INHIBITORS OF INORGANIC POLYPHOSPHATE AND NUCLEIC ACIDS ATTENUATE IN VITRO THROMBIN GENERATION IN PLASMA FROM TRAUMA PATIENTS.

ABSTRACT: Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8). Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 µg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, P < 0.05 significant. Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], P < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], P = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], P = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], P < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], P < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all P < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, P < 0.001). Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.

A murine multiple-injury model for the study of thromboinflammation.

INTRODUCTION: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation. METHODS: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test. RESULTS: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009). CONCLUSION: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury.

Optimizing resource utilization: palliative care consultations in critically ill pediatric trauma patients.

Objectives: The American College of Surgeons Trauma Quality Improvement Program (TQIP) and Committee on Trauma released a best practice guideline for palliative care in trauma patients in 2017. Utilization of pediatric palliative care services for pediatric trauma patients has not been studied. We sought to identify patients who received the consultation and develop criteria for patients who would benefit from these resources at our institution. Methods: The institutional pediatric trauma registry was queried to identify all admissions age 0-17 years old to the pediatric intensive care unit (PICU) or trauma ICU (TICU) from 2014 to 2021. Demographic and clinical features were obtained from the registry. Electronic medical records were reviewed to identify and review consultations to the ComPASS team. A clinical practice guideline (CPG) for palliative care consultations was developed based on the TQIP guideline and applied retrospectively to patients admitted 2014-2021. The CPG was then prospectively applied to patients admitted from March through November 2022. Results: A total of 399 patients were admitted to the PICU/TICU. There were 30 (7.5%) deaths, 20 (66.7%) within 24 hours of admission. Palliative care consultations were obtained in 21 (5.3%). Of these, 10 (47.6%) patients were infants/toddlers

Utility of computed tomography reconstructed thoracolumbar spinal imaging in blunt trauma.

OBJECTIVES: Fractures of the thoracolumbar (TL) spine are common and may cause neurologic damage, pain, and reduced quality of life. Computed tomography (CT) TL reconstructions from CT chest, abdomen, and pelvis (CAP) are used to identify TL fractures; however, their benefit over CAP imaging is unclear. We hypothesized that reformatted TL images do not identify additional clinically significant injuries or change outcomes. METHODS: Retrospective data were collected 2016 to 2021 from trauma patients at a level 1 trauma center. All patients 18 years or older with TL fractures on CT CAP with/without CT TL reformats were included. Clinically significant TL fractures were defined as requiring operative fixation, brace, or spinal rehabilitation. A binary classification model was created to assess the diagnostic utility of CTCAP compared with CTTL in predicting clinically significant fractures in patients who underwent CT CAP/TL. RESULTS: There were 828 patients with TL fractures, 634 had both CT CAP/CT TL (CAPTL) and 194 CTCAP only (CAP). There were 134 clinically significant TL fractures (16%) (14 [7.2%] CT CAP vs. 120 [18.9%] CT CAPTL, p < 0.001). There were no differences among unstable fractures, fractures on magnetic resonance imaging (MRI) only, mortality, or neurologic deficits on discharge between CAPTL and CAP ( p > 0.05). Among clinically significant fractures, CAPTL was not associated with increased MRI utilization, surgery, spinal brace, or spinal cord rehabilitation ( p > 0.05). Among clinically insignificant fractures, CAPTL was associated with increased MRIs, length of stay (LOS), and intensive care unit LOS ( p < 0.05). CAPTL was also an independent predictor of increased MRIs (odds ratio, 5.79; 95% confidence interval, 2.29-14.65; p < 0.01) and spine consultation (odds ratio, 2.39; 95% confidence interval, 1.64-3.67; p < 0.01). More CT CAP/TL were performed in those with clinically significant fractures; however, CTCAP was equivalent to CTTL for detection of fractures ( p > 0.05). CONCLUSION: CTCAP alone is sufficient to identify clinically significant TL fractures. While the addition of TL reformatted imaging minimizes missed injuries, it is associated with increased hospital LOS and MRI resource utilization. Therefore, careful consideration is needed for appropriate CT TL patient selection. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Plasma thrombin generation kinetics vary by injury pattern and resuscitation characteristics in pediatric and young adult trauma patients.

