Evaluation of the Glasgow Coma Scale-Pupils score for predicting inpatient mortality among patients with traumatic subdural hematoma at United States trauma centers.

OBJECTIVE: The Glasgow Coma Scale-Pupils (GCS-P) score has been suggested to better predict patient outcomes compared with GCS alone, while avoiding the need for more complex clinical models. This study aimed to compare the prognostic ability of GCS-P versus GCS in a national cohort of traumatic subdural hematoma (SDH) patients. METHODS: Patient data were obtained from the National Trauma Data Bank (2017-2019). Inclusion criteria were traumatic SDH diagnosis with available data on presenting GCS score, pupillary reactivity, and discharge disposition. Patients with severe polytrauma or nonsurvivable head injury at presentation were excluded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of GCS-P versus GCS scores for inpatient mortality prediction were evaluated across the entire cohort, as well as in subgroups based on age and traumatic brain injury (TBI) type (blunt vs penetrating). Calibration curves were plotted based on predicted probabilities and actual outcomes. RESULTS: A total of 196,747 traumatic SDH patients met the study inclusion criteria. Sensitivity (0.707 vs 0.702), specificity (0.821 vs 0.823), and AUC (0.825 vs 0.814, p < 0.001) of GCS-P versus GCS scores for prediction of inpatient mortality were similar. Calibration curve analysis revealed that GCS scores slightly underestimated inpatient mortality risk, whereas GCS-P scores did not. In patients > 65 years of age with blunt TBI (51.9%, n = 102,148), both GCS-P and GCS scores underestimated inpatient mortality risk. In patients with penetrating TBI (2.4%, n = 4,710), the AUC of the GCS-P score was significantly higher (0.902 vs 0.851, p < 0.001). In this subgroup, both GCS-P and GCS scores underestimated inpatient mortality risk among patients with lower rates of observed mortality and overestimated risk among patients with higher rates of observed mortality. This effect was more pronounced in the GCS-P calibration curve. CONCLUSIONS: The GCS-P score provides better short-term prognostication compared with the GCS score alone among traumatic SDH patients with penetrating TBI. The GCS-P score overestimates inpatient mortality risk among penetrating TBI patients with higher rates of observed mortality. For penetrating TBI patients, which comprised 2.4% of our SDH cohort, a low GCS-P score should not justify clinical nihilism or forgoing aggressive treatment.

Sleeve Migration Following Sleeve Gastrectomy: A Systematic Review of Current Literature.

Sleeve gastrectomy (SG) is the most frequently performed bariatric procedure worldwide. The incidence and consequences of sleeve migration (SM) are not clearly understood. There is no clear consensus on appropriate measures to reduce the risk of SM. This study systematically reviewed the literature and identified 405 cases of SM from 21 studies. Age ranged from 18 to 68 years. Thirty-two percent and 11% of patients were females and males respectively, while sex was not reported in 57%. Time to diagnosis ranged from 1 day to 5 years postoperatively. A total of 9.6% and 58.8% of patients had or had no previous hiatal hernia respectively. SM incidence, risk factors, proposed mechanisms, clinical presentation, diagnosis, management, and potential preventive strategies are described in this review.

Machine Learning Identifies Variation in Timing of Palliative Care Consultations Among Traumatic Brain Injury Patients.

