Explainable Machine Learning Model to Preoperatively Predict Postoperative Complications in Inpatients With Cancer Undergoing Major Operations.

PURPOSE: Preoperative prediction of postoperative complications (PCs) in inpatients with cancer is challenging. We developed an explainable machine learning (ML) model to predict PCs in a heterogenous population of inpatients with cancer undergoing same-hospitalization major operations. METHODS: Consecutive inpatients who underwent same-hospitalization operations from December 2017 to June 2021 at a single institution were retrospectively reviewed. The ML model was developed and tested using electronic health record (EHR) data to predict 30-day PCs for patients with Clavien-Dindo grade 3 or higher (CD 3+) per the CD classification system. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), and calibration plots. Model explanation was performed using the Shapley additive explanations (SHAP) method at cohort and individual operation levels. RESULTS: A total of 988 operations in 827 inpatients were included. The ML model was trained using 788 operations and tested using a holdout set of 200 operations. The CD 3+ complication rates were 28.6% and 27.5% in the training and holdout test sets, respectively. Training and holdout test sets' model performance in predicting CD 3+ complications yielded an AUROC of 0.77 and 0.73 and an AUPRC of 0.56 and 0.52, respectively. Calibration plots demonstrated good reliability. The SHAP method identified features and the contributions of the features to the risk of PCs. CONCLUSION: We trained and tested an explainable ML model to predict the risk of developing PCs in patients with cancer. Using patient-specific EHR data, the ML model accurately discriminated the risk of developing CD 3+ complications and displayed top features at the individual operation and cohort level.

Recurrence patterns after complex multimodality therapy and hepatic arterial infusion for colorectal liver metastases: A reflection of biology and technique.

BACKGROUND AND METHODS: We characterized colorectal liver metastasis recurrence and survival patterns after surgical resection and intraoperative ablation ± hepatic arterial infusion pump (HAIP) placement. We estimated patterns of recurrence and survival in patients undergoing contemporary multimodal treatments. Between 2017 and 2021, patient, tumor characteristics, and recurrence data were collected. Primary outcomes included recurrence patterns and survival data based on operative intervention. RESULTS: There were 184 patients who underwent hepatectomy and intraoperative ablation. Sixty patients (32.6%) underwent HAIP placement. A total of 513 metastases were ablated, median total of 2 ablations per patient. Median time to recurrence was 31 [22-40] months. Recurrence patterns included tumor at ablative margin on first scheduled postoperative imaging (8, 4.3%), local tumor recurrence at ablative site (69, 37.5%), and non-ablated liver tumor recurrence (38, 20.6%). In patients who underwent HAIP placement, the rate of liver recurrence was reduced (45% vs 70.9%, p = 0.0001). Median overall survival was 64 [41-58] months and prolonged survival was associated with HAIP treatment (85 [66-109] vs 60 [51-70] months. CONCLUSIONS AND DISCUSSION: Hepatic recurrence is common and combination of intraoperative ablation and HAIP treatments were associated with prolonged survival. These data may reflect patient selection however, future work will clarify preoperative tumor and patient characteristics that may better predict recurrence expectations.

Pilot study of HER2 targeted 64 Cu-DOTA-tagged PET imaging in gastric cancer patients.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) is an important biomarker for targeted gastric cancer (GC) immunotherapy. However, heterogeneous HER2 overexpression in GC, loss of HER2 expression during therapy, and inability to non-invasively identify HER2 overexpressing tumors impede effective targeting therapies. Improved HER2-specific functional imaging can address these challenges. Trastuzumab is a HER2-directed mAb to treat HER2 overexpressing cancers. The 64 Cu-DOTA-trastuzumab radiotracer is used to detect HER2+ metastatic breast cancer. We aimed to develop 64 Cu-DOTA-trastuzumab PET-CT to detect and characterize tumor uptake in HER2+ or - GC patients. METHODS: We conducted a single-arm phase II pilot study exploring the feasibility of 64 Cu-DOTA-trastuzumab for PET imaging of HER2 overexpressing GC compared to HER2 non-expressing tumors. Eight patients with biopsy-confirmed gastric adenocarcinoma were included. Immunohistochemistry was used to evaluate primary tumor biopsies for HER2 overexpression. Patients were injected with 45 mg of cold trastuzumab followed by 5 mg of 64 Cu-DOTA-trastuzumab. PET-CT scans were performed 24-48 h post radiotracer injection and compared to standard staging CT scans. RESULTS: We observed limited toxicity following 64 Cu-DOTA-trastuzumab injections. While there was uptake of the radiotracer in portions of HER2+ lesions, there was no statistically significant distinction between tumor and background by standardized uptake value analysis. CONCLUSION: Despite the potential of 64 Cu-DOTA-trastuzumab PET imaging of HER2+ metastatic breast cancer, a 5 mg dose of this radiotracer injected 24-48 h before imaging was insufficient to identify HER2+ GC. These results inform future GC imaging studies to optimize biomarker-targeted therapies based on dosage and timing for more clinically relevant imaging.