BACKGROUND: Thrombin generation kinetics are not well studied in children. This study aimed to assess how thrombin generation kinetics vary in pediatric and young adult (YA) trauma patients by clinical characteristics and injury pattern. METHODS: Prospective cohort study where plasma samples were obtained from pediatric (ages 0-17 years) and YA (ages 18-21 years) trauma patients upon emergency department arrival. Thrombin generation (calibrated automated thrombogram [CAT]) was quantified as lag time (LT, minutes), peak height (PH, nM), time to peak (ttPeak, minutes), and endogenous thrombin potential (ETP, nM × minute). Results are expressed as median and quartiles [Q1, Q3] and compared using Wilcoxon rank sum testing with p < 0.05 considered significant. RESULTS: We enrolled 47 pediatric (median age, 15 [14, 17] years, 78% male, 87% blunt, median Injury Severity Score, 12) and 49 YA (median age 20 [18, 21] years, 67% male, 84% blunt, median Injury Severity Score, 12) patients. Pediatric and YA patients had similar rates of operative intervention (51% vs. 57%), transfusion (25% vs. 20%), and traumatic brain injury (TBI) (53% vs. 49%). Pediatric patients who required an operation had accelerated initiation of thrombin generation, with shorter LT than those who did not (2.58 [2.33, 2.67]; 2.92 [2.54, 3.00], p = 0.034). Shorter LT (2.41 [2.22, 2.67]; 2.67 [2.53, 3.00]) and ttPeak (4.50 [4.23, 4.73]; 5.22 [4.69, 5.75], both p < 0.01) were noted in pediatric patients who required transfusion as compared with those who did not. The YA patients requiring transfusion had shorter LT (2.33 [2.19, 2.74]; 2.83 [2.67, 3.27]) and ttPeak (4.48 [4.33, 5.65]; 5.33 [4.85, 6.28] both p < 0.04) than those who were not transfused. Young adults with TBI had greater ETP than those without (1509 [1356, 1671]; 1284 [1154, 1471], p = 0.032). CONCLUSION: Thrombin generation kinetics in pediatric trauma patients prior to intervention vary with need for operation and transfusion, while thrombin generation kinetics in young adult patients are influenced by TBI and need for operation or transfusion. This is a promising tool for assessing coagulopathy in young trauma patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

Quantification of von Willebrand factor and ADAMTS-13 after traumatic injury: a pilot study.

BACKGROUND: Von Willebrand factor (VWF) is an acute phase reactant synthesized in the megakaryocytes and endothelial cells. VWF forms ultra-large multimers (ULVWF) which are cleaved by the metalloprotease ADAMTS-13, preventing spontaneous VWF-platelet interaction. After trauma, ULVWF is released into circulation as part of the acute phase reaction. We hypothesized that trauma patients would have increased levels of VWF and decreased levels of ADAMTS-13 and that these patients would have accelerated thrombin generation. METHODS: We assessed plasma concentrations of VWF antigen and ADAMTS-13 antigen, the Rapid Enzyme Assays for Autoimmune Diseases (REAADS) activity of VWF, which measure exposure of the platelet-binding A1 domain, and thrombin generation kinetics in 50 samples from 30 trauma patients and an additional 21 samples from volunteers. Samples were analyzed at 0 to 2 hours and at 6 hours from the time of injury. Data are presented as median (IQR) and Kruskal-Wallis test was performed between trauma patients and volunteers at both time points. RESULTS: REAADS activity was greater in trauma patients than volunteers both at 0 to 2 hours (190.0 (132.0-264.0) vs. 92.0 (71.0-114.0), p<0.002) and at 6 hours (167.5 (108.0-312.5.0) vs. 92.0 (71.0-114.0), p<0.001). ADAMTS-13 antigen levels were also decreased in trauma patients both at 0 to 2 hours (0.84 (0.51-0.94) vs. 1.00 (0.89-1.09), p=0.010) and at 6 hours (0.653 (0.531-0.821) vs. 1.00 (0.89-1.09), p<0.001). Trauma patients had accelerated thrombin generation kinetics, with greater peak height and shorter time to peak than healthy volunteers at both time points. DISCUSSION: Trauma patients have increased exposure of the VWF A1 domain and decreased levels of ADAMTS-13 compared with healthy volunteers. This suggests that the VWF burst after trauma may exceed the proteolytic capacity of ADAMTS-13, allowing circulating ULVWF multimers to bind platelets, potentially contributing to trauma-induced coagulopathy. LEVEL OF EVIDENCE: Prospective case cohort study.