Background and Objective Timely palliative care involvement offers demonstrable benefits for traumatic brain injury (TBI) patients; however, palliative care consultations (PCCs) are used inconsistently during TBI management. This study aimed to employ advanced machine learning techniques to elucidate the primary drivers of PCC timing variability for TBI patients. Methods Data on admission, hospital course, and outcomes were collected for a cohort of 232 TBI patients who received both PCCs and neurosurgical consultations during the same hospitalization. Principal Component Analysis (PCA) and K-means clustering were used to identify patient phenotypes, which were then compared using Kaplan-Meier analysis. An extreme gradient boosting model (XGBoost) was employed to determine drivers of PCC timing, with model interpretation performed using SHapley Additive exPlanations (SHAP). Results Cluster A (n = 86) consisted mainly of older (median [IQR] = 87 [78, 94] years), White females with mild TBIs and demonstrated the shortest time-to-PCC (2.5 [1.0, 7.0] days). Cluster B (n = 108) also sustained mild TBIs but comprised moderately younger (81 [75, 86] years) married White males with later PCC (5.0 [3.0, 10.8] days). Cluster C (n = 38) represented much younger (46.5 [29.5, 59.8] years), more severely injured, non-White patients with the latest PCC initiation (9.0 [4.2, 17.0] days). The clusters did not differ by discharge disposition (p = 0.4) or frequency inpatient mortality (p > 0.9); however, Kaplan-Meier analysis revealed a significant difference in the time from admission to PCC (p < 0.001), despite no differences in time from admission to mortality (p = 0.18). SHAP analysis of the XGBoost model identified age, sex, and race as the most influential drivers of PCC timing. Conclusions This study highlights crucial disparities in PCC timing for TBI patients and underscores the need for targeted strategies to ensure timely and equitable palliative care integration for this vulnerable population.

Advancing Resident Education: Experiential Success in the Creation of a Comprehensive Clinical Didactic Series in Radiation Oncology.

Purpose: An effective didactic curriculum is a cornerstone for a successful residency program, as it is the basis upon which residents acquire the necessary knowledge and perspective to provide high-quality, evidence-based care. Here we describe our success in creating a standardized curriculum in clinical radiation oncology - one that was well-received and led to significantly improved performance on the national in-service examination. Methods and Materials: One-hundred and fifty topics were outlined in accordance with the American Board of Radiology; to accommodate this breadth of material, didactic frequency was increased from biweekly to daily. As a clinical correlate to these sessions, a teaching library of over 100 real-world cases was compiled for individual learning. Finally, comprehensive dosimetric constraints were compiled to aid residents in radiation therapy plan evaluation. To evaluate these curricular changes, anonymous questionnaires were provided to all residents and faculty, and de-identified resident clinical performance from the annual in-service examination was analyzed. Results: Before the introduction of the standardized curriculum, the mean clinical percentage on the in-service examination was 46%, equivalent to the 17th percentile. Within 2 years of implementation of the new curriculum, both the mean percentage and percentile were significantly improved, with the mean percentage correct at 69.3% and the mean percentile at the 59th percentile (P < .001 and P = .034, respectively). Feedback showed the curriculum to be well-received and used frequently outside of standard didactic hours. Conclusions: This is the first report of the creation of a standardized curriculum and outcomes in radiation oncology. Although there are certainly developmental challenges, addressing these barriers creates an education model that effectively imparts knowledge, fosters multidisciplinary thinking, and prepares residents for the diverse challenges of clinical practice. We present our institutional experience with the intent of publishing this curriculum on a national platform in the coming years.

