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Background The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) which carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. Methods To assess the long-term survival and economic benefits of allocation policy reforms, a decision analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. Results For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 vs 12.6 years), superior quality-adjusted life years (12.6 vs 9.8), and lower costs ($529 512 vs $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 months for a CMV D- kidney. Conclusions Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.

BACKGROUND Obesity, defined as a high body mass index (hBMI) of 30 kg/m or greater, is a growing epidemic worldwide and is associated with multiple comorbidities. High BMI individuals account for an increasing portion of potential liver donors. Here we evaluate trends in the utilization and outcomes of hBMI donors on a national and regional level and the potential role of liver biopsy in donor evaluation. METHODS United Network for Organ Sharing Standard Transplant Analysis and Research database was evaluated for deceased donor liver transplants between 2006 and 2016 across 11 Organ Procurement and Transplantation Network regions. High BMI donors were compared with lower BMI counterparts and evaluated for biopsy rates, utilization rates and allograft outcomes. Univariate and multivariable analyses were performed. RESULTS Seventy-seven thousand fifty potential donors were identified and 60 200 transplants were evaluated. Utilization rates for hBMI donors were 66.1% versus 78.1% for lower BMI donors (P < 0.001). Pretransplant biopsy was performed more frequently in hBMI donors (52.1% vs 33.1%, P < 0.001) and macrosteatosis of 30% or greater was identified more often (21.1% vs 12.2%, P < 0.001). Biopsy performance increased utilization rate of hBMI donors in 7 of 11 Organ Procurement and Transplantation Network regions. region 6 showed the highest rate of biopsy performance, high rate of hBMI donor utilization, and highest 5-year estimated graft survival rates of all regions. CONCLUSIONS High BMI donors have not previously been associated with worse graft survival in multivariable analyses; however, they are used much less frequently. Liver biopsy may increase the utilization rate of hBMI donors and improve donor selection. Further evaluation of regions with high rates of utilization and good outcomes is warranted.

Historically, strategies to reduce acute rejection and improve graft survival in kidney transplant recipients included blood transfusions (BTs) before transplantation. While advents in recipient immunosuppression strategies have replaced this practice, the impact of BTs in the organ donor on recipient graft outcomes has not been evaluated. We hypothesize that BTs in organ donors after neurologic determination of death (DNDDs) translate into improved recipient renal graft outcomes, as measured by a decrease in delayed graft function (DGF).Donor demographics, critical care end points, the use of BTs, and graft outcome data were prospectively collected on DNDDs from March 2012 to October 2013 in the United Network for Organ Sharing Region 5 Donor Management Database. Propensity analysis determined each DNDD's probability of receiving packed red blood cells based on demographic and critical care data as well as provider bias. The primary outcome measure was the rate of DGF (dialysis in the first week after transplantation) in different donor BT groups as follows: no BT, any BT, 1 to 5, 6 to 10, or greater than 10 packed red blood cell units. Regression models determined the relationship between donor BTs and recipient DGF after accounting for known predictors of DGF as well as the propensity to receive a BT.Data were complete for 1,884 renal grafts from 1,006 DNDDs; 52% received any BT, 32% received 1 to 5 U, 11% received 6 to 10, and 9% received greater than 10 U of blood. Grafts from transfused donors had a lower rate of DGF compared with those of the nontransfused donors (26% vs. 34%, p0.001). After adjusting for known confounders, grafts from donors with any BT had a lower odds of DGF (odds ratio, 0.76; p = 0.030), and this effect was greatest in those with greater than 10 U transfused.Any BT in a DNDD was associated with a 23% decrease in the odds of recipients developing DGF, and this effect was more pronounced as the number of BTs increased.Therapeutic study, level III; epidemiologic/prognostic study, level II.

The Share 35 policy for liver allocation prioritizes patients with Model for End-Stage Liver Disease (MELD) scores ≥ 35 for regional sharing of liver allografts. To better assess donor-recipient interactions and inform expectations, this study identified factors affecting graft survival independent of MELD score and derived a risk index for transplantation in the MELD ≥ 35 population.The United Network for Organ Sharing (UNOS) STAR database was evaluated for deceased donor liver transplants with recipients' MELD ≥ 35, between January 2006 and June 2016. Data were randomly split into test and validate cohorts. Four individual models of graft survival spanning 90 days to 5 years were evaluated with univariate and multivariate Cox proportional hazards analyses against donor- and recipient-specific characteristics. Significant factors were compiled to generate the Liver Transplant Survival Index (LTSI-35), and survival analyses were performed.Five risk groups (very low, low, moderate, high, and severe) were identified, with 1-year graft survival rates of 90.8% ± 0.2%, 89.3% ± 0.3%, 85.0% ± 0.3%, 79.8% ± 0.3%, and 70.3% ± 0.4% (p0.001 across groups), respectively. The greatest risk of graft loss was associated with donation after circulatory death (DCD) donors (1-year hazard ratio [HR] = 1.61 [95% CI 1.26 to 2.05], p = 0.001), recipients' requiring ventilator support (HR 1.32 [95% CI 1.17 to 1.51], p0.001), and recipient portal vein thrombosis (HR 1.21 [95% CI 1.03 to 1.42], p = 0.003). Subgroup analysis revealed increased risk of graft loss with graft macrosteatosis ≥ 30% on pre-donation biopsy at 90 days (HR 1.64 [1.33 to 1.99], p0.001).The LTSI-35 identifies risk factors for graft loss in a high-MELD population which, when combined, may portend worse outcomes. The LTSI-35 may be used to influence donor selection, organ allocation, and to inform expectations for allograft survival.