Hepatic Surgical Stress Promotes Systemic Immunothrombosis That Results in Distant Organ Injury.

Innate immunity can initiate platelet activation during the development of thrombosis through a process, termed immunothrombosis. Neutrophils form neutrophil extracellular traps (NETs) that have been shown to interact directly with platelets and play pro-coagulant roles in a variety of infectious and sterile inflammatory settings. Hepatic surgical stress initiated by ischemia/reperfusion (I/R) injury has wide systemic consequences on distant organs. However, the mechanisms of this remote injury phenomenon are not well-understood. Here, we sought to determine the role of NETs in causing systemic immunothrombosis and distant organ injury following a local inflammatory insult with liver I/R. Postoperative thromboelastographic revealed that the speed of clot formation (alpha-angle) was significantly increased whereas time to clot formation (R-time) were decreased by in patients undergoing liver resection, indicating a hypercoagulable state after surgery. In mice subjected to liver I/R, circulating platelet activation and platelet-neutrophil aggregates were significantly increased. Injured distant organs such as the lung and kidney displayed NETs and platelet-rich micro-thrombi in the microvasculature following liver I/R. The immune-thrombi and organ damage were dramatically decreased when NETs were inhibited by DNase treatment. Depletion of Tlr4 on platelets limited NET-induced activation of platelets but had no effect on NET formation. Furthermore, platelet-specific TLR4 KO mice had significantly reduced distant organ injury with decreased circulating platelet activation, platelet-neutrophil aggregates following liver I/R in comparison to their control counterparts. These data establish that after an acute local inflammatory process, NET-activated platelets can lead to a systemic pro-coagulant state with resultant remote organ injury by immunothrombosis.

Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive, inflammatory form of fatty liver disease. It is the most rapidly rising risk factor for the development of hepatocellular carcinoma (HCC), which can arise in NASH with or without cirrhosis. The inflammatory signals promoting the progression of NASH to HCC remain largely unknown. The propensity of neutrophils to expel decondensed chromatin embedded with inflammatory proteins, known as neutrophil extracellular traps (NETs), has been shown to be important in chronic inflammatory conditions and in cancer progression. In this study, we asked whether NET formation occurs in NASH and contributes to the progression of HCC. We found elevated levels of a NET marker in serum of patients with NASH. In livers from STAM mice (NASH induced by neonatal streptozotocin and high-fat diet), early neutrophil infiltration and NET formation were seen, followed by an influx of monocyte-derived macrophages, production of inflammatory cytokines, and progression of HCC. Inhibiting NET formation, through treatment with deoxyribonuclease (DNase) or using mice knocked out for peptidyl arginine deaminase type IV (PAD4-/- ), did not affect the development of a fatty liver but altered the consequent pattern of liver inflammation, which ultimately resulted in decreased tumor growth. Mechanistically, we found that commonly elevated free fatty acids stimulate NET formation in vitro. CONCLUSION: Our findings implicate NETs in the protumorigenic inflammatory environment in NASH, suggesting that their elimination may reduce the progression of liver cancer in NASH. (Hepatology 2018).

