Introduction: Variations in light exposure are associated with changes in inflammation. The risk of thrombotic events such as ischemic stroke have been found to oscillate with the day-light cycle. Aim: To investigate the impact of altering the light spectrum on ischemic stroke brain injury. Methods: Mice were exposed to ambient (mice-white, 300lux), red light (mice-red, 617nm) or blue light (mice-blue, 442 nm) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, male and female mice were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed at 24 hours. Results: Exposure to long wavelength red light resulted in a significant reduction in infarct volume following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p<0.01 vs mice-blue 72.9±27.9 mm3; p<0.001). Red light exposure significantly improved neurological function compared to white and blue light exposure based on a modified Neurological Score (p<0.05). Furthermore, red light significantly improved motor function as measured by a reduced latency to turn and fall on a rotarod (p<0.05). The change in thrombosis only occurred when mice were pre-exposed to red light. Furthermore, red light had no effect on thrombosis in blind Vsx2 orJ /J mice. Red light exposure reduced platelet deposition in the brain while neutrophil levels were similar between light exposure groups. However, neutrophil extracellular traps (NETs) were significantly reduced (p<0.05) after ischemic stroke brain injury in mice exposued to red light. As platelets are known to activate neutrophils during ischemic stroke, we assessed the effect of red light on platelet function. Red light exposure reduced platelet aggregation (p=.02) and activation (p=.02). RNA-seq analysis demonstrated little transcriptomic changes between light exposed mice. However, red light exposure altered the platelet metabolome, suggesting red light altered platelet metabolism to effect platelet function. To examine if red light reduced platelet-dependent NET formation, releasate from activated platelets were incubated with neutrophils. Releasate from red light exposure platelets resulted in reduced NET formation (p=.03). Conclusion: Exposure to long wavelength red light reduced ischemic stroke burden through a reduction in platelet-dependent NET formation. Light exposure modulation is a promising alternative for prophylaxis and treatment from ischemic stroke brain injury.

Survivors of sepsis suffer from an elevated risk of premature death that is not explained by a higher burden of chronic diseases prior to the infection. Nearly 1 out of 4 survivors have persistent elevations of inflammation biomarkers, such as interleukin (IL) 6. These observations suggest that sepsis imparts durable changes to organismal biology. Eukaryotic life depends upon ATP and calcium (Ca2+). During sepsis, mitochondrial dysfunction, a failure of Ca2+ homeostasis, and sustained elevations in cytosolic [Ca2+] occur. These insults may serve as sufficient pressure to select for cells uniquely able to adapt. In this study of murine and human sepsis survivors, we observe that sepsis induces in lymphoid tissues a restructuring of the mitochondrial calcium uniporter (MCU) complex: the critical channel mediating the electrophoretic uptake of Ca2+ into the mitochondrion. We show these changes persist after clinical resolution of sepsis and lead to alterations in mitochondrial Ca2+ regulation, Ca2+ signaling, oxidative metabolism, and sensitivity to programmed cell death pathways. These biochemical changes manifest as fundamental alterations in phenotype: i.e., heightened systemic IL-6 concentration. Inhibiting lysosomal pathways partially restores the MCU complex stoichiometry, mitochondrial Ca2+ homeostasis, and lymphoid tissue phenotype to a sepsis naïve state.

INTRODUCTION:Blue light (peak wavelength 442 nm) has been shown to modulate the immune response in preclinical models of intra-abdominal sepsis and pneumonia. In vivo pathways involve optic nerve stimulation with transmission to the central nervous system, activation of parasympathetic pathways terminating at the spleen, and downstream immune effects including decreased inflammatory tissue damage and improved pathogen clearance. Related effects on pain mediators including proinflammatory cytokines (interleukin 6, TNF- α) and autonomic tone (increased parasympathetic outflow) suggest possible analgesic properties that would be highly relevant to a trauma population. METHODS AND ANALYSIS:This is a randomised controlled trial in which adult trauma inpatients (≥18 years) with painful rib fractures will be allocated 1:1:1 to three arms: bright blue light intervention (peak 442 nm, ~1400 lux), bright full-spectrum light comparison (~1400 lux) and usual ambient light control. Bright light exposures will be administered for 4 consecutive hours daily for up to 3 days. The primary outcome will be any measurable changes in chest wall pain intensity during deep breathing, quantified using an 11-point Numerical Rating Scale. Secondary outcomes will assess chest wall pain intensity at rest, opioid requirements, delirium incidence, pulmonary complication incidence, hospital-free and intensive care unit-free days, and physiological markers of autonomic nervous system, circadian, and immune activation. Sample size analysis yields a total of 75 participants needed to detect a 2-point difference in pain scores with >80% power and assuming a 20% non-completion rate. ETHICS AND DISSEMINATION:Full ethical approval for this trial has been granted by the University of Pittsburgh Institutional Review Board. On study completion, results will be published in the peer-reviewed literature and at ClinicalTrials.gov. TRIAL REGISTRATION NUMBER:NCT06626334.

