A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.

Roadmap for Transforming Preoperative Assessment to Preoperative Optimization.

Preoperative assessment typically equates to evaluating and accepting the presenting condition of the patient (unless extreme) and commonly occurs only a few days before the planned surgery. While this timing enables a preoperative history and examination and mitigates unexpected findings on the day of surgery that may delay throughput, it does not allow for meaningful preoperative management of modifiable medical conditions. Evidence is limited regarding how best to balance efforts to mitigate modifiable risk factors versus the timing of surgery. Furthermore, while the concept of preoperative risk modification is not novel, evidence is lacking for successful and sustained implementation of such an interdisciplinary, collaborative program. A better understanding of perioperative care coordination and, specifically, implementing a preoperative preparation process can enhance the value of surgery and surgical population health. In this article, we describe the implementation of a collaborative preoperative clinic with the primary goal of improving patient outcomes.

Delaying Elective Surgery in Geriatric Patients: An Opportunity for Preoperative Optimization.

Deciding whether to pursue elective surgery is a complex process for older adults. Comprehensive geriatric assessment (CGA) can help refine estimates of benefits and risks, at times leading to a delay of surgery to optimize surgical readiness. We describe a cohort of geriatric patients who were evaluated in anticipation of elective abdominal surgery and whose procedures were delayed for any reason. Themes behind the reasons for delay are described, and a holistic framework to guide preoperative discussion is suggested.

Development and validation of machine learning models to identify high-risk surgical patients using automatically curated electronic health record data (Pythia): A retrospective, single-site study.

BACKGROUND: Pythia is an automated, clinically curated surgical data pipeline and repository housing all surgical patient electronic health record (EHR) data from a large, quaternary, multisite health institute for data science initiatives. In an effort to better identify high-risk surgical patients from complex data, a machine learning project trained on Pythia was built to predict postoperative complication risk. METHODS AND FINDINGS: A curated data repository of surgical outcomes was created using automated SQL and R code that extracted and processed patient clinical and surgical data across 37 million clinical encounters from the EHRs. A total of 194 clinical features including patient demographics (e.g., age, sex, race), smoking status, medications, comorbidities, procedure information, and proxies for surgical complexity were constructed and aggregated. A cohort of 66,370 patients that had undergone 99,755 invasive procedural encounters between January 1, 2014, and January 31, 2017, was studied further for the purpose of predicting postoperative complications. The average complication and 30-day postoperative mortality rates of this cohort were 16.0% and 0.51%, respectively. Least absolute shrinkage and selection operator (lasso) penalized logistic regression, random forest models, and extreme gradient boosted decision trees were trained on this surgical cohort with cross-validation on 14 specific postoperative outcome groupings. Resulting models had area under the receiver operator characteristic curve (AUC) values ranging between 0.747 and 0.924, calculated on an out-of-sample test set from the last 5 months of data. Lasso penalized regression was identified as a high-performing model, providing clinically interpretable actionable insights. Highest and lowest performing lasso models predicted postoperative shock and genitourinary outcomes with AUCs of 0.924 (95% CI: 0.901, 0.946) and 0.780 (95% CI: 0.752, 0.810), respectively. A calculator requiring input of 9 data fields was created to produce a risk assessment for the 14 groupings of postoperative outcomes. A high-risk threshold (15% risk of any complication) was determined to identify high-risk surgical patients. The model sensitivity was 76%, with a specificity of 76%. Compared to heuristics that identify high-risk patients developed by clinical experts and the ACS NSQIP calculator, this tool performed superiorly, providing an improved approach for clinicians to estimate postoperative risk for patients. Limitations of this study include the missingness of data that were removed for analysis. CONCLUSIONS: Extracting and curating a large, local institution's EHR data for machine learning purposes resulted in models with strong predictive performance. These models can be used in clinical settings as decision support tools for identification of high-risk patients as well as patient evaluation and care management. Further work is necessary to evaluate the impact of the Pythia risk calculator within the clinical workflow on postoperative outcomes and to optimize this data flow for future machine learning efforts.

