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Background Prolonged storage of packed red blood cells (pRBCs) induces a series of harmful biochemical and metabolic changes known as the RBC storage lesion. RBCs are currently stored in an acidic storage solution, but the effect of pH on the RBC storage lesion is unknown. We investigated the effect of modulation of storage pH on the RBC storage lesion and on erythrocyte survival after transfusion. Methods Murine pRBCs were stored in Additive Solution-3 (AS3) under standard conditions (pH, 5.8), acidic AS3 (pH, 4.5), or alkalinized AS3 (pH, 8.5). pRBC units were analyzed at the end of the storage period. Several components of the storage lesion were measured, including cell-free hemoglobin, microparticle production, phosphatidylserine externalization, lactate accumulation, and byproducts of lipid peroxidation. Carboxyfluorescein-labeled erythrocytes were transfused into healthy mice to determine cell survival. Results Compared with pRBCs stored in standard AS3, those stored in alkaline solution exhibited decreased hemolysis, phosphatidylserine externalization, microparticle production, and lipid peroxidation. Lactate levels were greater after storage in alkaline conditions, suggesting that these pRBCs remained more metabolically viable. Storage in acidic AS3 accelerated erythrocyte deterioration. Compared with standard AS3 storage, circulating half-life of cells was increased by alkaline storage but decreased in acidic conditions. Conclusions Storage pH significantly affects the quality of stored RBCs and cell survival after transfusion. Current erythrocyte storage solutions may benefit from refinements in pH levels.

A growing number of renal transplant recipients have a body mass index ≥40. While previous studies have shown that patient and graft survival are significantly decreased in renal transplant recipients with body mass indexes ≥40, less is known about perioperative outcomes and resource utilization in morbidly obese patients. We aimed to analyze the effects of morbid obesity on these parameters in renal transplant.Using a linkage between the Scientific Registry of Transplant Recipients and the databases of the University HealthSystem Consortium, we identified 29,728 adult renal transplant recipients and divided them into 2 cohorts based on body mass index (40 vs ≥40 kg/mBody mass index ≥40 recipients incurred greater direct costs ($84,075 vs $79,580, P .01), index admission costs ($91,169 vs $86,141, P .01), readmission costs ($5,306 vs $4,596, P = .01), and combined costs ($99,590 vs $93,939, P .001). Thirty-day readmission rates were also greater among body mass index ≥40 recipients (33.92% vs 26.9%, P .01). Morbid obesity was not predictive of stay (odds ratio 1.01, P = .75).Morbidly obese renal transplant recipients incur greater costs and readmission rates compared with nonobese patients. Recognition of increased resource utilization should be accompanied by appropriate, risk-adjustment reimbursement.

Background and Objectives Pasireotide decreases leak rates after pancreatic resection, though significant drug cost may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile. Methods A cost-effectiveness model compared pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify influential clinical components of the model. Results With the cost of pasireotide included, per patient costs of pancreatectomy, including those for readmission, were lower in the intervention arm (41,769 versus 42,159$; net savings of 390$, or 1%). This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9–9.2%). Pasireotide cost would need to increase by over 15.4% to make the intervention strategy more costly than usual care. Sensitivity analyses exploring variability of key model inputs demonstrated that the three strongest drivers of cost were (i) cost of pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A. Conclusions Prophylactic pasireotide administration following pancreatectomy is cost savings, reducing expensive post-operative sequealae (major complications and readmissions). Pasireotide should be utilized as a cost-saving measure in pancreatic resection. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Background The rate and consequences of reoperation after liver transplantation (LT) are unknown in the United States. Study Design Adult patients (n = 10,295; 45% of all LT) undergoing LT from 2009 through 2012 were examined using a linkage of the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases providing recipient, donor, center, hospitalization, and survival details. Median follow-up was 2 years. Reoperations were identified within 90 days after LT. Results Overall 90-day reoperation rate after LT was 29.3%. Risk factors for 90-day reoperation included recipients with a history of hemodialysis, severely ill functional status, government insurance, increasing Model for End-Stage Liver Disease score, and increasing donor risk index. Reoperation within 90 days was found to be an independent predictor of adjusted 1-year mortality (odds ratio = 1.8; 95% CI, 1.5–2.1), as was government-provided insurance and increasing donor risk index. Additionally, patients undergoing delayed reoperative intervention (after 30 days) were found to have increased risk of 1-year mortality compared with those undergoing early reoperative intervention (odds ratio = 1.96; 95% CI, 1.4–2.7; p Conclusions This is the first national study reporting that nearly one-third of transplant recipients undergo reoperation within 90 days of LT. Although necessary at times, reoperation is associated with increased risk of death at 1 year; however, it appears that the timing of these interventions can be critical, due to the type of intervention required. Early reoperative intervention does not appear to influence long-term outcomes, and delayed intervention (after 30 days) is strongly associated with decreased survival.

