Comparison of two equivalent model for end-stage liver disease scores for hepatocellular carcinoma patients using data from the United Network for Organ Sharing liver transplant waiting list registry.

Patients with hepatocellular carcinoma (HCC) have been advantaged on the liver transplant waiting list within the United States, and a 6-month delay and exception point cap have recently been implemented to address this disparity. An alternative approach to prioritization is an HCC-specific scoring model such as the MELD Equivalent (MELDEQ ) and the mixed new deMELD. Using data on adult patients added to the UNOS waitlist between 30 September 2009 and 30 June 2014, we compared projected dropout and transplant probabilities for patients with HCC under these two models. Both scores matched actual non-HCC dropout in groups with scores <22 and improved equity with non-HCC transplant probabilities overall. However, neither score matched non-HCC dropout accurately for scores of 25-40 and projected dropout increased beyond non-HCC probabilities for scores <16. The main differences between the two scores were as follows: (i) the MELDEQ assigns 6.85 more points after 6 months on the waitlist and (ii) the deMELD gives greater weight to tumor size and laboratory MELD. Post-transplant survival was lower for patients with scores in the 22-30 range compared with those with scores <16 (P = 0.007, MELDEQ ; P = 0.015, deMELD). While both scores result in better equity of waitlist outcomes compared with scheduled progression, continued development and calibration is recommended.

Projected outcomes of 6-month delay in exception points versus an equivalent Model for End-Stage Liver Disease score for hepatocellular carcinoma liver transplant candidates.

The United Network for Organ Sharing (UNOS) recently implemented a 6-month delay before granting exception points to liver transplantation candidates with hepatocellular carcinoma (HCC) to address disparity in transplantation access between HCC and non-HCC patients. An HCC-specific scoring scheme, the Model for End-Stage Liver Disease equivalent (MELDEQ ), has also been developed. We compared projected dropout and transplant probabilities and posttransplant survival for HCC and non-HCC patients under the 6-month delay and the MELDEQ using UNOS data from October 1, 2009, to June 30, 2014, and multistate modeling. Overall (combined HCC and non-HCC) wait-list dropout was similar under both schemes and slightly improved (though not statistically significant) compared to actual data. Projected HCC wait-list dropout was similar between the MELDEQ and 6-month delay at 6 months but thereafter started to differ, with the 6-month delay eventually favoring HCC patients (3-year dropout 10.0% [9.0%-11.0%] for HCC versus 14.1% [13.6%-14.6%]) for non-HCC) and the MELDEQ favoring non-HCC patients (3-year dropout 16.0% [13.2%-18.8%] for HCC versus 12.3% [11.9%-12.7%] for non-HCC). Projected transplant probabilities for HCC patients were substantially lower under the MELDEQ compared to the 6-month delay (26.6% versus 83.8% by 3 years, respectively). Projected HCC posttransplant survival under the 6-month delay was similar to actual, but slightly worse under the MELDEQ (2-year survival 82.9% [81.7%-84.2%] versus actual of 85.5% [84.3%-86.7%]). In conclusion, although the 6-month delay improves equity in transplant and dropout between HCC and non-HCC candidates, disparity between the 2 groups may still exist after 6 months of wait-list time. Projections under the MELDEQ , however, appear to disadvantage HCC patients. Therefore, modification to the exception point progression or refinement of an HCC prioritization score may be warranted. Liver Transplantation 22 1343-1355 2016 AASLD.

Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.

Immunobiology in VCA.

Transplantation of vascularized composite tissue is a relatively new field that is an amalgamation of experience in solid organ transplantation and reconstructive plastic and orthopedic surgery. What is novel about the immunobiology of VCA is the addition of tissues with unique immunologic characteristics such as skin and vascularized bone, and the nature of VCA grafts, with direct exposure to the environment, and external forces of trauma. VCAs are distinguished from solid organ transplants by the requirement of rigorous physical therapy for optimal outcomes and the fact that these procedures are not lifesaving in most cases. In this review, we will discuss the immunobiology of these systems and how the interplay can result in pathology unique to VCA as well as provide potential targets for therapy.

MELDEQ : An alternative Model for End-Stage Liver Disease score for patients with hepatocellular carcinoma.

