Geographic Variation in Cesarean Sections in the United States: Trends, Correlates, and Other Interesting Facts.

Analyzing data spanning three decades covering the near universe of births, we study county-level differences in Cesarean section (C-section) rates among first-time mothers of singleton births. Our research reveals persistent geographic variation in C-section rates for both low- and high-risk groups. Counties with elevated C-section rates consistently perform more C-sections across mothers at all levels of appropriateness for the procedure. These elevated rates of C-section in high C-section counties are associated with reduced maternal and infant morbidity. We also find that C-section decisions are less responsive to underlying risks for Black mothers relative to white mothers, suggesting potential welfare-reducing disparities.

Does Practice Match Protocol? A Comparison of Triage-to-Provider Time Among More vs. Less Acute Emergency Department Patients.

Introduction The Emergency Severity Index (ESI) stratifies emergency department (ED) patients for triage, from "most acute" (level 1) to "least acute" (level 5). Many EDs have a split flow model where less acute (ESI 4 and 5) are seen in a fast track, while more acute (ESI 1, 2, and 3) are seen in the acute care area. A core principle of emergency medicine (EM) is to attend to more acute patients first. Deliberately designating an area for less acute patients to be initially assessed quickly by a first provider might result in them being seen before more acute patients. This study aims to determine the percentage of less acute patients seen by a provider sooner after triage than more acute patients who arrived within 10 minutes of one another. Additionally, this study compares the fast track and acute care areas to see if location affects triage-to-provider time. Methods A random convenience sample of 252 ED patients aged ≥18 was taken. Patients were included if their ESI was available for the provider during sign-up. Patients were excluded if they were directly sent to the ED psychiatric area or attended to by the author. We collected data on the ESI level, time stamps for triage and first provider sign-up, and the location to which the patient was triaged (fast track vs. acute care). Paired patients' ESI levels, locations, and triage and first provider sign-up times were compared. Results  The study included 126 pairs of patients. There was a statistically significant difference in triage-to-provider times for paired ESI 2 vs. 3 patients (60.5 vs. 35.5 minutes, p = 0.0007) and overall paired high- vs. low-acuity patients (55 vs. 39.5 minutes, p = 0.004). However, in 34.8% of paired ESI 2 vs. 3 patients, the ESI 3 patient was seen prior to the paired ESI 2 patient, and in 39.4% of overall paired high vs. low acuity patients, the less acute patient was seen before the more acute patient. Additionally, patients in the acute care area had significantly shorter median triage-to-provider times (~40 minutes) compared to those in the fast track area for ESI 2 (acute care) vs. ESI 3 (fast track) and overall high acuity (acute care) vs. low acuity (fast track). Nonetheless, approximately one-third of ESI 3 patients triaged to fast track were seen before ESI 2 patients triaged to the acute care area. Conclusion The split flow model reduces overall ED length of stay, improving flow volume, revenue, and patient satisfaction. However, it comes at the expense of the fundamental ethos of EM and potentially subverts the intended triage process. Although most more acute patients are seen by a provider sooner after triage than less acute patients, a substantial number are seen later, which could delay urgent medical needs and negatively impact patients' outcomes. Furthermore, patients triaged to acute care are, in general, seen sooner post-triage than identical-ESI-level fast track patients, suggesting fast track might not function as intended (for low-acuity patients to be quickly assessed and initiate diagnostic and treatment plans). We intend to follow this exploratory study with a more comprehensive, multivariate analysis that will consider confounding variables such as initial vital signs, how busy a provider was that day, etc. The future study will also examine patient outcomes to determine the impact on more acute patients of the split flow model and, in particular, on less acute patients being seen sooner by a first provider.

Exploring patient and system factors impacting undertriage of injured patients meeting national field triage guideline criteria.

