Presentation Acuity and Surgical Outcomes for Patients With Health Insurance Living in Highly Deprived Neighborhoods.

Importance: Insurance coverage expansion has been proposed as a solution to improving health disparities, but insurance expansion alone may be insufficient to alleviate care access barriers. Objective: To assess the association of Area Deprivation Index (ADI) with postsurgical textbook outcomes (TO) and presentation acuity for individuals with private insurance or Medicare. Design, Setting, and Participants: This cohort study used data from the National Surgical Quality Improvement Program (2013-2019) merged with electronic health record data from 3 academic health care systems. Data were analyzed from June 2022 to August 2023. Exposure: Living in a neighborhood with an ADI greater than 85. Main Outcomes and Measures: TO, defined as absence of unplanned reoperations, Clavien-Dindo grade 4 complications, mortality, emergency department visits/observation stays, and readmissions, and presentation acuity, defined as having preoperative acute serious conditions (PASC) and urgent or emergent cases. Results: Among a cohort of 29 924 patients, the mean (SD) age was 60.6 (15.6) years; 16 424 (54.9%) were female, and 13 500 (45.1) were male. A total of 14 306 patients had private insurance and 15 618 had Medicare. Patients in highly deprived neighborhoods (5536 patients [18.5%]), with an ADI greater than 85, had lower/worse odds of TO in both the private insurance group (adjusted odds ratio [aOR], 0.87; 95% CI, 0.76-0.99; P = .04) and Medicare group (aOR, 0.90; 95% CI, 0.82-1.00; P = .04) and higher odds of PASC and urgent or emergent cases. The association of ADIs greater than 85 with TO lost significance after adjusting for PASC and urgent/emergent cases. Differences in the probability of TO between the lowest-risk (ADI ≤85, no PASC, and elective surgery) and highest-risk (ADI >85, PASC, and urgent/emergent surgery) scenarios stratified by frailty were highest for very frail patients (Risk Analysis Index ≥40) with differences of 40.2% and 43.1% for those with private insurance and Medicare, respectively. Conclusions and Relevance: This study found that patients living in highly deprived neighborhoods had lower/worse odds of TO and higher presentation acuity despite having private insurance or Medicare. These findings suggest that insurance coverage expansion alone is insufficient to overcome health care disparities, possibly due to persistent barriers to preventive care and other complex causes of health inequities.

A Surgical Desirability of Outcome Ranking (DOOR) Reveals Complex Relationships Between Race/Ethnicity, Insurance Type, and Neighborhood Deprivation.

OBJECTIVE: Develop an ordinal Desirability of Outcome Ranking (DOOR) for surgical outcomes to examine complex associations of Social Determinants of Health. BACKGROUND: Studies focused on single or binary composite outcomes may not detect health disparities. METHODS: Three health care system cohort study using NSQIP (2013-2019) linked with EHR and risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status and operative stress assessing associations of multilevel Social Determinants of Health of race/ethnicity, insurance type (Private 13,957; Medicare 15,198; Medicaid 2835; Uninsured 2963) and Area Deprivation Index (ADI) on DOOR and the binary Textbook Outcomes (TO). RESULTS: Patients living in highly deprived neighborhoods (ADI>85) had higher odds of PASC [adjusted odds ratio (aOR)=1.13, CI=1.02-1.25, P <0.001] and urgent/emergent cases (aOR=1.23, CI=1.16-1.31, P <0.001). Increased odds of higher/less desirable DOOR scores were associated with patients identifying as Black versus White and on Medicare, Medicaid or Uninsured versus Private insurance. Patients with ADI>85 had lower odds of TO (aOR=0.91, CI=0.85-0.97, P =0.006) until adjusting for insurance. In contrast, patients with ADI>85 had increased odds of higher DOOR (aOR=1.07, CI=1.01-1.14, P <0.021) after adjusting for insurance but similar odds after adjusting for PASC and urgent/emergent cases. CONCLUSIONS: DOOR revealed complex interactions between race/ethnicity, insurance type and neighborhood deprivation. ADI>85 was associated with higher odds of worse DOOR outcomes while TO failed to capture the effect of ADI. Our results suggest that presentation acuity is a critical determinant of worse outcomes in patients in highly deprived neighborhoods and without insurance. Including risk adjustment for living in deprived neighborhoods and urgent/emergent surgeries could improve the accuracy of quality metrics.

