Transcriptomic Differences in Peripheral Monocyte Populations in Septic Patients Based on Outcome.

ABSTRACT: Post-sepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness (CCI) with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. As classical and non-classical monocytes are key leukocytes in both the innate and adaptive immune systems, we sought to delineate the transcriptomic response of these cell types. Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNFα production based on clinical outcome. This may provide therapeutic targets for those at risk for CCI in order to improve their phenotype/endotype, morbidity, and long-term mortality.

The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells.

Introduction: Sepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness. Methods: Cellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering. Results: We identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome. Discussion: The origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

Longitudinal clinical decision support for assessing decisions over time: State-of-the-art and future directions.

Objective: Patients and clinicians rarely experience healthcare decisions as snapshots in time, but clinical decision support (CDS) systems often represent decisions as snapshots. This scoping review systematically maps challenges and facilitators to longitudinal CDS that are applied at two or more timepoints for the same decision made by the same patient or clinician. Methods: We searched Embase, PubMed, and Medline databases for articles describing development, validation, or implementation of patient- or clinician-facing longitudinal CDS. Validated quality assessment tools were used for article selection. Challenges and facilitators to longitudinal CDS are reported according to PRISMA-ScR guidelines. Results: Eight articles met inclusion criteria; each article described a unique CDS. None used entirely automated data entry, none used living guidelines for updating the evidence base or knowledge engine as new evidence emerged during the longitudinal study, and one included formal readiness for change assessments. Seven of eight CDS were implemented and evaluated prospectively. Challenges were primarily related to suboptimal study design (with unique challenges for each study) or user interface. Facilitators included use of randomized trial designs for prospective enrollment, increased CDS uptake during longitudinal exposure, and machine-learning applications that are tailored to the CDS use case. Conclusions: Despite the intuitive advantages of representing healthcare decisions longitudinally, peer-reviewed literature on longitudinal CDS is sparse. Existing reports suggest opportunities to incorporate longitudinal CDS frameworks, automated data entry, living guidelines, and user readiness assessments. Generating best practice guidelines for longitudinal CDS would require a greater depth and breadth of published work and expert opinion.

Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (3-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B's favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the sequential organ failure assessment scores, the clustering results did not simply provide a recapitulation of previous acuity assessments. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.

Gender differences in autonomy and performance assessments in a national cohort of vascular surgery trainees.

OBJECTIVE: Gender disparities in surgical training and assessment are described in the general surgery literature. Assessment disparities have not been explored in vascular surgery. We sought to investigate gender disparities in operative assessment in a national cohort of vascular surgery integrated residents (VIRs) and fellows (VSFs). METHODS: Operative performance and autonomy ratings from the Society for Improving Medical Professional Learning (SIMPL) application database were collected for all vascular surgery participating institutions from 2018 to 2023. Logistic generalized linear mixed models were conducted to examine the association of faculty and trainee gender on faculty and self-assessment of autonomy and performance. Data were adjusted for post-graduate year and case complexity. Random effects were included to account for clustering effects due to participant, program, and procedure. RESULTS: One hundred three trainees (n = 63 VIRs; n = 40 VSFs; 63.1% men) and 99 faculty (73.7% men) from 17 institutions (n = 12 VIR and n = 13 VSF programs) contributed 4951 total assessments (44.4% by faculty, 55.6% by trainees) across 235 unique procedures. Faculty and trainee gender were not associated with faculty ratings of performance (faculty gender: odds ratio [OR], 0.78; 95% confidence interval [CI], 0.27-2.29; trainee gender: OR, 1.80; 95% CI, 0.76-0.43) or autonomy (faculty gender: OR, 0.99; 95% CI, 0.41-2.39; trainee gender: OR, 1.23; 95% CI, 0.62-2.45) of trainees. All trainees self-assessed at lower performance and autonomy ratings as compared with faculty assessments. However, women trainees rated themselves significantly lower than men for both autonomy (OR, 0.57; 95% CI, 0.43-0.74) and performance (OR, 0.40; 95% CI, 0.30-0.54). CONCLUSIONS: Although gender was not associated with differences in faculty assessment of performance or autonomy among vascular surgery trainees, women trainees perceive themselves as performing with lower competency and less autonomy than their male colleagues. These findings suggest utility for exploring gender differences in real-time feedback delivered to and received by trainees and targeted interventions to align trainee self-perception with actual operative performance and autonomy to optimize surgical skill acquisition.

