual by orientation or behavior are significantly more likely to engage in behaviors associated with infectious disease transmission and to experience stigma and drug overdose. Given the growing recognition of bisexuality as a distinct orientation that warrants individualized consideration, interventions that are specifically acknowledging and affirming to the circumstances of this group are needed. Keywords: Infectious Disease; Overdose; People who use drugs; Rural