Application of the RAND-UCLA Appropriateness Methodology to a Large Multidisciplinary Stakeholder Group Evaluating the Validity and Feasibility of Patient-Centered Standards in Geriatric Surgery.

OBJECTIVES: To explore (1) differences in validity and feasibility ratings for geriatric surgical standards across a diverse stakeholder group (surgeons vs. nonsurgeons, health care providers vs. nonproviders, including patient-family, advocacy, and regulatory agencies); (2) whether three multidisciplinary discussion subgroups would reach similar conclusions. DATA SOURCE/STUDY SETTING: Primary data (ratings) were reported from 58 stakeholder organizations. STUDY DESIGN: An adaptation of the RAND-UCLA Appropriateness Methodology (RAM) process was conducted in May 2016. DATA COLLECTION/EXTRACTION METHODS: Stakeholders self-administered ratings on paper, returned via mail (Round 1) and in-person (Round 2). PRINCIPAL FINDINGS: In Round 1, surgeons rated standards more critically (91.2 percent valid; 64.9 percent feasible) than nonsurgeons (100 percent valid; 87.0 percent feasible) but increased ratings in Round 2 (98.7 percent valid; 90.6 percent feasible), aligning with nonsurgeons (99.7 percent valid; 96.1 percent feasible). Three parallel subgroups rated validity at 96.8 percent (group 1), 100 percent (group 2), and 97.4 percent (group 3). Feasibility ratings were 76.9 percent (group 1), 96.1 percent (group 2), and 92.2 percent (group 3). CONCLUSIONS: There are differences in validity and feasibility ratings by health professions, with surgeons rating standards more critically than nonsurgeons. However, three separate discussion subgroups rated a high proportion (96-100 percent) of standards as valid, indicating the RAM can be successfully applied to a large stakeholder group.

Association of Integrated Care Coordination With Postsurgical Outcomes in High-Risk Older Adults: The Perioperative Optimization of Senior Health (POSH) Initiative.

Importance: Older adults undergoing elective surgery experience higher rates of preventable postoperative complications than younger patients. Objective: To assess clinical outcomes for older adults undergoing elective abdominal surgery via a collaborative intervention by surgery, geriatrics, and anesthesia focused on perioperative health optimization. Design, Setting, and Participants: Perioperative Optimization of Senior Health (POSH) is a quality improvement initiative with prospective data collection. Participants in an existing geriatrics-based clinic within a single-site academic health center were included if they were at high risk for complications (ie, older than 85 years or older than 65 years with cognitive impairment, recent weight loss, multimorbidity, or polypharmacy) undergoing elective abdominal surgery. Outcomes were compared with a control group of patients older than 65 years who underwent similar surgeries by the same group of general surgeons immediately before implementation of POSH. Main Outcomes and Measures: Primary outcomes included length of stay, 7- and 30-day readmissions, and level of care at discharge. Secondary outcomes were delirium and other major postoperative complications. Outcomes data were derived from institutional databases linked with electronic health records and billing data sets. Results: One hundred eighty-three POSH patients were compared with 143 patients in the control group. On average, patients in the POSH group were older compared with those in the control group (75.6 vs 71.9 years; P < .001; 95% CI, 2.27 to 5.19) and had more chronic conditions (10.6 vs 8.5; P = .001; 95% CI, 0.86 to 3.35). Median length of stay was shorter among POSH patients (4 days vs 6 days; P < .001; 95% CI, -1.06 to -4.21). Patients in the POSH group had lower readmission rates at 7 days (5 of 180 [2.8%] vs 14 of 142 [9.9%]; P = .007; 95% CI, 0.09 to 0.74) and 30 days (14 of 180 [7.8%] vs 26 of 142 [18.3%]; P = .004; 95% CI, 0.19 to 0.75) and were more likely to be discharged home with self-care (114 of 183 [62.3%] vs 73 of 143 [51.1%]; P = .04; 95% CI, 1.02 to 2.47). Patients in the POSH group experienced fewer mean number of complications (0.9 vs 1.4; P < .001; 95% CI, -0.13 to -0.89) despite higher rates of documented delirium (52 of 183 [28.4%] vs 8 of 143 [5.6%]; P < .001; 95% CI, 3.06 to 14.65). A greater proportion of POSH patients underwent laparoscopic procedures (92 of 183 [50%] vs 55 of 143 [38.5%]; P = .001; 95% CI, 1.04 to 2.52). Tests for interactions between POSH patients and procedure type were insignificant for all outcomes. Conclusions and Relevance: Despite higher mean age and morbidity burden, older adults who participated in an interdisciplinary perioperative care intervention had fewer complications, shorter hospitalizations, more frequent discharge to home, and fewer readmissions than a comparison group.