Intraoperative hypotension and postoperative acute kidney injury: A systematic review.

BACKGROUND: There is no consensus regarding safe intraoperative blood pressure thresholds that protect against postoperative acute kidney injury (AKI). This review aims to examine the existing literature to delineate safe intraoperative hypotension (IOH) parameters to prevent postoperative AKI. METHODS: PubMed, Cochrane Central, and Web of Science were systematically searched for articles published between 2015 and 2022 relating the effects of IOH on postoperative AKI. RESULTS: Our search yielded 19 articles. IOH risk thresholds ranged from <50 to <75 â€‹mmHg for mean arterial pressure (MAP) and from <70 to <100 â€‹mmHg for systolic blood pressure (SBP). MAP below 65 â€‹mmHg for over 5 â€‹min was the most cited threshold (N â€‹= â€‹13) consistently associated with increased postoperative AKI. Greater magnitude and duration of MAP and SBP below the thresholds were generally associated with a dose-dependent increase in postoperative AKI incidence. CONCLUSIONS: While a consistent definition for IOH remains elusive, the evidence suggests that MAP below 65 â€‹mmHg for over 5 â€‹min is strongly associated with postoperative AKI, with the risk increasing with the magnitude and duration of IOH.

Operating Room Supply Cost and Value of Care after Implementing a Sustainable Quality Intervention.

BACKGROUND: Variability in operating room supply cost is a modifiable cause of suboptimal resource use and low value of care (outcomes vs cost). This study describes implementation of a quality improvement intervention to decrease operating room supply costs. STUDY DESIGN: An automated electronic health record data pipeline harmonized operating room supply cost data with patient and case characteristics and outcomes. For inpatient procedures, predicted mortality and length of stay were used to calculate observed-to-expected ratios and value of care using validated equations. For commonly performed (1 or more per week) procedures, the pipeline generated figures illustrating individual surgeon performance vs peers, costs for each surgeon performing each case type, and control charts identifying out-of-control cases and surgeons with more than 90th percentile costs, which were shared with surgeons and division chiefs alongside guidance for modifying case-specific supply instructions to operating room nurses and technicians. RESULTS: Preintervention control (1,064 cases for 7 months) and postintervention (307 cases for 2 months) cohorts had similar baseline characteristics across all 16 commonly performed procedures. Median costs per case were lower in the intervention cohort ($811 [$525 to $1,367] vs controls: $1,080 [$603 to $1,574], p < 0.001), as was the incidence of out-of-control cases (19 (6.2%) vs 110 (10.3%), p = 0.03). Duration of surgery, length of stay, discharge disposition, and 30-day mortality and readmission rates were similar between cohorts. Value of care was higher in the intervention cohort (1.1 [0.1 to 1.5] vs 1.0 [0.2 to 1.4], p = 0.04). Pipeline runtime was 16:07. CONCLUSIONS: An automated, sustainable quality improvement intervention was associated with decreased operating room supply costs and increased value of care.

Are we ready for "green surgery" to promote environmental sustainability in the operating room? Results from the WSES STAR investigation.