Quantifying the Association Between Surgical Spine Approach and Tracheostomy Timing After Traumatic Cervical Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Recent evidence suggests earlier tracheostomy is associated with fewer complications in patients with complete cervical spinal cord injury (SCI). This study aims to evaluate the influence of spine surgical approach on the association between tracheostomy timing and in-hospital adverse events treating patients with complete cervical SCI. METHODS: This retrospective cohort study was performed using Trauma Quality Improvement Program data from 2017 to 2020. All patients with acute complete (American Spinal Injury Association-A) cervical SCI who underwent tracheostomy and spine surgery were included. Tracheostomy timing was dichotomized to early (within 1 week after surgery) and delayed (more than 1 week after surgery). Primary outcome was the occurrence of major in-hospital complications. Secondary outcomes included occurrences of immobility-related complications, surgical-site infection, hospital and intensive care unit length of stay, and time on mechanical ventilation. RESULTS: The study included 1592 patients across 358 trauma centers. Mean time to tracheostomy from surgery was 8.6 days. A total of 495 patients underwent anterior approach, 670 underwent posterior approach, and 427 underwent combined anterior and posterior approach. Patients who underwent anterior approach were significantly more likely to have delayed tracheostomy compared with posterior approach (53% vs 40%, P < .001). Early tracheotomy significantly reduced major in-hospital complications (odds ratio 0.67, 95% CI 0.53-0.84) and immobility complications (odds ratio = 0.78, 95% CI 0.6-1.0). Those undergoing early tracheostomy spent 6.0 (95% CI -8.47 to -3.43) fewer days in hospital, 5.7 (95% CI -7.8 to -3.7) fewer days in the intensive care unit, and 5.9 (95% CI -8.2 to -3.7) fewer days ventilated. Surgical approach had no significant negative effect on the association between tracheostomy timing and the outcomes of interest. CONCLUSION: Earlier tracheostomy for patients with cervical SCI is associated with reduced complications, length of stay, and ventilation time. This relationship appears independent of the surgical approach. These findings emphasize that tracheostomy need not be delayed because of the SCI treatment approach.

Phototrophic Fe(II) oxidation by Rhodopseudomonas palustris TIE-1 in organic and Fe(II)-rich conditions.

Rhodopseudomonas palustris TIE-1 grows photoautotrophically with Fe(II) as an electron donor and photoheterotrophically with a variety of organic substrates. However, it is unclear whether R. palustris TIE-1 conducts Fe(II) oxidation in conditions where organic substrates and Fe(II) are available simultaneously. In addition, the effect of organic co-substrates on Fe(II) oxidation rates or the identity of Fe(III) minerals formed is unknown. We incubated R. palustris TIE-1 with 2 mM Fe(II), amended with 0.6 mM organic co-substrate, and in the presence/absence of CO2 . We found that in the absence of CO2 , only the organic co-substrates acetate, lactate and pyruvate, but not Fe(II), were consumed. When CO2 was present, Fe(II) and all organic substrates were consumed. Acetate, butyrate and pyruvate were consumed before Fe(II) oxidation commenced, whereas lactate and glucose were consumed at the same time as Fe(II) oxidation proceeded. Lactate, pyruvate and glucose increased the Fe(II) oxidation rate significantly (by up to threefold in the case of lactate). 57 Fe Mössbauer spectroscopy revealed that short-range ordered Fe(III) oxyhydroxides were formed under all conditions. This study demonstrates phototrophic Fe(II) oxidation proceeds even in the presence of organic compounds, and that the simultaneous oxidation of organic substrates can stimulate Fe(II) oxidation.

Robotic Technology in Emergency General Surgery Cases in the Era of Minimally Invasive Surgery.