Hospital Standards to Promote Optimal Surgical Care of the Older Adult: A Report From the Coalition for Quality in Geriatric Surgery.

OBJECTIVE: The aim of this study was to establish high-quality, valid standards to improve surgical care of the older adult. BACKGROUND: The aging population increases demand for high-quality surgical care. Building upon prior guidelines, quality indicators, and pilot projects, the Coalition for Quality in Geriatric Surgery (CQGS) includes 58 diverse stakeholder organizations committed to improving geriatric surgery. METHODS: Using a modified RAND-UCLA Appropriateness Methodology, 44 of 58 CQGS Stakeholders twice rated validity (primary outcome) and feasibility for 308 standards, ranging from goals and decision-making, pre-operative assessment and optimization, perioperative and postoperative care, to transitions of care beyond the acute care hospital. RESULTS: Three hundred six of 308 (99%) standards were rated as valid to improve quality of geriatric surgery. There were 4 sections. Section 1 included 157 (57%) standards and focused on goals and decision-making, preoperative optimization, and transitions into and out of the hospital. Section 2 included 84 (27.3%) standards focused on in-hospital care, across the immediate preoperative, intraoperative, and postoperative phases. Section 3 included 59 (19.1%) standards about program management, including personnel and committee structure, credentialing, and education. Section 4 included 8 (2.6%) standards establishing overarching concepts for data collection and patient follow-up. Two hundred ninety of 308 standards (94.2%) were rated as feasible; 18 (5.8%) were rated as uncertain in feasibility. CONCLUSIONS: CQGS Stakeholders rated the vast majority of standards of care as highly valid (99%) and feasible (94%) for improving the quality of surgical care provided to older adults. Future work will focus on a pilot phase to better understand and address challenges to implementation of the standards.

The impact of functional dependency on outcomes after complex general and vascular surgery.

OBJECTIVE: To describe the outcomes of functionally dependent patients who undergo major general or vascular surgery and to determine the relationship between functional health status and early postoperative outcomes. BACKGROUND: In contrast to frailty, functional health status is a relatively easy entity to define and to measure and therefore may be a more practical variable to assess in patients who are being considered for major surgery. To date, few studies have assessed the impact of functional health status on surgical outcomes. METHODS: Patients undergoing 1 of 10 complex general or vascular operations were extracted from the 2005 to 2010 America College of Surgeons National Surgical Quality Improvement Program database. Propensity score techniques were used to match patients with and without preoperative functional dependency on known patient- and procedure-related factors. The postoperative outcomes of this matched cohort were then compared. RESULTS: A total of 10,246 functionally dependent surgical patients were included for analysis. These patients were more acutely and chronically ill than functionally independent patients, and they had higher rates of mortality and morbidity for each of the 10 procedures analyzed. Propensity-matching techniques resulted in the creation of a cohort of functionally independent and dependent patients who were well matched for known patient- and procedure-related variables. Dependent patients from the matched cohort had a 1.75-fold greater odds of postoperative death (95% confidence interval: 1.54-1.98, P < 0.0001) than functionally independent patients. CONCLUSIONS: Preoperative functional dependency is an independent risk factor for mortality after major operation. Functional health status should be routinely assessed in patients who are being considered for complex surgery.

Innovative bridging of the rural-urban divide: comparison of scope, safety, and impact of collaborative rural surgery camps and an urban surgical program.

