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Item The launch of a new review journal(Elsevier, 2021) Ekser, Burcin; Surgery, School of MedicineItem A year in review: Highlights of health sciences review in 2022(Elsevier, 2022) Grach, Stephanie L.; Ekser, Burcin; Surgery, School of MedicineItem The development and initial validation of the PROMIS®+HF‐27 and PROMIS+HF‐10 profiles(Wiley, 2022) Ahmad, Faraz S.; Jackson, Kathryn L.; Yount, Susan E.; Rothrock, Nan E.; Kallen, Michael A.; Lacson, Leilani; Bilimoria, Karl Y.; Kho, Abel N.; Mutharasan, Raja Kannan; McCullough, Peter A.; Bruckel, Jeffrey; Fedson, Savitri; Kimmel, Stephen E.; Eton, David T.; Grady, Kathleen L.; Yancy, Clyde W.; Cella, David; Surgery, School of MedicineAims: Heart failure (HF) is a common and morbid condition impacting multiple health domains. We previously reported the development of the PROMIS®-Plus-HF (PROMIS+HF) profile measure, including universal and HF-specific items. To facilitate use, we developed shorter, PROMIS+HF profiles intended for research and clinical use. Methods and results: Candidate items were selected based on psychometric properties and symptom range coverage. HF clinicians (n = 43) rated item importance and clinical actionability. Based on these results, we developed the PROMIS+HF-27 and PROMIS+HF-10 profiles with summary scores (0-100) for overall, physical, mental, and social health. In a cross-sectional sample (n = 600), we measured internal consistency reliability (Cronbach's alpha and Spearman-Brown), test-retest reliability (intraclass coefficient; n = 100), known-groups validity via New York Heart Association (NYHA) class, and convergent validity with Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. In a longitudinal sample (n = 75), we evaluated responsiveness of baseline/follow-up scores by calculating mean differences and Cohen's d and comparing with paired t-tests. Internal consistency was good to excellent (α 0.82-0.94) for all PROMIS+HF-27 scores and acceptable to good (α/Spearman-Brown 0.60-0.85) for PROMIS+HF-10 scores. Test-retest intraclass coefficients were acceptable to excellent (0.75-0.97). Both profiles demonstrated known-groups validity for the overall and physical health summary scores based on NYHA class, and convergent validity for nearly all scores compared with KCCQ scores. In the longitudinal sample, we demonstrated responsiveness for PROMIS+HF-27 and PROMIS+HF-10 overall and physical summary scores. For the PROMIS+HF overall summary scores, a group-based increase of 7.6-8.3 points represented a small to medium change (Cohen's d = 0.40-0.42). For the PROMIS+HF physical summary scores, a group-based increase of 5.0-5.9 points represented a small to medium change (Cohen's d = 0.29-0.35). Conclusions: The PROMIS+HF-27 and PROMIS+HF-10 profiles demonstrated good psychometric characteristics with evidence of responsiveness for overall and physical health. These new measures can facilitate patient-centred research and clinical care, such as improving care quality through symptom monitoring, facilitating shared decision-making, evaluating quality of care, assessing new interventions, and monitoring during the initiation and titration of guideline-directed medical therapy.Item Amalgamation of cloud-based colonoscopy videos with patient-level metadata to facilitate large-scale machine learning(Thieme, 2021) Keswani, Rajesh N.; Byrd, Daniel; Garcia Vicente, Florencia; Heller, J. Alex; Klug, Matthew; Mazumder, Nikhilesh R.; Wood, Jordan; Yang, Anthony D.; Etemadi, Mozziyar; Surgery, School of MedicineBackground and study aims: Storage of full-length endoscopic procedures is becoming increasingly popular. To facilitate large-scale machine learning (ML) focused on clinical outcomes, these videos must be merged with the patient-level data in the electronic health record (EHR). Our aim was to present a method of accurately linking patient-level EHR data with cloud stored colonoscopy videos. Methods: This study was conducted at a single academic medical center. Most procedure videos are automatically uploaded to the cloud server but are identified only by procedure time and procedure room. We developed and then tested an algorithm to match recorded videos with corresponding exams in the EHR based upon procedure time and room and subsequently extract frames of interest. Results: Among 28,611 total colonoscopies performed over the study period, 21,170 colonoscopy videos in 20,420 unique patients (54.2 % male, median age 58) were matched to EHR data. Of 100 randomly sampled videos, appropriate matching was manually confirmed in all. In total, these videos represented 489,721 minutes of colonoscopy performed by 50 endoscopists (median 214 colonoscopies per endoscopist). The most common procedure indications were polyp screening (47.3 %), surveillance (28.9 %) and inflammatory bowel disease (9.4 %). From these videos, we extracted procedure highlights (identified by image capture; mean 8.5 per colonoscopy) and surrounding frames. Conclusions: We report the successful merging of a large database of endoscopy videos stored with limited identifiers to rich patient-level data in a highly accurate manner. This technique facilitates the development of ML algorithms based upon relevant patient outcomes.Item Unbundling Bundles: Evaluating the Association of Individual Colorectal Surgical Site Infection Reduction Bundle Elements on Infection Rates in a Statewide Collaborative(Wolters Kluwer, 2022) Schlick, Cary Jo R.; Huang, Reiping; Brajcich, Brian C.; Halverson, Amy L.; Yang, Anthony D.; Kreutzer, Lindsey; Bilimoria, Karl Y.; McGee, Michael F.; Illinois Surgical Quality Improvement Collaborative; Surgery, School of MedicineBACKGROUND: Surgical site infection reduction bundles are effective but can be complex and resource intensive. Understanding which bundle elements are associated with reduced surgical site infections may guide concise bundle implementation. OBJECTIVE: To evaluate the association of individual surgical site infection reduction bundle elements with infection rates. DESIGN: Post-hoc analysis of a prospective cohort study SETTING: Illinois Surgical Quality Improvement Collaborative hospitals PATIENTS: Elective colorectal resections at participating hospitals from 2016–2017 INTERVENTIONS: 16-element colorectal surgical site infection reduction bundle MAIN OUTCOME MEASURES: Surgical site infection rates were compared among patients by adherence with each bundle element using Chi-squared tests and multivariable logistic regression. Principal component analysis identified composites of correlated bundle elements. Coincidence analysis identified combinations of bundle elements or principal component composites associated with the absence of surgical site infection. RESULTS: Among 2,722 patients, 192 (7.1%) developed a surgical site infection. Infections were less likely when oral antibiotics (OR 0.63 [95% CI 0.41–0.97]), wound protectors (OR 0.55 [95% CI 0.37–0.81]), and occlusive dressings (OR 0.71 [95% CI 0.51–1.00]) were used. Bundle elements were reduced into 5 principal component composites. Adherence with the combination of (1) oral antibiotics, (2) wound protector, or (3) redosing intravenous antibiotic prophylaxis plus chlorhexidine-alcohol intraoperative skin preparation were associated with the absence of infection (consistency=0.94, coverage=0.96). Four of the five principal component composites in various combinations were associated with the absence of surgical site infection, while the composite consisting of occlusive dressing placement, postoperative dressing removal, and daily postoperative chlorhexidine incisional cleansing had no association with the outcome. LIMITATIONS: The inclusion of hospitals engaged in quality improvement initiatives may limit the generalizability of these data. CONCLUSION: Bundle elements had varying association with infection reduction. Implementation of colorectal surgical site infection reduction bundles should focus on the specific elements associated with low surgical site infections. See Video Abstract at http://links.lww.com/DCR/Bxxx.Item Association of Transport Time, Proximity, and Emergency Department Pediatric Readiness With Pediatric Survival at US Trauma Centers(American Medical Association, 2023) Glass, Nina E.; Salvi, Apoorva; Wei, Ran; Lin, Amber; Malveau, Susan; Cook, Jennifer N. B.; Mann, N. Clay; Burd, Randall S.; Jenkins, Peter C.; Hansen, Matthew; Mohr, Nicholas M.; Stephens, Caroline; Fallat, Mary E.; Lerner, E. Brooke; Carr, Brendan G.; Wall, Stephen P.; Newgard, Craig D.; Surgery, School of MedicineImportance: Emergency department (ED) pediatric readiness is associated with improved survival among children. However, the association between geographic access to high-readiness EDs in US trauma centers and mortality is unclear. Objective: To evaluate the association between the proximity of injury location to receiving trauma centers, including the level of ED pediatric readiness, and mortality among injured children. Design, setting, and participants: This retrospective cohort study used a standardized risk-adjustment model to evaluate the association between trauma center proximity, ED pediatric readiness, and in-hospital survival. There were 765 trauma centers (level I-V, adult and pediatric) that contributed data to the National Trauma Data Bank (January 1, 2012, through December 31, 2017) and completed the 2013 National Pediatric Readiness Assessment (conducted from January 1 through August 31, 2013). The study comprised children aged younger than 18 years who were transported by ground to the included trauma centers. Data analysis was performed between January 1 and March 31, 2022. Exposures: Trauma center proximity within 30 minutes by ground transport and ED pediatric readiness, as measured by weighted pediatric readiness score (wPRS; range, 0-100; quartiles 1 [low readiness] to 4 [high readiness]). Main outcomes and measures: In-hospital mortality. We used a patient-level mixed-effects logistic regression model to evaluate the association of transport time, proximity, and ED pediatric readiness on mortality. Results: This study included 212 689 injured children seen at 765 trauma centers. The median patient age was 10 (IQR, 4-15) years, 136 538 (64.2%) were male, and 127 885 (60.1%) were White. A total of 4156 children (2.0%) died during their hospital stay. The median wPRS at these hospitals was 79.1 (IQR, 62.9-92.7). A total of 105 871 children (49.8%) were transported to trauma centers with high-readiness EDs (wPRS quartile 4) and another 36 330 children (33.7%) were injured within 30 minutes of a quartile 4 ED. After adjustment for confounders, proximity, and transport time, high ED pediatric readiness was associated with lower mortality (highest-readiness vs lowest-readiness EDs by wPRS quartiles: adjusted odds ratio, 0.65 [95% CI, 0.47-0.89]). The survival benefit of high-readiness EDs persisted for transport times up to 45 minutes. The findings suggest that matching children to trauma centers with high-readiness EDs within 30 minutes of the injury location may have potentially saved 468 lives (95% CI, 460-476 lives), but increasing all trauma centers to high ED pediatric readiness may have potentially saved 1655 lives (95% CI, 1647-1664 lives). Conclusions and relevance: These findings suggest that trauma centers with high ED pediatric readiness had lower mortality after considering transport time and proximity. Improving ED pediatric readiness among all trauma centers, rather than selective transport to trauma centers with high ED readiness, had the largest association with pediatric survival. Thus, increased pediatric readiness at all US trauma centers may substantially improve patient outcomes after trauma.Item Evaluation of Emergency Department Treat-and-Release Encounters After Major Gastrointestinal Surgery(Wiley, 2023) Brajcich, Brian C.; Johnson, Julie K.; Holl, Jane L.; Bilimoria, Karl Y.; Shallcross, Meagan L.; Chung, Jeanette; Joung, Rachel Hae Soo; Iroz, Cassandra B.; Odell, David D.; Bentrem, David J.; Yang, Anthony D.; Franklin, Patricia D.; Slota, Jennifer M.; Silver, Casey M.; Skolarus, Ted; Merkow, Ryan P.; Surgery, School of MedicineBackground and objectives: Emergency department (ED) utilization after gastrointestinal cancer operations is poorly characterized. Our study objectives were to determine the incidence of, reasons for, and predictors of ED treat-and-release encounters after gastrointestinal cancer operations. Methods: Patients who underwent elective esophageal, hepatobiliary, gastric, pancreatic, small intestinal, or colorectal operations for cancer were identified in the 2015-2017 Healthcare Cost and Utilization Project State Inpatient and State Emergency Department Databases for New York, Maryland, and Florida. The primary outcomes were the incidence of ED treat-and-release encounters and readmissions within 30 days of discharge. Results: Among 51 527 patients at 406 hospitals, 4047 (7.9%) had an ED treat-and-release encounter, and 5573 (10.8%) had an ED encounter with readmission. In total, 40.7% of ED encounters were treat-and-release encounters. ED treat-and-release encounters were most frequently for pain (12.0%), device/ostomy complaints (11.7%), or wound complaints (11.4%). ED treat-and-release encounters predictors included non-Hispanic Black race/ethnicity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.12-1.37) and Medicare (OR 1.27, 95% CI 1.16-1.40) or Medicaid (OR 1.82, 95% CI 1.62-2.40) coverage. Conclusions: ED treat-and-release encounters are common after major gastrointestinal operations, making up nearly half of postdischarge ED encounters. The reasons for ED treat-and-release encounters differ from those for ED encounters with readmissions.Item Ischemia-Selective Cardioprotection by Malonate for Ischemia/Reperfusion Injury(American Heart Association, 2022) Prag, Hiran A.; Aksentijevic, Dunja; Dannhorn, Andreas; Giles, Abigail