Associations of neighborhood sociodemographic environment with mortality and circulating metabolites among low-income black and white adults living in the southeastern United States.

BACKGROUND: Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). METHODS: The SCCS is a prospective cohort of primarily low-income adults aged 40-79, enrolled from the southeastern United States during 2002-2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. RESULTS: Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively. CONCLUSIONS: Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.

Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec.

BACKGROUND: Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy vector expressing the high-activity factor IX (FIX) variant FIX-R338L, is in development for hemophilia B. One-stage clotting (OS) assays and chromogenic substrate (CS) assays are commonly used to measure FIX-R338L variant activity. Data from ongoing trials suggest FIX activity varies between different OS and CS assays. MATERIAL AND METHODS: To better understand FIX-R338L activity in clinical samples, an international multisite field study was conducted across a central laboratory and 18 local laboratories, using standard protocols, reagents, and instrumentation, with individual participant samples from a phase 1/2a study of fidanacogene elaparvovec. RESULTS: Unlike the wild-type FIX control, FIX-R338L activity was higher with the OS silica-based assay versus OS ellagic acid-based and CS assays. Variation in FIX activity was greater at the lowest activity levels. Activated FIX (FIXa) in plasma could result in higher OS assay activity or increased thrombin generation, which could overestimate FIX activity. However, FIXa was not detected in the participant samples, indicating that it was not contributing to the OS assay differences. Since individuals on gene therapy may receive exogenous replacement FIX products, replacement products were spiked into patient plasma samples to target a therapeutic concentration. Exogenous FIX was additive to endogenous FIX-R338L, with no interference from FIX-R338L. CONCLUSION: These results demonstrate FIX-R338L activity can be measured with OS and CS assays in clinical laboratories and provide insight into assay variability when measuring FIX with endogenously produced FIX-R338L. The findings may help establish best practices for measuring FIX-R338L activity (Clinicaltrials.gov identifier: NCT02484092).

Technology accountability groups: A novel form of technology learning and support for graduate students and faculty in STEM.

In academia, particularly in science, technology, engineering, and mathematics (STEM), writing accountability groups have emerged as an effective technique to enhance writing productivity by offering structure, increasing the commitment to write, and fostering social commitment. The rapid development of technology has introduced a new challenge across STEM fields: technostress, where individuals face heightened stress due to novel applications of technology. To address this, we introduce Technology Accountability Groups (TAGs), a novel form of community support for graduate students and faculty. TAGs are tailored to help individuals navigate technological innovations, alleviate technostress, acquire new skills, motivate, and connect with leaders in the field. This paper presents a framework for establishing, implementing, and sustaining TAGs in STEM.

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Hospitalists as Facilitators of Surge and Contingency Medical Operations and Planning.

Hospital medicine, a specialty encompassing physicians and advanced practice providers in internal medicine, pediatrics, and family medicine, has been a core and rapidly growing component of civilian health care for the past two decades. More recently, hospitalists have been taking on key roles during surge and contingency planning and operations, most notably during the COVID-19 pandemic which necessitated marked changes in inpatient care across the United States. The military health system has been slower to incorporate hospitalists into clinical care and planning than civilian organizations due to its unique features. However, an increasing focus on future distributed operations in contested environments, pandemic care, and humanitarian assistance/disaster response requires new consideration of their role in military medicine. This stems from hospitalists' value as clinicians who include triage, resource utilization stewardship, medical inpatient care, pre-/post-operative management of surgical patients, and high acuity patient stabilization and management within their scope, often working collaboratively with other specialists such as emergency medicine physicians, surgeons, and intensivists. Just as importantly, hospitalists are system-level facilitators and leaders of patient capacity expansion and/or clinical process changes when needed for response to incidents in a variety of acute care scenarios. With uniformed billets being increasingly targeted to military platform requirements, there is now an opportunity to revisit the value of hospitalists in military medicine. In this Commentary, we review the roles that hospitalists can fill in hospital and operational medical settings, with a focus on surge and contingency operations. To demonstrate this capability, we present here the experience of two operational units employing hospitalists for high acuity patient management and two civilian hospitals implementing surge operations during the 2022-2023 "tripledemic" of viral respiratory infections in the United States. Their innovations facilitated the care of higher acuity and higher volume during times when medical care requirements were limited by traditional staffing models. We end by reviewing opportunities and challenges related to expanding hospitalist use within the military health system and describing efforts that are underway to address the challenges.