BACKGROUND: The importance of environmental sustainability is acknowledged in all sectors, including healthcare. To meet the United Nations Sustainable Development Goals 2030 Agenda, healthcare will need a paradigm shift toward more environmentally sustainable practices that will also impact clinical decision-making. The study investigates trauma and emergency surgeons' perception, acceptance, and employment of environmentally friendly habits. METHODS: An online survey based on the most recent literature regarding environmental sustainability in healthcare and surgery was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to the 917 WSES members through the society's website and Twitter/X profile. RESULTS: 450 surgeons from 55 countries participated in the survey. Results underline both a generally positive attitude toward environmental sustainability but also a lack of knowledge about several concepts and practices, especially concerning the potential contribution to patient care. DISCUSSION: The topic of environmental sustainability in healthcare and surgery is still in its infancy. There is a clear lack of salient guidance and knowledge, and there is a critical need for governments, institutions, health agencies, and scientific societies to promote, disseminate, and report environmentally friendly initiatives and their potential impacts while employing an interdisciplinary approach.

Surgical leadership: Ensuring financial stability through growth.

Maintaining financial stability is important for leaders in surgery because it (1) allows consistent, fair (market value) reimbursement for employees, which conveys that they are valued; (2) enables strategic investment in new programs that may not generate direct financial gains but are required; and (3) builds trust with stakeholders outside the department while strengthening the department's position in negotiations. Key strategies that we have used to increase revenue (income) over the past 6 years have been hiring more faculty, advocating for greater operating room and staffing capacity, staffing surgeons at other institutions using affiliation agreements, attempting to shift grant-funded efforts to non-clinical (research) faculty to mitigate National Institutes of Health salary cap penalties, and increasing efforts to identify external funding for educational and administrative tasks performed by surgeons (eg, increasing contact hours with medical students to secure a greater proportion of state general revenue). Using these strategies, our total revenue has increased 66% over the past 6 years, whereas Academic Support Agreement funds from the College of Medicine concurrently have decreased by 75%. Key strategies that we have used for curtailing expenses have been increasing clinic workflow efficiency; shifting advance practice provider contractual expenses and trainee indirect costs to the hospital; focusing on driving down delayed accounts receivable over time; and using net collections to preferentially invest in research likely to receive future external funding, for which indirect costs return to the department. Despite using these strategies, the total expenses of our department have increased 74% over the past 6 years, driven primarily by the doubling of clinic costs and contractual expenses for advance practice providers. These losses could theoretically be offset by (1) increasing billing by advance practice providers who can also facilitate excellent continuity of surgical care while allowing residents and fellows to shift their effort from service toward education and (2) increasing clinic capacity to generate increasing operative volumes. A department's financial stability is affected by complex interactions among several stakeholders, including the College of Medicine, faculty group practices, and hospitals, with competing interests. Leaders in surgery must understand and manage major categories of revenue and expenses to create a financially stable environment in which they can fulfill their multi-prong missions.

Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot.

BACKGROUNDSepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 following ICU admission.RESULTSCompared with 46 healthy participants, unstimulated and stimulated whole-blood IFN-γ expression was either increased or unchanged, respectively, in septic and nonseptic ICU patients. However, in septic patients who did not survive 180 days, stimulated whole-blood IFN-γ expression was significantly reduced on ICU days 1, 4, and 7 (all P < 0.05), due to both significant reductions in total number of IFN-γ-producing cells and amount of IFN-γ produced per cell (all P < 0.05). Importantly, IFN-γ total expression on days 1 and 4 after admission could discriminate 180-day mortality better than absolute lymphocyte count (ALC), IL-6, and procalcitonin. Septic patients with low IFN-γ expression were older and had lower ALCs and higher soluble PD-L1 and IL-10 concentrations, consistent with an immunosuppressed endotype.CONCLUSIONSA whole-blood IFN-γ ELISpot assay can both identify septic patients at increased risk of late mortality and identify immunosuppressed septic patients.TRIAL REGISTRYN/A.FUNDINGThis prospective, observational, multicenter clinical study was directly supported by National Institute of General Medical Sciences grant R01 GM-139046, including a supplement (R01 GM-139046-03S1) from 2022 to 2024.

Resident Operative Autonomy and Attending Verbal Feedback Differ by Resident and Attending Gender.