Therapeutic Efficacy of Temsirolimus in a Patient-derived Model of Metastatic Fibrolamellar Hepatocellular Carcinoma.

BACKGROUND/AIM: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare tumor presenting in younger patients without chronic liver disease. Up to 80-100% develop recurrent disease, necessitating additional surgery or systemic treatment. Systemic options and pre-clinical treatment studies are lacking. We previously described patient-derived xenograft (PDX) development, allowing for pre-clinical studies. Herein, we develop FLHCC PDX models and utilize these to define tumor characteristics and determine the efficacy of systemic agents. MATERIALS AND METHODS: Primary and lymph node metastatic tumor tissues were obtained at the time of FLHCC resection in two patients. Tumor lysates were screened for protein upregulation. Cell lines were generated from metastatic and primary tumor tissue. The viability of the cell lines was assessed after treatment with temsirolimus, gemcitabine/oxaliplatin, and FOLFIRINOX. Two PDX models were developed from metastatic tissue. For in vivo studies, tumor-bearing mice were treated with temsirolimus, FOLFIRINOX, and Gemcitabine/oxaliplatin. RESULTS: PDX models were successfully generated from metastatic FLHCC, which closely recapitulated the original tumor. Upregulation of mTOR was seen in metastatic tissue compared to primary tumors. Cell lines from metastatic tissue demonstrated significant sensitivity to temsirolimus. In vivo testing of PDX models demonstrated a significant response to single-agent temsirolimus with minimal toxicity. CONCLUSION: Herein, we demonstrate the feasibility of developing PDX models that closely recapitulate FLHCC. Upregulation of mTOR was seen in metastatic tissue compared to primary tissue. The efficacy of mTOR inhibition with temsirolimus treatment suggests that the upregulation of the mTOR pathway may be a significant mechanism for growth in metastatic lesions and a potential target for therapeutics.

Low anterior resection syndrome.

Low anterior resection syndrome represents a clinical state wherein a constellation of gastrointestinal symptoms is a direct result of anatomic changes to the rectum. Patients who undergo operations to create a neorectum often develop persistent symptoms of increased frequency, urgency, diarrhea, and these symptoms are debilitating and impact patients' quality of life. A stepwise approach to treatment can improve many patients' symptoms with the most invasive options reserved for highly refractory symptoms.

Legal Firearm Sales at State Level and Rates of Violent Crime, Property Crime, and Homicides.

INTRODUCTION: The effects of firearm sales and legislation on crime and violence are intensely debated, with multiple studies yielding differing results. We hypothesized that increased lawful firearm sales would not be associated with the rates of crime and homicide when studied using a robust statistical method. METHODS: National and state rates of crime and homicide during 1999-2015 were obtained from the United States Department of Justice and the Centers for Disease Control and Prevention. National Instant Criminal Background Check System background checks were used as a surrogate for lawful firearm sales. A general multiple linear regression model using log event rates was used to assess the effect of firearm sales on crime and homicide rates. Additional modeling was then performed on a state basis using an autoregressive correlation structure with generalized estimating equation estimates for standard errors to adjust for the interdependence of variables year to year within a particular state. RESULTS: Nationally, all crime rates except the Centers for Disease Control and Prevention-designated firearm homicides decreased as firearm sales increased over the study period. Using a naive national model, increases in firearm sales were associated with significant decreases in multiple crime categories. However, a more robust analysis using generalized estimating equation estimates on state-level data demonstrated increases in firearms sales were not associated with changes in any crime variables examined. CONCLUSIONS: Robust analysis does not identify an association between increased lawful firearm sales and rates of crime or homicide. Based on this, it is unclear if efforts to limit lawful firearm sales would have any effect on rates of crime, homicide, or injuries from violence committed with firearms.

