Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation.

BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 â€‹h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â€‹+ â€‹renal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â€‹% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

Survival following liver transplantation: A population-based nested case-control study.

BACKGROUND: Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study. METHODS: Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival. RESULTS: 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI â€‹= â€‹2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios. CONCLUSIONS: Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery.

Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Ventricular Remodeling Following Metabolic and Bariatric Surgery Decreases Need for Heart Transplantation: A Predictive Model.

PURPOSE: For patients with obesity and congestive heart failure (CHF) who require heart transplantation (HT), aggressive weight loss has been associated with ventricular remodeling, or subclinical alterations in left and right ventricular structure that affect systolic function. Many have suggested offering metabolic and bariatric surgery (MBS) for these patients. As such, we evaluated the role of MBS in HT for patients with obesity and CHF using predictive modelling techniques. MATERIALS AND METHODS: Markov decision analysis was performed to simulate the life expectancy of 30,000 patients with concomitant obesity, CHF, and 30% ejection fraction (EF) who were deemed ineligible to be waitlisted for HT unless they achieved a BMI < 35 kg/m2. Life expectancy following diet and exercise (DE), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: RYGB patients had lower rates of HT and received HT quicker when needed. Base case patients who underwent RYGB gained 2.2 additional mean years survival compared with patients who underwent SG and 10.3 additional mean years survival compared with DE. SG patients gained 6.2 mean years of life compared with DE. CONCLUSION: In this simulation of 30,000 patients with obesity, CHF, and reduced EF, MBS was associated with improved survival by not only decreasing the need for transplantation due to improvements in EF, but also increasing access to HT when needed due to lower average BMI.

Early predictors of prolonged intensive care utilization following liver transplantation.

INTRODUCTION: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU. METHODS: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU. RESULTS: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P â€‹< â€‹0.001) and low tPA TEG LY30 (OR 3.7, P â€‹= â€‹0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p â€‹< â€‹0.001) was observed patients who had these risk factors for pICU. CONCLUSION: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT.

The in-vitro influence of urea concentration on thromboelastrography in patients with and without end stage renal disease.

BACKGROUND: End stage renal disease (ESRD) is associated with platelet dysfunction but also thromboembolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is unclear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. METHODS: We collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. RESULTS: Blood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r = -0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r = -0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. CONCLUSIONS: ESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed.

Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: Analysis of the US Multicenter HCC Transplant Consortium.

HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

Uncontrolled donation after cardiac death kidney transplantation: Opportunity to expand the donor pool?

BACKGROUND: Compared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation. METHODS: From January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients. RESULTS: Rates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P < 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P < 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32). CONCLUSION: Although initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool.

Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.

Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation.

Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.

Choledochoduodenostomy continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Debate continues as to whether choledochoduodenostomy (CDD) can be used instead of Roux-en-Y choledochojejunostomy (CDJ) when duct-to-duct (DTD) is not an option. We hypothesized that CDD and CDJ had similar rates of complications. All deceased-donor liver transplantations from September 2011 to March 2020 were categorized by biliary reconstruction. Primary outcomes were bleeding, bile leak, anastomotic stricture, and cholangitis. Of the 1,086 patients, 812 (74.8%) received a DTD; 225 (20.7%) received a CDD; and 49 (4.5%) received a CDJ. Cholangitis was significantly higher in CDJ compared to DTD and CDD (26.5% vs 6% vs 13.8%, p < 0.0001). When controlling for significant confounders, CDJ had 10.2 higher odds of cholangitis (95% CI 4.4-23.2) compared to DTD, and 3.3 higher odds compared to CDD (95% CI 1.4-7.8). When compared to DTD, CDJ and CDD had significantly lower odds of stricture. CDD continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

Low viscoelastic clot strength, platelet transfusions, and graft dysfunction are associated with persistent postoperative ascites following liver transplantation.

INTRODUCTION: High output, persistent ascites (PA) is a common complication following liver transplant (LT). Recent work has identified that platelets help maintain endothelial integrity and can decrease leakage in pathological states. We sought to assess the association of PA following LT with platelet count and platelet function. METHODS: Clot strength (MA) is a measure of platelet function and was quantified using thrombelastography (TEG). Total drain output following surgery was recorded in 24-h intervals during the same time frame as TEG. PA was considered >1 L on POD7, as that much output prohibits drain removal. RESULTS: 105 LT recipients with moderate or high volume preoperative ascites were prospectively enrolled. PA occurred in 28%. Platelet transfusions before and after surgery were associated with PA, in addition to POD5 TEG MA and POD5 MELD score. Patients with PA had a longer hospital length of stay and an increased rate of intraabdominal infections. CONCLUSION: Persistent ascites following liver transplant is relatively common and associated with platelet transfusions, low clot strength, and graft dysfunction.