Multiple studies have demonstrated an advantage for hepatocellular carcinoma (HCC) patients under the current liver allocation system, such that the United Network for Organ Sharing (UNOS) recently voted in support of a proposal to delay granting Model for End-Stage Liver Disease (MELD) exception points to all HCC patients for 6 months, independently of a candidate's native MELD score or alpha-fetoprotein (AFP) level. We obtained UNOS data on adult patients who were added to the wait list between January 22, 2005 and September 30, 2009, and we explored the relationship between HCC, MELD, AFP, and other factors that contribute to not only dropout on the wait list but posttransplant survival as well. The aim was to establish an equivalent Model for End-Stage Liver Disease (MELDEQ ) score for HCC patients that would reduce the disparity in access to transplantation between HCC and non-HCC patients. We determined risk groups for HCC patients with dropout hazards equivalent to those of non-HCC patients, and we evaluated projections for HCC wait-list dropout/transplantation probabilities on the basis of the MELDEQ prioritization scheme. Projections indicate that lower risk HCC patients (MELDEQ ≤ 18) would have dropout probabilities similar to those of non-HCC patients in the same MELD score range, whereas dropout probabilities for higher risk HCC patients would actually be improved. The posttransplant survival of all HCC risk groups is lower than that of their non-HCC counterparts, with 1-year survival of 0.77 (95% CI, 0.70-0.85) for MELDEQ scores ≥ 31. These results suggest that HCC patients with a combination of a low biochemical MELD score and a low AFP level (MELDEQ ≤ 15) would receive a marked advantage in comparison with patients with chemical MELD scores in a similar range and that a delay of 6 months for listing may be appropriate. In contrast, patients with MELDEQ scores > 15 would likely be adversely affected by a universal 6-month delay in listing.

The impact of recipient obesity on outcomes after renal transplantation.

BACKGROUND: The benefit of renal transplantation in obese patients is controversial, with many centers setting upper limits on body mass index (BMI) in consideration for listing patients for transplant. This study was undertaken to determine the effect of recipient obesity on delayed graft function (DGF) and graft survival after renal transplantation. METHODS: Retrospective review of all renal transplant recipients in the United Network for Organ Sharing database from January 1, 2004, through December 31, 2009, was performed. Primary endpoints were DGF and non-death-censored graft survival. Comparisons were made on the basis of the following weight classes: nonobese (BMI < 30), class I obese (30 ≤ BMI < 35), class II obese (35 ≤ BMI < 40), and class III obese (BMI ≥ 40). RESULTS: Multivariable logistic regression indicated a significantly increased risk for DGF in obese patients. The odds ratios for DGF compared with nonobese patients were 1.34 [95% confidence interval (CI) 1.27-1.42; P < 0.001], 1.68 (95% CI 1.56-1.82; P < 0.001), and 2.68 (95% CI 2.34-3.07; P < 0.001) for the class I obese, class II obese, and class III obese groups, respectively. Class I obesity was not a significant risk for non-death-censored graft failure [hazard ratio (HR) 1.00, 95% CI 0.95-1.05; P = 0.901] compared with nonobese patients. Patients in the class II obese (HR 1.15, 95% CI 1.07-1.24; P < 0.001) and class III obese (HR 1.26, 95% CI 1.11-1.43; P < 0.001) groups were at a significantly increased risk for graft failure than their nonobese counterparts. CONCLUSIONS: Obese patients in all weight classes are at an increased risk for DGF after renal transplantation, although differences in non-death-censored graft survival are such that transplantation should not be denied on the basis of BMI criteria alone.

Inflammatory myofibroblastic tumor of the liver in children.

Inflammatory pseudotumors, now more aptly termed inflammatory myofibroblastic tumors (IMTs), are uncommon benign neoplasms, which have been reported in most organs and tissues in the body. Originally described and commonly found in the lung, they are also found in the liver of children and adults. We review the literature and analyze the features of the hepatic IMTs reported in children, along with a case report of a 15-month-old boy who had a persistent IMT in the liver and underwent surgical resection for the same following a trial of conservative management.