Importance: Although robotic surgery has become an established approach for a wide range of elective operations, data on its utility and outcomes are limited in the setting of emergency general surgery. Objectives: To describe temporal trends in the use of laparoscopic and robotic approaches and compare outcomes between robotic and laparoscopic surgery for 4 common emergent surgical procedures. Design, Setting, and Participants: A retrospective cohort study of an all-payer discharge database of 829 US facilities was conducted from calendar years 2013 to 2021. Data analysis was performed from July 2022 to November 2023. A total of 1 067 263 emergent or urgent cholecystectomies (n = 793 800), colectomies (n = 89 098), inguinal hernia repairs (n = 65 039), and ventral hernia repairs (n = 119 326) in patients aged 18 years or older were included. Exposure: Surgical approach (robotic, laparoscopic, or open) to emergent or urgent cholecystectomy, colectomy, inguinal hernia repair, or ventral hernia repair. Main Outcomes and Measures: The primary outcome was the temporal trend in use of each operative approach (laparoscopic, robotic, or open). Secondary outcomes included conversion to open surgery and length of stay (both total and postoperative). Temporal trends were measured using linear regression. Propensity score matching was used to compare secondary outcomes between robotic and laparoscopic surgery groups. Results: During the study period, the use of robotic surgery increased significantly year-over-year for all procedures: 0.7% for cholecystectomy, 0.9% for colectomy, 1.9% for inguinal hernia repair, and 1.1% for ventral hernia repair. There was a corresponding decrease in the open surgical approach for all cases. Compared with laparoscopy, robotic surgery was associated with a significantly lower risk of conversion to open surgery: cholecystectomy, 1.7% vs 3.0% (odds ratio [OR], 0.55 [95% CI, 0.49-0.62]); colectomy, 11.2% vs 25.5% (OR, 0.37 [95% CI, 0.32-0.42]); inguinal hernia repair, 2.4% vs 10.7% (OR, 0.21 [95% CI, 0.16-0.26]); and ventral hernia repair, 3.5% vs 10.9% (OR, 0.30 [95% CI, 0.25-0.36]). Robotic surgery was associated with shorter postoperative lengths of stay for colectomy (-0.48 [95% CI, -0.60 to -0.35] days), inguinal hernia repair (-0.20 [95% CI, -0.30 to -0.10] days), and ventral hernia repair (-0.16 [95% CI, -0.26 to -0.06] days). Conclusions and Relevance: While robotic surgery is still not broadly used for emergency general surgery, the findings of this study suggest it is becoming more prevalent and may be associated with better outcomes as measured by reduced conversion to open surgery and decreased length of stay.

"God, I hope it doesn't fade out": Team Member Perspectives on the Future of Veterans Treatment Courts.

Despite their rapid spread over the last 15 years, little research has explored the perceptions of Veterans Treatment Courts (VTCs) team members regarding the viability and longevity of VTCs. The present qualitative study explores the perceptions of 145 VTC team members from 20 VTCs around the United States regarding the future of their own VTC and VTCs in general. Our analysis revealed four overarching themes about team members' expectations and hopes for VTCs in the future: the need for continued funding and increased resources; desires to expand participation in VTCs; hope and uncertainty about the future of VTCs; and depending on specific people to ensure the future of VTCs. While interviewees in general felt quite hopeful and optimistic that VTCs would continue to exist and may even expand, there was unease about exactly how this would occur. These concerns included securing stable funding sources, maintaining 'buy in' from key individuals, and resource needs for expanding the participation and eligibility criteria of VTCs. Given the important role that VTCs can play in effectively supporting justice-involved veterans, and offering more benefits compared to a traditional justice-system response, it seems vital to ensure that VTCs are able to continue operating in the future.

Advanced and alternative research methods for the acute care surgeon scientist.

Clinical research has evolved significantly over the last few decades to include many advanced and alternative study designs to answer unique questions. Recognizing a potential knowledge gap, the AAST Associate Member Council and Educational Development Committee created a research course at the 2022 Annual Meeting in Chicago to introduce junior researchers to these methodologies. This manuscript presents a summary of this AAST Annual Meeting session, and reviews topics including hierarchical modeling, geospatial analysis, patient-centered outcomes research, mixed methods designs, and negotiating complex issues in multicenter trials.

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.

The Role of the Ophthalmic Genetics Multidisciplinary Team in the Management of Inherited Retinal Degenerations-A Case-Based Review.

(1) Background: Inherited retinal degenertions are rare conditions which may have a dramatic impact on the daily life of those affected and how they interact with their environment. Coordination of clinical services via an ophthalmic genetics multidisciplinary team (OG-MDT) allows better efficiency of time and resources to reach diagnoses and facilitate patient needs. (2) Methods: This clinical case series was conducted by a retrospective review of patient records for patients enrolled in the Target 5000 programme and managed by the OG-MDT, at the Mater Hospital Dublin, Ireland (n = 865) (3) Results: Herein we describe clinical cases and how the use of the OG-MDT optimizes care for isolated and syndromic IRD pedigrees. (4) Conclusions: this paper demonstrates the benefits of an OG-MDT to patients with IRDs resulting in the holistic resolution of complex and syndromic cases. Furthermore, we demonstrate that this format can be adopted/developed by similar centres around the world, bringing with it the myriad benefits.