Fibrinolysis resistance after liver transplant as a predictor of early infection.

BACKGROUND: Infection is a leading cause of morbidity in liver transplant (LT). Considering that the fibrinolytic system is altered in sepsis, we investigated the relationship between fibrinolysis resistance (FR) and post-transplant infection. METHODS: Fibrinolysis was quantified using thrombelastography (TEG) with the addition of tPA to quantify FR. FR was defined as LY30 = 0% and stratified as transient if present on POD1 or POD5 (tFR), persistent (pFR) if present on both, or no FR (nFR) if absent. RESULTS: 180 LT recipients were prospectively enrolled. 52 (29%) recipients developed infection. 72 had tFR; 37 had pFR; and 71 had nFR. Recipients with pFR had significantly greater incidence of infections (51% vs. 26% tFR vs. 20% nFR, p = 0.002). pFR was independently associated with increased odds of post-transplant infection (adjusted OR 3.39, p = 0.009). CONCLUSIONS: Persistent fibrinolysis resistance is associated with increased risk of post-transplant infection.

The vexing triad of obesity, alcohol, and coagulopathy predicts the need for multiple operations in liver transplantation.

INTRODUCTION: One in four liver transplants (LT) require return to the operating room(R-OR) within 48 h of surgery. We hypothesize that donor, recipient, and intraoperative factors will predict R-OR. METHODS: LT recipients were enrolled in an observational study to measure coagulation with thrombelastography (TEG) were assessed with transplant recipient and donor variables for risk of R-OR. RESULTS: 160 recipients with a median age of 55 years and a MELD-Na of 22 were analyzed. R-OR occurred in 22%. Recipient BMI (p = 0.006), donor heavy alcohol use (p = 0.017), TEG MA (p = 0.013) during the anhepatic phase of surgery, TEG MA at anhepatic and 30-min after reperfusion (p < 0.05), and red blood cell transfusions (p < 0.001) were associated with R-OR. CONCLUSION: The vexing triad of recipient obesity, heavy donor alcohol use, and low TEG MA were associated with a high rate of R-OR. Strategies to reduce this sub-optimal combination of risk factors could reduce the frequency of unplanned re-operations.

Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non-Hepatocellular Carcinoma Factors.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: An intraoperative diagnostic tool with real time assessment of graft function.

INTRODUCTION: During the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). METHODS: Assessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). RESULTS: Seventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30-5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). CONCLUSION: LT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation.

BACKGROUND: An NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. METHODS: TEGs were performed and coagulopathy scores (1, normal bleeding - 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. RESULT: Transfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays CONCLUSION: The combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation.

BACKGROUND: End stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. METHODS: Kidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining "good" graft function. Follow up was done at 6, 12, and 24 months. RESULTS: Percent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. CONCLUSIONS: Post-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Reverse epidemiology and the obesity paradox for patients with chronic kidney disease: a Markov decision model.

BACKGROUND: Obesity has been associated with both increased progression of chronic kidney disease (CKD) as well as with a paradoxical improvement in survival among end-stage renal disease patients undergoing hemodialysis. As such, the optimal weight management strategy for obese CKD patients remains unclear. OBJECTIVE: To estimate the outcomes of obese, CKD stage 3b patients after 3 weight loss interventions, including medical weight management, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), were followed to determine which strategy optimizes long-term survival. SETTING: University hospital, Aurora, Colorado. METHODS: A decision analytic Markov state transition model was created to simulate the life of 30,000 obese patients with CKD stage 3b, as they progressed to end-stage renal disease, transplantation, and death. Life expectancy after conservative medical weight management, RYGB, and SG were estimated. Base case patients were defined as being 50 years old and having a preintervention BMI of 40 kg/m2. Sensitivity analysis of initial BMI was performed. All Markov parameters were extracted from literature review. RESULTS: RYGB and SG were associated with improved survival for patients with preintervention body mass index of >38 kg/m2. Compared with conservative weight management, base case patients who underwent RYGB gained 10.6 months of life, and gained 8.3 months of life after SG. CONCLUSIONS: Balancing progression of CKD with improved survival on end-stage renal disease for obese patients requires selective use of weight management strategies. RYGB and SG improved survival for CKD patients with Class II and III obesity, but not for patients with Class I obesity. As such, aggressive weight loss interventions should be reserved for patients with Class II and III obesity, while more conservative methods should be offered to those with Class I obesity.