BACKGROUND:Variations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous thrombosis (VT) and arterial thrombosis is largely unexplored. OBJECTIVES:To investigate the impact of altering light spectrum on platelet function in thrombosis. METHODS:Wild-type C57BL/6J mice were exposed to ambient (micewhite, 400 lux), blue (miceblue, 442 nm, 1400 lux), or red light (micered, 617 nm, 1400 lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating neutrophil extracellular trap formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light-filtering cataract patients were evaluated over an 8-year period for rate of venous thromboembolism with multivariable logistic regression clustered by hospital. RESULTS:Exposure to long-wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between micered and micewhite. However, there were global metabolomic changes in platelets from micered compared with micewhite. Releasate from activated platelets resulted in reduced neutrophil extracellular trap formation. Micered also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer had a lower lifetime risk of venous thromboembolism after implantation with lenses that filter low-wavelength light. CONCLUSION:Light therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation.

Medical students require assessment and actionable feedback to develop clinical competency. However, feedback is of inconsistent quality and is frequently ineffective. To further our understanding about faculty and students’ perceptions about challenges to feedback and improve the feedback experience on the surgery clerkship, we aimed to use Group Concept Mapping (GCM), a participatory research methodology, to 1) identify barriers to exchanging feedback on the surgery clerkship and 2) examine how an institutional quality initiative to improve feedback (the Flash Feedback tool) might address the identified barriers. We prospectively enrolled study participants from 10/2022 to 03/2023. Third-year medical students completing their surgery clerkship during the 2022–2023 academic year and department of surgery faculty at a single institution were eligible for inclusion. GCM participants utilized an asynchronous web-based platform to brainstorm barriers to feedback. Participants then individually sorted the brainstormed ideas into categories based on perceived relatedness. Sorted items were analyzed to generate a two-dimensional graphical representation of associations between ideas and concepts. GCM was also used to evaluate faculty and student perceptions about the effectiveness of the Flash Feedback tool implemented during the same academic year. 20 participants identified 44 unique barriers to providing/receiving feedback. Hierarchical cluster analysis resulted in a four-cluster solution composed of the following domains: 1) lack of longitudinal exposure, 2) time constraints, 3) perceived interpersonal challenges, and 4) lack of objectivity/standardization. Both students and faculty rated the Flash Feedback tool favorably in addressing these barriers. The barriers identified by the students and faculty in our GCM study represent a cohesive knowledge structure with which to conceptualize challenges to exchanging feedback. Standardized, immediate post-encounter web-based applications such as our Flash Feedback tool may be especially helpful to address issues with subjectivity, non-specific feedback, and perceived interpersonal challenges that impede trust between educator and learner.

Diversity is crucial to the success of healthcare teams and inclusive patient care. The emphasis on traditional academic metrics has served as a barrier to the diversification of graduate medical education (GME) programs. Holistic review, defined by the Association of American Medical Colleges as an emphasis on experiences rather than academic metrics, has been proposed as a solution to improve diversity in medical education. However, skepticism about the implementation of holistic review and a lack of data to support that it improves diversity in GME exist. We, therefore, performed a systematic review and meta-analysis aiming to identify the components of holistic review described by programs employing it and quantify its impact on diversity. We hypothesized that programs implementing holistic review would have increased odds of interviewing and matriculating those that are underrepresented in medicine (URiM) and women when compared to those utilizing traditional applicant review. PubMed and Embase were searched from inception to February 2023 for articles studying holistic review in United States GME programs. Articles were included if they described components of holistic review and/or compared the diversity of traditionally reviewed cohorts to those holistically reviewed. Two authors performed title/abstract screening; any disagreements were adjudicated by a third reviewer. Eligible studies were submitted to full-text screening. The association between holistic review and the proportion of URiM students interviewed/matriculated was assessed using random-effects meta-analysis. In addition, components of holistic review were categorized and described. Of 201 screened abstracts, 21 articles were included. Four features of holistic review were consistently described by the included studies: (1) incorporating a mission-guided approach to applicant selection, (2) mitigating bias, (3) de-emphasizing academic metrics, (4) commitment to diversity, equity, and inclusion. Six studies compared proportions of URiM students interviewed using holistic versus traditional applicant review; holistic review was associated with increased odds of interviewing URiM students at these programs (pooled OR 2.30, 95