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

OBJECTIVE: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. METHODS: The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. RESULTS: The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. CONCLUSIONS: Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

Racial and Ethnic Disparities in Ambulatory Heart Failure Ventricular Assist Device Implantation and Survival.

BACKGROUND: Durable left ventricular assist devices (VADs) improve survival in eligible patients, but allocation has been associated with patient race in addition to presumed heart failure (HF) severity. OBJECTIVES: This study sought to determine racial and ethnic differences in VAD implantation rates and post-VAD survival among patients with ambulatory HF. METHODS: Using the INTERMACS (Interagency Registry of Mechanically Assisted Circulatory Support) database (2012-2017), this study examined census-adjusted VAD implantation rates by race, ethnicity, and sex in patients with ambulatory HF (INTERMACS profile 4-7) using negative binomial models with quadratic effect of time. Survival was evaluated using Kaplan-Meier estimates and Cox models adjusted for clinically relevant variables and an interaction of time with race/ethnicity. RESULTS: VADs were implanted in 2,256 adult patients with ambulatory HF (78.3% White, 16.4% Black, and 5.3% Hispanic). The median age at implantation was lowest in Black patients. Implantation rates peaked between 2013 and 2015 before declining in all demographic groups. From 2012 to 2017, implantation rates overlapped for Black and White patients but were lower for Hispanic patients. Post-VAD survival was significantly different among the 3 groups (log rank P = 0.0067), with higher estimated survival among Black vs White patients (12-month survival: Black patients: 90% [95% CI: 86%-93%]; White patients: 82% [95% CI: 80%-84%]). Low sample size for Hispanic patients resulted in imprecise survival estimates (12-month survival: 85% [95% CI: 76%-90%]). CONCLUSIONS: Black and White patients with ambulatory HF had similar VAD implantation rates but rates were lower for Hispanic patients. Survival differed among the 3 groups, with the highest estimated survival at 12 months in Black patients. Given higher HF burden in minoritized populations, further investigation is needed to understand differences in VAD implantation rates in Black and Hispanic patients.

Immune profiling of murine cardiac leukocytes identifies triggering receptor expressed on myeloid cells 2 as a novel mediator of hypertensive heart failure.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. METHODS AND RESULTS: Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. CONCLUSIONS: Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure.

Juneteenth in STEMM and the barriers to equitable science.

We are 52 Black scientists. Here, we establish the context of Juneteenth in STEMM and discuss the barriers Black scientists face, the struggles they endure, and the lack of recognition they receive. We review racism's history in science and provide institutional-level solutions to reduce the burdens on Black scientists.

Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study.

OBJECTIVE: Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS: TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher's exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS: The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS: Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Differences in Cardiac Mechanics and Exercise Physiology Among Heart Failure With Preserved Ejection Fraction Phenomapping Subgroups.

Unsupervised machine learning (phenomapping) has been used successfully to identify novel subgroups (phenogroups) of heart failure with preserved ejection fraction (HFpEF). However, further investigation of pathophysiological differences between HFpEF phenogroups is necessary to help determine potential treatment options. We performed speckle-tracking echocardiography and cardiopulmonary exercise testing (CPET) in 301 and 150 patients with HFpEF, respectively, as part of a prospective phenomapping study (median age 65 [25th to 75th percentile 56 to 73] years, 39% Black individuals, 65% female). Linear regression was used to compare strain and CPET parameters by phenogroup. All indicies of cardiac mechanics except for left ventricular global circumferential strain worsened in a stepwise fashion from phenogroups 1 to 3 after adjustment for demographic and clinical factors. After further adjustment for conventional echocardiographic parameters, phenogroup 3 had the worst left ventricular global longitudinal, right ventricular free wall, and left atrial booster and reservoir strain. On CPET, phenogroup 2 had the lowest exercise time and absolute peak oxygen consumption (VO2), driven primarily by obesity, whereas phenogroup 3 achieved the lowest workload, relative peak oxygen consumption (VO2), and heart rate reserve on multivariable-adjusted analyses. In conclusion, HFpEF phenogroups identified by unsupervised machine learning analysis differ in the indicies of cardiac mechanics and exercise physiology.

Understanding Violence Against Women in the Caribbean Through an Exploration of Men's Perspectives.