BACKGROUND: Trauma systems save lives by coordinating timely and effective responses to injury. However, trauma system effectiveness varies geographically, with worse outcomes observed in rural settings. Prior data suggest that undertriage may play a role in this disparity. Our aim was to explore potential driving factors for decision making among clinicians for undertriaged trauma patients. METHODS: We performed a retrospective analysis of the National Emergency Medical Services Information System database among patients who met physiologic or anatomic national field triage guideline criteria for transport to the highest level of trauma center. Undertriage was defined as transport to a non-level I/II trauma center. Multivariable logistic regression was used to determine demographic, injury, and system characteristics associated with undertriage. Undertriaged patients were then categorized into "recognized" and "unrecognized" groups using the documented reason for transport destination to identify underlying factors associated with undertriage. RESULTS: A total of 36,094 patients were analyzed. Patients in urban areas were more likely to be transported to a destination based on protocol rather than the closest available facility. As expected, patients injured in urban regions were less likely to be undertriaged than their suburban (adjusted odds ratio [aOR], 2.69; 95% confidence interval [95% CI], 2.21-3.31), rural (aOR, 2.71; 95% CI, 2.28-3.21), and wilderness counterparts (aOR, 3.99; 95% CI, 2.93-5.45). The strongest predictor of undertriage was patient/family choice (aOR, 6.29; 5.28-7.50), followed by closest facility (aOR, 5.49; 95% CI, 4.91-6.13) as the reason for hospital selection. Nonurban settings had over twice the odds of recognizing the presence of triage criteria among undertriaged patients (p < 0.05). CONCLUSION: Patients with injuries in nonurban settings and those with less apparent causes of severe injury are more likely to experience undertriage. By analyzing how prehospital clinicians choose transport destinations, we identified patient and system factors associated with undertriage. Targeting these at-risk demographics and contributing factors may help alleviate regional disparities in undertriage. LEVEL OF EVIDENCE: Diagnostic; Level IV.

Association between timing of operative interventions and mortality in emergency general surgery.

Background: Emergency general surgery (EGS) often demands timely interventions, yet data for triage and timing are limited. This study explores the relationship between hospital arrival-to-operation time and mortality in EGS patients. Study design: We performed a retrospective cohort study using an EGS registry at four hospitals, enrolling adults who underwent operative intervention for a primary American Association for the Surgery of Trauma-defined EGS diagnosis between 2021 and 2023. We excluded patients undergoing surgery more than 72 hours after admission as non-urgent and defined our exposure of interest as the time from the initial vital sign capture to the skin incision timestamp. We assessed the association between operative timing quintiles and in-hospital mortality using a mixed-effect hierarchical multivariable model, adjusting for patient demographics, comorbidities, organ dysfunction, and clustering at the hospital level. Results: A total of 1199 patients were included. The median time to operating room (OR) was 8.2 hours (IQR 4.9-20.5 hours). Prolonged time to OR increased the relative likelihood of in-hospital mortality. Patients undergoing an operation between 6.7 and 10.7 hours after first vitals had the highest odds of in-hospital mortality compared with operative times <4.2 hours (reference quintile) (adjusted OR (aOR) 68.994; 95% CI 4.608 to 1032.980, p=0.002). A similar trend was observed among patients with operative times between 24.4 and 70.9 hours (aOR 69.682; 95% CI 2.968 to 1636.038, p=0.008). Conclusion: Our findings suggest that prompt operative intervention is associated with lower in-hospital mortality rates among EGS patients. Further work to identify the most time-sensitive populations is warranted. These results may begin to inform benchmarking for triaging interventions in the EGS population to help reduce mortality rates. Level of evidence: IV.

Association of Frailty with Healthcare Utilization for Patients over One Year Following Surgical Evaluation.

OBJECTIVE: Characterize the distribution of healthcare utilization associated with pre-operative frailty in the year following evaluation by a surgeon. SUMMARY BACKGROUND DATA: Frailty is associated with increased morbidity, mortality, and costs for surgical patients. However, the total financial burden for frail patients beyond the index surgery and inpatient stay remains unknown. METHODS: Prospective cohort assembled from February 2016 to December 2020 within a multi-hospital integrated healthcare delivery and finance system (IDFS), from patients evaluated with the Risk Analysis Index (RAI) of frailty. Inclusion criteria: age greater than 18, valid RAI, membership in the IDFS Health Plan. Data were stratified by frailty and surgical status. RESULTS: The mean (SD) age was 54.7 (16.1) and 58.2% female of the cohort (n=86,572). For all patients with reimbursement for surgery (n=53,856), frail and very frail patients incurred respective increases of 8% ( P =0.027) and 29% ( P <0.001) on utilization relative to the normal group. Robust patients saw a 52% ( P <0.001) decrease. This pattern was more pronounced in the cohort without surgery (n=32,716). The increase over normal utilization for frail and very frail patients increased to 23% ( P =0.004) and 68% ( P <0.001), respectively. Utilization among robust patients decreased 62% ( P <0.001). Increases among the frail were primarily due to increased inpatient medical and post-acute care services (all P <0.001). CONCLUSIONS: Patient frailty is associated with increased total healthcare utilization, primarily via increased inpatient medical and post-acute care following surgery. Quantifying these frailty-related financial burdens may inform clinical decision making as well as the design of value-based reimbursement strategies.

