Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.

BACKGROUND: The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD. METHODS: Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRSAAA was also assessed among the FMD cases and controls. RESULTS: Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P=0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RRAAA of 2.3 ([95% CI, 1.12-4.6]; P=0.014) compared with population estimates. The PRSFMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=2.6×10-3), and the PRSAAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P=9.0×10-5) as well. CONCLUSIONS: FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.

Associations of 4 Geographic Social Vulnerability Indices With US COVID-19 Incidence and Mortality.

Objectives. To examine and compare how 4 indices of population-level social disadvantage-the Social Vulnerability Index (SVI), the Area Deprivation Index (ADI), the COVID-19 Community Vulnerability Index (CCVI), and the Minority Health-Social Vulnerability Index (MH-SVI)-are associated with COVID-19 outcomes. Methods. Spatial autoregressive models adjusted for population density, urbanicity, and state fixed effects were used to estimate associations of county-level SVI, MH-SVI, CCVI, and ADI values with COVID-19 incidence and mortality. Results. All 4 disadvantage indices had similar positive associations with COVID-19 incidence. Each index was also significantly associated with COVID-19 mortality, but the ADI had a stronger association than the CCVI, MH-SVI, and SVI. Conclusions. Despite differences in component measures and weighting, all 4 of the indices we assessed demonstrated associations between greater disadvantage and COVID-19 incidence and mortality. Public Health Implications. Our findings suggest that each of the 4 disadvantage indices can be used to assist public health leaders in targeting ongoing first-dose and booster or third-dose vaccines as well as new vaccines or other resources to regions most vulnerable to negative COVID-19 outcomes, weighing potential tradeoffs in their political and practical acceptability. (Am J Public Health. 2022;112(11):1584-1588. https://doi.org/10.2105/AJPH.2022.307018).

Trends in Hospitalizations for Ambulatory Care-Sensitive Conditions During the COVID-19 Pandemic.

Importance: The association of the COVID-19 pandemic with the quality of ambulatory care is unknown. Hospitalizations for ambulatory care-sensitive conditions (ACSCs) are a well-studied measure of the quality of ambulatory care; however, they may also be associated with other patient-level and system-level factors. Objective: To describe trends in hospital admissions for ACSCs in the prepandemic period (March 2019 to February 2020) compared with the pandemic period (March 2020 to February 2021). Design, Setting, and Participants: This cross-sectional study of adults enrolled in a commercial health maintenance organization in Michigan included 1 240 409 unique adults (13 011 176 person-months) in the prepandemic period and 1 206 361 unique adults (12 759 675 person-months) in the pandemic period. Exposure: COVID-19 pandemic (March 2020 to February 2021). Main Outcomes and Measures: Adjusted relative risk (aRR) of ACSC hospitalizations and intensive care unit stays for ACSC hospitalizations and adjusted incidence rate ratio of the length of stay of ACSC hospitalizations in the prepandemic (March 2019 to February 2020) vs pandemic (March 2020 to February 2021) periods, adjusted for patient age, sex, calendar month of admission, and county of residence. Results: The study population included 1 240 409 unique adults (13 011 176 person-months) in the prepandemic period and 1 206 361 unique adults (12 759 675 person-months) in the pandemic period, in which 51.3% of person-months (n = 6 547 231) were for female patients, with a relatively even age distribution between the ages of 24 and 64 years. The relative risk of having any ACSC hospitalization in the pandemic period compared with the prepandemic period was 0.72 (95% CI, 0.69-0.76; P < .001). This decrease in risk was slightly larger in magnitude than the overall reduction in non-ACSC, non-COVID-19 hospitalization rates (aRR, 0.82; 95% CI, 0.81-0.83; P < .001). Large reductions were found in the relative risk of respiratory-related ACSC hospitalizations (aRR, 0.54; 95% CI, 0.50-0.58; P < .001), with non-statistically significant reductions in diabetes-related ACSCs (aRR, 0.91; 95% CI, 0.83-1.00; P = .05) and a statistically significant reduction in all other ACSC hospitalizations (aRR, 0.79; 95% CI, 0.74-0.85; P < .001). Among ACSC hospitalizations, no change was found in the percentage that included an intensive care unit stay (aRR, 0.99; 95% CI, 0.94-1.04; P = .64), and no change was found in the length of stay (adjusted incidence rate ratio, 1.02; 95% CI, 0.98-1.06; P = .33). Conclusions and Relevance: In this cross-sectional study of adults enrolled in a large commercial health maintenance organization plan, the COVID-19 pandemic was associated with reductions in both non-ACSC and ACSC hospitalizations, with particularly large reductions seen in respiratory-related ACSCs. These reductions were likely due to many patient-level and health system-level factors associated with hospitalization rates. Further research into the causes and long-term outcomes associated with these reductions in ACSC admissions is needed to understand how the pandemic has affected the delivery of ambulatory and hospital care in the US.

Image-based prenatal predictors correlate with postnatal survival, extracorporeal life support use, and defect size in left congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the association between prenatal imaging predictors of patients with left-sided congenital diaphragmatic hernia (LCDH) and postnatal outcomes. STUDY DESIGN: CDH study group data were reviewed for LCDH infants born 2015-2019. Prenatal ultrasound (US) and magnetic resonance imaging (MRI) data were collected and correlated with postnatal information including CDHSG defect size (A through D or non-repair (NR)). RESULTS: In total, 929 LCDH patients were included. Both US and MRI imaging predictors correlated with postnatal survival (72.2%) and ECLS use (29.6%). Logistic regression models confirmed increased survival and decreased ECLS use with larger values for all predictors. Importantly, all prenatal values evaluated showed no significant difference between defect size D and NR patients. CONCLUSIONS: This is the largest cohort of LCDH patients and demonstrates that prenatal imaging factors correlate with postnatal outcomes and confirms that patients in the non-repair group are prenatally similar to type D defects.

Contribution of Individual- and Neighborhood-Level Social, Demographic, and Health Factors to COVID-19 Hospitalization Outcomes.

BACKGROUND: Although disparities in COVID-19 outcomes have been observed, factors contributing to these differences are not well understood. OBJECTIVE: To determine whether COVID-19 hospitalization outcomes are related to neighborhood-level social vulnerability, independent of patient-level clinical factors. DESIGN: Pooled cross-sectional study of prospectively collected data. SETTING: 38 Michigan hospitals. PATIENTS: Adults older than 18 years hospitalized for COVID-19 in a participating site between March and December 2020. MEASUREMENTS: COVID-19 outcomes included acute organ dysfunction, organ failure, invasive mechanical ventilation, intensive care unit stay, death, and discharge disposition. Social vulnerability was measured by the social vulnerability index (SVI), a composite measure of social disadvantage. RESULTS: Compared with patients in low-vulnerability ZIP codes, those living in high-vulnerability ZIP codes were more frequently treated in the intensive care unit (29.0% vs. 24.5%); more frequently received mechanical ventilation (19.3% vs. 14.2%); and experienced higher rates of organ dysfunction (51.9% vs. 48.6%), organ failure (54.7% vs. 51.6%), and in-hospital death (19.4% vs. 16.7%). In mixed-effects regression analyses accounting for age, sex, and comorbid conditions, an increase in a patient's neighborhood SVI by 0.25 (1 quartile) was associated with greater likelihood of mechanical ventilation (increase of 2.1 percentage points), acute organ dysfunction (increase of 2.8 percentage points), and acute organ failure (increase of 2.8 percentage points) but was not associated with intensive care unit stay, mortality, or discharge disposition. LIMITATION: Observational data focused on hospitalizations in a single state. CONCLUSION: Hospitalized patients with COVID-19 from socially vulnerable neighborhoods presented with greater illness severity and required more intensive treatment, but once hospitalized they did not experience differences in hospital mortality or discharge disposition. Policies that target socially vulnerable neighborhoods and access to COVID-19 care may help ameliorate health disparities. PRIMARY FUNDING SOURCE: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships Program, the Michigan Public Health Institute, and the Michigan Department of Health & Human Services.

Longitudinal trends in enrollees' employment and student status after Medicaid expansion.