Because of ongoing advances in transplant immunology and surgical techniques, organ transplantation has become the standard of care for many patients with end-stage organ failure.1 The success of transplantation and the growing demand for organs are exemplified by a perpetually burgeoning waiting list. Currently, 103,446 people are on this waiting list, and one new patient is added every 10 minutes.2 Unfortunately, the growing demand for organ transplantation has not had a corresponding growth in organ availability. In 2008, only 27,963 transplants were performed, which is close to the 27,029 transplants performed in 2004.2 More than 7,000 patients die per year while awaiting transplantation related to the lack of organs and lack of growth in transplant operations.3 This ongoing shortage of transplantable organs continues to be a national crisis. Despite aggressive efforts such as the Organ Donation Breakthrough Collaborative and the Organ Transplantation Breakthrough Collaborative,4 organ shortages continue to persist. The Institute of Medicine, in a 2006 report, offered a number of recommendations that could impact organ donation.5 Educating the public about organ donation and encouraging registration through donor cards, drivers' license, and donor registries were some of the actions recommended to help address the shortage of transplantable organs. In July 2006, California's Online Organ and Tissue Registry, Donate Life California, joined forces with the Department of Motor Vehicles (DMV) in an effort to compel Californians to share their organ donation wishes by registering online.6 With this alliance, an individual could sign up with the registry when applying for a driver license or identity card through the California DMV or by signing up online. This campaign involved public and media education regarding the organ donor shortage. We set out to analyze whether this campaign had a beneficial effect on organ donor demographics in a catchment area covered by one of the California's organ procurement organizations (OPO). If improvement in organ donor demographics is documented, then similar campaigns can be replicated throughout the United States to improve the growing organ donor shortage.

BACKGROUND Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. METHODS Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. RESULTS Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 +/- 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 +/- 1 with one early death and 2.2 +/- 1.2 with two early deaths, respectively, analysis of variance p < 0.003). CONCLUSION The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

Background: Deep venous thromboses (DVT) continue to cause significant morbidity in critically ill patients. Standard prophylaxis for high risk patients includes twice-daily dosing with 30 mg enoxaparin. Despite prophylaxis, DVT rates still exceed 10% to 15%. Anti-Xa levels are used to measure the activity of enoxaparin and 12-hour trough levels ≤0.1 IU/mL have been associated with higher rates of DVT in orthopedic patients. We hypothesized that low Anti-Xa levels would be found in critically ill trauma and surgical patients and that low levels would be associated with higher rates of DVT. Methods: All patients on the surgical intensive care unit (ICU) service were prospectively followed. In the absence of contraindications, patients were given prophylactic enoxaparin and anti-Xa levels were drawn after the third dose. Trough levels ≤0.1 IU/mL were considered low. Screening duplex exams were obtained within 48 hours of admission and then weekly. Patients were excluded if they did not receive a duplex, if they had a prior DVT, or if they lacked correctly timed anti-Xa levels. DVT rates and demographic data were compared between patients with low and normal anti-Xa levels. Results: Data were complete for 54 patients. Eighty-five percent suffered trauma (Injury Severity Score of 25 ± 12) and 74% were male. Overall, 27 patients (50%) had low anti-Xa levels. Patients with low anti-Xa levels had significantly more DVTs than those with normal levels (37% vs. 11%, p = 0.026), despite similar age, body mass index, Injury Severity Score, creatinine clearance, high risk injuries, and ICU/ventilator days. Conclusion: Standard dosing of enoxaparin leads to low anti-Xa levels in half of surgical ICU patients. Low levels are associated with a significant increase in the risk of DVT. These data support future studies using adjusted-dose enoxaparin.

BACKGROUND Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. METHODS Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. RESULTS Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. CONCLUSIONS Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.

In a previous retrospective study, we demonstrated that pelvic radiographs (PXRs) in the evaluation of blunt trauma patients undergoing abdominal computed tomographic (CT) scanning have limited utility in the absence of hemodynamic instability and significant physical findings. The purpose of this study was to prospectively validate an algorithm defining indications for PXR in blunt trauma patients in the emergency department.We performed a prospective observational study of consecutive blunt trauma patients over 6 months at a single Level 1 trauma center. The trauma faculty agreed to implement an algorithm of obtaining PXRs in patients undergoing abdominal CT scanning only if a specific set of criteria were met: systolic blood pressure90 mm Hg, hemoglobin8 mg/dL, a drop in Hgb of more than 3 mg/dL while in the trauma bay, or significant physical examination findings. The algorithm could be overridden at the discretion of the attending physician.Nine hundred ninety-five consecutive blunt trauma patients whose evaluation was to include an abdominal CT scan were included in the study. Only 54 patients (6%) received a PXR. Fifty-six indications for PXR were provided: 35 (63%) severe pelvic pain, 14 (25%) proximal fractures, 3 (5%) hip dislocations, and only 4 (7%) had unexplained hypotension. No adverse events or delays in care occurred such as hypotension in the CT scanner or a delay in contacting interventional radiology, blood transfusion, or application of a pelvic binder. The algorithm selected PXR for patients who were more likely to have a pelvic fracture (33% vs. 4.5%, p0.001), hip dislocation (7.4% vs. 0.1%, p0.001), femur fracture (22.2% vs. 2.7%, p0.001), and to require blood transfusion (11.1% vs. 1.9%, p0.001). Implementation of this algorithm resulted in a decrease in charges of$226,000 in 6 months.When objective evaluation of the abdomen is to be obtained via CT scanning, PXR in the emergency department is obsolete in the absence of hemodynamic instability and significant physical examination findings. Implementation of a selective algorithm in this patient population can result in significant cost savings without adverse patient outcomes.