Impact of patient, system, and environmental factors on utilization of air medical transport after trauma.

BACKGROUND: Air medical transport (AMT) improves outcomes for severely injured patients. The decision to fly patients is complex and must consider multiple factors. Our objective was to evaluate the interaction between geography, patient and environmental factors, and emergency medical services (EMS) system resources on AMT after trauma. We hypothesize that significant geographic variation in AMT utilization will be associated with varying levels of patient, environmental, and EMS resources. METHODS: Patients transported by EMS in the Pennsylvania state trauma registry 2000 to 2017 were included. We used our previously developed Air Medical Prehospital Triage (AMPT; ≥2 points triage to AMT) score and Geographic Emergency Medical Services Index (GEMSI; higher indicates more system resources) as measures for patient factors and EMS resources, respectively. A mixed-effects logistic regression model determined the association of AMT utilization with patient, system, and environmental variables. RESULTS: There were 195,354 patients included. Fifty-five percent of variation in AMT utilization was attributed to geographic differences. Triage to AMT by the AMPT score was associated with nearly twice the odds of AMT utilization (adjusted odds ratio, 1.894; 95% confidence interval, 1.765-2.032; p < 0.001). Each 1-point increase in GEMSI was associated with a 6.1% reduction in odds of AMT (0.939; 0.922-0.957; p < 0.001). Younger age, rural location, and more severe injuries were also associated with increased odds of AMT ( p < 0.05). When categorized by GEMSI level, the AMPT score and patient factors were more important for predicting AMT utilization in the middle tercile (moderate EMS resources) compared with the lower (low EMS resources) and higher tercile (high EMS resources). Weather, season, time-of-day, and traffic were all associated with AMT utilization ( p < 0.05). CONCLUSION: Patient, system, and environmental factors are associated with AMT utilization, which varies geographically and by EMS/trauma system resource availability. A more comprehensive approach to AMT triage could reduce variation and allow more tailored efforts toward optimizing resource allocation and outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients.

OBJECTIVE: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. BACKGROUND: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. METHODS: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality. RESULTS: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01). CONCLUSIONS: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.

Evaluating potential disparities in geospatial access to American College of Surgeons/American Association for the Surgery of Trauma-verified emergency general surgery centers.

BACKGROUND: The American Association for the Surgery of Trauma and the American College of Surgeons have recently introduced emergency general surgery (EGS) center verification, which could enhance patient outcomes. Distance and resource availability may affect access to these centers, which has been linked to higher mortality. Although many patients can receive adequate care at community centers, those with critical conditions may require specialized treatment at EGS-verified centers. We aimed to evaluate geospatial access to potential EGS-verified centers and identify disparities across different scenarios of EGS verification program uptake in the United States. METHODS: We used hospital capabilities and verified pilot centers to estimate potential patterns of which centers would become EGS verified under four scenarios (EGS centers, high-volume EGS centers, high-volume EGS plus level 1 trauma centers, and quaternary referral centers). We calculated the spatial accessibility index using an enhanced two-step floating catchment technique to determine geospatial access for each scenario. We also evaluated social determinants of health across geospatial access using the Area Deprivation Index (ADI). RESULTS: A total of 1,932 hospitals were categorized as EGS centers, 307 as high-volume EGS centers, 401 as high-volume EGS plus level 1trauma centers, and 146 as quaternary centers. Spatial accessibility index decreased as the stringency of EGS verification increased in each scenario (226.6 [111.7-330.7], 51.8 [0-126.1], 71.52 [3.34-164.56], 6.2 [0-62.2]; p < 0.001). Within each scenario, spatial accessibility index also declined as the ADI quartile increased ( p < 0.001). The high-volume EGS plus level 1trauma center scenario had the most significant disparity in access between the first and fourth ADI quartiles (-54.68). CONCLUSION: Access to EGS-verified centers may vary considerably based on the program's implementation. Disadvantaged communities may be disproportionately affected by limited access. Further work to study regional needs can allow a strategic implementation of the EGS verification program to optimize outcomes while minimizing disparities. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Predictors of acute incisional hernia incarceration at initial hernia diagnosis on computed tomography.