Concomitant Traumatic Brain Injury Delays Surgery in Patients With Traumatic Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Growing evidence supports prompt surgical decompression for patients with traumatic spinal cord injury (tSCI). Rates of concomitant tSCI and traumatic brain injury (TBI) range from 10% to 30%. Concomitant TBI may delay tSCI diagnosis and surgical intervention. Little is known about real-world management of this common injury constellation that carries significant clinical consequences. This study aimed to quantify the impact of concomitant TBI on surgical timing in a national cohort of patients with tSCI. METHODS: Patient data were obtained from the National Trauma Data Bank (2007-2016). Patients admitted for tSCI and who received surgical intervention were included. Delayed surgical intervention was defined as surgery after 24 hours of admission. Multivariable hierarchical regression models were constructed to measure the risk-adjusted association between concomitant TBI and delayed surgical intervention. Secondary outcome included favorable discharge status. RESULTS: We identified 14 964 patients with surgically managed tSCI across 377 North American trauma centers, of whom 2444 (16.3%) had concomitant TBI and 4610 (30.8%) had central cord syndrome (CCS). The median time to surgery was 20.0 hours for patients without concomitant TBI and 24.8 hours for patients with concomitant TBI. Hierarchical regression modeling revealed that concomitant TBI was independently associated with delayed surgery in patients with tSCI (odds ratio [OR], 1.3; 95% CI, 1.1-1.6). Although CCS was associated with delayed surgery (OR, 1.5; 95% CI, 1.4-1.7), we did not observe a significant interaction between concomitant TBI and CCS. In the subset of patients with concomitant tSCI and TBI, patients with severe TBI were significantly more likely to experience a surgical delay than patients with mild TBI (OR, 1.4; 95% CI, 1.0-1.9). CONCLUSION: Concomitant TBI delays surgical management for patients with tSCI. This effect is largest for patients with tSCI with severe TBI. These findings should serve to increase awareness of concomitant TBI and tSCI and the likelihood that this may delay time-sensitive surgery.

Variant reclassification and clinical implications.

Genomic technologies have transformed clinical genetic testing, underlining the importance of accurate molecular genetic diagnoses. Variant classification, ranging from benign to pathogenic, is fundamental to these tests. However, variant reclassification, the process of reassigning the pathogenicity of variants over time, poses challenges to diagnostic legitimacy. This review explores the medical and scientific literature available on variant reclassification, focusing on its clinical implications.Variant reclassification is driven by accruing evidence from diverse sources, leading to variant reclassification frequency ranging from 3.6% to 58.8%. Recent studies have shown that significant changes can occur when reviewing variant classifications within 1 year after initial classification, illustrating the importance of early, accurate variant assignation for clinical care.Variants of uncertain significance (VUS) are particularly problematic. They lack clear categorisation but have influenced patient treatment despite recommendations against it. Addressing VUS reclassification is essential to enhance the credibility of genetic testing and the clinical impact. Factors affecting reclassification include standardised guidelines, clinical phenotype-genotype correlations through deep phenotyping and ancestry studies, large-scale databases and bioinformatics tools. As genomic databases grow and knowledge advances, reclassification rates are expected to change, reducing discordance in future classifications.Variant reclassification affects patient diagnosis, precision therapy and family screening. The exact patient impact is yet unknown. Understanding influencing factors and adopting standardised guidelines are vital for precise molecular genetic diagnoses, ensuring optimal patient care and minimising clinical risk.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O2-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O2-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2-GeMs. In vivo evaluation confirmed robust insertion and positioning of O2-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

A Technique to Enable Efficient Adaptive Radiation Therapy: Automated Contouring of Prostate and Adjacent Organs.