Association of Insurance Type with Inpatient Surgical 30-day Readmissions, Emergency Department Visits/Observation Stays, and Costs.

OBJECTIVE: To assess the association of Private, Medicare, and Medicaid/Uninsured insurance type with 30-day Emergency Department visits/Observation Stays (EDOS), readmissions, and costs in a safety-net hospital (SNH) serving diverse socioeconomic status patients. SUMMARY BACKGROUND DATA: Medicare's Hospital Readmission Reduction Program (HRRP) disproportionately penalizes SNHs. METHODS: This retrospective cohort study used inpatient National Surgical Quality Improvement Program (2013-2019) data merged with cost data. Frailty, expanded Operative Stress Score, case status, and insurance type were used to predict odds of EDOS and readmissions, as well as index hospitalization costs. RESULTS: The cohort had 1,477 Private; 1,164 Medicare; and 3,488 Medicaid/Uninsured cases with a patient mean age 52.1 years [SD=14.7] and 46.8% of the cases were performed on male patients. Medicaid/Uninsured (aOR=2.69, CI=2.38-3.05, P<.001) and Medicare (aOR=1.32, CI=1.11-1.56, P=.001) had increased odds of urgent/emergent surgeries and complications versus Private patients. Despite having similar frailty distributions, Medicaid/Uninsured compared to Private patients had higher odds of EDOS (aOR=1.71, CI=1.39-2.11, P<.001), and readmissions (aOR=1.35, CI=1.11-1.65, P=.004), after adjusting for frailty, OSS, and case status, while Medicare patients had similar odds of EDOS and readmissions versus Private. Hospitalization variable cost %change was increased for Medicare (12.5%) and Medicaid/Uninsured (5.9%), but Medicaid/Uninsured was similar to Private after adjusting for urgent/emergent cases. CONCLUSIONS: Increased rates and odds of urgent/emergent cases in Medicaid/Uninsured patients drive increased odds of complications and index hospitalization costs versus Private. SNHs care for higher cost populations while receiving lower reimbursements and are further penalized by the unintended consequences of HRRP. Increasing access to care, especially for Medicaid/Uninsured patients, could reduce urgent/emergent surgeries resulting in fewer complications, EDOS/readmissions, and costs.

Independent Associations of Neighborhood Deprivation and Patient-level Social Determinants of Health with Textbook Outcomes after Inpatient Surgery.

Objective: Assess associations of Social Determinants of Health (SDoH) using Area Deprivation Index (ADI), race/ethnicity and insurance type with Textbook Outcomes (TO). Summary Background Data: Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included. Methods: Three healthcare system cohort study using National Surgical Quality Improvement Program (2013-2019) linked with ADI risk-adjusted for frailty, case status and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, Emergency Department/Observation Stays and readmissions). Results: Cohort (34,251 cases) mean age 58.3 [SD=16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI>85, and 81.8% TO. Racial and ethnic minorities, non-Private insurance, and ADI>85 patients had increased odds of urgent/emergent surgeries (aORs range: 1.17-2.83, all P<.001). Non-Hispanic Black patients, ADI>85 and non-Private insurances had lower TO odds (aORs range: 0.55-0.93, all P<.04), but ADI>85 lost significance after including case status. Urgent/emergent versus elective had lower TO odds (aOR=0.51, P<.001). ADI>85 patients had higher complication and mortality odds. Estimated reduction in TO probability was 9.9% (CI=7.2%-12.6%) for urgent/emergent cases, 7.0% (CI=4.6%-9.3%) for Medicaid, and 1.6% (CI=0.2%-3.0%) for non-Hispanic Black patients. TO probability difference for lowest-risk (White-Private-ADI≤85-elective) to highest-risk (Black-Medicaid-ADI>85-urgent/emergent) was 29.8% for very frail patients. Conclusion: Multi-level SDoH had independent effects on TO, predominately affecting outcomes through increased rates/odds of urgent/emergent surgeries driving complications and worse outcomes. Lowest-risk versus highest-risk scenarios demonstrated the magnitude of intersecting SDoH variables. Combination of insurance type and ADI should be used to identify high-risk patients to redesign care pathways to improve outcomes. Risk adjustment including contextual neighborhood deprivation and patient-level SDoH could reduce unintended consequences of value-based programs.