V.; Mulvey, John F.; Sauchanka, Olga; Du, Luping; Bates, Georgina; Reinhold, Johannes; Kula-Alwar, Duvaraka; Xu, Zhelong; Pellerin, Luc; Goodwin, Richard J. A.; Murphy, Michael P.; Krieg, Thomas; Surgery, School of MedicineBackground: Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored. Methods: C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused ex vivo (Langendorff) or subjected to in vivo left anterior descending coronary artery ligation as models of ischemia/reperfusion injury. Succinate and malonate levels were assessed by liquid chromatography-tandem mass spectrometry LC-MS/MS, in vivo by mass spectrometry imaging, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining. Results: Malonate was robustly protective against cardiac ischemia/reperfusion injury, but only if administered at reperfusion and not when infused before ischemia. The extent of malonate uptake into the heart was proportional to the duration of ischemia. Malonate entry into cardiomyocytes in vivo and in vitro was dramatically increased at the low pH (≈6.5) associated with ischemia. This increased uptake of malonate was blocked by selective inhibition of MCT1 (monocarboxylate transporter 1). Reperfusion of the ischemic heart region with malonate led to selective SDH inhibition in the at-risk region. Acid-formulation greatly enhances the cardioprotective potency of malonate. Conclusions: Cardioprotection by malonate is dependent on its entry into cardiomyocytes. This is facilitated by the local decrease in pH that occurs during ischemia, leading to its selective uptake upon reperfusion into the at-risk tissue, via MCT1. Thus, malonate's preferential uptake in reperfused tissue means it is an at-risk tissue-selective drug that protects against cardiac ischemia/reperfusion injury.Item A pragmatic, stepped-wedge, hybrid type II trial of interoperable clinical decision support to improve venous thromboembolism prophylaxis for patients with traumatic brain injury(Springer Nature, 2024-08-05) Tignanelli, Christopher J.; Shah, Surbhi; Vock, David; Siegel, Lianne; Serrano, Carlos; Haut, Elliott; Switzer, Sean; Martin, Christie L.; Rizvi, Rubina; Peta, Vincent; Jenkins, Peter C.; Lemke, Nicholas; Thyvalikakath, Thankam; Osheroff, Jerome A.; Torres, Denise; Vawdrey, David; Callcut, Rachael A.; Butler, Mary; Melton, Genevieve B.; Surgery, School of MedicineBackground: Venous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes. This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation. Methods: The SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE2-AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a "Living Guideline" process model for the VTE prevention CDS system. Discussion: The stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics.Item CDMS Analysis of Intact 19S, 20S, 26S, and 30S Proteasomes: Evidence for Higher-Order 20S Assemblies at a Low pH†(American Chemical Society, 2023) Anthony, Adam J.; Gautam, Amit K. S.; Miller, Lohra M.; Ma, Yiran; Hardwick, Anya G.; Sharma, Anu; Ghatak, Subhadip; Matouschek, Andreas; Jarrold, Martin F.; Clemmer, David E.; Surgery, School of MedicineCharge detection mass spectrometry (CDMS) was examined as a means of studying proteasomes. To this end, the following masses of the 20S, 19S, 26S, and 30S proteasomes from Saccharomyces cerevisiae (budding yeast) were measured: m(20S) = 738.8 ± 2.9 kDa, m(19S) = 926.2 ± 4.8 kDa, m(26S) = 1,637.0 ± 7.6 kDa, and m(30S) = 2,534.2 ± 10.8 kDa. Under some conditions, larger (20S)x (where x = 1 to ∼13) assemblies are observed; the 19S regulatory particle also oligomerizes, but to a lesser extent, forming (19S)x complexes (where x = 1 to 4, favoring the x = 3 trimer). The (20S)x oligomers are favored in vitro, as the pH of the solution is lowered (from 7.0 to 5.4, in a 20 mM ammonium acetate solution) and may be related to in vivo proteasome storage granules that are observed under carbon starvation. From measurements of m(20S)x (x = 1 to ∼13) species, it appears that each multimer retains all 28 proteins of the 20S complex subunit. Several types of structures that might explain the formation of (20S)x assemblies are considered. We stress that each structural type [hypothetical planar, raft-like geometries (where individual proteasomes associate through side-by-side interactions); elongated, rodlike geometries (where subunits are bound end-to-end); and geometries that are roughly spherical (arising from aggregation through nonspecific subunit interactions)] is highly speculative but still interesting to consider, and a short discussion is provided. The utility of CDMS for characterizing proteasomes and related oligomers is discussed.