BACKGROUND: Acute incisional hernia incarceration is associated with high morbidity and mortality yet there is little evidence to guide which patients will benefit most from prophylactic repair. We explored baseline computed tomography (CT) characteristics associated with incarceration. METHODS: A case-control study design was utilized to explore adults (≥18 years) diagnosed with an incisional hernia between 2010 and 2017 at a single institution with a 1-year minimum follow-up. Computed tomography imaging at the time of initial hernia diagnosis was examined. Following propensity score matching for baseline characteristics, multivariable logistic regression was performed to identify independent predictors associated with acute incarceration. RESULTS: A total of 532 patients (27.26% male, mean 61.55 years) were examined, of whom 238 experienced an acute incarceration. Between two well-matched cohorts with and without incarceration, the presence of small bowel in the hernia sac (odds ratio [OR], 7.50; 95% confidence interval [CI], 3.35-16.38), increasing sac height (OR, 1.34; 95% CI, 1.10-1.64), more acute hernia angle (OR, 0.98 per degree; 95% CI, 0.97-0.99), decreased fascial defect width (OR, 0.68; 95% CI, 0.58-0.81), and greater outer abdominal fat (OR, 1.28; 95% CI, 1.02-1.60) were associated with acute incarceration. Using threshold analysis, a hernia angle of <91 degrees and a sac height of >3.25 cm were associated with increased incarceration risk. CONCLUSION: Computed tomography features present at the time of hernia diagnosis provide insight into later acute incarceration risk. Improved understanding of acute incisional hernia incarceration can guide selection for prophylactic repair and thereby may mitigate the excess morbidity associated with incarceration. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Blood-derived lysophospholipid sustains hepatic phospholipids and fat storage necessary for hepatoprotection in overnutrition.

The liver has a high demand for phosphatidylcholine (PC), particularly in overnutrition, where reduced phospholipid levels have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). Whether other pathways exist in addition to de novo PC synthesis that contribute to hepatic PC pools remains unknown. Here, we identified the lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (Mfsd2a) as critical for maintaining hepatic phospholipid pools. Hepatic Mfsd2a expression was induced in patients having NAFLD and in mice in response to dietary fat via glucocorticoid receptor action. Mfsd2a liver-specific deficiency in mice (L2aKO) led to a robust nonalcoholic steatohepatitis-like (NASH-like) phenotype within just 2 weeks of dietary fat challenge associated with reduced hepatic phospholipids containing linoleic acid. Reducing dietary choline intake in L2aKO mice exacerbated liver pathology and deficiency of liver phospholipids containing polyunsaturated fatty acids (PUFAs). Treating hepatocytes with LPCs containing oleate and linoleate, two abundant blood-derived LPCs, specifically induced lipid droplet biogenesis and contributed to phospholipid pools, while LPC containing the omega-3 fatty acid docosahexaenoic acid (DHA) promoted lipid droplet formation and suppressed lipogenesis. This study revealed that PUFA-containing LPCs drive hepatic lipid droplet formation, suppress lipogenesis, and sustain hepatic phospholipid pools - processes that are critical for protecting the liver from excess dietary fat.

Decreased DHA-containing phospholipids in the neocortex of dementia with Lewy bodies are associated with soluble Aß42 , phosphorylated α-synuclein, and synaptopathology.