Validation of the American Association for the Surgery of Trauma Emergency General Surgery Grading System for Colorectal Resection: An EAST Multicenter Study.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a grading system for emergency general surgery (EGS) conditions. We sought to validate the AAST EGS grades for patients undergoing urgent/emergent colorectal resection. METHODS: Patients enrolled in the "Eastern Association for the Surgery of Trauma Multicenter Colorectal Resection in EGS-to anastomose or not to anastomose" study undergoing urgent/emergent surgery for obstruction, ischemia, or diverticulitis were included. Baseline demographics, comorbidity severity as defined by Charlson comorbidity index (CCI), procedure type, and AAST grade were prospectively collected. Outcomes included length of stay (LOS) in-hospital mortality, and surgical complications (superficial/deep/organ-space surgical site infection, anastomotic leak, stoma complication, fascial dehiscence, and need for further intervention). Multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication or mortality. RESULTS: There were 367 patients, with a mean (± SD) age of 62 ± 15 years. 39% were women. The median interquartile range (IQR) CCI was 4 (2-6). Overall, the pathologies encompassed the following AAST EGS grades: I (17, 5%), II (54, 15%), III (115, 31%), IV (95, 26%), and V (86, 23%). Management included laparoscopic (24, 7%), open (319, 87%), and laparoscopy converted to laparotomy (24, 6%). Higher AAST grade was associated with laparotomy (P = .01). The median LOS was 13 days (8-22). At least 1 surgical complication occurred in 33% of patients and the mortality rate was 14%. Development of at least 1 surgical complication, need for unplanned intervention, mortality, and increased LOS were associated with increasing AAST severity grade. On multivariable analysis, factors predictive of in-hospital mortality included AAST organ grade, CCI, and preoperative vasopressor use (odds ratio (OR) 1.9, 1.6, 3.1, respectively). The American Association for the Surgery of Trauma emergency general surgery grade was also associated with the development of at least 1 surgical complication (OR 2.5), while CCI, preoperative vasopressor use, respiratory failure, and pneumoperitoneum were not. CONCLUSION: The American Association for the Surgery of Trauma emergency general surgery grading systems display construct validity for mortality and surgical complications after urgent/emergent colorectal resection. These results support incorporation of AAST EGS grades for quality benchmarking and surgical outcomes research.

Association of scooter-related injury and hospitalization with electronic scooter sharing systems in the United States.

INTRODUCTION: We used interrupted time series (ITS) analysis to determine whether e-scooter shares' introduction in September 2017 increased serious scooter-related injury across the United States. METHODS: Using the National Electronic Injury Surveillance System, we queried emergency department visits involving motorized scooter-related injuries from January 2010-December 2019. Cases originating where e-scooter shares launched between September 1, 2017-December 1, 2019 (intervention period) were considered exposed. The first month of launch (September 2017) was chosen as the time point for pre- and post-intervention analysis. The primary outcome was change in hospitalizations following scooter injury in association with the month/year launch. RESULTS: This analysis includes 2754 unweighted encounters, representing 102614 estimated injuries involving motorized scooters nationwide. Hospitals within 20 miles of e-scooter shares also experienced a significant monthly increase of 0.24 scooter-related injury hospitalizations/1000 product-related injury hospitalizations ([0.17,0.31]) compared to a non-significant change in hospitalizations of 0.02 [-0.05,0.09] for control hospitals. CONCLUSION: An increase in serious motorized scooter injuries coincides with e-scooter shares' introduction in the US. Future works should explore effective polices to improve public safety.

Small bowel obstruction managed without hospital admission: A safe way to reduce both cost and time in the hospital?