BACKGROUND: Medicaid community engagement requirements previously received federal approval in 12 states, despite limited data on their impact on enrollees' employment-related activities. Our objective was to assess longitudinal changes in enrollees' employment and student status after implementation of Michigan's Medicaid expansion. METHODS: Longitudinal telephone survey of Michigan Medicaid expansion enrollees in 2016 (response rate [RR] = 53.7%), 2017 (RR = 83.4%), and 2018 (N = 2,608, RR = 89.4%) serially assessing self-reported employment or student status. Survey responses were benchmarked against statewide changes in assessed similar low-income adults in the U.S. Census Bureau Current Population Survey. We used mixed models with individual random effects to assess changes in the proportion of enrollees who were employed or students by year. RESULTS: Most respondents had incomes < 100% FPL (61.7% with 0-35% of the federal poverty level [FPL], 22.9% with 36-99% FPL, and 15.4% with 100-133% FPL), 89.3% had at least a high school diploma/equivalent, and they ranged in age (39.6% age 19-34, 34.5% age 35-50, 25.9% age 51-64). Employment or student status increased significantly among Michigan Medicaid expansion respondents, from 54.5% in 2016 to 61.4% in 2018 (P < 0.001), including among those with a chronic condition (47.8% to 53.8%, P < 0.001) or mental health/substance use disorder (48.5% to 56.0%, P < 0.001). In contrast, the statewide proportion of low-income non-elderly adults who were employed or students did not change significantly (from 42.7% in 2016 to 46.0% in 2018, P = 0.57). CONCLUSIONS: Medicaid expansion, absent a community engagement requirement, was associated with increased employment and related activities. The role of Medicaid in providing safety-net coverage to individuals during times of economic stress is likely to grow.

Increased Intraoperative Faculty Entrustment and Resident Entrustability Does Not Compromise Patient Outcomes After General Surgery Procedures.

BACKGROUND: Intraoperative resident autonomy has been compromised secondary to expectations for increased supervision without defined parameters for safe progressive independence, diffusion of training experience, and more to learn with less time. Surgical residents who are insufficiently entrusted during training attain less autonomy, confidence, and even clinical competency, potentially affecting future patient outcomes. OBJECTIVE: To determine if OpTrust, an educational intervention for increasing intraoperative faculty entrustment and resident entrustability, negatively impacts patient outcomes after general surgery procedures. METHODS: Surgical faculty and residents received OpTrust training and instruction to promote intraoperative faculty entrustment and resident entrustability. A post-intervention OpTrust cohort was compared to historical and pre-intervention OpTrust cohorts. Multivariable logistic and negative binomial regression was used to evaluate the impact of the OpTrust intervention and time on patient outcomes. SETTING: Single tertiary academic center. PARTICIPANTS: General surgery faculty and residents. MAIN OUTCOMES AND MEASURES: Thirty-day postoperative outcomes, including mortality, any complication, reoperation, readmission, and length of stay. RESULTS: A total of 8890 surgical procedures were included. After risk adjustment, overall patient outcomes were similar. Multivariable regression estimating the effect of the OpTrust intervention and time revealed similar patient outcomes with no increased risk (P > 0.05) of mortality {odds ratio (OR), 2.23 [95% confidence interval (CI), 0.87-5.6]}, any complication [OR, 0.98 (95% CI, 0.76-1.3)], reoperation [OR, 0.65 (95% CI, 0.42-1.0)], readmission [OR, 0.82 (95% CI, 0.57-1.2)], and length of stay [OR, 0.99 (95% CI, 0.86-1.1)] compared to the historic and pre-intervention OpTrust cohorts. CONCLUSIONS: OpTrust, an educational intervention to increase faculty entrustment and resident entrustability, does not compromise postoperative patient outcomes. Integrating faculty and resident development to further enhance entrustment and entrustability through OpTrust may help facilitate increased resident autonomy within the safety net of surgical training without negatively impacting clinical outcomes.

Transhiatal robot-assisted minimally invasive esophagectomy: unclear benefits compared to traditional transhiatal esophagectomy.

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p < 0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.

Fetal Risk Stratification and Outcomes in Children with Prenatally Diagnosed Lung Malformations: Results from a Multi-Institutional Research Collaborative.