Docosahexaenoic acid (DHA) is an essential omega-3 polyunsaturated fatty acid implicated in cognitive functions by promoting synaptic protein expression. While alterations of specific DHA-containing phospholipids have been described in the neocortex of patients with Alzheimer's disease (AD), the status of these lipids in dementia with Lewy bodies (DLB), known to manifest aggregated α-synuclein-containing Lewy bodies together with variable amyloid pathology, is unclear. In this study, post-mortem samples from the parietal cortex of 25 DLB patients and 17 age-matched controls were processed for phospholipidomics analyses using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform. After controlling for false discovery rate, six out of the 46 identified putative DHA-phospholipid species were significantly decreased in DLB, with only one showing increase. Altered putative DHA-phospholipid species were subsequently validated with further LC-MS/MS measurements. Of the DHA-containing phospholipid (DCP) species showing decreases, five negatively correlated with soluble beta-amyloid (Aß42) levels, whilst three also correlated with phosphorylated α-synuclein (all p < 0.05). Furthermore, five of these phospholipid species correlated with deficits of presynaptic Rab3A, postsynaptic neurogranin, or both (all p < 0.05). Finally, we found altered immunoreactivities of brain lysolipid DHA transporter, MFSD2A, and the fatty acid binding protein FABP5 in DLB parietal cortex. In summary, we report alterations of specific DCP species in DLB, as well as their associations with markers of neuropathological burden and synaptopathology. These results support the potential role of DHA perturbations in DLB as well as therapeutic targets.

Mfsd2a-mediated lysolipid transport is important for renal recovery after acute kidney injury.

Acute kidney injury (AKI) is a global public health concern with high mortality and morbidity. In ischemic-reperfusion injury (IRI), a main cause of AKI, the brush border membrane of S3 proximal tubules (PT) is lost to the tubular lumen. How injured tubules reconstitute lost membrane lipids during renal recovery is not known. Here, we identified Mfsd2a, a sodium-dependent lysophosphatidylcholine (LPC) transporter, to be expressed specifically in the basolateral membrane of S3 PT. Using an in vivo activity probe for Mfsd2a, transport activity was found to be specific to the S3 PT. Mice with haploinsufficiency of Mfsd2a exhibited delayed recovery of renal function after acute IRI, with depressed urine osmolality and elevated levels of histological markers of damage, fibrosis, and inflammation, findings corroborated by transcriptomic analysis. Lipidomics revealed a deficiency in docosahexaenoic acid (DHA) containing phospholipids in Mfsd2a haploinsufficiency. Treatment of Mfsd2a haploinsufficient mice with LPC-DHA improved renal function and reduced markers of injury, fibrosis, and inflammation. Additionally, LPC-DHA treatment restored S3 brush border membrane architecture and normalized DHA-containing phospholipid content. These findings indicate that Mfsd2a-mediated transport of LPC-DHA is limiting for renal recovery after AKI and suggest that LPC-DHA could be a promising dietary supplement for improving recovery following AKI.

Timing, triage, and mode of emergency general surgery interfacility transfers in the United States: A scoping review.

ABSTRACT: Interfacility transfer of emergency general surgery (EGS) patients continues to rise, especially in the context of ongoing system consolidation. This scoping review aims to identify and summarize the literature on triage, timing, and mode of interfacility emergency general surgery transfer. While common, EGS transfer systems are not optimized to improve outcomes or ensure value-based care. We identified studies investigating emergency general surgery interfacility transfer using Ovid Medline, EMBASE, and Cochrane Library between 1990 and 2022. English studies that evaluated EGS interfacility timing, triage or transfer mode were included. Studies were assessed by two independent reviewers. Studies were limited to English-language articles in the United States. Data were extracted and summarized with a narrative synthesis of the results and gaps in the literature. There were 423 articles identified, of which 66 underwent full-text review after meeting inclusion criteria. Most publications were descriptive studies or outcomes investigations of interfacility transfer. Only six articles described issues related to the logistics behind the interfacility transfer and were included. The articles were grouped into the predefined themes of transfer timing, triage, and mode of transfer. There were mixed results for the impact of transfer timing on outcomes with heterogeneous definitions of delay and populations. Triage guidelines for EGS transfer were consensus or expert opinion. No studies were identified addressing the mode of interfacility EGS transfer. Further research should focus on better understanding which populations of patients require expedited transfer and by what mode. The lack of high-level data supports the need for robust investigations into interfacility transfer processes to optimize triage using scarce resources and optimized value-based care.

The cellular supply-side economics for phospholipids.

Choline is an essential nutrient, but how cells acquire it was not known. Two studies by Kenny et al. and Tsuchiya et al. identified the plasma membrane proteins FLVCR1 and FLVCR2 to be the bona fide choline transporters mediating choline uptake for de novo synthesis of phospholipids in all cells.