BACKGROUND: Small bowel obstruction management has evolved to incorporate the Gastrografin challenge. We expanded its use to the emergency department observation unit, potentially avoiding hospital admission for highly select small bowel obstruction patients. We hypothesized that the emergency department observation unit small bowel obstruction protocol would reduce admissions, costs, and the total time spent in the hospital without compromising outcomes. METHODS: We reviewed patients who presented with small bowel obstruction from January 2015 to December 2018. Patients deemed to require urgent surgical intervention were admitted directly and excluded. The emergency department observation unit small bowel obstruction guidelines were introduced in November 2016. Patients were divided into pre and postintervention groups based on this date. The postintervention group was further subclassified to examine the emergency department observation unit patients. Cost analysis for each patient was performed looking at number of charges, direct costs, indirect cost, and total costs during their admission. RESULTS: In total, 125 patients were included (mean age 69 ± 14.3 years). The preintervention group (n = 62) and postintervention group (n = 63) had no significant difference in demographics. The postintervention group had a 51% (36.7 hours, P < .001) reduction in median duration of stay and a total cost reduction of 49% (P < .001). The emergency department observation unit subgroup (n = 46) median length of stay was 23.6 hours. The readmission rate was 16% preintervention compared to 8% in the postintervention group (P = .18). CONCLUSION: Management of highly selected small bowel obstruction patients with the emergency department observation unit small bowel obstruction protocol was associated with decreased length of stay and total cost, without an increase in complications, surgical intervention, or readmissions.

Surgical stabilization of rib fractures in octogenarians and beyond-what are the outcomes?

BACKGROUND: Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older. METHODS: Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0-2 days postinjury) to late (3-7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management. RESULTS: Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24-0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48-0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups. CONCLUSION: Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians. LEVEL OF EVIDENCE: Therapeutic, Level IV.

CT-derived sarcopenia should not preclude surgical stabilization of traumatic rib fractures.

BACKGROUND: Rib fractures are associated with considerable morbidity and mortality. Surgical stabilization of rib fractures (SSRF) can be performed to mitigate complications. Sarcopenia is in general known to be associated with poor clinical outcomes. We investigated if sarcopenia impacted number of days of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay in patients who underwent SSRF. METHODS: A retrospective single institutional review was performed including patients who underwent SSRF (2009-2017). Skeletal muscle index (SMI) was semiautomatically calculated at the L3 spinal level on computed tomography (CT) images and normalized by patient height. Sarcopenia was defined as SMI < 55 cm2/m2 in males and < 39 cm2/m2 in females. Demographics, operative details, and postoperative outcomes were reviewed. Univariate and multivariate analyses were performed. RESULTS: Of 238 patients, 88 (36.9%) had sarcopenia. There was no significant difference in number of days of mechanical ventilation (2.8 ± 4.9 versus 3.1 ± 4.3, p = 0.304), ICU stay (5.9 ± 6.5 versus 4.9 ± 5.7 days, p = 0.146), or total hospital stay (13.3 ± 7.2 versus 12.9 ± 8.2 days, p = 0.183) between sarcopenic and nonsarcopenic patients. Sarcopenic patients demonstrated increased modified frailty index scores (1.5 ± 1.1 versus 0.9 ± 0.9, p < 0.001) compared to nonsarcopenic patients. CONCLUSIONS: For patients who underwent SSRF for rib fractures, sarcopenia did not increase the number of days of mechanical ventilation, ICU stay, or total hospital stay. Sarcopenia should not preclude the utilization of SSRF in these patients.

Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas.

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion-positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer. SIGNIFICANCE: These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer.

Colorectal resection in emergency general surgery: An EAST multicenter trial.

OBJECTIVE: Evidence comparing stoma creation (STM) versus anastomosis after urgent or emergent colorectal resection is limited. This study examined outcomes after colorectal resection in emergency general surgery patients. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored prospective observational multicenter study of patients undergoing urgent/emergent colorectal resection. Twenty-one centers enrolled patients for 11 months. Preoperative, intraoperative, and postoperative variables were recorded. χ, Mann-Whitney U test, and multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication/mortality. RESULTS: A total of 439 patients were enrolled (ANST, 184; STM, 255). The median (interquartile range) age was 62 (53-71) years, and the median Charlson Comorbidity Index (CCI) was 4 (1-6). The most common indication for surgery was diverticulitis (28%). Stoma group was older (64 vs. 58 years, p < 0.001), had a higher CCI, and were more likely to be immunosuppressed. Preoperatively, STM patients were more likely to be intubated (57 vs. 15, p < 0.001), on vasopressors (61 vs. 13, p < 0.001), have pneumoperitoneum (131 vs. 41, p < 0.001) or fecal contamination (114 vs. 33, p < 0.001), and had a higher incidence of elevated lactate (149 vs. 67, p < 0.001). Overall mortality was 13%, which was higher in STM patients (18% vs. 8%, p = 0.02). Surgical complications were more common in STM patients (35% vs. 25%, p = 0.02). On multivariable analysis, management with an open abdomen, intraoperative blood transfusion, and larger hospital size were associated with development of a surgical complication, while CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion were independently associated with mortality. CONCLUSION: This study highlights a tendency to perform fecal diversion in patients who are acutely ill at presentation. There is a higher morbidity and mortality rate in STM patients. Independent predictors of mortality include CCI, preoperative vasopressor use, steroid use, open abdomen, and intraoperative blood transfusion. Following adjustment by clinical factors, method of colon management was not associated with surgical complications or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Damage Control Laparotomy: High-Volume Centers Display Similar Mortality Rates Despite Differences in Country Income Level.