Hand-assisted laparoscopic nephrectomy for polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Historically, nephrectomy for autosomal dominant polycystic kidney disease was performed by an open technique. We performed this study to compare outcomes in hand-assisted laparoscopic nephrectomy with open nephrectomy in this population. METHODS: Charts of patients with autosomal dominant polycystic kidney disease who underwent nephrectomy by a transplant surgeon from January 1, 2000, to December 31, 2011, were reviewed. The hand-assisted laparoscopic nephrectomy group was compared with the open group. Data collected included unilateral versus bilateral nephrectomy, operative time, complications, transfusion requirement, and length of stay. RESULTS: Of the 78 patients identified, 18 underwent open transabdominal nephrectomy, 56 underwent hand-assisted laparoscopic nephrectomy, and 2 underwent hand-assisted laparoscopic nephrectomy that was converted to an open procedure. Two patients were excluded because another major procedure was performed at the same time as the nephrectomy. Operative times were similar. Patients undergoing open bilateral nephrectomy were more likely to receive transfusion (odds ratio, 3.57 [95% confidence interval, 0.74-17.19]; P = .016), and the length of stay was longer in the open groups (5.9 days vs 4.0 days for unilateral [P = .013] and 7.8 days vs 4.6 days for bilateral [P = .001]). Overall complication rates were similar. The most frequent complications associated with hand-assisted laparoscopic nephrectomy were the development of an incisional hernia at the hand-port site and arteriovenous fistula thrombosis. CONCLUSION: Hand-assisted laparoscopic nephrectomy can be safely performed without increased operative times or complications. The hand-assisted laparoscopic nephrectomy group enjoyed a shorter length of stay, and fewer patients in this group received transfusion. For patients considering renal transplantation, avoidance of transfusion is important to prevent sensitization and limiting access to compatible organs.

Monitoring and long-term outcomes in vascularized composite allotransplantation.

PURPOSE OF REVIEW: The field of vascularized composite allotransplantation (VCA) is young, with less than 150 transplants worldwide. However, we now possess as much as 14 years of clinical follow-up. There are similarities and distinct differences between solid-organ transplantation (SOT) and VCA. This review will summarize how VCA recipients are monitored, outcomes observed, and what aspects are unique to VCA. RECENT FINDINGS: Of about 90 documented cases, 10% of VCA recipients are out more than 10 years and 14% are out 5 or more years. There have been both graft losses and patient mortality. In most cases, these losses have been acute, most within the first year, and all within 3 years. Unlike SOT, VCA grafts function well during severe rejection. Chronic rejection-like sequelae are less frequent than in SOT, but do appear. Immunosuppression ranges from standard protocols to novel trials aimed at immunosuppression minimization. Patient selection greatly affects the outcome. Graft loss after year 1 is associated with compliance issues. SUMMARY: Functional outcomes have exceeded expectations. VCA recipients enjoy a quality of life not achievable with conventional reconstruction. Outstanding long-term results of more than a decade have been achieved. Monitoring of VCA patients will require new strategies to incorporate external visualization and effects of environment on rejection. Graft loss has occurred early, suggesting we focus improvement on this time period. More follow-up is needed to determine the rates and targets of chronic rejection, and the characteristics of VCA unique to face vs. hand transplantation.

Employment outcomes following successful renal transplantation.

BACKGROUND: Data on employment outcomes after successful renal transplantation are few. We conducted this study to identify favorable factors for employment after transplantation. METHODS: Adult patients <65 yr of age who underwent renal transplantation between January 1, 2002 and December 31, 2007 were surveyed. Patients with graft survival <1 yr were excluded. We also tested their knowledge of Medicare coverage after transplantation. Data were analyzed using chi-squared and Fisher's exact tests. p-Value <0.05 was considered statistically significant. RESULTS: A 55% response rate was obtained where 56% of respondents were employed after transplantation. Race, marital status, previous transplant, and complicated post-operative course did not influence employment. Favorable factors include male gender (p=0.04), younger age (<40 [p=0.0003] or <50 yr [p<0.0001]), having ≥1 dependent (p=0.04), higher education (minimum high school degree [p=0.003] or some college [p=0.002]), live donor recipient (p=0.004), wait time <2 yr (p=0.03), dialysis <2 yr (p<0.0001) or pre-dialysis (p=0.04), and pre-transplantation employment (p<0.0001). Mean time for employment was 4.9±6.3 months (median three months). Common reasons for unemployment were disability (59%) and retirement (27%). Finally, 7% correctly responded that Medicare benefits end 36 months following transplantation. CONCLUSIONS: Potentially modifiable factors to improve employment are earlier referral and better education regarding Medicare eligibility.

A review of the United States experience with combined heart-liver transplantation.