Differentiating Urgent from Elective Cases Matters in Minority Populations: Developing an Ordinal "Desirability of Outcome Ranking" to Increase Granularity and Sensitivity of Surgical Outcomes Assessment.

BACKGROUND: Surgical analyses often focus on single or binary outcomes; we developed an ordinal Desirability of Outcome Ranking (DOOR) for surgery to increase granularity and sensitivity of surgical outcome assessments. Many studies also combine elective and urgent procedures for risk adjustment. We used DOOR to examine complex associations of race/ethnicity and presentation acuity. STUDY DESIGN: NSQIP (2013 to 2019) cohort study assessing DOOR outcomes across race/ethnicity groups risk-adjusted for frailty, operative stress, preoperative acute serious conditions, and elective, urgent, and emergent cases. RESULTS: The cohort included 1,597,199 elective, 340,350 urgent, and 185,073 emergent cases with patient mean age of 60.0 ± 15.8, and 56.4% of the surgeries were performed on female patients. Minority race/ethnicity groups had increased odds of presenting with preoperative acute serious conditions (adjusted odds ratio [aORs] range 1.22 to 1.74), urgent (aOR range 1.04 to 2.21), and emergent (aOR range 1.15 to 2.18) surgeries vs the White group. Black (aOR range 1.23 to 1.34) and Native (aOR range 1.07 to 1.17) groups had increased odds of higher/worse DOOR outcomes; however, the Hispanic group had increased odds of higher/worse DOOR (aOR 1.11, CI 1.10 to 1.13), but decreased odds (aORs range 0.94 to 0.96) after adjusting for case status; the Asian group had better outcomes vs the White group. DOOR outcomes improved in minority groups when using elective vs elective/urgent cases as the reference group. CONCLUSIONS: NSQIP surgical DOOR is a new method to assess outcomes and reveals a complex interplay between race/ethnicity and presentation acuity. Combining elective and urgent cases in risk adjustment may penalize hospitals serving a higher proportion of minority populations. DOOR can be used to improve detection of health disparities and serves as a roadmap for the development of other ordinal surgical outcomes measures. Improving surgical outcomes should focus on decreasing preoperative acute serious conditions and urgent and emergent surgeries, possibly by improving access to care, especially for minority populations.

Cost of Failure to Achieve Textbook Outcomes: Association of Insurance Type with Outcomes and Cumulative Cost for Inpatient Surgery.

BACKGROUND: Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization. STUDY DESIGN: This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions. RESULTS: Cases were performed on patients (private 1,506; Medicare 1,218; Medicaid 1,420; uninsured 2,178) with a mean age 52.3 years (SD 14.7) and 47.5% male. Medicaid and uninsured patients had higher odds of presenting with preoperative acute serious conditions (adjusted odds ratios 1.89 and 1.81, respectively) and undergoing urgent/emergent surgeries (adjusted odds ratios 2.23 and 3.02, respectively) vs private. Medicaid and uninsured patients had lower odds of textbook outcomes (adjusted odds ratios 0.53 and 0.78, respectively) and higher odds of emergency department visits/observation stays and readmissions vs private. Not achieving textbook outcomes was associated with a greater than 95.1% increase in cumulative costs. Medicaid patients had a relative increase of 23.1% in cumulative costs vs private, which was 18.2% after adjusting for urgent/emergent cases. Return costs were 37.5% and 65.8% higher for Medicaid and uninsured patients, respectively, vs private. CONCUSIONS: Higher costs for Medicaid patients were partially driven by increased presentation acuity (increased rates/odds of preoperative acute serious conditions and urgent/emergent surgeries) and higher rates of multiple emergency department visits/observation stays and readmission occurrences. Decreasing surgical costs/improving outcomes should focus on reducing urgent/emergent surgeries and improving postoperative care coordination, especially for Medicaid and uninsured populations.

