Patient Perspectives in the Diagnosis and Treatment of Gallstone Disease: A Qualitative Analysis.

INTRODUCTION: Gallstone disease is one of the most common surgical diagnoses in the United States. Notably absent from the literature is the patient's perspective on priorities in management. Understanding patient values will assist surgeons and systems in achieving high-quality, patient-focused care for biliary disease. METHODS: Patients who underwent elective or urgent cholecystectomy were invited to participate in a semistructured interview to assess their experience. Interviews were performed over the phone or in person and recordings were transcribed. Each transcription was analyzed independently by two authors using the MAXQDA software, and a mixed deductive-inductive approach was used to develop themes. Anonymized quotes were used to illustrate themes and subthemes regarding the patient's experiences and priorities surrounding gallstone disease. RESULTS: A total of 29 interviews were completed. Most participants were female, but represented a diverse racial and educational group. The most common diagnosis was acute cholecystitis (48%), and 76% of patients underwent an emergency operation. Patients indicated that their main priority regarding treatment was prompt pain control with definitive management so they could return to their previous quality of life. Most patients wanted face-to-face communication with the surgical team both pre and postoperatively. Patients wished they had more information about postoperative care and expectations in the preoperative setting. CONCLUSIONS: Patients' priorities in their care for gallstone disease are centered around definitive management and quality of life. Improvements in communication were identified regarding meeting the surgeon, and postoperative communication. These results can inform surgeons how to prioritize patient perspectives in an acute care surgical system that was not designed with patient input.

Development and validation of prediction models for fetal growth restriction and birthweight: an individual participant data meta-analysis.

Background: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors: Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight. Analysis: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model. Results: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g). Limitations: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data. Future work: International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation. Conclusion: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management. Study registration: This study is registered as PROSPERO CRD42019135045. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

One in ten babies is born small for their age. A third of such small babies are considered to be 'growth-restricted' as they have complications such as dying in the womb (stillbirth) or after birth (newborn death), cerebral palsy, or needing long stays in hospital. When growth restriction is suspected in fetuses, they are closely monitored and often delivered early to avoid complications. Hence, it is important that we identify growth-restricted babies early to plan care. Our goal was to provide personalised and accurate estimates of the mother's chances of having a growth-restricted baby and predict the baby's weight if delivered at various time points in pregnancy. To do so, first we tested how accurate existing risk calculators ('prediction models') were in predicting growth restriction and birthweight. We then developed new risk-calculators and studied their clinical and economic benefits. We did so by accessing the data from individual pregnant women and their babies in our large database library (International Prediction of Pregnancy Complications). Published risk-calculators had various definitions of growth restriction and none predicted the chances of having a growth-restricted baby using our definition. One predicted baby's birthweight. This risk-calculator performed well, but underpredicted the birthweight by up to 143 g. We developed two new risk-calculators to predict growth-restricted babies (International Prediction of Pregnancy Complications-fetal growth restriction) and birthweight (International Prediction of Pregnancy Complications-birthweight). Both calculators accurately predicted the chances of the baby being born with growth restriction, and its birthweight. The birthweight was underpredicted by <9.7 g. The calculators performed well in both mothers predicted to be low and high risk. Further research is needed to determine the impact of using these calculators in practice, and challenges to implementing them in practice. Both International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight risk calculators will inform healthcare professionals and empower parents make informed decisions on monitoring and timing of delivery.

Development and validation of a prognostic model to predict birth weight: individual participant data meta-analysis.

Objective: To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit. Design: Individual participant data meta-analysis. Data sources: Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset. Eligibility criteria for selecting studies: Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model. Results: The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making. Conclusions: The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required. Trial registration: PROSPERO CRD42019135045.

Best Case/Worst Case-ICU: protocol for a multisite, stepped-wedge, randomised clinical trial of scenario planning to improve communication in the ICU in US trauma centres for older adults with serious injury.