The primary role of the cardiorespiratory system is to meet the metabolic demands of the body by delivering adequate amounts of oxygen (O2). The quantity of oxygen extracted by the body’s tissues can be increased significantly under physiologic conditions to satisfy cellular needs. This provides an important buffer that allows the maintenance of adequate oxygen consumption during times of increased demand. Despite this reserve, multiple pathophysiologic insults can disrupt this balance and result in shock states, including hypovolemia, cardiac failure, neurologic injury, anaphylaxis, and sepsis.

BACKGROUND Serial neurological examinations (NEs) are routinely recommended in the intensive care unit (ICU) within the first 24 hours following a traumatic brain injury (TBI). There are currently no widely accepted guidelines for the frequency of NEs. Disruptions to the sleep-wake cycles increase the delirium rate. We aimed to evaluate whether there is a correlation between prolonged hourly (Q1)-NE and development of delirium and to determine if this practice reduces the likelihood of missing the detection of a process requiring emergent intervention. METHODS A retrospective analysis of patients with mild/moderate TBI, admitted to the ICU with serial NEs, was performed. Cohorts were stratified by the duration of exposure to Q1-NE, into prolonged (≥24 hours) and nonprolonged (<24 hours). Our primary outcomes of interest were delirium, evaluated using the Confusion Assessment Method; radiological progression from baseline images; neurological deterioration (focal neurological deficit, abnormal pupillary examination, or Glasgow Coma Scale score decrease >2); and neurosurgical procedures. RESULTS A total of 522 patients were included. No significant differences were found in demographics. Patients in the prolonged Q1-NE group (26.1%) had higher Injury Severity Score with similar head Abbreviated Injury Score, significantly higher delirium rate (59% vs. 35%, p < 0.001), and a longer hospital/ICU length of stay when compared with the nonprolonged Q1-NE group. No neurosurgical interventions were found to be performed emergently as a result of findings on NEs. Multivariate analysis demonstrated that prolonged Q1-NE was the only independent risk factor associated with a 2.5-fold increase in delirium rate. The number needed to harm for prolonged Q1-NE was 4. CONCLUSION Geriatric patients with mild/moderate TBI exposed to Q1-NE for periods longer than 24 hours had nearly a threefold increase in ICU delirium rate. One of five patients exposed to prolonged Q1-NE is harmed by the development of delirium. No patients were found to directly benefit as a result of more frequent NEs. LEVEL OF EVIDENCE Prognostic and Epidemiological; Level IV.

Background:Necrotizing soft tissue infections (NSTIs) are life-threatening infections. The aim of this study is to evaluate the safety of clindamycin plus vancomycin versus linezolid as empiric treatment of NSTIs. Methods:This was a retrospective, single-center, quasi-experimental study of patients admitted from 1 June 2018 to 30 June 2019 (preintervention) and 1 May 2020 to 15 October 2021 (postintervention). Patients who received surgical management within 24 hours of NSTI diagnosis and at least 1 dose of linezolid or clindamycin were included. The primary endpoint was death at 30 days. The secondary outcomes included rates of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). Results:A total of 274 patients were identified by admission diagnosis code for NSTI or Fournier gangrene; 164 patients met the inclusion criteria. Sixty-two matched pairs were evaluated. There was no difference in rates of 30-day mortality (8.06% vs 6.45%; hazard ratio [HR], 1.67 [95% confidence interval {CI}, .32-10.73]; P = .65). There was no difference in CDI (6.45% vs 1.61%; HR, Infinite [Inf], [95% CI, .66-Inf]; P = .07) but more AKI in the preintervention group (9.68% vs 1.61%; HR, 6 [95% CI, .73-276]; P = .05). Conclusions:In this small, retrospective, single-center, quasi-experimental study, there was no difference in 30-day mortality in patients receiving treatment with clindamycin plus vancomycin versus linezolid in combination with standard gram-negative and anaerobic therapy and surgical debridement for the treatment of NSTIs. A composite outcome of death, AKI, or CDI within 30 days was more common in the clindamycin plus vancomycin group.