Faster sorting algorithms discovered using deep reinforcement learning.

Fundamental algorithms such as sorting or hashing are used trillions of times on any given day1. As demand for computation grows, it has become critical for these algorithms to be as performant as possible. Whereas remarkable progress has been achieved in the past2, making further improvements on the efficiency of these routines has proved challenging for both human scientists and computational approaches. Here we show how artificial intelligence can go beyond the current state of the art by discovering hitherto unknown routines. To realize this, we formulated the task of finding a better sorting routine as a single-player game. We then trained a new deep reinforcement learning agent, AlphaDev, to play this game. AlphaDev discovered small sorting algorithms from scratch that outperformed previously known human benchmarks. These algorithms have been integrated into the LLVM standard C++ sort library3. This change to this part of the sort library represents the replacement of a component with an algorithm that has been automatically discovered using reinforcement learning. We also present results in extra domains, showcasing the generality of the approach.

The Geography of Injuries in Trauma Systems: Using Home as a Proxy for Incident Location.

INTRODUCTION: Effective trauma system organization is crucial to timely access to care and requires accurate understanding of injury and resource locations. Many systems rely on home zip codes to evaluate geographic distribution of injury; however, few studies have evaluated the reliability of home as a proxy for incident location after injury. METHODS: We analyzed data from a multicenter prospective cohort collected from 2017 to 2021. Injured patients with both home and incident zip codes were included. Outcomes included discordance and differential distance between home and incident zip code. Associations of discordance with patient characteristics were determined by logistic regression. We also assessed trauma center catchment areas based on home versus incident zip codes and variation regionally at each center. RESULTS: Fifty thousand one hundred seventy-five patients were included in the analysis. Home and incident zip codes were discordant in 21,635 patients (43.1%). Injuries related to motor vehicles (aOR: 4.76 [95% CI 4.50-5.04]) and younger adults 16-64 (aOR: 2.46 [95% CI 2.28-2.65]) were most likely to be discordant. Additionally, as injury severity score increased, discordance increased. Trauma center catchment area differed up to two-thirds of zip codes when using home versus incident location. Discordance rate, discordant distance, and catchment area overlap between home and incident zip codes all varied significantly by geographic region. CONCLUSIONS: Home location as proxy for injury location should be used with caution and may impact trauma system planning and policy, especially in certain populations. More accurate geolocation data are warranted to further optimize trauma system design.

Deficiency in the omega-3 lysolipid transporter Mfsd2a leads to aberrant oligodendrocyte lineage development and hypomyelination.

Patients with autosomal recessive microcephaly 15 caused by deficiency in the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain-containing 2a (Mfsd2a) present with both microcephaly and hypomyelination, suggesting an important role for LPC uptake by oligodendrocytes in the process of myelination. Here we demonstrate that Mfsd2a is specifically expressed in oligodendrocyte precursor cells (OPCs) and is critical for oligodendrocyte development. Single-cell sequencing of the oligodendrocyte lineage revealed that OPCs from OPC-specific Mfsd2a-KO mice (2aOKO mice) underwent precocious differentiation into immature oligodendrocytes and impaired maturation into myelinating oligodendrocytes, correlating with postnatal brain hypomyelination. 2aOKO mice did not exhibit microcephaly, a finding consistent with the notion that microcephaly is the consequence of an absence of LPC uptake at the blood-brain barrier rather than a deficiency in OPCs. Lipidomic analysis showed that OPCs and iOLs from 2aOKO mice had significantly decreased levels of phospholipids containing omega-3 fatty acids, with a corresponding increase in unsaturated fatty acids, the latter being products of de novo synthesis governed by Srebp-1. RNA-Seq indicated activation of the Srebp-1 pathway and defective expression of regulators of oligodendrocyte development. Taken together, these findings indicate that the transport of LPCs by Mfsd2a in OPCs is important for maintaining OPC state to regulate postnatal brain myelination.

Sex, race, and socioeconomic distinctions in incisional hernia management.