INTRODUCTION: Poor communication about serious injury in older adults can lead to treatment that is inconsistent with patient preferences, create conflict and strain healthcare resources. We developed a communication intervention called Best Case/Worst Case-intensive care unit (ICU) that uses daily scenario planning, that is, a narrative description of plausible futures, to support prognostication and facilitate dialogue among patients, their families and the trauma ICU team. This article describes a protocol for a multisite, randomised, stepped-wedge study to test the effectiveness of the intervention on the quality of communication (QOC) in the ICU. METHODS AND ANALYSIS: We will follow all patients aged 50 and older admitted to the trauma ICU for 3 or more days after a serious injury at eight high-volume level 1 trauma centres. We aim to survey one family or 'like family' member per eligible patient 5-7 days following their loved ones' admission and clinicians providing care in the trauma ICU. Using a stepped-wedge design, we will use permuted block randomisation to assign the timing for each site to begin implementation of the intervention and routine use of the Best Case/Worst Case-ICU tool. We will use a linear mixed-effects model to test the effect of the tool on family-reported QOC (using the QOC scale) as compared with usual care. Secondary outcomes include the effect of the tool on reducing clinician moral distress (using the Measure of Moral Distress for Healthcare Professionals scale) and patients' length of stay in the ICU. ETHICS AND DISSEMINATION: Institutional review board (IRB) approval was granted at the University of Wisconsin, and all study sites ceded review to the primary IRB. We plan to report results in peer-reviewed publications and national meetings. TRIAL REGISTRATION NUMBER: NCT05780918.

Efficacy of refrigerated gel packs for therapeutic hypothermia in neonatal retrieval: a retrospective cohort study.

OBJECTIVE: To determine the efficacy of refrigerated gel packs in achieving and maintaining target temperature in neonates receiving therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy during neonatal retrieval. DESIGN: Retrospective cohort study. SETTING: Paediatric Infant Perinatal Emergency Retrieval, Victoria, Australia. PATIENTS: 200 neonates treated with TH during retrieval between 1 January 2015 and 31 December 2020. INTERVENTIONS: Active cooling with refrigerated gel packs or passive cooling. MAIN OUTCOME MEASURES: The primary outcomes were the proportion of neonates who achieved therapeutic cooling rectal temperature (33-34°C) within 6 hours of birth and maintained target temperature range once TH was achieved. Secondary outcomes included need for respiratory support, inotropes, anticonvulsant therapy, sedation and survival at 7 days of life. RESULTS: 200 neonates received TH. Median gestational age was 39 weeks and median birth weight 3300 g. 120 (60%) were actively cooled with refrigerated gel packs and the remainder passively cooled. 121 neonates (61%) reached target temperature within 6 hours and 14 (7%) after 6 hours of birth. Of those who achieved target temperature, 38% were maintained in therapeutic cooling range for the remainder of the retrieval. CONCLUSIONS: Achieving and maintaining TH during neonatal retrieval with gel packs is challenging. Target temperature was not maintained in most neonates in this study. These findings support existing evidence favouring the use of servo-controlled cooling devices to optimise TH in the retrieval setting.

Can We Actually Predict Long-Term Patient Satisfaction After Traumatic Brain Injury?

INTRODUCTION: The Traumatic Brain Injury - Patient Reported Outcome (TBI-PRO) model was previously derived to predict long-term patient satisfaction as assessed by the Quality of Life After Brain Injury (QOLIBRI) score. The aim of this study is to externally and prospectively validate the TBI-PRO model to predict long-term patient-reported outcomes and to derive a new model using a larger dataset of older adults with TBI. METHODS: Patients admitted to a Level I trauma center with TBI were prospectively followed for 1 y after injury. Outcomes predicted by the TBI-PRO model based on admission findings were compared to actual QOLIBRI scores reported by patients at 3,6, and 12 mo. When deriving a new model, Collaborative European NeuroTrauma Effectiveness Research in TBI and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury databases were used to identify older adults (≥50 y) with TBI from 2014 to 2018. Bayesian additive regression trees were used to identify predictive admission covariates. The coefficient of determination was used to identify the fitness of the model. RESULTS: For prospective validation, a total of 140 patients were assessed at 3 mo, with follow-up from 69 patients at 6 mo and 13 patients at 12 mo postinjury. The area under receiver operating curve of the TBI-PRO model for predicting favorable outcomes at 3, 6, and 12 mo were 0.65, 0.57, and 0.62, respectively. When attempting to derive a novel predictive model, a total of 1521 patients (80%) was used in the derivation dataset while 384 (20%) were used in the validation dataset. A past medical history of heart conditions, initial hospital length of stay, admission systolic blood pressure, age, number of reactive pupils on admission, and the need for craniectomy were most predictive of long-term QOLIBRI-Overall Scale. The coefficient of determination for the validation model including only the most predictive variables were 0.28, 0.19, and 0.27 at 3, 6, and 12 mo, respectively. CONCLUSIONS: In the present study, the prospective validation of a previously derived TBI-PRO model failed to accurately predict a long-term patient reported outcome measures in TBI. Additionally, the derivation of a novel model in older adults using a larger database showed poor accuracy in predicting long-term health-related quality of life. This study demonstrates limitations to current targeted approaches in TBI care. This study provides a framework for future studies and more targeted datasets looking to assess long-term quality of life based upon early hospital variables and can serve as a starting point for future predictive analysis.