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

INTRODUCTION:Diversity in the physician workforce improves patient-centred outcomes. Patients are more likely to trust in and comply with care when seeing gender/racially concordant providers. A current emphasis on standardised metrics in academic achievement often serves as a barrier to the recruitment and retention of gender and racial minorities in medicine. Holistic review of residency applicants has been supported as a means of encouraging diversification but is not yet standardised. The current body of evidence examining the effects of holistic review on the recruitment of racial and gender minorities in surgical residencies is small. We therefore propose a systematic review to summarise the state of holistic review in graduate medical education in the USA and its impact on diversification.METHODS AND ANALYSIS:Our systematic review protocol has been designed with plans to report our review findings in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. PubMed and Embase will be searched with the assistance of a health sciences librarian with expertise in systematic review. We will include studies of graduate medical education programmes that describe the implementation of holistic review, outline the components of their holistic review process and compare proportions of under-represented minorities (URM) and women interviewed and matriculating before and after holistic review implementation. We will first report a summary of the findings regarding the operationalisation of holistic review as described by studies included. We will then pool the percentages of URM and women for interviewee and matriculant populations from each study and report the collective odds ratios of each for holistic review compared with traditional review as our primary outcome.ETHICS AND DISSEMINATION:This study is a protocol for systematic review, and therefore does not involve any human subjects. Findings will be published in the form of a manuscript submitted to a peer-reviewed journal.PROSPERO REGISTRATION NUMBER:CRD42023401389.

ABSTRACT When do the many become one? Why does one join with others? In his political writings of self-government, Rousseau proposes “when the obstacles to their self-preservation in the state of nature are too great to be overcome by the forces each individual is capable of exerting to maintain himself in that state.” Few obstacles are more threatening to an individual than disease and death, and our response as a civilization is the institution of healthcare. The impetus for this perspective piece budded from personal experience and a resultant sentiment that emerged from more deliberate contemplation. It is purposed to conjure in the reader a certain joy of that which can be accomplished through collaboration, but concomitantly, to offer perspective as to characteristics opined to be vital to creating and maintaining a great team.

BACKGROUND Evidence suggests that variation in light exposure strongly influences the dynamic of inflammation, coagulation, and the immune system. Multiple injuries induce systemic inflammation that can lead to end-organ injury. Here, we hypothesize that alterations in light exposure influence posttrauma inflammation, coagulopathy, and end-organ injury. METHODS C57BL/6 mice underwent a validated multiple-injury and hemorrhage model performed following 72 hours of exposure to red (617 nm, 1,700 lux), blue (321 nm, 1,700 lux), and fluorescent white light (300 lux) (n = 6–8/group). The animals were sacrificed at 6 hours posttrauma. Plasma samples were evaluated and compared for proinflammatory cytokine expression levels, coagulation parameters, markers of liver and renal injury, and histological changes (Carstairs staining). One-way analysis of variance statistical tests were applied to compare study groups. RESULTS Preexposure to long-wavelength red light significantly reduced the inflammatory response at 6 hours after multiple injuries compared with blue and ambient light, as evidenced by decreased levels of interleukin 6, monocyte chemoattractant protein-1 (both p < 0.001), liver injury markers (alanine transaminase, p < 0.05), and kidney injury markers (cystatin C, p < 0.01). In addition, Carstairs staining of organ tissues revealed milder histological changes in the red light–exposed group, indicating reduced end-organ damage. Furthermore, prothrombin time was significantly lower ( p < 0.001), and fibrinogen levels were better maintained ( p < 0.01) in the red light–exposed mice compared with those exposed to blue and ambient light. CONCLUSION Prophylactic light exposure can be optimized to reduce systemic inflammation and coagulopathy and minimize acute organ injury following multiple injuries. Understanding the mechanisms by which light exposure attenuates inflammation may provide a novel strategy to reducing trauma-related morbidity.