OBJECTIVE: The aim of this study was to assess current clinical outcomes in children with prenatally diagnosed congenital lung malformations (CLMs) and to identify prenatal characteristics associated with adverse outcomes. SUMMARY BACKGROUND DATA: Despite a wide spectrum of clinical disease, the identification of fetal CLM subgroups at increased risk for hydrops and respiratory compromise at delivery has not been well defined. METHODS: A retrospective cohort study was conducted using an operative database of prenatally diagnosed CLMs managed at 11 children's hospitals from 2009 to 2016. Statistical analyses were performed using nonparametric bivariate or multivariable logistic regression. RESULTS: Three hundred forty-four children were analyzed. Fifteen (5.5%) fetuses were managed with maternal steroids in the setting of hydrops, and prenatal surgical intervention was uncommon (1.7%). Seventy-five (21.8%) had respiratory symptoms at birth, and 34 (10.0%) required neonatal lung resection. Congenital pulmonary airway malformation volume ratio (CVR) measurements were recorded in 169 (49.1%) cases and were significantly associated with perinatal outcome, including hydrops, respiratory distress at birth, need for supplemental oxygen, neonatal ventilator use, and neonatal resection ( P < 0.001). An initial CVR ≤1.4 was significantly correlated with a reduced risk for hydrops [area under the curve (AUC), 0.93; 95% confidence interval (CI), 0.87-1.00]. A maximum CVR <0.9 (AUC, 0.72; 95% CI, 0.67-0.85) was associated with a low risk for respiratory symptoms at birth. CONCLUSIONS: In this large, multi-institutional study, an initial CVR ≤ 1.4 identifies fetuses at very low risk for hydrops, and a maximum CVR < 0.9 is associated with asymptomatic disease at birth. These findings represent an opportunity for standardization and quality improvement for prenatal counseling and delivery planning.

Association of Social and Demographic Factors With COVID-19 Incidence and Death Rates in the US.

Importance: Descriptive data have revealed significant racial/ethnic disparities in coronavirus disease 2019 (COVID-19) cases in the US, but underlying mechanisms of disparities remain unknown. Objective: To examine the association between county-level sociodemographic risk factors and US COVID-19 incidence and mortality. Design, Setting, and Participants: This cross-sectional study analyzed the association between US county-level sociodemographic risk factors and COVID-19 incidence using mixed-effects negative binomial regression, and COVID-19 mortality using zero-inflated negative binomial regression. Data on COVID-19 incidence and mortality were collected from January 20 to July 29, 2020. The association of social risk factors with weekly cumulative incidence and mortality was also examined by interacting time with the index measures, using a random intercept to account for repeated measures. Main Outcomes and Measures: Sociodemographic data from publicly available data sets, including the US Centers for Disease Control and Prevention's Social Vulnerability Index (SVI), which includes subindices of socioeconomic status, household composition and disability, racial/ethnic minority and English language proficiency status, and housing and transportation. Results: As of July 29, 2020, there were a total of 4 289 283 COVID-19 cases and 147 074 COVID-19 deaths in the US. An increase of 0.1 point in SVI score was associated with a 14.3% increase in incidence rate (incidence rate ratio [IRR], 1.14; 95% CI, 1.13-1.16; P < .001) and 13.7% increase in mortality rate (IRR, 1.14; 95% CI, 1.12-1.16; P < .001), or an excess of 87 COVID-19 cases and 3 COVID-19 deaths per 100 000 population for a SVI score change from 0.5 to 0.6 in a midsize metropolitan county; subindices were also associated with both outcomes. A 0.1-point increase in the overall SVI was associated with a 0.9% increase in weekly cumulative increase in incidence rate (IRR, 1.01; 95% CI, 1.01-1.01; P < .001) and 0.5% increase in mortality rate (IRR, 1.01; 95% CI, 1.01-1.01; P < .001). Conclusions and Relevance: In this cross-sectional study, a wide range of sociodemographic risk factors, including socioeconomic status, racial/ethnic minority status, household composition, and environmental factors, were significantly associated with COVID-19 incidence and mortality. To address inequities in the burden of the COVID-19 pandemic, these social vulnerabilities and their root causes must be addressed.

The Impact of the Affordable Care Act Medicaid Expansion on Racial/Ethnic and Sex Disparities in HIV Testing: National Findings from the Behavioral Risk Factor Surveillance System.