Implementation of the 300-mL Rule for the Management of Traumatic Hemothorax.

BACKGROUND: Traumatic hemothorax (HTX) is often managed with tube thoracostomy (TT); however, TT carries a high complication rate. In 2017, a guideline was implemented at our Level I trauma center to observe traumatic HTX ≤300mL in hemodynamically stable patients. We hypothesized that this guideline would decrease TT placement without increasing observation failure rates. METHODS: This was a single-center retrospective review of all adult patients admitted with a HTX on computed tomography (CT) before (2015-2016) and after (2018-2019) the guideline implementation. Exclusion criteria were TT placement prior to CT scan, absence of CT scan, death within 5 days of admission, and a concurrent pneumothorax (PTX) >20mm. HTX volume was calculated using CT scan images and Mergo's formula: V=d 2xL (V: volume; d: depth; L: length). The primary outcome was observation failure, defined as the need for TT, video-assisted thoracoscopic surgery, thoracotomy after repeat imaging or worsening of symptoms and pulmonary morbidity. RESULTS: A total of 357 patients met inclusion criteria, of whom 210 were admitted after guideline implementation. There were no significant differences in baseline demographics, comorbidities, or injury characteristics across both cohorts. The post-implementation cohort had a significant increase in observation rate (75% vs 59%) and a decrease in TT placement (42% vs 57%). Moreover, the post-implementation group had a statistically significant shorter hospital (6 vs 8 days) and ICU (2 vs 3 days) LOS. No significant differences in observation failure, pulmonary complications, 30-day readmission, or 30-day mortality were observed across both cohorts. CONCLUSION: The implementation of the 300mL guideline led to a decrease in TT placement without increasing observation failure or complication rates. LEVEL OF EVIDENCE: Level III, Therapeutic/Care Management.

Prospective validation of a hospital triage predictive model to decrease undertriage: an EAST multicenter study.

Background: Tiered trauma team activation (TTA) allows systems to optimally allocate resources to an injured patient. Target undertriage and overtriage rates of <5% and <35% are difficult for centers to achieve, and performance variability exists. The objective of this study was to optimize and externally validate a previously developed hospital trauma triage prediction model to predict the need for emergent intervention in 6 hours (NEI-6), an indicator of need for a full TTA. Methods: The model was previously developed and internally validated using data from 31 US trauma centers. Data were collected prospectively at five sites using a mobile application which hosted the NEI-6 model. A weighted multiple logistic regression model was used to retrain and optimize the model using the original data set and a portion of data from one of the prospective sites. The remaining data from the five sites were designated for external validation. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used to assess the validation cohort. Subanalyses were performed for age, race, and mechanism of injury. Results: 14 421 patients were included in the training data set and 2476 patients in the external validation data set across five sites. On validation, the model had an overall undertriage rate of 9.1% and overtriage rate of 53.7%, with an AUROC of 0.80 and an AUPRC of 0.63. Blunt injury had an undertriage rate of 8.8%, whereas penetrating injury had 31.2%. For those aged ≥65, the undertriage rate was 8.4%, and for Black or African American patients the undertriage rate was 7.7%. Conclusion: The optimized and externally validated NEI-6 model approaches the recommended undertriage and overtriage rates while significantly reducing variability of TTA across centers for blunt trauma patients. The model performs well for populations that traditionally have high rates of undertriage. Level of evidence: 2.

Thoracic irrigation for prevention of secondary intervention after thoracostomy tube drainage for hemothorax: A Western Trauma Association multi-center study.

BACKGROUND: Retained hemothorax (rHTX) requiring intervention occurs in up to 20% of patients who undergo chest tube (TT) placement for a hemothorax (HTX). Thoracic irrigation at the time of TT placement decreases the need for secondary intervention in this patient group but those findings are limited because of the single center design. A multi-center study was conducted to evaluate the effectiveness of thoracic irrigation. METHODS: A multi-center, prospective, observational study was conducted between June 2018 and July 2023. Eleven sites contributed patients. Patients were included if they had a TT placed for a HTX and were excluded if: age < 18 years, TT for pneumothorax, thoracotomy or VATS performed within 6 hours of TT, TT >24 hours after injury, TT removed <24 hours, or death within 48 hours. Thoracic irrigation was performed at the discretion of the attending. Each hemithorax was considered separately if bilateral HTX. The primary outcome was secondary intervention for HTX-related complications (rHTX, effusion, or empyema). Secondary intervention was defined as: TT placement, instillation of thrombolytics, VATS, or thoracotomy. Irrigated and non-irrigated hemithoraces were compared using a propensity weighted analysis with age, sex, mechanism of injury, Abbreviated Injury Scale (AIS) chest and TT size as predictors. RESULTS: 493 patients with 462 treated hemothoraces were included, 123 (25%) had thoracic irrigation at TT placement. There were no significant demographic differences between the cohorts. Fifty-seven secondary interventions were performed, 10 (8%) and 47 (13%) in the irrigated and non-irrigated groups, respectively (p = 0.015). Propensity weighted analysis demonstrated a reduction in secondary interventions in the irrigated cohort (Odds Ratio 0.56 (0.34-0.85); p = 0.005). CONCLUSION: This Western Trauma Association multi-center study demonstrates a benefit of thoracic irrigation at the time of TT placement for a HTX. Thoracic irrigation reduces the odds of a secondary intervention for rHTX-related complications by 44%. LEVEL OF EVIDENCE: Therapeutic Study, Level II.

Cardiac Magnetic Resonance Imaging Used to Determine a Rare Etiology of a Layered Left Ventricular Apical Thrombus.

Eosinophilic myocarditis (EM) is a rare disease, often associated with hypereosinophilic syndrome (HES). Historically, the diagnostic gold standard was endomyocardial biopsy (EMB). We present a unique case of a 58-year-old female who presents after a syncopal episode and was found to have a layered left ventricular (LV) thrombus. Using laboratory studies and cardiac magnetic resonance imaging (MRI), we were able to delineate the etiology, avoiding any invasive testing.

A collaborative multidisciplinary trauma program improvement team improves VTE chemoprophylaxis guideline compliance in non-operative stable TBI.

BACKGROUND: Delays in initiating venous thromboembolism (VTE) prophylaxis in patients suffering from traumatic brain injury (TBI) persist despite guidelines recommending early initiation. We hypothesized that the expansion of a Trauma Program Performance Improvement (PI) team will improve compliance of early (24-48 hours) initiation of VTE prophylaxis and will decrease VTE events in TBI patients. METHODS: We performed a single-center retrospective review of all TBI patients admitted to a Level I trauma center before (2015-2016,) and after (2019-2020,) the expansion of the Trauma Performance Improvement and Patient Safety (PIPS) team and the creation of trauma process and outcome dashboards. Exclusion criteria included discharge or death within 48 hours of admission, expanding intracranial hemorrhage on CT scan, and a neurosurgical intervention (craniotomy, pressure monitor, or drains) prior to chemoprophylaxis initiation. RESULTS: A total of 1,112 patients met the inclusion criteria, of which 54% (n = 604) were admitted after Trauma PIPS expansion. Following the addition of a dedicated PIPS nurse in the trauma program and creation of process dashboards, the time from stable CT to VTE prophylaxis initiation decreased (52 hours to 35 hours; p < 0.001) and more patients received chemoprophylaxis at 24 hours to 48 hours (59% from 36%, p < 0.001) after stable head CT. There was no significant difference in time from first head CT to stable CT (9 vs. 9 hours; p = 0.15). The Contemporary group had a lower rate of VTE events (1% vs. 4%; p < 0.001) with no increase in bleeding events (2% vs. 2%; p = 0.97). On multivariable analysis, being in the Early cohort was an independent predictor of VTE events (adjusted odds ratio, 3.74; 95% confidence interval, 1.45-6.16). CONCLUSION: A collaborative multidisciplinary Trauma PIPS team improves guideline compliance. Initiation of VTE chemoprophylaxis within 24 hours to 48 hours of stable head CT is safe and effective. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Thoracic cavity irrigation prevents retained hemothorax and decreases surgical intervention in trauma patients.

INTRODUCTION: Retained hemothorax (HTX) is a common complication following thoracic trauma. Small studies demonstrate the benefit of thoracic cavity irrigation at the time of tube thoracostomy (TT) for the prevention of retained HTX. We sought to assess the effectiveness of chest irrigation in preventing retained HTX leading to a secondary surgical intervention. METHODS: We performed a single-center retrospective study from 2017 to 2021 at a Level I trauma center, comparing bedside thoracic cavity irrigation via TT versus no irrigation. Using the trauma registry, patients with traumatic HTX were identified. Exclusion criteria were TT placement at an outside hospital, no TT within 24 hours of admission, thoracotomy or video-assisted thoracoscopic surgery (VATS) prior to or within 6 hours after TT placement, VATS as part of rib fixation or diaphragmatic repair, and death within 96 hours of admission. Bivariate and multivariable analyses were conducted. RESULTS: A total of 370 patients met the inclusion criteria, of whom 225 (61%) were irrigated. Patients who were irrigated were more likely to suffer a penetrating injury (41% vs. 30%, p = 0.03) and less likely to have a flail chest (10% vs. 21%, p = 0.01). On bivariate analysis, irrigation was associated with lower rates of VATS (6% vs. 19%, p < 0.001) and retained HTX (10% vs. 21%, p < 0.001). The irrigated cohort had a shorter TT duration (4 vs. 6 days, p < 0.001) and hospital length of stay (7 vs. 9 days, p = 0.04). On multivariable analysis, thoracic cavity irrigation had lower odds of VATS (adjusted odds ratio, 0.37; 95% confidence interval [CI], 0.30-0.54), retained HTX (adjusted odds ratio, 0.42; 95% CI, 0.25-0.74), and a shorter TT duration ( ß = -1.58; 95% CI, -2.52 to -0.75). CONCLUSION: Our 5-year experience with thoracic irrigation confirms findings from smaller studies that irrigation prevents retained HTX and decreases the need for surgical intervention. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Early venous thromboembolism chemoprophylaxis in traumatic brain injury requiring neurosurgical intervention: Safe and effective.

BACKGROUND: Traumatic brain injury patients who require neurosurgical intervention are at the highest risk of worsening intracranial hemorrhage. This subgroup of patients has frequently been excluded from prior research regarding the timing of venous thromboembolism chemoprophylaxis. This study aims to assess the efficacy and safety of early venous thromboembolism chemoprophylaxis in patients with traumatic brain injuries requiring neurosurgical interventions. METHODS: This is a single-center retrospective review (2016-2020) of traumatic brain injury patients requiring neurosurgical intervention admitted to a level I trauma center. Interventions included intracranial pressure monitoring, subdural drain, external ventricular drain, craniotomy, and craniectomy. Exclusion criteria included neurosurgical intervention after chemoprophylaxis initiation, death within 5 days of admission, and absence of chemoprophylaxis. The total population was stratified into Early (≤72 hours of intervention) versus Late (>72 hours after intervention) chemoprophylaxis initiation. RESULTS: A total of 351 patients met the inclusion criteria, of whom 204 (58%) had early chemoprophylaxis initiation. Overall, there were no significant differences in baseline and admission characteristics between cohorts. The Early chemoprophylaxis cohort had a statistically significant lower venous thromboembolism rate (5% vs 13%, P < .001) with no increased risk of worsening intracranial hemorrhage (10% vs 13%, P = .44) or neurosurgical reintervention (8% vs 10%, P = .7). On subgroup analysis, a total of 169 patients required either a craniotomy or a craniectomy before chemoprophylaxis. The Early chemoprophylaxis cohort had statistically significant lower venous thromboembolism rates (2% vs 11%, P < .001) with no increase in intracranial hemorrhage (8% vs 11%, P = .6) or repeat neurosurgical intervention (8% vs 10%, P = .77). CONCLUSION: Venous thromboembolism prophylaxis initiation within 72 hours of neurosurgical intervention is safe and effective. Further prospective research is warranted to validate the results of this study.

Artificial intelligence-powered discovery of small molecules inhibiting CTLA-4 in cancer.

BACKGROUND/OBJECTIVES: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4. SUBJECTS/METHODS: In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the hits molecules with biochemical, biophysical, immunological, and experimental animal assays. RESULTS: The primary hits obtained from the virtual screening were successfully validated in vitro and in vivo. We then optimized lead compounds and obtained inhibitors (inhibitory concentration, 1 micromole) that disrupted the CTLA-4/CD80 interaction without degrading CTLA-4. CONCLUSIONS: Several compounds inhibited tumor development prophylactically and therapeutically in syngeneic and CTLA-4-humanized mice. Our findings support using AI-based frameworks to design small molecules targeting immune checkpoints for cancer therapy.

Open versus endovascular repair of penetrating non-aortic arterial injuries: A systematic review and meta analysis.

BACKGROUND: Non-aortic arterial injuries are common and are associated with high morbidity and mortality. Historically, open surgical repair (OSR) was the conventional method of repair. With recent advancements in minimally invasive techniques, endovascular repair (ER) has gained popularity. We sought to compare outcomes in patients undergoing endovascular and open repairs of traumatic non-aortic penetrating arterial injuries. METHODS: A systematic review and meta-analysis was conducted using MEDLINE (OVID), Web of Science, Cochrane Library, and Scopus Database from January 1st, 1990, to March 20th, 2023. Titles and abstracts were screened, followed by full text review. Articles assessing clinically important outcomes between OSR and ER in penetrating arterial injuries were included. Exclusion criteria included blunt injuries, aortic injuries, pediatric populations, review articles, and non-English articles. Odds ratios (OR) and Cohen's d ratios were used to quantify differences in morbidity and mortality. RESULTS: A total of 3770 articles were identified, of which 8 met inclusion criteria and were included in the review. The articles comprised a total of 8369 patients of whom 90 % were male with a median age of 28 years. 85 % of patients were treated with OSR while 15 % underwent ER. With regards to injury characteristics, those who underwent ER were less likely to present with concurrent venous injuries (OR: 0.41; 95 %CI: 0.18, 0.94; p = 0.03). Regarding hospital outcomes, patients who underwent ER had a lower likelihood of in-hospital or 30-day mortality (OR: 0.72; 95 %CI: 0.55, 0.95; p = 0.02) and compartment syndrome (OR: 0.29, 95 %CI: 0.12, 0.71; p = 0.007). The overall risk of bias was moderate. CONCLUSION: Endovascular repair of non-aortic penetrating arterial injuries is increasingly common, however open repair remains the most common approach. Compared to ER, OSR was associated with higher odds of compartment syndrome and mortality. Further prospective research is warranted to determine the patient populations and injury patterns that most significantly benefit from an endovascular approach. LEVEL OF EVIDENCE: Level III, Systematic Reviews & Meta-Analyses.

TK1 expression influences pathogenicity by cell cycle progression, cellular migration, and cellular survival in HCC 1806 breast cancer cells.

Breast cancer is the most common cancer diagnosis worldwide accounting for 1 out of every 8 cancer diagnoses. The elevated expression of Thymidine Kinase 1 (TK1) is associated with more aggressive tumor grades, including breast cancer. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement in breast cancer has not been identified. Here, we evaluate potential pathogenic effects of elevated TK1 expression by comparing HCC 1806 to HCC 1806 TK1-knockdown cancer cells (L133). Transcriptomic profiles of HCC 1806 and L133 cells showed cell cycle progression, apoptosis, and invasion as potential pathogenic pathways affected by TK1 expression. Subsequent in-vitro studies confirmed differences between HCC 1806 and L133 cells in cell cycle phase progression, cell survival, and cell migration. Expression comparison of several factors involved in these pathogenic pathways between HCC 1806 and L133 cells identified p21 and AKT3 transcripts were significantly affected by TK1 expression. Creation of a protein-protein interaction map of TK1 and the pathogenic factors we evaluated predict that the majority of factors evaluated either directly or indirectly interact with TK1. Our findings argue that TK1 elevation directly increases HCC 1806 cell pathogenicity and is likely occurring by p21- and AKT3-mediated mechanisms to promote cell cycle arrest, cellular migration, and cellular survival.

Early career acute care surgeons' priorities and perspectives: A mixed-methods analysis to better understand full-time employment.

BACKGROUND: Understanding the expectations of early career acute care surgeons will help clarify the practice and employment models that will attract and retain high-quality surgeons, thereby sustaining our workforce. This study aimed to outline the clinical and academic preferences and priorities of early career acute care surgeons and to better define full-time employment. METHODS: A survey on clinical responsibilities, employment preferences, work priorities, and compensation was distributed to early career acute care surgeons in the first 5 years of practice. A subset of agreeable respondents underwent virtual semistructured interviews. Both quantitative and thematic analysis were used to describe current responsibilities, expectations, and perspectives. RESULTS: Of 471 surgeons, 167 responded (35%), the majority of whom were assistant professors within the first 3 years of practice (80%). The median desired clinical volume was 24 clinical weeks and 48 call shifts per year, 4 weeks less than their median current clinical volume. Most respondents (61%) preferred a service-based model. The top priorities cited in choosing a job were geography, work schedule, and compensation. Qualitative interviews identified themes related to defining full-time employment, first job expectations and realities, and the often-misaligned system and surgeon. CONCLUSION: Understanding the perspectives of early career surgeons entering the workforce is important particularly in the field of acute care surgery where no standard workload or practice model exists. The wide variety of expectations, practice models, and schedule preferences may lead to a mismatch between surgeon desires and employment expectation. Consistent employment standards across our specialty would provide a framework for sustainability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

The Variation of Withdrawal of Life Sustaining Therapy in Older Adults With Traumatic Brain Injury.

INTRODUCTION: The decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing. METHODS: All traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed. RESULTS: We included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints. CONCLUSIONS: Patient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers.

Early Shared Decision-Making for Older Adults with Traumatic Brain Injury: Using Time-Limited Trials and Understanding Their Limitations.

Older adults account for a disproportionate share of the morbidity and mortality after traumatic brain injury (TBI). Predicting functional and cognitive outcomes for individual older adults after TBI is challenging in the acute phase of injury. Given that neurologic recovery is possible and uncertain, life-sustaining therapy may be pursued initially, even if for some, there is a risk of survival to an undesired level of disability or dependence. Experts recommend early conversations about goals of care after TBI, but evidence-based guidelines for these discussions or for the optimal method for communicating prognosis are limited. The time-limited trial (TLT) model may be an effective strategy for managing prognostic uncertainty after TBI. TLTs can provide a framework for early management: specific treatments or procedures are used for a defined period of time while monitoring for an agreed-upon outcome. Outcome measures, including signs of worsening and improvement, are defined at the outset of the trial. In this Viewpoint article, we discuss the use of TLTs for older adults with TBI, their potential benefits, and current challenges to their application. Three main barriers limit the implementation of TLTs in these scenarios: inadequate models for prognostication; cognitive biases faced by clinicians and surrogate decision-makers, which may contribute to prognostic discordance; and ambiguity regarding appropriate endpoints for the TLT. Further study is needed to understand clinician behaviors and surrogate preferences for prognostic communication and how to optimally integrate TLTs into the care of older adults with TBI.