Dissemination of Minimally Invasive Liver Resection for Primary Malignancy: Reevaluating Effectiveness.

BACKGROUND: Experiences at specialized hepatobiliary centers have demonstrated efficacy of minimally invasive liver resection, but concerns exist regarding whether these procedures would remain effective once disseminated to a broad range of clinical practices. We sought to present the first comparison of MILR and open liver resection (OLR) for primary liver malignancy from a nationally representative cancer registry. METHODS: Cases of liver and intrahepatic bile duct cancer were identified from the National Cancer Data Base Participant Use File. Mixed effects logistic regression and stratified Cox proportional hazards regression were used for analysis. A propensity score matched cohort was used as an alternative form of analysis to evaluate the robustness of results. RESULTS: A total of 3236 cases were analyzed from 2010 to 2011 with 2581 OLR (80%) and 655 MILR (20%). Of the variation in patient selection for MILR 28.5% was related to treatment at a specific treatment center; however, the proportion of MILR was similar among low-, medium-, and high-volume centers. Overall 90-day mortality was lower at high-volume centers (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.40-0.85) compared with low-volume centers. MILR was similar to OLR in both 90-day mortality and overall survival (OR 0.9; 95% CI 0.62-1.10) and hazard ratio [HR] 0.88 (95% CI 0.72-1.07), regardless of treatment center volume. CONCLUSIONS: MILR for primary liver malignancy is used across a variety of practice settings, with similar outcomes to OLR. While volume is associated with short-term outcomes of liver resection as a whole, this relationship is not explained by adoption of MILR at low-volume centers.

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response.

BACKGROUND: Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined. METHODS: Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon-γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15Rα and MHC class I (MHC-I) were analysed by western blot. Exosomes along with CpG adjuvant were injected into tumour models to assess the antitumour effects. Tumours were harvested for immunofluorescence staining. Splenocytes from tumour-bearing mice were co-cultured with tumour cells. The IFNγ-positive and granzyme B-positive CD8α+ splenocyte cells were quantified by flow cytometry. RESULTS: The IRF-1-Exo or IFN-Exo displayed increased IL-15Rα and MHC-I expression. Injection of IRF-1-Exo or IFN-Exo combined with CpG had improved antitumour effects in mice. This effect may be a result of increased infiltration of tumours by CD4+ and CD8α+ T cells. Antibody-mediated depletion of CD4+ or CD8+ T cells abrogated the antitumour effects. Splenocytes isolated from CpG+IRF-1-Exo-injected Hepa 1-6 tumour mice had increased IFNγ-positive and granzyme B-positive CD8+ cells after co-culturing with Hepa 1-6 cells as compared with MC38 cells. CONCLUSIONS: The IRF-1 priming of TEXs enhances antitumour immune response.

Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion.

INTRODUCTION: Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. METHODS: Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. RESULTS: After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines. CONCLUSIONS: DRPs significantly attenuated metastatic tumor development and growth. DRPs warrant further investigation as a potential treatment for liver I/R injury in the clinical setting to improve cancer-specific outcomes.

Minimally Invasive Resection of Colorectal Cancer Liver Metastases Leads to an Earlier Initiation of Chemotherapy Compared to Open Surgery.