In recent centuries, an increasing understanding of the physiologic changes resulting in clinically significant portal hypertension has led to innumerable advances in the management of these patients. Highly morbid operative decompression has been largely replaced by medical therapy, endoscopic intervention, and endovascular techniques. A number of novel operations to relieve portal hypertension are still occasionally indicated due to the limited availability of liver transplantation. The high complexity of these patients requires a multidisciplinary approach with a clear understanding of both the natural history of cirrhosis and portal hypertension as well as the evolving techniques available to alter the progression of this disease.

Chronic pancreatitis is a complex disease process best addressed by a multidisciplinary approach. The surgical treatment of chronic pancreatitis requires a detailed understanding of the ductal anatomy and natural history of the disease. Surgical drainage of the distal pancreatic duct via longitudinal pancreatojejunostomy can successfully alleviate ductal hypertension, relieve pain, and preserve endocrine and exocrine function. Preferred approaches, as described by several prominent surgeons of the past, include the Frey and Puestow procedures. With a growing understanding of the pathophysiology of ductal hypertension, pancreatic pain, and chronic inflammation, modern modifications of classic surgical techniques remain critical tools in successful, sustained management for patients requiring ductal decompression.

Introduction: Pasireotide was recently shown to decrease leak rates after pancreatic resection, though the significant cost of the drug may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile by improving outcomes. Methods: A cost-effectiveness model was constructed to compare pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a recent randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify the most influential clinical components of the model. Results: Without considering pasireotide cost, prophylactic use of the drug saved an average of $8,109 per patient. However, when the cost of pasireotide was included, per patient costs increased from $42,159 to $77,202. This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A) (21.9% to 9.2%). The resultant cost per PF/PL/A avoided was $301,628. Threshold analysis demonstrated that for this intervention to be cost neutral, either the purchase price of pasireotide ($43,172) must be reduced by 92.3% (to $3324) or drug reimbursement must be $39,848. Sensitivity analyses exploring variable perioperative mortality, rate of PF/PL/A, and readmission rates did not significantly alter model outcomes. Conclusions: Our analyses demonstrate that when prophylactic pasireotide is administered, the cost per PF/PL/A avoided is approximately $300,000. Aggressive pricing negotiation, payer reimbursement for the drug, high-volume use, and consensus among the public, payers, and surgical community regarding the value of reducing morbidity will ultimately determine the utility of widespread pasireotide application in pancreatic resection.

Background Metabolic syndrome is increasing among patients undergoing liver transplantation. Nonalcoholic steatohepatitis is a manifestation of metabolic syndrome and is an increasingly common cause of end-stage liver disease necessitating orthotopic liver transplantation. We sought to determine the effect of preoperative risk factors on the development of post-transplant metabolic syndrome, complications, readmissions, and mortality. Methods We conducted a review of 114 orthotopic liver transplantations at our institution from May 2012 to April 2014. Results Patients with (n = 19) and without (n = 95) metabolic syndrome were similar with regard to age, race, and model for end-stage liver disease at time of transplant. Donor and operative factors also were similar between the groups. Preoperative diabetes was found to be associated with an increased rate of readmission (odds ratio 3.45, P = .03). While preoperative metabolic syndrome itself was not a significant predictor of worse outcomes, postoperative metabolic syndrome was associated with significantly greater readmissions in the first year. Major predictors of new onset metabolic syndrome after orthotopic liver transplantation included preoperative diabetes and obesity (odds ratio 8.54 and odds ratio 5.49, P Conclusion Efforts to decrease the incidence of postoperative metabolic syndrome after orthotopic liver transplantation may decrease readmissions and improve outcomes, along with decreasing resource utilization.

Background/Aims: During storage, units of human red blood cells (pRBCs) experience membrane destabilization and hemolysis which may cause harm to transfusion recipients. This study investigates whether inhibition of acid sphingomyelinase could stabilize erythrocyte membranes and prevent hemolysis during storage. Methods: Human and murine pRBCs were stored under standard blood banking conditions with and without the addition of amitriptyline, a known acid sphingomyelinase inhibitor. Hemoglobin was measured with an electronic hematology analyzer and flow cytometry was used to measure erythrocyte size, complexity, phosphatidylserine externalization, and band 3 protein expression. Results: Cell-free hemoglobin, a marker of hemolysis, increased during pRBC storage. Amitriptyline treatment decreased hemolysis in a dose-dependent manner. Standard pRBC storage led to loss of erythrocyte size and membrane complexity, increased phosphatidylserine externalization, and decreased band 3 protein integrity as determined by flow cytometry. Each of these changes was reduced by treatment with amitriptyline. Transfusion of amitriptyline-treated pRBCs resulted in decreased circulating free hemoglobin. Conclusion: Erythrocyte storage is associated with changes in cell size, complexity, membrane molecular composition, and increased hemolysis. Acid sphingomyelinase inhibition reduced these changes in a dose-dependent manner. Our data suggest a novel mechanism to attenuate the harmful effects after transfusion of aged blood products.

Anemia and hemorrhagic shock are leading causes of morbidity and mortality worldwide, and transfusion of human blood products is the ideal treatment for these conditions. As human erythrocytes age during storage in blood banks they undergo many biochemical and structural changes, termed the red blood cell ‘storage lesion’. Specifically, ATP and pH levels decrease as metabolic end products, oxidative stress, cytokines, and cell-free hemoglobin increase. Also, membrane proteins and lipids undergo conformational and organizational changes that result in membrane loss, viscoelastic changes and microparticle formation. As a result, transfusion of aged blood is associated with a host of adverse consequences such as decreased tissue perfusion, increased risk of infection, and increased mortality. This review summarizes current research detailing the known parts of the erythrocyte storage lesion and their physiologic consequences.

BACKGROUND For nearly a decade, our center performed thromboelastograms (TEGs) to analyze coagulation profiles, allowing rapid data-driven blood component therapy. After consensus recommendations for massive transfusion protocols (MTPs), we implemented an MTP in October 2009 with 1:1:1 ratio of blood (red blood cells [RBC]), plasma (fresh-frozen plasma [FFP]), and platelets. We hypothesized that TEG-directed resuscitation is equivalent to MTP resuscitation. METHODS All patients receiving 6 units (U) or more of RBC in the first 24 hours for 21 months before and after MTP initiation in an urban Level I trauma center were examined. Demographics, mechanism of injury (MOI), Injury Severity Score (ISS), 24-hour volume of RBC, FFP, platelets, crystalloid, and 30-day mortality were compared, excluding patients with traumatic brain injuries. Variables were analyzed using Student's t-test and χ2 or Fisher's exact test. RESULTS For the preMTP group, there were 165 patients. In the MTP group, there were 124 patients. There were no significant differences in ISS, age, or sex. PreMTP patients with 6U or more RBC had significantly more penetrating MOI (p = 0.017), whereas preMTP patients with 10U or more RBC had similar MOIs. All patients received less crystalloid after MTP adoption (p < 0.001). There was no difference in volume of blood products or mortality in patients receiving 6U or more RBC. Blunt trauma MTP patients who received 10U or more RBC received more FFP (p = 0.02), with no change in mortality. Penetrating trauma patients who received 10U or more RBC received a similar volume of FFP; however, mortality increased from 54.1% for MTP versus 33.3% preMTP (p = 0.04). CONCLUSION TEG-directed resuscitation is equivalent to standardized MTP for patients receiving 6U or more RBC and for blunt MOI patients receiving 10U or more RBC. MTP therapy worsened mortality in penetrating MOI patients receiving 10U or more RBC, indicating a continued need for TEG-directed therapy. A 1:1:1 strategy may not be adequate in all patients. LEVEL OF EVIDENCE Therapeutic study, level IV.

Safety-net hospitals care for vulnerable patients, providing complex surgery at increased costs. These hospitals are at risk due to changing health care reimbursement policies and demand for better value in surgical care.To model different techniques for reducing the cost of complex surgery performed at safety-net hospitals.Hospitals performing pancreaticoduodenectomy (PD) were queried from the University HealthSystem Consortium database (January 1, 2009, to December 31, 2013) and grouped according to safety-net burden. A decision analytic model was constructed and populated with clinical and cost data. Sensitivity analyses were then conducted to determine how changes in the management or redistribution of patients between hospital groups affected cost.Overall cost per patient after PD.During the 5 years of the study, 15 090 patients underwent PD. Among safety-net hospitals, low-burden hospitals (LBHs), medium-burden hospitals (MBHs), and high-burden hospitals (HBHs) treated 4220 (28.0%), 9505 (63.0%), and 1365 (9.0%) patients, respectively. High-burden hospitals had higher rates of complications or comorbidities and more patients with increased severity of illness. Perioperative mortality was twice as high at HBHs (3.7%) than at LBHs (1.6%) and MBHs (1.7%) (P .001). In the base case, when all clinical and cost data were considered, PD at HBHs cost $35 303 per patient, 30.1% and 36.2% higher than at MBHs ($27 130) and LBHs ($25 916), respectively. Reducing perioperative complications or comorbidities by 50% resulted in a cost reduction of up to $4607 for HBH patients, while reducing mortality rates had a negligible effect. However, redistribution of HBH patients to LBHs and MBHs resulted in significantly more cost savings of $9155 per HBH patient, or $699 per patient overall.Safety-net hospitals performing PD have inferior outcomes and higher costs, and improving perioperative outcomes may have a nominal effect on reducing these costs. Redirecting patients away from safety-net hospitals for complex surgery may represent the best option for reducing costs, but the implementation of such a policy will undoubtedly meet significant challenges.