BACKGROUND: In medically under-resourced regions worldwide, non-permanent surgery programs or camps have been conducted to expand access to surgical services. Surgery camp programs have been reported in rural India, primarily in the ophthalmic and obstetric fields; however, the provision of general surgical services in these settings is largely unknown. METHODS: A 12-month retrospective review of non-ambulatory procedures performed at a rural hospital surgery camp program and at an urban hospital in Maharashtra, India, was completed to characterize relative differences in procedural activity, frequency and severity of perioperative complications, and to evaluate efficacy of care. RESULTS: A total of 449 cases performed in rural hospital surgery camps were compared with 344 cases performed in an urban hospital during the course of the study period. The majority of rural surgical cases were elective and of intermediate complexity. Approximately 4% of rural cases were complex-major compared to 17% of urban cases. Intraoperative complications occurred in 0.2% rural cases compared to 5.5% of urban cases; p = 0.01. Postoperative complications were predominantly low grade in both groups. The postoperative complication rate was higher among rural surgical patients (43.4%; 23.5%; p < 0.01), though the Surgical Risk Score was significantly lower in this group (p < 0. 01). Rural surgery camp activity over 12 months achieved diagnostic and/or therapeutic goals in 92.2% of procedures and rendered 1.74-2.69 disability-adjusted life-years (DALYs) averted per patient. CONCLUSIONS: Rural general surgery camps can safely and effectively provide a wide range of surgical services under appropriate collaborative and clinical conditions. Surgery camps may be a safe, temporizing solution to unmet needs until substantial gains in rural healthcare are realized.

Expectations and outcomes in geriatric patients with do-not-resuscitate orders undergoing emergency surgical management of bowel obstruction.

OBJECTIVE: To describe the outcomes and the expected postoperative course for patients with do-not-resuscitate (DNR) orders (DNR patients) who undergo emergency surgical management of bowel obstruction. DESIGN: We retrospectively identified all patients who underwent emergency surgical management of intestinal obstruction and who were classified previously as DNR using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Participant Use Data File for 2005 through 2009. We constructed a forward stepwise multivariate logistic regression model to determine predictors of postoperative mortality. We used propensity score analysis to determine the effect of DNR status on postoperative outcomes. SETTING: Institutions participating in the NSQIP. PATIENTS: All patients entered in the NSQIP database. MAIN OUTCOME MEASURES: Thirty-day postoperative mortality and complication rates. RESULTS: We identified 242 patients who met the study criteria. Mean age was 80.9 years. Thirty-day mortality was 29.8%, with 47.1% of patients experiencing a postoperative complication. The presence of a postoperative complication was an independent predictor of postoperative mortality. Comparison of matched cohorts revealed a significantly higher postoperative mortality in DNR patients even after adjusting for comorbidities and overall complication rate. CONCLUSIONS: Outcomes are poor after emergency surgical intervention for bowel obstruction in elderly DNR patients, with high postoperative complication and mortality rates. The presence of a DNR order is an independent risk factor for postoperative mortality. Patients, their families, and their physicians must be counseled on surgical expectations preoperatively and made aware of the significantly higher risks involved when a DNR order exists in the setting of emergency surgical management of bowel obstruction.

Advanced age is an independent predictor for increased morbidity and mortality after emergent surgery for diverticulitis.