INTRODUCTION: Previous studies have shown benefit not only from postoperative chemotherapy but also from a short interval to initiation of treatment after resection of primary colorectal cancer. The aim of this study was to determine difference in timing to postoperative chemotherapy for minimally invasive resection (MIR) vs. open resection (OR) of colorectal cancer liver metastases (CRCLM). METHODS: This is a retrospective review of 1:1 matched patients undergoing MIR (n = 66) and OR (n = 66) for CRCLM at a single institution. RESULTS: Patients undergoing MIR of CRCLM had significantly shorter length of hospital stay, fewer major complications, and shorter interval to postoperative chemotherapy (median 42 vs. 63 days, p < 0.001). Univariable analysis showed that surgical approach, postoperative complications, blood loss, number of lesions, and length of stay were associated with timing to chemotherapy. On multivariable analysis, surgical approach was still associated with timing to chemotherapy, and postoperative complications resulted in a delay of chemotherapy among patients who underwent OR but not among those who underwent MIR. In addition, worse disease-free survival was seen among patients who received postoperative chemotherapy more than 60 days after surgery. CONCLUSION: By modifying the deleterious effects of postoperative complications on timing of postoperative chemotherapy, patients undergoing MIR for CRCLM are treated with chemotherapy sooner after surgery compared to those undergoing OR.

Prior inpatient admission increases the risk of post-operative infection in hepatobiliary and pancreatic surgery.

BACKGROUND: Hepatobiliary and pancreatic (HPB) operations have a high incidence of post-operative nosocomial infections. The aim of the present study was to determine whether hospitalization up to 1 year before HPB surgery is associated with an increased risk of post-operative infection, surgical-site infection (SSI) and infection resistant to surgical chemoprophylaxis. METHODS: A retrospective cohort study of patients undergoing HPB surgeries between January 2008 and June 2013 was conducted. A multivariable logistic regression model was used for controlling for potential confounders to determine the association between pre-operative admission and post-operative infection. RESULTS: Of the 1384 patients who met eligibility criteria, 127 (9.18%) experienced a post-operative infection. Pre-operative hospitalization was independently associated with an increased risk of a post-operative infection [adjusted odds ratio (aOR): 1.61, 95% confidence interval [CI]: 1.06-2.46] and SSI (aOR: 1.79, 95% CI: 1.07-2.97). Pre-operative hospitalization was also associated with an increased risk of post-operative infections resistant to standard pre-operative antibiotics (OR: 2.64, 95% CI: 1.06-6.59) and an increased risk of resistant SSIs (OR: 3.99, 95% CI: 1.25-12.73). DISCUSSION: Pre-operative hospitalization is associated with an increased incidence of post-operative infections, often with organisms that are resistant to surgical chemoprophylaxis. Patients hospitalized up to 1 year before HPB surgery may benefit from extended spectrum chemoprophylaxis.

Intraoperative fluid administration is associated with perioperative outcomes in pancreaticoduodenectomy: a single center retrospective analysis.

BACKGROUND: Recent studies on perioperative fluid administration in patients undergoing major abdominal surgery have suggested that increased fluid loads are associated with worse perioperative outcomes. However, results of retrospective analyses of the relationship between intraoperative fluid (IOF) administration and perioperative outcomes in patients undergoing pancreaticoduodenectomy (PD) are conflicted. We sought to investigate this relationship in patients undergoing PD at our academic center. METHODS: A retrospective analysis of 124 patients undergoing PD from 2007 to 2012 was performed. IOF administration rate (ml/kg/hr) was correlated with perioperative outcomes. Outcomes were also stratified by preoperative serum albumin level. RESULTS: Regression analyses were performed comparing independent perioperative variables, including IOF rate, to four outcomes variables: length of stay, severity of complications, number of complications per patient, and 30-day mortality. Both univariate and multivariate regression analyses showed IOF rate correlated with one or more perioperative outcomes. Patients with an albumin ≤ 3.0 g/dl who received more than the median IOF rate experienced more severe complications, while patients with an albumin >3.0 g/dl did not. CONCLUSION: Increased IOF administration is associated with worse perioperative outcomes in patients undergoing PD. Patients with low preoperative serum albumin levels (≤ 3.0 g/dl) may be a group particularly sensitive to volume overload.

Safety and efficacy of LigaSure usage in pancreaticoduodenectomy.

BACKGROUND: Over recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques. METHODS: One hundred and forty-eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri-operative outcomes were compared. RESULTS: Vascular intra-operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra-operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73. CONCLUSION: LigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD.