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.

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.

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.

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.

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.

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.

Surgical Considerations for Pediatric Snake Bites in Low- and Middle-Income Countries.

BACKGROUND: Snake envenomation is associated with major morbidity especially in low- and middle-income countries and may require fasciotomy. We determined patient factors associated with the need for fasciotomy after venomous snake bites in children located in KwaZulu-Natal, South Africa. METHODS: Single institutional review of historical data (2012-2017) for children (<18 years) sustaining snake envenomation was performed. Clinical data, management, and outcomes were abstracted. Syndromes after snake bite were classified according to Blaylock nomenclature: progressive painful swelling (PPS), progressive weakness (PW), or bleeding (B), as it is difficult to reliably identify the species of snake after a bite. Comparative and multivariable analyses to determine factors associated with fasciotomy were performed. RESULTS: There were 72 children; mean age was 7 (±3) years, 59% male. Feet were most commonly affected (n = 27, 38%) followed by legs (n = 18, 25%). Syndromes (according to Blaylock) included PPS (n = 63, 88%), PW (n = 5, 7%), and B (n = 4, 5%). Eighteen patients underwent fasciotomy, and one required above knee amputation. Nine patients received anti-venom. Few patients (15%) received prophylactic beta-lactam antibiotics. Hemoglobin < 11 mg/dL, leukocytosis, INR >1.2, and age-adjusted shock index were associated with fasciotomy. On regression, age-adjusted shock index and hemoglobin concentration < 11 mg/dL, presentation >24 h after snake bite, and INR >1.2 were independently associated with fasciotomy. Model sensitivity was 0.89 and demonstrated good fit. CONCLUSIONS: Patient factors were associated with the fasciotomy. These factors, coupled with clinical examination, may identify those who need early operative intervention. Improving time to treatment and the appropriate administration of anti-venom will minimize the need for surgery. LEVEL OF EVIDENCE: III.

Disease Severity and Cost in Adhesive Small Bowel Obstruction.

BACKGROUND: Adhesive small bowel obstruction (ASBO) severity has been associated with important clinical outcomes. However, the impact of ASBO severity on hospitalization cost is unknown. The American Association for the Surgery of Trauma (AAST) developed an Emergency General Surgery (EGS) disease severity grading system for ASBO. We stratified patients' ASBO severity and captured hospitalization costs hypothesizing that increased disease severity would correlate with greater costs. METHODS: This was a single-center study of hospitalized adult patients with SBO during 2015-2017. Clinical data and estimated total cost (direct + indirect) were abstracted. AAST EGS grades (I-IV) stratified disease severity. Costs were normalized to the median grade I cost. Univariate and multivariate analyses evaluated the relationship between normalized cost and AAST EGS grade, length of hospital and ICU stay, operative time, and Charlson comorbidity index. RESULTS: There were 214 patients; 119 (56%) were female. AAST EGS grades included: I (62%, n = 132), II (23%, n = 49), III (7%, n = 16), and IV (8%, n = 17). Relative to grade I, median normalized cost increased by 1.4-fold for grade II, 1.6-fold for grade III, and 4.3-fold for grade IV disease. No considerable differences in patient comorbidity between grades were observed. Pair-wise comparisons demonstrated that grade I disease cost less than higher grades (corrected p < 0.001). Non-operative management was associated with lower normalized cost compared to operative management (1.1 vs. 4.5, p < 0.0001). In patients who failed non-operative management, normalized cost was increased 7.2-fold. Collectively, the AAST EGS grade correlated well with cost (Spearman's p = 0.7, p < 0.0001). After adjustment for covariates, AAST EGS grade maintained a persistent relationship with cost. CONCLUSION: Increasing ASBO severity is independently associated with greater costs. Efforts to identify and mitigate costs associated with this burdensome disease are warranted. LEVEL OF EVIDENCE: III, economic/decision.

Injury patterns and mechanisms related to refrigerator and freezer utilization in the United States.