INTRODUCTION: Over half of Americans have not been tested for HIV in their lifetime, and over a third of all HIV diagnoses are made less than a year before progression to AIDS. The Affordable Care Act (ACA) Medicaid expansion of 2014 had potential to improve HIV and other health screenings. We assessed the differential impacts of Medicaid expansion on racial/ethnic and racial/ethnic-sex disparities in HIV testing. METHODS: Using Behavioral Risk Factor Surveillance System data from all 50 states and D.C., we sampled low-income (≤ 138% of the federal poverty level) adults ages 19-64 who were non-pregnant and non-disabled. Using a difference-in-differences (DD) and triple difference-in-differences (DDD) study design, we assessed differential impacts by race/ethnicity (White, Black, Hispanic, and other) and race/ethnicity-sex between 2011 and 2013 and 2014-2018. Outcomes were (1) ever having received an HIV test and (2) having received an HIV test in the last year. RESULTS: Overall, Medicaid expansion was associated with a significant increase in HIV testing (p = 0.003). White females and Black males appeared most likely to benefit from this increase (DD 4.5 and 4.8 percentage points; p = 0.001 and 0.130 respectively). However, despite having baseline higher rates of HIV diagnosis, Black and Hispanic females did not have increased rates of ever having HIV testing following Medicaid expansion (DD - 1.9 and 0.9 percentage points; p = 0.391 and 0.703, respectively), including when compared to a White male reference subgroup and across other race/ethnicity-sex subgroups. CONCLUSIONS: Medicaid expansion was associated with an increased overall probability of HIV testing among low-income, nonelderly adults, but certain groups including Black females were not more likely to benefit from this increase, despite being disproportionately affected by HIV at baseline. Targeted and culturally informed interventions to increase Medicaid enrollment and access to primary care may be needed to expand HIV testing in vulnerable groups.

Changes in Health Care Access and Utilization for Low-SES Adults Aged 51-64 Years After Medicaid Expansion.

OBJECTIVES: Whether the Affordable Care Act (ACA) insurance expansions improved access to care and health for adults aged 51-64 years has not been closely examined. This study examined longitudinal changes in access, utilization, and health for low-socioeconomic status adults aged 51-64 years before and after the ACA Medicaid expansion. METHODS: Longitudinal difference-in-differences (DID) study before (2010-2014) and after (2016) Medicaid expansion, including N = 2,088 noninstitutionalized low-education adults aged 51-64 years (n = 633 in Medicaid expansion states, n = 1,455 in nonexpansion states) from the nationally representative biennial Health and Retirement Study. Outcomes included coverage (any, Medicaid, and private), access (usual source of care, difficulty finding a physician, foregone care, cost-related medication nonadherence, and out-of-pocket costs), utilization (outpatient visit and hospitalization), and health status. RESULTS: Low-education adults aged 51-64 years had increased rates of Medicaid coverage (+10.6 percentage points [pp] in expansion states, +3.2 pp in nonexpansion states, DID +7.4 pp, p = .001) and increased likelihood of hospitalizations (+9.2 pp in expansion states, -1.1 pp in nonexpansion states, DID +10.4 pp, p = .003) in Medicaid expansion compared with nonexpansion states after 2014. Those in expansion states also had a smaller increase in limitations in paid work/housework over time, compared to those in nonexpansion states (+3.6 pp in expansion states, +11.0 pp in nonexpansion states, DID -7.5 pp, p = .006). There were no other significant differences in access, utilization, or health trends between expansion and nonexpansion states. DISCUSSION: After Medicaid expansion, low-education status adults aged 51-64 years were more likely to be hospitalized, suggesting poor baseline access to chronic disease management and pent-up demand for hospital services.

Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity.

PURPOSE: Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes. METHODS: Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted. RESULTS: Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p < 0.0001). The area under the curve (95% CI) for distinguishing septic shock from NIC using CitH3 was 0.76 (0.65-0.86). CitH3 was positively correlated with PAD2 and PAD4 concentrations and Sequential Organ Failure Assessment Scores [total score (r = 0.36, p < 0.0001)]. The serum levels of CitH3 at 24 h (p < 0.01) and 48 h (p < 0.05) were significantly higher in the septic patients that did not survive. CONCLUSION: CitH3 is increased in patients with septic shock. Its serum concentrations correlate with disease severity and prognosis, which may yield vital insights into the pathophysiology of sepsis.

Bolus versus continuous feeding regimens post gastrostomy tube placement in children.