Purpose: The purpose of this work was to investigate the use of a segmentation approach that could potentially improve the speed and reproducibility of contouring during magnetic resonance-guided adaptive radiation therapy. Methods and Materials: The segmentation algorithm was based on a hybrid deep neural network and graph optimization approach that also allows rapid user intervention (Deep layered optimal graph image segmentation of multiple objects and surfaces [LOGISMOS] + just enough interaction [JEI]). A total of 115 magnetic resonance-data sets were used for training and quantitative assessment. Expert segmentations were used as the independent standard for the prostate, seminal vesicles, bladder, rectum, and femoral heads for all 115 data sets. In addition, 3 independent radiation oncologists contoured the prostate, seminal vesicles, and rectum for a subset of patients such that the interobserver variability could be quantified. Consensus contours were then generated from these independent contours using a simultaneous truth and performance level estimation approach, and the deviation of Deep LOGISMOS + JEI contours to the consensus contours was evaluated and compared with the interobserver variability. Results: The absolute accuracy of Deep LOGISMOS + JEI generated contours was evaluated using median absolute surface-to-surface distance which ranged from a minimum of 0.20 mm for the bladder to a maximum of 0.93 mm for the prostate compared with the independent standard across all data sets. The median relative surface-to-surface distance was less than 0.17 mm for all organs, indicating that the Deep LOGISMOS + JEI algorithm did not exhibit a systematic under- or oversegmentation. Interobserver variability testing yielded a mean absolute surface-to-surface distance of 0.93, 1.04, and 0.81 mm for the prostate, seminal vesicles, and rectum, respectively. In comparison, the deviation of Deep LOGISMOS + JEI from consensus simultaneous truth and performance level estimation contours was 0.57, 0.64, and 0.55 mm for the same organs. On average, the Deep LOGISMOS algorithm took less than 26 seconds for contour segmentation. Conclusions: Deep LOGISMOS + JEI segmentation efficiently generated clinically acceptable prostate and normal tissue contours, potentially limiting the need for time intensive manual contouring with each fraction.

Increasing Injury Intensity among 6,500 Violent Deaths in the State of Maryland.

BACKGROUND: Anecdotal evidence strongly suggests there has been a rise in violent crimes. This study sought to examine trends in injury characteristics of homicide victims in Maryland. We hypothesized that there would be an increase in the severity of wound characteristics. STUDY DESIGN: The Office of the Chief Medical Examiner is a statewide agency designated by law to investigate all homicides, suicides, or unusual or suspicious circumstances. Using individual autopsy reports, we collected data among all homicides from 2005 to 2017, categorizing them into 3 time periods: 2005 to 2008 (early), 2009 to 2013 (mid), and 2014 to 2017 (late). Primary outcomes included the number of gunshots, stabs, and fractures from assaults. High-violence intensity outcomes included victims having 10 or more gunshots, 5 or more stabs, or 5 or more fractures from assaults. RESULTS: Of 6,500 homicides (annual range 403 to 589), the majority were from firearms (75%), followed by stabbings (14%) and blunt assaults (10%). Most homicide victims died in the hospital (60%). The average number of gunshots per victim was 3.9 (range 1 to 54), stabs per victim was 9.4 (range 1 to 563), and fractures from assaults per victim was 3.7 (range 0 to 31). The proportion of firearm victims with at least 10 gunshots nearly doubled from 5.7% in the early period to 10% (p < 0.01) in the late period. Similarly, the proportion with 5 or more stabbings increased from 39% to 50% (p = 0.02) and assault homicides with 5 or more fractures increased from 24% to 38% (p < 0.01). CONCLUSIONS: In Maryland, the intensity of violence increased across all major mechanisms of homicide. Further follow-up studies are needed to elucidate the root causes underlying this escalating trend.

Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers.

Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas-entrapping material containing CO in a pre-clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.

Surgeon Supply by County-Level Rurality and Social Vulnerability From 2010 to 2020.

This cross-sectional study examines the surgical workforce in all counties across the US from 2010 to 2020.