INTRODUCTION: Refrigerators and freezers (R/F) are a common household item and injury patterns associated with these appliances are not well characterized. We aimed to characterize the injury patterns, mechanisms, and affected body parts in patients treated in the emergency departments nationally, hypothesizing that injury patterns would differ by age group. METHODS: A retrospective review of the National Electronic Injury Surveillance System for all patients injured using R/F during 2010-2016 was performed. Patient narrative was reviewed for injury mechanism. Comparative and multivariable analyses were performed with effects reported as odds ratios with 95% confidence intervals (CI). RESULTS: During the study period (January 1, 2010-December 31, 2016) there were 6913 R/F related injuries. The study cohort was predominantly male 3734 (55%) and the median [IQR] age was 38 [22-56] years. The annual frequency of R/F related injuries was stable between years. The most common injury mechanism was falling while using R/F (31%) followed up injuries sustained while moving the appliance (25%). Teenaged patients more frequently struck the appliance compared to adults (39% vs 14%, p < 0.001). On regression, pediatric and elderly patients, mechanical fall mechanism, and cranial injury were risk factors independently associated with the need for hospitalization. CONCLUSIONS: Falls in proximity to R/F were the most common injuries sustained and teenagers were more likely to strike/punch the appliance. Injury prevention efforts should support ongoing efforts of fall risk reduction for elderly populations. LEVEL OF EVIDENCE: IV. STUDY TYPE: Retrospective.

Outcomes after splenectomy in children: a 48-year population-based study.

PURPOSE: In children who have undergone splenectomy, there may be impaired immunologic function and an increased risk of infection. We aimed to define the long-term rate of and risk factors for post-splenectomy infection using a population-based cohort study. METHODS: All children (< 18 years) who underwent splenectomy from 1966 to 2011 in Olmsted County, MN were identified using the Rochester Epidemiology Project (REP). Descriptive statistics, Kaplan-Meier estimates, and Cox Proportional hazard ratios were performed to evaluate for risk factors associated with developing infection. RESULTS: Ninety patients underwent splenectomy and 46% were female. Indications included trauma (42%), benign hematologic disease (33%), malignancy (13%), and other (11%). Most were performed open. Vaccination was completed in (72%) for pneumococcal, H. influenza, and meningococcal vectors. Nineteen patients developed infection, and associated factors included non-traumatic, non-malignant disease [HR 4.83 (1.18-19.85)], and performance of multiple surgical procedures [HR 2.80 (1.09-7.21)]. Estimated survival free of infection rates at 15 and 20 years following surgery was both 97%. CONCLUSIONS: After splenectomy in children, most patients do not develop infection. Nearly three-quarters of patients were vaccinated with the lowest rates in patients that underwent a splenectomy for trauma. In patients who received multiple procedures during a splenectomy, the infection risk was higher.

Trauma registry data as a tool for comparison of practice patterns and outcomes between low- and middle-income and high-income healthcare settings.

PURPOSE: There is a lack of data-driven, risk-adjusted mortality estimates for injured children outside of high-income countries (HIC). To inform injury prevention and quality improvement efforts, an upper middle-income country (UMIC) pediatric trauma registry was compared to that of a HIC. METHODS: Clinical data, injury details, and mortality of injured children (< 18 years) hospitalized in two centers (USA and South African (SA)) from 2013 to 2017 were abstracted. Univariate and multivariable analyses evaluated risk of mortality and were expressed as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 2089 patients, SA patients had prolonged transfer times (21.1 vs 3.4 h) and were more likely referred (78.2% vs 53.9%; both p < 0.001). Penetrating injuries were more frequent in SA (23.2% vs 7.4%, p < 0.001); injury severity (9 vs 4) and shock index (0.90 vs 0.80) were greater (both p < 0.001). SA utilized cross-sectional imaging more frequently (66.4% vs 37.3%, p < 0.001). In-hospital mortality was similar (1.9% SA, 1.3% USA, p = 0.31). Upon multivariable analysis, ISS > 25 [210.50 (66.0-671.0)] and penetrating injury [5.5 (1.3-23.3)] were associated with mortality, while institution [1.7 (0.7-4.2)] was not. CONCLUSIONS: Despite transfer time, the centers demonstrated comparable survival rates. Comparison of registry data can alert clinicians to problematic practice patterns, assisting initiatives to improve trauma systems.

Platelet-derived growth factor regulates YAP transcriptional activity via Src family kinase dependent tyrosine phosphorylation.

The Hippo pathway effector YAP is implicated in the pathogenesis of cholangiocarcinoma (CCA). The Hippo pathway relies on signaling cross talk for its regulation. Given the importance of platelet derived growth factor receptor (PDGFR) signaling in CCA biology, our aim was to examine potential YAP regulation by PDGFR. We employed human and mouse CCA specimens and cell lines for these studies. Initially, we confirmed upregulation of PDGFRß and PDGFR ligands in human and mouse CCA specimens and cell lines. YAP, a transcriptional co-activator, was localized to the nucleus in human CCA specimens and a cell line, as well as patient derived xenografts (PDX). PDGFR pharmacologic inhibition led to a redistribution of YAP from the nucleus to cytosol and downregulation of YAP target genes in a human CCA cell line. siRNA silencing of PDGFR-ß similarly downregulated YAP target genes. YAP activation (nuclear localization and target gene expression) was regulated by Src family kinases (SFKs) downstream of PDGFR. SFK activity resulted in phosphorylation of YAP on tyrosine357 (YAPY357 ). The importance of YAPY357 phosphorylation in regulating YAP activation was confirmed utilizing the SB-1 cell line, a mouse cell line expressing YAP S127A precluding canonical serine phosphorylation. PDGFR inhibition decreased cellular abundance of the survival protein Mcl-1, a known YAP target gene, and accordingly increased cell death in CCA cells in vitro and in vivo. These preclinical data demonstrate that a PDGFR-SFK cascade regulates YAP activation via tyrosine phosphorylation in CCA. Inhibiting this cascade may provide a viable therapeutic strategy for this human malignancy.

Fibroblast growth factor receptor inhibition induces loss of matrix MCL1 and necrosis in cholangiocarcinoma.

BACKGROUND & AIMS: Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays. Mitochondrial oxidative metabolism was examined using a XF24 extracellular flux analyser. The efficiency of FGFR inhibition in patient-derived xenografts (PDX) was also assessed. RESULTS: CCA cells expressed two species of MCL1, a full-length form localised to the outer mitochondrial membrane, and an N terminus-truncated species compartmentalised within the mitochondrial matrix. The pan-FGFR inhibitor LY2874455 induced non-apoptotic cell death in the CCA cell lines associated with cellular depletion of both MCL1 species. The cell death was accompanied by failure of mitochondrial oxidative metabolism and was most consistent with necrosis. Enforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. LY2874455 treatment of PDX-bearing mice was associated with tumour cell loss of MCL1 and cell necrosis. CONCLUSIONS: FGFR inhibition induces loss of matrix MCL1, resulting in cell necrosis. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. LAY SUMMARY: Herein, we report that therapeutic inhibition of a cell receptor expressed by bile duct cancer cells resulted in the loss of a critical survival protein termed MCL1. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy using receptor inhibition with immunotherapy.

Measuring Anatomic Severity in Pediatric Appendicitis: Validation of the American Association for the Surgery of Trauma Appendicitis Severity Grade.

OBJECTIVE: To assess whether the American Association for the Surgery of Trauma (AAST) grading system accurately corresponds with appendicitis outcomes in a US pediatric population. STUDY DESIGN: This single-institution retrospective review included patients <18 years of age (n = 331) who underwent appendectomy for acute appendicitis from 2008 to 2012. Demographic, clinical, procedural, and follow-up data (primary outcome was measured as Clavien-Dindo grade of complication severity) were abstracted. AAST grades were generated based on intraoperative findings. Summary, univariate, and multivariable regression analyses were performed to compare AAST grade and outcomes. RESULTS: Overall, 331 patients (46% female) were identified with a median age of 12 (IQR, 8-15) years. Appendectomy was laparoscopic in 90% and open in 10%. AAST grades included: Normal (n = 13, 4%), I (n = 152, 46%), II (n = 90, 27%), III (n = 43, 13%), IV (n = 24 7.3%), and V (n = 9 2.7%). Increased AAST grade was associated with increased Clavien-Dindo severity, P =.001. The overall complication rate was 13.6% and was comprised by superficial surgical site infection (n = 13, 3.9%), organ space infection (n = 15, 4.5%), and readmission (n = 17, 5.1%). Median duration of stay increased with AAST grade (P < .0001). Nominal logistic regression identified the following as predictors of any complication (P < .05): AAST grade and febrile temperature at admission. CONCLUSIONS: The AAST appendicitis grading system is valid in a single-institution pediatric population. Increasing AAST grade incrementally corresponds with patient outcomes including increased risk of complications and severity of complications. Determination of the generalizability of this grading system is required.