BACKGROUND/PURPOSE: Owing to the frequency of gastrostomy tube placement in children and the numerous regimens used to start feeds after placement we attempted to see if it matters if the initial feeds after a gastrostomy tube placement are provided in a bolus or continuous manner. METHODS: Using a prospective randomized trial, children were randomized to initial bolus or continuous chimney feeding after gastrostomy tube placement. Feeding tolerance and complications related to the gastrostomy tube were collected for 4 weeks after placement. RESULTS: Demographics were similar in the two groups. Times to goal feeds were similar in both groups, but in the first two weeks more feeding modifications were required in the bolus group. Other than the rate of leakage during the second week after placement which occurred more in the bolus group, all other clinical outcomes were similar in the two groups. CONCLUSIONS: Other than minor, clinically insignificant differences noted above, the method of initial feeding after a gastrostomy tube placement does not affect feeding tolerance or gastrostomy tube complication in the first month after placement. LEVEL OF EVIDENCE: Therapeutic, level II.

Predicting lethal pulmonary hypoplasia in congenital diaphragmatic hernia (CDH): Institutional experience combined with CDH registry outcomes.

BACKGROUND: The Severe Pulmonary Hypoplasia and Evaluation for Resuscitative Efforts (SPHERE) protocol was developed to attempt to identify CDH patients with likely lethal pulmonary hypoplasia. We present our experience with this protocol and utilize the CDH Registry to critically assess the protocol. METHODS: SPHERE patients identified based on prenatal imaging (10/2009-1/2018) were offered ECMO if meeting postnatal physiologic criteria, while others received comfort measures. Within the CDH Registry, patients with suspected severe CDH were identified and separated into "passed" (lowest pCO2 ≤100) versus "failed" (lowest pCO2 >100) groups. RESULTS: Of 23 SPHERE patients, 57% (13/23) passed criteria for ECMO and survival was 46% (6/13) in that cohort. Of 4912 patients in the CDH Registry, 265 met criteria. There was no difference in survival rates between those that "passed" (122/227; 54%) versus "failed" (18/38; 47%). However, the latter had longer ECMO runs and more required ventilator/ECMO support at 30 days. Amongst survivors, the "failed" group had longer hospital stays and more frequently required tube feeds at discharge. CONCLUSIONS: The SPHERE protocol did not predict mortality in the CDH Registry. However, our data suggest resource utilization is significant when unable to reach pCO2 ≤100 despite resuscitation. Morbidity remains high in this group. LEVEL OF EVIDENCE: Level III ANNOTATION OF CHANGES: Institutional Review Board Approval at University of Michigan (HUM00031524 and HUM00044010) TYPE OF STUDY: Retrospective Review.

Designing and implementing a practical prehospital emergency trauma care curriculum for lay first responders in Guatemala.

BACKGROUND: Injury disproportionately affects low-income and middle-income countries, yet robust emergency medical services are often lacking to effectively address the prehospital injury burden. A half-day prehospital emergency trauma care curriculum was designed for first responders and piloted in the Sacatepéquez, Chimaltenango, and Escuintla departments in Guatemala. METHODS: Three hundred and fifty-four law enforcement personnel, firefighters, and civilians volunteered to participate in a 5-hour emergency care course teaching scene safety, triage, airway management, cardiopulmonary resuscitation, fracture management, and victim transport. A validated 26-question pretest/post-test study instrument was contextually adapted and used to measure overall test performance, the primary study outcome, as well as test performance stratified by occupation, the secondary study outcome. Pretest/post-test score distributions were compared using a Wilcoxon signed-rank test. For test evaluation, knowledge acquisition on a by-question and by-category basis was examined using McNemar's χ² test, whereas item difficulty indices used frequency-of-distribution tests and item discrimination indices used point biserial correlation. RESULTS: Two hundred and eighty-seven participants qualified for inclusion. Participant mean pretest versus post-test scores improved 24 percentage points after course completion (43% vs 68%, p<0.001). Cronbach's alpha yielded values of 0.86 (pretest) and 0.94 (post-test), suggesting testing instrument reliability. Between-group analyses demonstrated law enforcement and civilian participants improved more than firefighters (p<0.001). Performance on 23 of 26 questions improved significantly. All test questions except one showed an increase in their PPDI. DISCUSSION: A 1-day, contextually adapted, 5-hour course targeting laypeople demonstrates significant improvements in emergency care knowledge. Future investigations of similar curricula should be trialed in alternate low-resource settings with increased civilian participation to evaluate efficacy and replicability as adequate substitutes for longer courses. This study suggests future courses teaching emergency care for lay first responders may be reduced to 5 hours duration. LEVEL OF EVIDENCE: Level II.