BACKGROUND: The objectives of our study were to determine the association between age and postoperative outcomes after emergency surgery for diverticulitis and to identify risk factors for postoperative mortality among elderly patients. METHODS: All patients from the American College of Surgeons National Surgical Quality Improvement Program 2005-2009 Participant User Files undergoing emergent surgery for diverticulitis were included. Multivariate logistic regression was used to determine the association between age and postoperative morbidity and mortality after adjustment for perioperative variables. A separate regression model was used to determine risk factors for postoperative mortality among elderly patients, with specific postoperative complications being included as potential predictors. RESULTS: We included 2,264 patients for analysis, of whom 1,267 (56%) were <65 years old (nonelderly), 648 (28.6%) were 65-79 years old (elderly), and 349 (15.4%) were ≥80 years old (super-elderly). Advanced age was a significant predictor of 30-day postoperative mortality, and to a lesser extent postoperative morbidity. Among those patients ≥65 years old, super-elderly age classification remained a significant predictor of mortality after adjustment for the presence or absence of postoperative complications. Mortality among elderly and super-elderly patients was greatest in the setting of specific complications, such as septic shock, prolonged postoperative mechanical ventilation, and acute renal failure. CONCLUSION: Advanced age is an independent risk factor for death after emergency surgery for diverticulitis, with mortality being greatest among elderly patients who experience certain postoperative complications. Prevention of these complications should form the cornerstone of initiatives designed to lower the mortality associated with emergency surgery in elderly patients.

Exploring predictors of complication in older surgical patients: a deficit accumulation index and the Braden Scale.

OBJECTIVES: To determine whether readily collected perioperative information might identify older surgical patients at higher risk of complications. DESIGN: Retrospective cohort study. SETTING: Medical chart review at a single academic institution. PARTICIPANTS: One hundred two individuals aged 65 and older who underwent abdominal surgery between January 2007 and December 2009. MEASUREMENTS: Primary predictor variables were first postoperative Braden Scale score (within 24 hours of surgery) and a Deficit Accumulation Index (DAI) constructed based on 39 available preoperative variables. The primary outcome was presence or absence of complication within 30 days of surgery. RESULTS: Of 102 patients, 64 experienced at least one complication, with wound infection being the most common. In models adjusted for age, race, sex, and open versus laparoscopic surgery, lower Braden Scale scores were predictive of 30-day postoperative complication (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.06-1.60), longer length of stay (ß = 1.44 (0.25) days; P ≤ .001), and discharge to an institution rather than home (OR = 1.23, 95% CI = 1.02-1.48). The cut-off value for the Braden score with the highest predictive value for complication was ≤ 18 (OR = 3.63, 95% CI = 1.43-9.19; c statistic 0.744). The DAI and several traditional surgical risk factors were not significantly associated with 30-day postoperative complications. CONCLUSION: This is the first study to identify the perioperative Braden Scale score, a widely used risk-stratifier for pressure ulcers, as an independent predictor of other adverse outcomes in geriatric surgical patients. Further studies are needed to confirm this finding and to investigate other uses for this tool, which correlates well to phenotypic models of frailty.

SMAD4 is required for development of maximal endotoxin tolerance.

Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1R-associated kinase (IRAK)-M and SHIP-1 proteins, negative regulators of TLR4 signaling, increase in tolerized cells. TGF-beta1, an anti-inflammatory cytokine, is upregulated following LPS stimulation, mediating its effect through SMAD family proteins. Using a monocytic cell line, THP1, we show that LPS activates endogenous SMAD4, inducing its migration into the nucleus and increasing its expression. Secondary challenge with high dose LPS following initial low-dose LPS exposure does not increase IRAK-M or SHIP1 protein expression in small hairpin (sh)SMAD4 THP-1 cells compared with control shLUC THP1 cells. TNF-alpha concentrations in culture supernatants after second LPS challenge are higher in shSMAD4 THP-1 cells than shLUC THP1 cells, indicating failure to induce maximal tolerance in absence of SMAD4 signaling. Identical results are seen in primary murine macrophages and mouse embryonic fibroblasts, demonstrating the biological significance of our findings. TGF-beta1 treatment does not increase IRAK-M or SHIP1 protein expression in shSMAD4 THP-1 cells, whereas it does so in shLUC THP1 cells, indicating that TGF-beta1 regulates IRAK-M and SHIP1 expression through a SMAD4-dependent pathway. Knockdown of endogenous SHIP1 by shSHIP1 RNA decreases native and inducible IRAK-M protein expression and prevents development of endotoxin tolerance in THP1 cells. We conclude that in THP-1 cells and primary murine cells, SMAD4 signaling is required for maximal induction of endotoxin tolerance via modulation of SHIP1 and IRAK-M.