Validation of the American Association for the Surgery of Trauma's emergency general surgery breast infection grading system.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) developed emergency general surgery (EGS) grading systems for multiple diseases to standardize classification of disease severity. The grading system for breast infections has not been validated. We aimed to validate the AAST breast infection grading system. METHODS: Multi-institutional retrospective review of all adult patients with a breast infection diagnosis at Mayo Clinic Rochester 1/2015-10/2015 and Pietermaritzburg South African Hospital 1/2010-4/2016 was performed. AAST EGS grades were assigned by two independent reviewers. Inter-rater reliability was measured using the agreement statistic (kappa). Final AAST grade was correlated with patient and treatment factors using Pearson's correlation coefficient. RESULTS: Two hundred twenty-five patients were identified: grade I (n = 152, 67.6%), II (n = 44, 19.6%), III (n = 25, 11.1%), IV (n = 0, 0.0%), and V (n = 4, 1.8%). At Mayo Clinic Rochester, AAST grades ranged from I-III. The kappa was 1.0, demonstrating 100% agreement between reviewers. Within the South African patients, grades included II, III, and V, with a kappa of 0.34, due to issues of the grading system application to this patient population. Treatment received correlated with AAST grade; less severe breast infections (grade I-II) received more oral antibiotics (correlation [-0.23, P = 0.0004]), however, higher AAST grades (III) received more intravenous antibiotics (correlation 0.29, P <0.0001). CONCLUSIONS: The AAST EGS breast infection grading system demonstrates reliability and ease for disease classification, and correlates with required treatment, in patients presenting with low-to-moderate severity infections at an academic medical center; however, it needs further refinement before being applicable to patients with more severe disease presenting for treatment in low-/middle-income countries.

The American Association for the Surgery of Trauma Emergency General Surgery Anatomic Severity Scoring System as a predictor of cost in appendicitis.

BACKGROUND: The World Society for Emergency Surgery determined that for appendicitis managed with appendectomy, there is a paucity of evidence evaluating costs with respect to disease severity. The American Association for the Surgery of Trauma (AAST) disease severity grading system is valid and generalizable for appendicitis. We aimed to evaluate hospitalization costs incurred by patients with increasing disease severity as defined by the AAST. We hypothesized that increasing disease severity would be associated with greater cost. METHODS: Single-institution review of adults (≥ 18 years old) undergoing appendectomy for acute appendicitis during 2010-2016. Demographics, comorbidities, operative details, hospital stay, complications, and institutional cost data were collected. AAST grades were assigned by two independent reviewers based on operative findings. Total cost was ascertained from billing data and normalized to median grade I cost. Non-parametric linear regression was utilized to assess the association of several covariates and cost. RESULTS: Evaluated patients (n = 1187) had a median [interquartile range] age of 37 [26-55] and 45% (n = 542) were female. There were 747 (63%) patients with Grade I disease, 219 (19%) with Grade II, 126 (11%) with Grade III, 50 (4%) with Grade IV, and 45 (4%) with Grade V. The median normalized cost of hospitalization was 1 [0.9-1.2]. Increasing AAST grade was associated with increasing cost (ρ = 0.39; p < 0.0001). Length of stay exhibited the strongest association with cost (ρ = 0.5; p < 0.0001), followed by AAST grade (ρ = 0.39), Clavien-Dindo Index (ρ = 0.37; p < 0.0001), age-adjusted Charlson score (ρ = 0.31; p < 0.0001), and surgical wound classification (ρ = 0.3; p < 0.0001). CONCLUSIONS: Increasing anatomic severity, as defined by AAST grade, is associated with increasing cost of hospitalization and clinical outcomes. The AAST grade compares favorably to other predictors of cost. Future analyses evaluating appendicitis reimbursement stand to benefit from utilization of the AAST grade.