Surgical management of pediatric renin-mediated hypertension secondary to renal artery occlusive disease and abdominal aortic coarctation.

BACKGROUND: Renovascular hypertension (RVH) associated with renal artery and abdominal aortic narrowings is the third most common cause of pediatric hypertension. Untreated children may experience major cardiopulmonary complications, stroke, renal failure, and death. The impetus of this study was to describe the increasingly complex surgical practice for such patients with an emphasis on anatomic phenotype and contemporary outcomes after surgical management as a means of identifying those factors responsible for persistent or recurrent hypertension necessitating reoperation. METHODS: A retrospective analysis was performed of consecutive pediatric patients with RVH undergoing open surgical procedures at the University of Michigan from 1991 to 2017. Anatomic phenotype and patient risk factors were analyzed to predict outcomes of blood pressure control and the need for secondary operations using ordered and binomial logistic multinomial regression models, respectively. RESULTS: There were 169 children (76 girls, 93 boys) who underwent primary index operations at a median age of 8.3 years; 31 children (18%) had neurofibromatosis type 1, 76 (45%) had abdominal aortic coarctations, and 28 (17%) had a single functioning kidney. Before treatment at the University of Michigan, 51 children experienced failed previous open operations (15) or endovascular interventions (36) for RVH at other institutions. Primary surgical interventions (342) included main renal artery (136) and segmental renal artery (10) aortic reimplantation, renal artery bypass (55), segmental renal artery embolization (10), renal artery patch angioplasty (8), resection with reanastomosis (4), and partial or total nephrectomy (25). Non-renal artery procedures included patch aortoplasty (32), aortoaortic bypass (32), and splanchnic arterial revascularization (30). Nine patients required reoperation in the early postoperative period. During a mean follow-up of 49 months, secondary interventions were required in 35 children (21%), including both open surgical (37) and endovascular (14) interventions. Remedial intervention to preserve primary renal artery patency or a nephrectomy if such was impossible was required in 22 children (13%). The remaining secondary procedures were performed to treat previously untreated disease that became clinically evident during follow-up. Age at operation and abdominal aortic coarctation were independent predictors for reoperation. The overall experience revealed hypertension to be cured in 74 children (44%), improved in 78 (46%), and unchanged in 17 (10%). Children undergoing remedial operations were less likely (33%) to be cured of hypertension. There was no perioperative death or renal insufficiency requiring dialysis after either primary or secondary interventions. CONCLUSIONS: Contemporary surgical treatment of pediatric RVH provides a sustainable overall benefit to 90% of children. Interventions in the very young (<3 years) and concurrent abdominal aortic coarctation increase the likelihood of reoperation. Patients undergoing remedial surgery after earlier operative failures are less likely to be cured of hypertension. Judicious postoperative surveillance is imperative in children surgically treated for RVH.

Depot-specific adipocyte-extracellular matrix metabolic crosstalk in murine obesity.

Subcutaneous (SAT) and visceral (VAT) adipose tissues have distinct metabolic phenotypes. We hypothesized that the extracellular matrix (ECM) regulates depot-specific differences in adipocyte metabolic function in murine obesity. VAT and SAT preadipocytes from lean or obese mice were subject to adipogenic differentiation in standard 2D culture on plastic tissue culture plates or in 3D culture in ECM, followed by metabolic profiling. Adipocytes from VAT relative to SAT manifested impaired insulin-stimulated glucose uptake and decreased adipogenic capacity. In 3D-ECM-adipocyte culture, ECM regulated adipocyte metabolism in a depot-specific manner, with SAT ECM rescuing defects in glucose uptake and adipogenic gene expression in VAT adipocytes, while VAT ECM impaired adipogenic gene expression in SAT adipocytes. These findings demonstrate that ECM-adipocyte crosstalk regulates depot-specific differences in adipocyte metabolic dysfunction in murine obesity.