BACKGROUND: Comprehensive analysis of trauma care between high-, middle-, and low-income countries (HIC/MIC/LIC) is needed to improve global health. Comparison of HIC and MIC outcomes after damage control laparotomy (DCL) for patients is unknown. We evaluated DCL utilization among patients treated at high-volume trauma centers in the USA and South Africa, an MIC, hypothesizing similar mortality outcomes despite differences in resources and setting. METHODS: Post hoc analysis of prospectively collected trauma databases from participating centers was performed. Injury severity, physiologic, operative data and post-operative outcomes were abstracted. Univariate and multivariable analyses were performed to assess differences between HIC/MIC for the primary outcome of mortality. RESULTS: There were 967 HIC and 602 MIC patients who underwent laparotomy. DCL occurred in 144 MIC patients (25%) and 241 HIC (24%) patients. Most sustained (58%) penetrating trauma with higher rates in the MIC compared to the HIC (71 vs. 32%, p = 0.001). Between groups, no differences were found for admission physiology, coagulopathy, or markers of shock except for increased presence of hypotension among patients in the HIC. Crystalloid infusion volumes were greater among MIC patients, and MIC patients received fewer blood products than those in the HIC. Overall mortality was 30% with similar rates between groups (29 in HIC vs. 33% in MIC, p = 0.4). On regression, base excess and penetrating injury were independent predictors of mortality but not patient residential status. CONCLUSION: Use and survival of DCL for patients with severe abdominal trauma was similar between trauma centers in HIC and MIC settings despite increased penetrating trauma and less transfusion in the MIC center. While the results overall suggest no gap in care for patients requiring DCL in this MIC, it highlights improvements that can be made in damage control resuscitation.

Mob Justice in South Africa: A comparison of blunt trauma secondary to community and non-community assaults.

BACKGROUND: The phenomenon of extrajudicial "mob justice" and community assault (CA) has been documented in news reports and anecdotes from a number of low- and middle-income countries, but there is little literature on its burden on trauma systems. This study reviews a single center's management of CA victims and compares the spectrum of injuries seen following mob assault with those sustained via other forms of interpersonal violence (IPV). METHODS: Clinical data, injury details, and mortality among injured patients (age≥18) hospitalized in a South African tertiary referral center from 2012-2018 were abstracted. Patients with penetrating injury or missing ISS were excluded. CA was determined at time of admission by either self-designation or by patients' escorts. Univariate analyses compared the presentation and outcomes for CAs and non-CAs. RESULTS: Overall, CA constituted 5% of total trauma admissions and 8% of IPV-related admissions during the study period. Of 1,323 incidents of blunt injury following IPV, 239 (18%) were CAs. One in two CA victims (n=119, 50%) were struck by an identifiable weapon. Patients injured in CA were more frequently male (97% vs 85%), presented with ISS>15 (28% vs 21%), and had a shock index>0.9 (25% vs 19%) compared to non-CA (all p<0.001). Rates of operative intervention, ICU admission, and mortality did not differ (all p>0.05). CAs were more likely to be complicated by acute kidney injury (9% vs 1%, p<0.001) but less likely to involve neurologic complications (3% vs 10%. P<0.001) compared to non-CAs. Acute kidney injury in CA showed a pattern of significant musculocutaneous injury with rhabdomyolysis. CONCLUSION: CA contributes considerably to the high rates of IPV in a single South African center. Victims of such assaults sustain more severe injury with unique mechanisms and subsequent complications. This evidence supports the need to strengthen local governance and improve law enforcement efforts to prevent such violence.