External Validation of a Tube Thoracostomy Complication Classification System.

BACKGROUND: Tube thoracostomy (TT) is a commonly performed procedure which is associated with significant complication rates. Currently, there is no validated taxonomy to classify and compare TT complications across different populations. This study aims to validate such TT complication taxonomy in a cohort of South African trauma patients. METHODS: Post hoc analysis of a prospectively collected trauma database from Pietermaritzburg Metropolitan Trauma Service (PMTS) in South Africa was performed for the period January 2010 to December 2013. Baseline demographics, mechanism of injury and complications were collected and categorized according to published classification protocols. All patients requiring bedside TT were included in the study. Patients who necessitated operatively placed or image-guided TT insertion were excluded. Summary and univariate analyses were performed. RESULTS: A total of 1010 patients underwent TT. The mean age was (±SD) of 26 ± 8 years. Unilateral TTs were inserted in n = 966 (96%) and bilateral in n = 44 (4%). Complications developed in 162 (16%) patients. Penetrating injury was associated with lower complication rate (11%) than blunt injury (26%), p = 0.0001. Higher complication rate was seen in TT placed by interns (17%) compared to TT placed by residents (7%), p = 0.0001. Complications were classified as: insertional (38%), positional (44%), removal (9%), infective/immunologic (9%), and instructional, educational or equipment related (0%). CONCLUSIONS: Despite being developed in the USA, this classification system is robust and was able to comprehensively assign and categorize all the complications of TT in this South African trauma cohort. A universal standardized definition and classification system permits equitable comparisons of complication rates. The use of this classification taxonomy may help develop strategies to improve TT placement techniques and reduce the complications associated with the procedure. LEVEL OF EVIDENCE: V. STUDY TYPE: Single Institution Retrospective review.

Prothrombin Complex Concentrate Reversal of Coagulopathy in Emergency General Surgery Patients.

BACKGROUND: Coagulopathy can delay or complicate surgical diseases that require emergent surgical treatment. Prothrombin complex concentrates (PCC) provide concentrated coagulation factors which may reverse coagulopathy more quickly than plasma (FFP) alone. We aimed to determine the time to operative intervention in coagulopathic emergency general surgery patients receiving either PCC or FFP. We hypothesize that PCC administration more rapidly normalizes coagulopathy and that the time to operation is diminished compared to FFP alone. METHODS: Single institution retrospective review was performed for coagulopathic EGS patients during 2/1/2008 to 8/1/2016. Patients were divided into three groups (1) PCC alone (2) FFP alone and (3) PCC and FFP. The primary outcome was the duration from clinical decision to operate to the time of incision. Summary and univariate analyses were performed. RESULTS: Coagulopathic EGS patients (n = 183) received the following blood products: PCC (n = 20, 11%), FFP alone (n = 119, 65%) and PCC/FFP (n = 44, 24%). The mean (± SD) patient age was 71 ± 13 years; 60% were male. The median (IQR) Charlson comorbidity index was similar in all three groups (PCC = 5(4-6), FFP = 5(4-7), PCC/FFP = 5(4-6), p = 0.33). The mean (± SD) dose of PCC administered was similar in the PCC/FFP group and the PCC alone group (2539 ± 1454 units vs. 3232 ± 1684, p = .09). The mean (±SD) time to incision in the PCC alone group was significantly lower than the FFP alone group (6.0 ± 3.6 vs. 8.8 ± 5.0 h, p = 0.01). The mean time to incision in the PCC + FFP group was also significantly lower than the FFP alone group (7.1 ± 3.6 vs. 8.8 ± 5.0, p = 0.03). The incidence of thromboembolic complications was similar in all three groups. CONCLUSIONS: PCC, alone or in combination with FFP, reduced INR and time to surgery effectively and safely in coagulopathic EGS patients without an apparent increased risk of thromboembolic events, when compared to FFP use alone. LEVEL OF EVIDENCE: IV single institutional retrospective review.

Pediatric Appendicitis Severity in KwaZulu-Natal, South Africa: A Retrospective Cohort Analysis.

BACKGROUND: Acute appendicitis is a common pediatric surgical emergency; however, there are few grading systems to assign disease severity. The American Association for the Surgery of Trauma (AAST) recently developed a grading system for a variety of emergency surgical conditions, including appendicitis. The severity of acute appendicitis in younger patients in KwaZulu-Natal (South Africa) is unknown. We aimed to describe the disease severity in this patient population using the AAST grading system hypothesizing that the AAST grade would correlate with morbidity, management type, and duration of stay. MATERIALS: Single institutional review of patients <18 years old with a final diagnosis of acute appendicitis during 2010-2016 in KwaZulu-Natal, South Africa, was performed. Demographics, physiologic and symptom data, procedural details, postoperative complications, and Clavien-Dindo classification were abstracted. AAST grades were generated based on intraoperative findings. Summary, univariate, and nominal logistic regression analyses were performed to compare AAST grade and outcomes. RESULTS: A total of 401 patients were identified with median [IQR] age of 11 [5-13], 65% male. Appendectomy was performed in all patients; 2.4% laparoscopic, 37.6% limited incision, and 60% midline laparotomy. Complications occurred in 41.6%, most commonly unplanned relaparotomy (22.4%), surgical site infection (8.9%), pneumonia (7.2%), and acute renal failure (2.9%). Complication rate and median length of stay increased with greater AAST grade (all p < 0.001). AAST grade was independently associated with increased risk of complications. CONCLUSION: Pediatric appendicitis is a morbid disease in a developing middle-income country. The AAST grading system is generalizable and accurately corresponds with management strategies as well as key clinical outcomes. LEVEL OF EVIDENCE: Retrospective study, Level IV. STUDY TYPE: Retrospective single institutional study.

Appendicitis: Rural Patient Status is Associated with Increased Duration of Prehospital Symptoms and Worse Outcomes in High- and Low-Middle-Income Countries.

INTRODUCTION: Appendicitis is a significant economic and healthcare burden in low-, middle-, and high-income countries. We aimed to determine whether urban and rural patient status would affect outcomes in appendicitis in a combined population regardless of country of economic status. We hypothesize that patients from rural areas and both high- and low-middle-income countries would have disproportionate outcomes and duration of symptoms compared to their urban counterparts. METHODS: Adults (≥18 years) with appendicitis during 2010-2016 in South Africa and USA were reviewed using multi-institutional data. Baseline demographic, operative details, durations of stay, and complications (Clavien-Dindo index) were collected. AAST grades were assigned by two independent reviewers based on operative findings. Summary, univariate, and multivariable analyses of rural and urban patients in both countries were performed. RESULTS: There were 2602 patients with a median interquartile range [IQR] of 26 [18-40] years; 45% were female. Initial management included McBurney incisions (n = 458, 18%), laparotomy (n = 915, 35%), laparoscopic appendectomy (n = 1185, 45%), and laparoscopy converted to laparotomy (n = 44, 2%). Comparing rural versus urban patient status, there were increased overall median [IQR] AAST grades (3 [1-5] vs. 2 [1-3], p = 0.001), prehospital duration of symptoms (2 [1-5] vs. 2 [1-3], p = 0.001), complications (44.3 vs. 23%, p = 0.001), and need for temporary abdominal closure (20.3 vs. 6.9%, p = 0.001). CONCLUSION: Despite socioeconomic status and country of origin, patients from more rural environments demonstrate poorer outcomes notwithstanding significant differences in overall disease severity. The AAST grading system may serve a potential benchmark to recognize areas with disparate disease burdens. This information could be used for strategic improvements for surgeon placement and availability.