Objectives: This study tests the null hypotheses that overall sentiment and gendered words in verbal feedback and resident operative autonomy relative to performance are similar for female and male residents. Background: Female and male surgical residents may experience training differently, affecting the quality of learning and graduated autonomy. Methods: A longitudinal, observational study using a Society for Improving Medical Professional Learning collaborative dataset describing resident and attending evaluations of resident operative performance and autonomy and recordings of verbal feedback from attendings from surgical procedures performed at 54 US general surgery residency training programs from 2016 to 2021. Overall sentiment, adjectives, and gendered words in verbal feedback were quantified by natural language processing. Resident operative autonomy and performance, as evaluated by attendings, were reported on 5-point ordinal scales. Performance-adjusted autonomy was calculated as autonomy minus performance. Results: The final dataset included objective assessments and dictated feedback for 2683 surgical procedures. Sentiment scores were higher for female residents (95 [interquartile range (IQR), 4-100] vs 86 [IQR 2-100]; P < 0.001). Gendered words were present in a greater proportion of dictations for female residents (29% vs 25%; P = 0.04) due to male attendings disproportionately using male-associated words in feedback for female residents (28% vs 23%; P = 0.01). Overall, attendings reported that male residents received greater performance-adjusted autonomy compared with female residents (P < 0.001). Conclusions: Sentiment and gendered words in verbal feedback and performance-adjusted operative autonomy differed for female and male general surgery residents. These findings suggest a need to ensure that trainees are given appropriate and equitable operative autonomy and feedback.

Machine Learning-Enabled Clinical Information Systems Using Fast Healthcare Interoperability Resources Data Standards: Scoping Review.

Background: Machine learning-enabled clinical information systems (ML-CISs) have the potential to drive health care delivery and research. The Fast Healthcare Interoperability Resources (FHIR) data standard has been increasingly applied in developing these systems. However, methods for applying FHIR to ML-CISs are variable. Objective: This study evaluates and compares the functionalities, strengths, and weaknesses of existing systems and proposes guidelines for optimizing future work with ML-CISs. Methods: Embase, PubMed, and Web of Science were searched for articles describing machine learning systems that were used for clinical data analytics or decision support in compliance with FHIR standards. Information regarding each system's functionality, data sources, formats, security, performance, resource requirements, scalability, strengths, and limitations was compared across systems. Results: A total of 39 articles describing FHIR-based ML-CISs were divided into the following three categories according to their primary focus: clinical decision support systems (n=18), data management and analytic platforms (n=10), or auxiliary modules and application programming interfaces (n=11). Model strengths included novel use of cloud systems, Bayesian networks, visualization strategies, and techniques for translating unstructured or free-text data to FHIR frameworks. Many intelligent systems lacked electronic health record interoperability and externally validated evidence of clinical efficacy. Conclusions: Shortcomings in current ML-CISs can be addressed by incorporating modular and interoperable data management, analytic platforms, secure interinstitutional data exchange, and application programming interfaces with adequate scalability to support both real-time and prospective clinical applications that use electronic health record platforms with diverse implementations.

Defining critical illness using immunological endotypes in patients with and without sepsis: a cohort study.

BACKGROUND: Sepsis is a heterogenous syndrome with limited therapeutic options. Identifying immunological endotypes through gene expression patterns in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical intensive care unit (ICU) with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical ICU and at set intervals. METHODS: We analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020. Using an FDA-cleared analytical platform (nCounter FLEX®, NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause mortality, development of chronic critical illness, and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding. RESULTS: Sepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive, though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p < 0.01). Endotypes changed during ICU hospitalization in 57.5% of patients. Patients who remained adaptive had overall better prognosis, while those who remained inflammopathic or coagulopathic had worse overall outcomes. For severity metrics, patients admitted with sepsis and a high predicted likelihood of mortality showed an inflammopathic (49.6%) endotype and had higher rates of cumulative adverse outcomes (67.4%). Patients at low mortality risk, whether septic or non-septic, almost uniformly presented with an adaptive endotype (100% and 93.4%, respectively). CONCLUSION: Critically ill surgical patients express different and evolving immunological endotypes depending upon both their sepsis status and severity of their clinical course. Future studies will elucidate whether endotyping critically ill, septic patients can identify individuals for targeted therapeutic interventions to improve patient management and outcomes.