BACKGROUND: We sought to explore the impact of sex, race, and insurance status on operative management of incisional hernias. METHODS: A retrospective cohort study was conducted to explore adult patients diagnosed with an incisional hernia. Adjusted odds for non-operative versus operative management and time to repair were queried. RESULTS: Of the 29,475 patients with an incisional hernia, 20,767 (70.5%) underwent non-operative management. In relation to private insurance, Medicaid (aOR 1.40, 95% CI 1.27-1.54), Medicare (aOR 1.53, 95% CI 1.42-1.65), and uninsured status (aOR 1.99, 95% CI 1.71-2.36) were independently associated with non-operative management. African American race (aOR 1.30, 95% CI 1.17-1.47) was associated with non-operative management while female sex (aOR 0.81, 95% CI 0.77-0.86) was predictive of elective repair. For patients who underwent elective repair, both Medicare (aOR 1.40, 95% CI 1.18-1.66) and Medicaid (aOR 1.49, 95% CI 1.29-1.71) insurance, but not race, were predictive of delayed repair (>90 days after diagnosis). CONCLUSIONS: Sex, race, and insurance status influence incisional hernia management. Development of evidence-based management guidelines may help to ensure equitable care.

Can men 75 and older safely receive a minimally invasive radical prostatectomy?

Men 75 and older presenting with localized prostate cancer have traditionally not been managed with surgery. Therefore, we compared the morbidity and operative outcomes of radical prostatectomy (RP) in men 75 and older to their younger counterparts. We utilized the American College of Surgeons National Surgical Quality Improvement Program database to gather subjects who received a minimally invasive RP (CPT: 55866) from 2016 to 2020. This cohort was then stratified by age to compare men 18-74 years old and men 75 and older. The preclinical profile, complications, and outcomes were analyzed. Chi-square and Mann-Whitney U test were used to analyze categorical and continuous variables, respectively. Of the 48,485 men identified, 2,009 (4.1%) were ≥ 75 years old. Within the 75 and older cohort, the median age was 76 (IQR: 75-78), the median BMI was 27.3 (IQR: 24.9-29.9), and 1,601 (79.7%) were Caucasian. Men 75 and older had higher rates of Clavien 3 (1.3% vs. 0.8%, p = 0.02) and Clavien 4 (7.8% vs. 5.0%, p < 0.001) complications. Reoperative rates (1.7% vs. 1.1%, p = 0.01), readmission rates (6.5% vs. 4.1%, p < 0.001), and mortality (0.4% vs. 0.1%, p < 0.001) were all higher in men 75 and older. Multivariate analysis shows older age to be a risk factor for readmission (OR 1.58, 95%CI 1.31-1.90). Complications and 30-day outcomes remain within an acceptable range to offer surgery in men 75 and older. Age alone should not disqualify men from receiving a RP, but appropriate patient selection and counseling are necessary.

Mfsd2a utilizes a flippase mechanism to mediate omega-3 fatty acid lysolipid transport.

Major Facilitator Superfamily Domain containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine (LPC) transporter expressed at the blood-brain barrier that constitutes the main pathway by which the brain obtains omega-3 fatty acids, such as docosahexanoic acid. Mfsd2a deficiency in humans results in severe microcephaly, underscoring the importance of LPC transport by Mfsd2a for brain development. Biochemical studies and recent cryo-electron microscopy (cryo-EM) structures of Mfsd2a bound to LPC suggest that Mfsd2a transports LPC via an alternating access mechanism between outward-facing and inward-facing conformational states in which the LPC inverts during transport between the outer and inner leaflet of a membrane. However, direct biochemical evidence of flippase activity by Mfsd2a has not been demonstrated and it is not understood how Mfsd2a could invert LPC between the outer and inner leaflet of the membrane in a sodium-dependent manner. Here, we established a unique in vitro assay using recombinant Mfsd2a reconstituted in liposomes that exploits the ability of Mfsd2a to transport lysophosphatidylserine (LPS) coupled with a small molecule LPS binding fluorophore that allowed for monitoring of directional flipping of the LPS headgroup from the outer to the inner liposome membrane. Using this assay, we demonstrate that Mfsd2a flips LPS from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner. Furthermore, using cryo-EM structures as guides together with mutagenesis and a cell-based transport assay, we identify amino acid residues important for Mfsd2a activity that likely constitute substrate interaction domains. These studies provide direct biochemical evidence that Mfsd2a functions as a lysolipid flippase.