BACKGROUND:Study of telemedicine and telerounding in surgical specialties is limited. The push for telemedicine during the COVID-19 pandemic has challenged the face-to-face rounding paradigm and creates an opportunity for reflection on the benefits of telemedicine, especially for balancing competing corporate and clinical demands.METHODS:The 117-month video-based inpatient telerounding experience of a colorectal surgeon in an academic medical system was recorded, including patient characteristics, diagnoses, technology, content of telerounding encounters, and logistical considerations. Data were analyzed using descriptive statistics.RESULTS:163 patients were seen in 201 telerounding encounters, primarily for routine postoperative care (90.5%). Most were admitted for inflammatory bowel disease (63.2%). Changes were made to plans of care during 28.9% of encounters, and discharge planning was part of 26.4%. Encounters were conducted primarily from the surgeon's administrative office (68.7%) or other work-related locations (10.9%), while 6.5% originated from the surgeon's home. Technologic issues occurred in 5.5% of encounters. 89.1% of patient feedback was positive and none was negative.CONCLUSION:Telerounding is technologically feasible and has clinical value, including for patients with complex surgical problems. Technologic problems are rare and patient satisfaction is high. Surgeons should consider telerounding as a means to balance competing demands.

The authors would like to revise eTable 1 in our Supplementary Data to be in compliance with the Agency for Healthcare Research and Quality (AHRQ) Data Use Agreement. This study is an analysis of the State Inpatient Database and State Emergency Department Database, which are restricted-access, publicly available datasets that are maintained by the AHRQ. One of the provisions of the Data Use Agreement is that no data observation involving less than or equal to 10 observations is to be published. This measure was put in place by AHRQ to protect individual patients' privacy and to prevent the potential disclosure of personal information. Teng SDC revised.doc The authors would like to apologise for any inconvenience caused. eTable 1Emergency General Surgery Diagnosis Categories across Types of Transfer EpisodesEGS Diagnosis Category∗EGS diagnosis categories as defined by the American Association for the Surgery of Trauma(1).Type of Transfer EpisodeAll Transfers (N=26,281)Transfers from Level 1 Trauma Centers (N=1,319)Potentially Avoidable Transfers (N=7,188)Potentially Avoidable Transfers from Level 1 Trauma Centers (N=446)Resuscitation1,085 (4.1)35 (2.7)153 (2.1)≤10†Cell sizes ≤10 are suppressed in accordance with Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases Data Use regulationsGeneral abdominal conditions3,167 (12.1)192 (14.6)1,105 (15.4)87 (19.5)Intestinal obstruction2,061 (7.8)144 (10.9)941 (13.1)77 (17.3)Upper GI tract5,180 (19.7)269 (20.4)890 (12.4)57 (12.8)Hepatopancreaticobiliary303 (1.2)23 (1.7)74 (1.0)≤10†Cell sizes ≤10 are suppressed in accordance with Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases Data Use regulationsColorectal4,184 (15.9)169 (12.8)1,212 (16.9)60 (13.5)Hernia442 (1.7)42 (3.2)169 (2.4)17 (3.8)Soft tissue858 (3.3)27 (2.1)163 (2.3)≤10†Cell sizes ≤10 are suppressed in accordance with Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases Data Use regulationsVascular1,467 (5.6)99 (7.5)502 (7.0)29 (6.5)Cardiothoracic6,358 (24.2)291 (22.1)1,819 (25.3)86 (19.3)Other1,176 (4.5)28 (2.1)160 (2.2)≤10†Cell sizes ≤10 are suppressed in accordance with Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases Data Use regulationsEGS, emergency general surgery; GI, gastrointestinal.All results reported as frequency (percentage).∗ EGS diagnosis categories as defined by the American Association for the Surgery of Trauma(1).† Cell sizes ≤10 are suppressed in accordance with Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases Data Use regulations Open table in a new tab EGS, emergency general surgery; GI, gastrointestinal. All results reported as frequency (percentage). Factors associated with potentially avoidable interhospital transfers in emergency general surgery–A call for quality improvement effortsSurgeryVol. 170Issue 5PreviewEmergency general surgery conditions are common, require urgent surgical evaluation, and are associated with high mortality and costs. Although appropriate interhospital transfers are critical to successful emergency general surgery care, the performance of emergency general surgery transfer systems remains unclear. We aimed to describe emergency general surgery transfer patterns and identify factors associated with potentially avoidable transfers. Full-Text PDF