Methods and evaluation metrics for reducing material waste in the operating room: a scoping review.

BACKGROUND: Operating rooms contribute up to 70% of total hospital waste. Although multiple studies have demonstrated reduced waste through targeted interventions, few examine processes. This scoping review highlights methods of study design, outcome assessment, and sustainability practices of operating room waste reduction strategies employed by surgeons. METHODS: Embase, PubMed, and Web of Science were screened for operating room-specific waste-reduction interventions. Waste was defined as hazardous and non-hazardous disposable material and energy consumption. Study-specific elements were tabulated by study design, evaluation metrics, strengths, limitations, and barriers to implementation in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: A total of 38 articles were analyzed. Among them, 74% of studies had pre- versus postintervention designs, and 21% used quality improvement instruments. No studies used an implementation framework. The vast majority (92%) of studies measured cost as an outcome, whereas others included disposable waste by weight, hospital energy consumption, and stakeholder perspectives. The most common intervention was instrument tray optimization. Common barriers to implementation included lack of stakeholder buy-in, knowledge gaps, data capture, additional staff time, need for hospital or federal policies, and funding. Intervention sustainability was discussed in few studies (23%) and included regular waste audits, hospital policy change, and educational initiatives. Common methodologic limitations included limited outcome evaluation, narrow scope of intervention, and inability to capture indirect costs. CONCLUSION: Appraisal of quality improvement and implementation methods are critical for developing sustainable interventions for reducing operating room waste. Universal evaluation metrics and methodologies may aid in both quantifying the impact of waste reduction initiatives and understanding their implementation in clinical practice.

Resource use for cholecystectomy with versus without cholangiography: A multicenter, propensity-matched analysis.

BACKGROUND: Intraoperative cholangiography may allow for earlier identification of common bile duct injury and choledocholithiasis. The role of intraoperative cholangiography in decreasing resource use related to biliary pathology remains unclear. This study tests the null hypothesis that there is no difference in resource use for patients undergoing laparoscopic cholecystectomy with versus without intraoperative cholangiography. METHODS: This retrospective, longitudinal cohort study included 3,151 patients who underwent laparoscopic cholecystectomy at 3 university hospitals. To minimize differences in baseline characteristics while maintaining adequate statistical power, propensity scores were used to match 830 patients who underwent intraoperative cholangiography at surgeon discretion and 795 patients who underwent cholecystectomy without intraoperative cholangiography. Primary outcomes were the incidence of postoperative endoscopic retrograde cholangiography, the interval between surgery and endoscopic retrograde cholangiography, and total direct costs. RESULTS: In the propensity-matched analysis, the intraoperative cholangiography and no intraoperative cholangiography cohorts had similar age, comorbidities, American Society of Anesthesiologists Sequential Organ Failure Assessment scores, and total/direct bilirubin ratios. The intraoperative cholangiography cohort had a lower postoperative endoscopic retrograde cholangiography (2.4% vs 4.3%; P = .04), a shorter interval between cholecystectomy and endoscopic retrograde cholangiography (2.5 [1.0-17.8] vs 4.5 [2.0-9.5] days; P = .04), and shorter length of stay (0.3 [0.2-1.5] vs 1.4 [0.3-3.2] days; P < .001). Patients undergoing intraoperative cholangiography had lower total direct costs ($4.0K [3.6K-5.4K] vs $8.1K [4.9K-13.0K]; P < .001). There were no differences in 30-day or 1-year mortality among the cohorts. CONCLUSION: Compared with laparoscopic cholecystectomy without intraoperative cholangiography, cholecystectomy with intraoperative cholangiography was associated with decreased resource use, which was primarily attributable to decreased incidence and the earlier timing of postoperative endoscopic retrograde cholangiography.