Qualitative research with 60 males (16-80 years) from two Caribbean countries was carried out to explore men's perspectives on domestic violence (DV). An inductive latent/thematic approach to data analysis supported by analytic software led to five key domains being identified: (1) meanings of violence; (2) patrinormative culture; (3) normalization of violence; (4) male victimization; and (5) blame attribution and empathy. Patriarchal values, together with childhood exposure to violence, were found to reduce empathic capacity and contribute to the normalization of DV. In addition, the minimization of male victimization and the lack of behavior-change support services for men were identified as contributory factors.

Draft genome sequences of Pseudomonas amygdali pv. loropetali pathotype strain DSM 105780 PT, isolated from Florida.

The pathogen that causes stem gall in Loropetalum chinense was first identified in Florida and Alabama in 2018 and named Pseudomonas amygdali pv. loropetali. We report the genome sequence of the pathotype strain of this pathogen, Pseudomonas amygdali pv. loropetali DSM105780 PT.

Building on Early Coronavirus (COVID-19) Pandemic Orientation Modifications to Improve Competency Validation for Newly Hired New-to-Practice and Experienced Nurses.

Nursing professional development and human resource leaders revised general nursing orientation content and structure based on changes because of COVID-19 in length, focus, and platforms from the early stages of the pandemic. The aim of this quality improvement project was to incorporate best of pandemic modifications with key stakeholders and new-to-practice and experienced nursing hire needs emerging from COVID-19 realities on the workforce. The benefit for nursing professional development practitioners is relatability of general nursing orientation revisions for sustainability of clinical excellence and safety.

Reduced Circumferential Strain in Athletes with Prior COVID-19.

Purpose: To characterize global and segmental circumferential systolic strain (CS) measured by cardiac MRI in athletes after SARS-CoV-2 infection. Materials and Methods: This retrospective observational cohort study included 188 soldiers and collegiate athletes referred for cardiac MRI after SARS-CoV-2 infection (C19+) between July 2020 and February 2021 and a control group of 72 soldiers, collegiate, and high school athletes who underwent cardiac MRI from May 2019 to February 2020, prior to the first SARS-CoV-2 case detected in our region (C19-). Global and segmental CS were measured by feature tracking, then compared between each group using unadjusted and multivariable- adjusted models. Acute myocarditis was diagnosed according to the modified Lake Louise criteria and the location of pathologic late gadolinium enhancement (LGE) was ascertained. Results: Among the 188 C19+ athletes (median age, 25 years [IQR, 23-30]; 131 men), the majority had mild illness. Global CS significantly differed between C19+ and C19- groups, with a median of -24.0 (IQR -25.8, -21.4) versus. -25.0 (-28.0, -22.4), respectively (p = .009). This difference in CS persisted following adjustment for age, sex, body mass index, heart rate, and systolic blood pressure ß coefficient 1.29 [95% CI: 0.20, 2.38], p = .02). In segmental analysis, the basal- and mid- inferoseptal, septal and inferolateral segments were significantly different (p < .05), which had a higher frequency of post-COVID late gadolinium enhancement. The global and segmental differences were similar after exclusion of athletes with myocarditis. Conclusion: Among athletes, SARS-CoV-2 infection was associated with a small but statistically significant reduced CS.

Validation of patient-reported vaso-occlusive crisis day as an endpoint in sickle cell disease studies.

Individuals with sickle cell disease (SCD) experience vaso-occlusive crises (VOC). Historically, VOC episodes have been assessed through medical utilization, thereby excluding events managed at home. In order to validate a daily patient-reported outcome for patients with SCD to accurately report their VOC status and experience of a pain crisis, a SCD Diary was included in Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS), a longitudinal, six-month, non-interventional study. The daily patient-completed diary included a description of SCD pain crisis, followed by questions on: pain crisis in the past 24 h (VOC Day question; respective response yes or no), worst pain, tiredness, and functioning. Thirty-five patients with SCD participated in ELIPSIS. Analyses were performed to validate the patient-reported VOC Day. Mean symptoms and functioning scores on the first or last VOC Day of a VOC Event were compared using t-tests with the mean of the three non-VOC Days before and after the event. Mean severity of symptoms and functioning scores on all VOC Days compared to all non-VOC Days were higher, with statistically significant mean differences between first/last VOC Days and respective three non-VOC Days (p's < .01). A subset of patients (n = 15) and caregivers (n = 9) were interviewed to evaluate their understanding of the SCD Diary questions. Nearly all confirmed that the pain crisis description accurately described the VOC experience, and participants expressed confidence differentiating SCD crisis pain from everyday pain. These results demonstrate patients can reliably report their experiences with VOC-related pain crises using the SCD Diary.