Comparison of the Pediatric Resuscitation and Trauma Outcome (PRESTO) Model and Pediatric Trauma Scoring Systems in a Middle-Income Country.

BACKGROUND: The pediatric resuscitation and trauma outcome (PRESTO) model was developed to aid comparisons of risk-adjusted mortality after injury in low- and middle-income countries (LMICs). We sought to validate PRESTO using data from a middle-income country (MIC) trauma registry and compare its performance to the Pediatric Trauma Score (PTS), Revised Trauma Score, and pediatric age-adjusted shock index (SIPA). METHODS: We included children (age < 15 years) admitted to a single trauma center in South Africa from December 2012 to January 2019. We excluded patients missing variables necessary for the PRESTO model-age, systolic blood pressure, pulse, oxygen saturation, neurologic status, and airway support. Trauma scores were assigned retrospectively. PRESTO's previously high-income country (HIC)-validated optimal threshold was compared to MIC-validated threshold using area under the receiver operating characteristic curves (AUROC). Prediction of in-hospital death using trauma scoring systems was compared using ROC analysis. RESULTS: Of 1160 injured children, 988 (85%) had complete data for calculation of PRESTO. Median age was 7 (IQR: 4, 11), and 67% were male. Mortality was 2% (n = 23). Mean predicted mortality was 0.5% (range 0-25.7%, AUROC 0.93). Using the HIC-validated threshold, PRESTO had a sensitivity of 26.1% and a specificity of 99.7%. The MIC threshold showed a sensitivity of 82.6% and specificity of 89.4%. The MIC threshold yielded superior discrimination (AUROC 0.86 [CI 0.78, 0.94]) compared to the previously established HIC threshold (0.63 [CI 0.54, 0.72], p < 0.0001). PRESTO showed superior prediction of in-hospital death compared to PTS and SIPA (all p < 0.01). CONCLUSION: PRESTO can be applied in MIC settings and discriminates between children at risk for in-hospital death following trauma. Further research should clarify optimal decision thresholds for quality improvement and benchmarking in LMIC settings.

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine.

BACKGROUND & AIMS: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog. METHODS: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq). RESULTS: Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies (p = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of CDKN2A, SMAD4, NRG1, TP53. Sequencing also identified worse survival in patients with tumors containing tetraploid genomes. CONCLUSIONS: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients. LAY SUMMARY: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.

Predicting the Outcome of Non-operative Management of Splenic Trauma in South Africa.

INTRODUCTION: We aimed to expand on the global surgical discussion around splenic trauma in order to understand locally and clinically relevant factors for operative (OP) and non-operative management (NOM) of splenic trauma in a South African setting. METHODS: A retrospective cohort study was performed using 2013-2017 data from the Pietermaritzburg Metropolitan Trauma Service. All adult patients (≥15 years) were included. Those managed with OP or NOM for splenic trauma were identified and analyzed descriptively. Multiple logistic regression analysis identified patients and clinical factors associated with management type. RESULTS: There were 127 patients with splenic injury. Median age was 29 [19-35] years with 42 (33%) women and 85 (67%) men. Blunt injuries occurred in the majority (81, 64%). Organ Injury Scale (OIS) grades included I (25, 20%), II (43, 34%), III (36, 28%), IV (15, 11%), and V (8, 6%). Nine patients expired. On univariate analysis, increasing OIS was associated with OP management, need for intensive care unit (ICU) admission, and hospital and ICU duration of stay, but not mortality. In patients with a delayed compared to early presentation, ICU utilization (62% vs. 36%, p = 0.008) and mortality (14% vs. 4%, p = 0.03) were increased. After adjusting for age, sex, presence of shock, and splenic OIS, penetrating trauma (adjusted odds ratio, 5.7; 95%CI, 1.7-9.8) and admission lactate concentration (adjusted odds ratio, 1.4; 95%CI 1.1-1.9) were significantly associated with OP compared to NOM (p = 0.002; area under the curve 0.81). CONCLUSIONS: We have identified injury mechanism and admission lactate as factors predictive of OP in South African patients with splenic trauma. Timely presentation to definitive care affects both ICU duration of stay and mortality outcomes. Future global surgical efforts may focus on expanding non-operative management protocols and improving pre-hospital care in patients with splenic trauma.