Since first described by Starzl, combined heart and liver transplantation (CHLT) has been a relatively rare event, although utilization has increased in the past decade. This study was undertaken to review the United States experience with this procedure; UNOS data on CHLT was reviewed. CHLT was compared with liver transplantation alone and heart transplantation alone in terms of acute rejection within 12 months, graft survival, and patient survival. Survival was calculated according to Kaplan-Meier and Cox proportional hazards. Continuous variables were compared using Student's t-test and categorical variables with chi-squared. Between 1987 and 2010, there were 97 reported cases of CHLT in the United States. Amyloidosis was the most common indication for both heart (n = 26, 26.8%) and liver (n = 27, 27.8%) transplantation in this cohort. Liver graft survival in the CHLT cohort at 1, 5, and 10 years was 83.4%, 72.8%, and 71.0%, whereas survival of the cardiac allograft was 83.5%, 73.2%, and 71.5%. This was similar to graft survival in liver alone transplantation (79.4%, 71.0%, 65.1%; P = 0.894) and heart transplantation alone (82.6%, 71.9%, 63.2%; P = 0.341). CHLT is a safe and effective procedure, with graft survival rates similar to isolated heart and isolated liver transplantation.

Region 11 MELD Na exception prospective study.

INTRODUCTION: Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation. MATERIAL AND METHODS: From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception. RESULTS: Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to standard adult recertification schedule. On data end of follow-up, December 28, 2010, 15,285 potential U.S. liver recipients met the inclusion criteria of true MELD between 6 and 22. In Region 11, 1,198 of total eligible liver recipients were listed. Sixty-two (5.2%) patients were eligible for Na exception (MELD Na); 823 patients (68.7%) were listed with standard MELD (SMELD); and 313 patients (26.1%) received HCC MELD exception. Ninety percent of MELD Na patients and 97% of HCC MELD patients were transplanted at end of follow up, compared to 49% of Region 11 standard MELD and 40% of U.S.A. standard MELD (USA MELD) patients (p < 0.001); with comparable dropout rates (6.5, 1.6, 6.9, 9% respectively; p = 0.2). MELD Na, HCC MELD, Region 11 SMELD, and USA MELD post-transplant six-month actual patient survivals were similar (92.9, 92.8, 92.2, and 93.9 %, respectively). CONCLUSION: The Region 11 MELD Na exception prospective trial improved hyponatremic cirrhotic patient access to transplant equitably, and without compromising transplant efficacy.

Perioperative anticoagulation and antiplatelet therapy in renal transplant: is there an increase in bleeding complication?

BACKGROUND: Renal transplant recipients may have comorbidities requiring anticoagulation or antiplatelet therapy. While the effects of warfarin may be neutralized with plasma infusion, those of aspirin and clopidogrel are not easily reversible and may be associated with an increased risk of bleeding. We conducted this study to evaluate the risk of bleeding complications in patients receiving perioperative anticoagulation or antiplatelet therapy. METHODS: Medical records of patients who underwent renal transplantation from July 1, 2005 to April 30, 2009 were retrospectively reviewed. Patients receiving perioperative anticoagulation or antiplatelet therapy were identified. The incidence of reoperation, transfusion utilization and decrease in serum hemoglobin from pre-operative value (ΔHgb) were compared to those on no therapy. RESULTS: Of the 327 patients identified, 105 received pre-operative anticoagulation or antiplatelet therapy, 28 received therapy post-operatively, while 213 patients received no therapy. The incidence of reoperation, transfusion utilization and ΔHgb were not significantly increased with pre-operative anticoagulation or antiplatelet therapy. With post-operative heparin infusion, the incidence of reoperation and transfusion utilization were significantly increased (p values < 0.001). Patients with activated partial thromboplastin times (aPTT) >80 s experienced significant bleeding complications. CONCLUSION: A supratherapeutic aPTT with post-operative heparin infusion was associated with the greatest risk of bleeding complication.

Prophylaxis against de novo hepatitis B for liver transplantation utilizing hep B core (+) donors: does hepatitis B immunoglobulin provide a survival advantage?

Donor liver allografts with positive serology for hepatitis B core antibody [HBc (+)] have been increasingly used for liver transplantation. However, the optimal prophylactic regimen to prevent development of de novo hepatitis B has not been determined. To evaluate this, we screened United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) registry data for adult recipients of HBc (+) organs who were HBsAg (-), and evaluated the effects of using prophylactic anti-viral therapies (HBIG and lamivudine) on patient and graft survival. Out of a total cohort of 958 patients transplanted since 2004, 61 received HBIG alone, 116 received lamivudine alone, 66 both, 509 neither and 206 were missing this information. Based on several multivariable Cox regression models, patients receiving HBIG therapy-only were observed to have a statistically significant (approximately 70%) reduction in risk of mortality compared with patients receiving lamivudine-only therapy [HR=0.29, 95% CI (0.10, 0.86), P=0.026], and a nonstatistically significant reduction in risk of graft failure. However, no graft failures were attributed to de novo hepatitis B, suggesting that any improved graft/patient survival possibly associated with HBIG therapy occurs independently of de novo hepatitis B virus (HBV) reduction. While this study cannot prove that HBIG therapy is protective for graft and patient survival after liver transplantation, these findings do highlight the need to further examine and study prophylactic use in recipients of HBc (+) donors.

BK viral disease in renal transplantation.

PURPOSE OF REVIEW: BK virus is one of the most frequent causes of graft loss after renal transplantation, with BK virus-associated nephropathy occurring in roughly 8% of patients, and graft loss rates reported as high as 50%. This review is meant to highlight the literature on BK viral disease following renal transplantation published in the most recent year. RECENT FINDINGS: Prevention of BK virus-associated graft loss requires early diagnosis of BK viral replication, which is best achieved by screening for BK viral DNA in the blood. Screening intervals more frequently than the currently recommended 3 months appear to offer increased efficacy. Reduction in immunosuppression remains the mainstay for treatment of BK viral disease, with consideration given to antiviral drug therapy with leflunomide. Acute rejection may be minimized by a short course of intravenous immunoglobulin. Sirolimus appears to be a promising addition to the therapeutic armamentarium. For patients requiring re-transplantation after BK virus-associated graft loss, viral clearance from the bloodstream prior to re-transplantation should be achieved to attain optimal results. SUMMARY: BK virus is a major pathogen affecting renal allografts, although intensive surveillance and targeted dose reduction in immunosuppression with the consideration of additional antiviral drug therapy can minimize graft loss resulting from infection.

Laparoscopic major hepatectomy: an evolution in standard of care.

OBJECTIVE: To analyze the results of 6 international surgical centers performing laparoscopic major liver resections. SUMMARY BACKGROUND DATA: The safety and feasibility of laparoscopy for minor liver resections has been previously demonstrated. Major anatomic liver resections, initially considered to be unsuitable for laparoscopy, are increasingly reported by several centers worldwide. METHODS: Prospective databases of 3 European, 2 U.S., and 1 Australian centers were combined. Between 1997 and 2008, 210 major liver resections were performed: 136 right and 74 left hepatectomies. Results and differences in surgical techniques between the 6 centers are outlined. RESULTS: Surgical duration was 250 minutes (range: 90-655 minutes). Operative blood loss was 300 mL (range: 20-2500 mL). Thirty patients (14.3%) received blood transfusion. Conversion to open surgery was required in 26 patients (12.4%). Portal triad clamping was performed in 24 patients (11.4%). Median tumor size was 5.4 cm (range: 1-25 cm) and surgical margin was 10.5 mm (range: 0-70 mm). Two patients died during the postoperative period from pulmonary embolism and urosepsis. Liver-specific and general complications occurred in 17 (8.1%) and 29 patients (13.8%), respectively. Hospital length of stay was 6 days (range: 1-34 days). A further analysis of early (n = 90) and late (n = 120) experience showed improved surgical and postoperative results in the latter group. CONCLUSIONS: This multicenter study demonstrates that laparoscopic major liver resections are feasible in selected patients and results improve with experience. However, proficiency in both open liver surgery and advanced laparoscopy is compulsory and surgeons must begin with minor laparoscopic resections.

Laparoscopic liver surgery.

Great advances have occurred in the field of laparoscopic hepatic surgery. It is now clear that in experienced hands, the laparoscopic method of liver resection is as safe as an open procedure. The key phrase in this last sentence is "in experienced hands". The new devices that are available might make an inexperienced hepatic surgeon, well-trained in laparoscopic surgery, embark on hepatic resection without thorough knowledge of hepatic anatomy. The converse may also be true. As no criteria for credentialing of laparoscopic hepatic surgeons exist, the decision as to who is sufficiently trained to perform these procedures is left to individual hospital credentialing boards. While a certification procedure defined by leaders in this field and supported by surgical societies would be welcomed, the ability to achieve and enforce these guidelines appear to be more of a challenge. In addition, while most comparison studies in this area conclude by suggesting that a randomized, clinical trial would be needed to definitively arrive at an answer regarding the benefits of minimally invasive liver surgery compared with open surgery, it would likely be extremely difficult to accrue patients, given the data presented in articles regarding the success of laparoscopic hepatic resections. The authors conclude that an internationalregistry of all laparoscopic cases should b e established to insure patient safety and a mechanism for self-monitoring.

Use of rapid Model for End-Stage Liver Disease (MELD) increases for liver transplant registrant prioritization after MELD-Na and Share 35, an evaluation using data from the United Network for Organ Sharing.

The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a 'delay and cap' policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant's change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need.

Minimization of Hypoglycemia as an Adverse Event During Insulin Infusion: Further Refinement of the Yale Protocol.

BACKGROUND: The management of hyperglycemia in the intensive care unit has been a controversial topic for more than a decade, with target ranges varying from 80-110 mg/dL to <200 mg/dL. Multiple insulin infusion protocols exist, including several computerized protocols, which have attempted to achieve these targets. Importantly, compliance with these protocols has not been a focus of clinical studies. METHODS: GlucoCare™, a Food and Drug Administration (FDA)-cleared insulin-dosing calculator, was originally designed based on the Yale Insulin Infusion Protocol to target 100-140 mg/dL and has undergone several modifications to reduce hypoglycemia. The original Yale protocol was modified from 100-140 mg/dL to a range of 120-140 mg/dL (GlucoCare 120-140) and then to 140 mg/dL (GlucoCare 140, not a range but a single blood glucose [BG] level target) in an iterative and evidence-based manner to eliminate hypoglycemia <70 mg/dL. The final modification [GlucoCare 140(B)] includes the addition of bolus insulin "midprotocol" during an insulin infusion to reduce peak insulin rates for insulin-resistant patients. This study examined the results of these protocol modifications and evaluated the role of compliance with the protocol in the incidence of hypoglycemia <70 mg/dL. RESULTS: Protocol modifications resulted in mean BG levels of 133.4, 136.4, 143.8, and 146.4 mg/dL and hypoglycemic BG readings <70 mg/dL of 0.998%, 0.367%, 0.256%, and 0.04% for the 100-140, 120-140, 140, and 140(B) protocols, respectively (P < 0.001). Adherence to the glucose check interval significantly reduced the incidence of hypoglycemia (P < 0.001). Protocol modifications led to a reduction in peak insulin infusion rates (P < 0.001) and the need for dextrose-containing boluses (P < 0.001). CONCLUSION: This study demonstrates that refinements in protocol design can improve glucose control in critically ill patients and that the use of GlucoCare 140(B) can eliminate all significant hypoglycemia while achieving mean glucose levels between 140 and 150 mg/dL. In addition, attention to the timely performance of glucose levels can also reduce hypoglycemic events.

Machine perfusion: not just for marginal kidney donors.

Interest in machine perfusion (MP) for donated kidneys has markedly increased in the past decade as a means to improve graft function, although the donor populations in which it should be applied have not yet been resolved. All adults undergoing de-novo isolated kidney transplantation from standard-criteria donors in the UNOS database 2005 to 2011 were reviewed with the primary endpoint of delayed graft function (DGF), defined as dialysis within seven days of transplantation, in those who received kidneys that underwent MP versus cold storage (CS) alone. Three methods were used to control for differences between groups. Multivariable logistic regression was performed, adjusting for donor and recipient characteristics significantly associated with DGF. Rates were also compared in a cohort of propensity-matched MP vs CS recipients. Finally, a paired-kidney study was performed, where one kidney underwent MP and the contralateral underwent CS. There were 36,323 patients, with unadjusted DGF rates of 18.6 per cent (n = 1830/9882) and 22.4 per cent (n = 5931/26,441; P < 0.001) in the MP vs CS groups, respectively. After multivariable analysis, the odds ratio for DGF in the MP group was 0.59 (P < 0.001) versus CS. In the propensity-matched cohort, there were 8929 patients each in the MP and CS groups. DGF occurred in 16.8 per cent of the MP group vs 25.3 per cent with CS (P < 0.001, OR 0.59). In the paired-kidney study, rates of DGF were 16.7 per cent vs 24.3 per cent (P < 0.001) in the 1665 recipients each in the MP versus CS groups (OR 0.6). In conclusion, machine perfusion is beneficial in reducing DGF even when standard donors are utilized, and thus should not be limited to marginal kidneys.