Association of Cumulative Colorectal Surgery Hospital Costs, Readmissions, and Emergency Department/Observation Stays with Insurance Type.

BACKGROUND/PURPOSE: Medicare's Hospital Readmission Reduction Program disproportionately penalizes safety-net hospitals (SNH) caring for vulnerable populations. This study assessed the association of insurance type with 30-day emergency department visits/observation stays (EDOS), readmissions, and cumulative costs in colorectal surgery patients. METHODS: Retrospective inpatient cohort study using the National Surgical Quality Improvement Program (2013-2019) with cost data in a SNH. The odds of EDOS and readmissions and cumulative variable (index hospitalization and all 30-day EDOS and readmissions) costs were modeled adjusting for frailty, case status, presence of a stoma, and open versus laparoscopic surgery. RESULTS: The cohort had 245 private, 195 Medicare, and 590 Medicaid/uninsured cases, with a mean age 55.0 years (SD = 13.3) and 52.9% of the cases were performed on male patients. Most cases were open surgeries (58.7%). Complication rates were 41.8%, EDOS 12.0%, and readmissions 20.1%. Medicaid/uninsured had increased odds of urgent/emergent surgeries (aOR = 2.15, CI = 1.56-2.98, p < 0.001) and complications (aOR = 1.43, CI = 1.02-2.03, p = 0.042) versus private patients. Medicaid/uninsured versus private patients had higher EDOS (16.6% versus 4.1%) and readmissions (22.9% versus 14.3%) rates and higher odds of EDOS (aOR = 4.81, CI = 2.57-10.06, p < 0.001), and readmissions (aOR = 1.62, CI = 1.07-2.50, p = 0.025), while Medicare patients had similar odds versus private. Cumulative variable cost %change was increased for Medicare and Medicaid/uninsured, but Medicaid/uninsured was similar to private after adjusting for urgent/emergent cases. CONCLUSIONS: Increased urgent/emergent cases in Medicaid/uninsured populations drive increased complications odds and higher costs compared to private patients, suggesting lack of access to outpatient care. SNH care for higher cost populations, receive lower reimbursements, and are penalized by value-based programs. Increasing healthcare access for Medicaid/uninsured patients could reduce urgent/emergent surgeries, resulting in fewer complications, EDOS/readmissions, and costs.

Association of Insurance Type With Inpatient Surgery 30-Day Complications and Costs.

INTRODUCTION: Safety-net hospitals (SNHs) have higher postoperative complications and costs versus low-burden hospitals. Do low socioeconomic status/vulnerable patients receive care at lower-quality hospitals or are there factors beyond providers' control? We studied the association of private, Medicare, and vulnerable insurance type with complications/costs in a high-burden SNH. METHODS: Retrospective inpatient cohort study using National Surgical Quality Improvement Program (NSQIP) data (2013-2019) with cost data risk-adjusted by frailty, preoperative serious acute conditions (PASC), case status, and expanded operative stress score (OSS) to evaluate 30-day unplanned reoperations, any complication, Clavien-Dindo IV (CDIV) complications, and hospitalization variable costs. RESULTS: Cases (Private 1517; Medicare 1224; Vulnerable 3648) with patient mean age 52.3 y [standard deviation = 14.7] and 47.3% male. Adjusting for frailty and OSS, vulnerable patients had higher odds of PASC (aOR = 1.71, CI = 1.39-2.10, P < 0.001) versus private. Adjusting for frailty, PASC and OSS, Medicare (aOR = 1.27, CI = 1.06-1.53, P = 0.009), and vulnerable (aOR = 2.44, CI = 2.13-2.79, P < 0.001) patients were more likely to undergo urgent/emergent surgeries. Vulnerable patients had increased odds of reoperation and any complications versus private. Variable cost percentage change was similar between private and vulnerable after adjusting for case status. Urgent/emergent case status increased percentage change costs by 32.31%. We simulated "switching" numbers of private (3648) versus vulnerable (1517) cases resulting in an estimated variable cost of $49.275 million, a 25.2% decrease from the original $65.859 million. CONCLUSIONS: Increased presentation acuity (PASC and urgent/emergent surgeries) in vulnerable patients drive increased odds of complications and costs versus private, suggesting factors beyond providers' control. The greatest impact on outcomes may be from decreasing the incidence of urgent/emergent surgeries by improving access to care.

Sex-Related Differences in Acuity and Postoperative Complications, Mortality and Failure to Rescue.

INTRODUCTION: Yentl syndrome describing sex-related disparities has been extensively studied in medical conditions but not after surgery. This retrospective cohort study assessed the association of sex, frailty, presenting with preoperative acute serious conditions (PASC), and the expanded Operative Stress Score (OSS) with postoperative complications, mortality, and failure-to-rescue. METHODS: The National Surgical Quality Improvement Program from 2015 to 2019 evaluating 30-d complications, mortality, and failure-to-rescue. RESULTS: Of 4,860,308 cases (43% were male; mean [standard deviation] age of 56 [17] y), 6.0 and 0.8% were frail and very frail, respectively. Frailty score distribution was higher in men versus women (P < 0.001). Most cases were low-stress OSS2 (44.9%) or moderate-stress OSS3 (44.5%) surgeries. While unadjusted 30-d mortality rates were higher (P < 0.001) in males (1.1%) versus females (0.8%), males had lower odds of mortality (adjusted odds ratio (aOR) = 0.92, 95% confidence interval [CI] = 0.90-0.94, P < 0.001) after adjusting for frailty, OSS, case status, PASC, and Clavien-Dindo IV (CDIV) complications. Males have higher odds of PASC (aOR = 1.33, CI = 1.31-1.35, P < 0.001) and CDIV complications (aOR = 1.13, CI = 1.12-1.15, P < 0.001). Male-PASC (aOR = 0.76, CI = 0.72-0.80, P < 0.001) and male-CDIV (aOR = 0.87, CI = 0.83-0.91, P < 0.001) interaction terms demonstrated that the increased odds of mortality associated with PASC or CDIV complications/failure-to-rescue were lower in males versus females. CONCLUSIONS: Our study provides a comprehensive analysis of sex-related surgical outcomes across a wide range of procedures and health care systems. Females presenting with PASC or experiencing CDIV complications had higher odds of mortality/failure to rescue suggesting sex-related care differences. Yentl syndrome may be present in surgical patients; possibly related to differences in presenting symptoms, patient care preferences, or less aggressive care in female patients and deserves further study.

Tailored Porous Carbon Xerogels for Fe-N-C Catalysts in Proton Exchange Membrane Fuel Cells.

Atomically dispersed Fe-N-C catalysts for the oxygen reduction reaction (ORR) have been synthesized with a template-free method using carbon xerogels (CXG) as a porous matrix. The porosity of the CXGs is easily tunable through slight variations in the synthesis procedure. In this work, CXGs are prepared by formaldehyde and resorcinol polymerization, modifying the pH during the process. Materials with a broad range of porous structures are obtained: from non-porous to micro-/meso-/macroporous materials. The porous properties of CXG have a direct effect on Fe-N-CXG activity against ORR in an acidic medium (0.5 M H2SO4). Macropores and wide mesopores are vital to favor the mass transport of reagents to the active sites available in the micropores, while narrower mesopores can generate additional tortuosity. The role of microporosity is investigated by comparing two Fe-N-C catalysts using the same CXG as the matrix but following a different Fe and N doping procedure. In one case, the carbonization of CXG occurs rapidly and simultaneously with Fe and N doping, whereas in the other case it proceeds slowly, under controlled conditions and before the doping process, resulting in the formation of more micropores and active sites and achieving higher activity in a three-electrode cell and a better durability during fuel cell measurements. This work proves the feasibility of the template-free method using CXG as a carbon matrix for Fe-N-C catalysts, with the novelty of the controlled porous properties of the carbon material and its effect on the catalytic activity of the Fe-N-C catalyst. Moreover, the results obtained highlight the importance of the carbon matrix's porous structure in influencing the activity of Fe-N-C catalysts against ORR.

Retrospective cohort study comparing surgical inpatient charges, total costs, and variable costs as hospital cost savings measures.

We analyzed differences (charges, total, and variable costs) in estimating cost savings of quality improvement projects using reduction of serious/life-threatening complications (Clavien-Dindo Level IV) and insurance type (Private, Medicare, and Medicaid/Uninsured) to evaluate the cost measures. Multiple measures are used to analyze hospital costs and compare cost outcomes across health systems with differing patient compositions. We used National Surgical Quality Improvement Program inpatient (2013-2019) with charge and cost data in a hospital serving diverse socioeconomic status patients. Simulation was used to estimate variable costs and total costs at 3 proportions of fixed costs (FC). Cases (Private 1517; Medicare 1224; Medicaid/Uninsured 3648) with patient mean age 52.3 years (Standard Deviation = 14.7) and 47.3% male. Medicare (adjusted odds ratio = 1.55, 95% confidence interval = 1.16-2.09, P = .003) and Medicaid/Uninsured (adjusted odds ratio = 1.41, 95% confidence interval = 1.10-1.82, P = .008) had higher odds of complications versus Private. Medicaid/Uninsured had higher relative charges versus Private, while Medicaid/Uninsured and Medicare had higher relative variable and total costs versus Private. Targeting a 15% reduction in serious complications for robust patients undergoing moderate-stress procedures estimated variable cost savings of $286,392. Total cost saving estimates progressively increased with increasing proportions of FC; $443,943 (35% FC), $577,495 (50% FC), and $1184,403 (75% FC). In conclusion, charges did not identify increased costs for Medicare versus Private patients. Complications were associated with > 200% change in costs. Surgical hospitalizations for Medicare and Medicaid/Uninsured patients cost more than Private patients. Variable costs should be used to avoid overestimating potential cost savings of quality improvement interventions, as total costs include fixed costs that are difficult to change in the short term.

Association of Insurance Type With Colorectal Surgery Outcomes and Costs at a Safety-Net Hospital: A Retrospective Observational Study.

Association of insurance type with colorectal surgical complications, textbook outcomes (TO), and cost in a safety-net hospital (SNH). Background: SNHs have higher surgical complications and costs compared to low-burden hospitals. How does presentation acuity and insurance type influence colorectal surgical outcomes? Methods: Retrospective cohort study using single-site National Surgical Quality Improvement Program (2013-2019) with cost data and risk-adjusted by frailty, preoperative serious acute conditions (PASC), case status and open versus laparoscopic to evaluate 30-day reoperations, any complication, Clavien-Dindo IV (CDIV) complications, TO, and hospitalization variable costs. Results: Cases (Private 252; Medicare 207; Medicaid/Uninsured 619) with patient mean age 55.2 years (SD = 13.4) and 53.1% male. Adjusting for frailty, open abdomen, and urgent/emergent cases, Medicaid/Uninsured patients had higher odds of presenting with PASC (adjusted odds ratio [aOR] = 2.02, 95% confidence interval [CI] = 1.22-3.52, P = 0.009) versus Private. Medicaid/Uninsured (aOR = 1.80, 95% CI = 1.28-2.55, P < 0.001) patients were more likely to undergo urgent/emergent surgeries compared to Private. Medicare patients had increased odds of any and CDIV complications while Medicaid/Uninsured had increased odds of any complication, emergency department or observations stays, and readmissions versus Private. Medicare (aOR = 0.51, 95% CI = 0.33-0.88, P = 0.003) and Medicaid/Uninsured (aOR = 0.43, 95% CI = 0.30-0.60, P < 0.001) patients had lower odds of achieving TO versus Private. Variable cost %change increased in Medicaid/Uninsured patients to 13.94% (P = 0.005) versus Private but was similar after adjusting for case status. Urgent/emergent cases (43.23%, P < 0.001) and any complication (78.34%, P < 0.001) increased %change hospitalization costs. Conclusions: Decreasing the incidence of urgent/emergent colorectal surgeries, possibly by improving access to care, could have a greater impact on improving clinical outcomes and decreasing costs, especially in Medicaid/Uninsured insurance type patients.

Association of Socioeconomic Area Deprivation Index with Hospital Readmissions After Colon and Rectal Surgery.

BACKGROUND: Risk adjustment for reimbursement and quality measures omits social risk factors despite adversely affecting health outcomes. Social risk factors are not usually available in electronic health records (EHR) or administrative data. Socioeconomic status can be assessed by using US Census data. Distressed Communities Index (DCI) is based upon zip codes, and the Area Deprivation Index (ADI) provides more granular estimates at the block group level. We examined the association of neighborhood disadvantage using the ADI, DCI, and patient-level insurance status on 30-day readmission risk after colorectal surgery. METHODS: Our 677 patient cohort was derived from the 2013-2017 National Surgical Quality Improvement Program at a safety net hospital augmented with EHR data to determine insurance status and 30-day readmissions. Patients' home addresses were linked to the ADI and DCI. RESULTS: Our cohort consisted of 53.9% males and 63.8% Hispanics with a 22.9% 30-day readmission rate from the date of discharge; > 50% lived in highly deprived neighborhoods. Controlling for medical comorbidities and complications, ADI was associated with increased risk of 30 days from the date of discharge readmissions among patients living in medium (OR = 2.15, p = .02) or high (OR = 1.88, p = .03) deprived areas compared to less-deprived neighborhoods, but not insurance status or DCI. CONCLUSIONS: The ADI identified patients living in deprived communities with increased readmission risk. Our results show that block-group level ADI can potentially be used in risk adjustment, to identify high-risk patients and to design better care pathways that improve health outcomes.

Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb.

The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.

Cost of Unnecessary Amylase and Lipase Testing at Multiple Academic Health Systems.

OBJECTIVES: To determine adherence to Choosing Wisely recommendations for using serum lipase to diagnose acute pancreatitis rather than amylase, avoiding concurrent amylase/lipase testing and avoiding serial measurements after the first elevated test as both are ineffective for tracking disease course. METHODS: Deidentified laboratory data from four large health systems were analyzed to determine concurrent testing rates, serial testing rates, and provider-ordering patterns. RESULTS: While most providers adhered to recommendations with 58,693 lipase-only tests ordered and performed, 86% of amylase tests were performed concurrently with lipase. Ambulatory, inpatient, and emergency department settings revealed concurrent rates of 51%, 41%, and 8%, respectively. Services with order sets containing both amylase and lipase were associated with higher rates of concurrent testing. CONCLUSIONS: Concurrent amylase/lipase testing is an area of opportunity to improve compliance, especially in ambulatory settings. Revision of order sets and provider education could be interventions to reduce unnecessary testing and save costs.

JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients.

To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 (P = 0.06) and PAX1 (P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage (n = 118). We also found that promoter methylation of PAX1 and PAX5 (n = 78), was correlated with neighborhood characteristics at the zip-code level (P < 0.05). Analyses also showed differences in the frequency of TP53 mutations (n = 32) and tumor-infiltrating lymphocyte (TIL) counts (n = 24), and the presence of a specific C → A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n = 73; P < 0.05), when compared with NLW (n = 37) patients. TIL counts are associated (P = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations.

Tox_(R)CNN: Deep learning-based nuclei profiling tool for drug toxicity screening.

Toxicity is an important factor in failed drug development, and its efficient identification and prediction is a major challenge in drug discovery. We have explored the potential of microscopy images of fluorescently labeled nuclei for the prediction of toxicity based on nucleus pattern recognition. Deep learning algorithms obtain abstract representations of images through an automated process, allowing them to efficiently classify complex patterns, and have become the state-of-the art in machine learning for computer vision. Here, deep convolutional neural networks (CNN) were trained to predict toxicity from images of DAPI-stained cells pre-treated with a set of drugs with differing toxicity mechanisms. Different cropping strategies were used for training CNN models, the nuclei-cropping-based Tox_CNN model outperformed other models classifying cells according to health status. Tox_CNN allowed automated extraction of feature maps that clustered compounds according to mechanism of action. Moreover, fully automated region-based CNNs (RCNN) were implemented to detect and classify nuclei, providing per-cell toxicity prediction from raw screening images. We validated both Tox_(R)CNN models for detection of pre-lethal toxicity from nuclei images, which proved to be more sensitive and have broader specificity than established toxicity readouts. These models predicted toxicity of drugs with mechanisms of action other than those they had been trained for and were successfully transferred to other cell assays. The Tox_(R)CNN models thus provide robust, sensitive, and cost-effective tools for in vitro screening of drug-induced toxicity. These models can be adopted for compound prioritization in drug screening campaigns, and could thereby increase the efficiency of drug discovery.

Pluripotency Surveillance by Myc-Driven Competitive Elimination of Differentiating Cells.

The mammalian epiblast is formed by pluripotent cells able to differentiate into all tissues of the new individual. In their progression to differentiation, epiblast cells and their in vitro counterparts, embryonic stem cells (ESCs), transit from naive pluripotency through a differentiation-primed pluripotent state. During these events, epiblast cells and ESCs are prone to death, driven by competition between Myc-high cells (winners) and Myc-low cells (losers). Using live tracking of Myc levels, we show that Myc-high ESCs approach the naive pluripotency state, whereas Myc-low ESCs are closer to the differentiation-primed state. In ESC colonies, naive cells eliminate differentiating cells by cell competition, which is determined by a limitation in the time losers are able to survive persistent contact with winners. In the mouse embryo, cell competition promotes pluripotency maintenance by elimination of primed lineages before gastrulation. The mechanism described here is relevant to mammalian embryo development and induced pluripotency.

ESC-Track: A computer workflow for 4-D segmentation, tracking, lineage tracing and dynamic context analysis of ESCs.

Embryonic stem cells (ESCs) can be established as permanent cell lines, and their potential to differentiate into adult tissues has led to widespread use for studying the mechanisms and dynamics of stem cell differentiation and exploring strategies for tissue repair. Imaging live ESCs during development is now feasible due to advances in optical imaging and engineering of genetically encoded fluorescent reporters; however, a major limitation is the low spatio-temporal resolution of long-term 3-D imaging required for generational and neighboring reconstructions. Here, we present the ESC-Track (ESC-T) workflow, which includes an automated cell and nuclear segmentation and tracking tool for 4-D (3-D + time) confocal image data sets as well as a manual editing tool for visual inspection and error correction. ESC-T automatically identifies cell divisions and membrane contacts for lineage tree and neighborhood reconstruction and computes quantitative features from individual cell entities, enabling analysis of fluorescence signal dynamics and tracking of cell morphology and motion. We use ESC-T to examine Myc intensity fluctuations in the context of mouse ESC (mESC) lineage and neighborhood relationships. ESC-T is a powerful tool for evaluation of the genealogical and microenvironmental cues that maintain ESC fitness.