Regional Social Vulnerability is Associated With Geographic Disparity in Waitlist Outcomes for Patients With Non-Hepatocellular Carcinoma Model for End-stage Liver Disease Exceptions in the United States.

OBJECTIVE: This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions. SUMMARY AND BACKGROUND: Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC. METHODS: Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. RESULTS: There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs ( P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs ( P = 0.037). CONCLUSIONS: An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.

Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.

Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling of the cytoskeleton, which is a tightly regulated process coordinated by Rho-specific guanine nucleotide exchange factors (GEFs) and the Rho family of small GTPases. Rho-associated kinase (ROCK) promotes assembly of focal adhesions and actin stress fibers by regulating cytoskeleton organization. GEF exchange protein directly activated by cAMP 1 (EPAC1) has been implicated in modulating TGFß1 and Rho signaling; however, its role in HSC migration has never been examined. The aim of this study was to evaluate the role of cAMP-degrading phosphodiesterase 4 (PDE4) enzymes in regulating EPAC1 signaling, HSC migration, and fibrogenesis. We show that PDE4 protein expression is increased in activated HSCs expressing alpha smooth muscle actin and active myosin light chain (MLC) in fibrotic tissues of human nonalcoholic steatohepatitis cirrhosis livers and mouse livers exposed to carbon tetrachloride. In human livers, TGFß1 levels were highly correlated with PDE4 expression. TGFß1 treatment of LX2 HSCs decreased levels of cAMP and EPAC1 and increased PDE4D expression. PDE4 specific inhibitor, rolipram, and an EPAC-specific agonist decreased TGFß1-mediated cell migration in vitro. In vivo, targeted delivery of rolipram to the liver prevented fibrogenesis and collagen deposition and decreased the expression of several fibrosis-related genes, and HSC activation. Proteomic analysis of mouse liver tissues identified the regulation of actin cytoskeleton by the kinase effectors of Rho GTPases as a major pathway impacted by rolipram. Western blot analyses confirmed that PDE4 inhibition decreased active MLC and endothelin 1 levels, key proteins involved in cytoskeleton remodeling and contractility. The current study, for the first time, demonstrates that PDE4 enzymes are expressed in hepatic myofibroblasts and promote cytoskeleton remodeling and HSC migration. © 2023 The Pathological Society of Great Britain and Ireland.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Perpetuating Disparity: Failure of the Kidney Transplant System to Provide the Most Kidney Transplants to Communities With the Greatest Need.

BACKGROUND: The burden of end-stage kidney disease (ESKD) and kidney transplant rates vary significantly across the United States. This study aims to examine the mismatch between ESKD burden and kidney transplant rates from a perspective of spatial epidemiology. METHODS: US Renal Data System data from 2015 to 2017 on incident ESKD and kidney transplants per 1000 incident ESKD cases was analyzed. Clustering of ESKD burden and kidney transplant rates at the county level was determined using local Moran's I and correlated to county health scores. Higher percentile county health scores indicated worse overall community health. RESULTS: Significant clusters of high-ESKD burden tended to coincide with clusters of low kidney transplant rates, and vice versa. The most common cluster type had high incident ESKD with low transplant rates (377 counties). Counties in these clusters had the lowest overall mean transplant rate (61.1), highest overall mean ESKD incidence (61.3), and highest mean county health scores percentile (80.9%, P <0.001 vs all other cluster types). By comparison, counties in clusters with low ESKD incidence and high transplant rates (n=359) had the highest mean transplant rate (110.6), the lowest mean ESKD incidence (28.9), and the lowest county health scores (20.2%). All comparisons to high-ESKD/low-transplant clusters were significant at P value <0.001. CONCLUSION: There was a significant mismatch between kidney transplant rates and ESKD burden, where areas with the greatest need had the lowest transplant rates. This pattern exacerbates pre-existing disparities, as disadvantaged high-ESKD regions already suffer from worse access to care and overall community health, as evidenced by the highest county health scores in the study.

Donor-reported barriers to living kidney donor follow-up.

BACKGROUND: Despite regulations mandating follow-up laboratory testing for living kidney donors, less than half of transplant centers are in compliance. We sought to understand barriers to follow-up testing from the donors' perspective. METHODS: We surveyed our center's living kidney donors. Binary logistic regression was used to assess factors associated with follow-up testing completion. RESULTS: Of 185 living kidney donors, 110 (59.4%) participated. Among them, 82 (74.5%) completed 6-month laboratory testing, 76 (69.1%) completed 12-month testing, 68 (61.8%) completed both, and 21 (19.0%) completed neither. Six-month testing completion was strongly associated with 12-month testing completion (OR 9.74, 95%CI: 2.23-42.50; p = .002). Those who disagreed with the statements, "Getting labs checked wasn't a priority for me," (OR for completing 6-month testing: 15.05, 95%CI: 3.70-61.18; p < .001; OR for completing 12-month testing: 5.85, 95%CI: 1.94-17.63; p = .002); and, "I forgot to get labs drawn [until I was reminded]" (OR for completing 6-month testing: 6.93, 95%CI: 1.59-30.08; p = .01; OR for completing 12-month testing: 6.55, 95%CI: 1.98-21.63; p = .002) were more likely to complete testing. CONCLUSIONS: To our knowledge, this is the only study providing perspective on donor insights regarding the need for follow-up testing post donation. Interventions to influence living donor attitudes toward follow-up testing may improve follow-up.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Hepatic macrosteatosis in the US pediatric deceased liver donor population.

INTRODUCTION: The pediatric obesity epidemic is associated with early development of hepatic macrosteatosis, a hallmark of non-alcoholic fatty LI disease, which is thought to be more rapidly progressive in children than adults. Macrosteatosis in adult allografts is associated with allograft loss, but this has not been examined in pediatric donors. METHODS: We studied all pediatric potential whole LI donors (2005-2018) who had a LI biopsy in the SRTR (n = 862) and whose LI was transplanted (n = 862). Macrosteatosis was abstracted from biopsy reports and compared to values in the SRTR standard analytic file. Recipients of macrosteatotic pediatric allografts were matched 1:1 to recipients of non-macrosteatotic pediatric allografts by propensity score matching on donor/recipient variables. All-cause allograft loss was estimated via Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: From 2005 to 2018, the proportion of pediatric donors (age ≥2 years) with obesity increased (14.8% to 21.7%; p < .001), as did the proportion of pediatric deceased whole LI-only donor allografts with macrosteatosis (n = 10 648; 1.8% to 3.9%; p < .001). The median degree of macrosteatosis among macrosteatotic donors was 10% (IQR 5-30). There were no significant differences in all-cause allograft loss between recipients of pediatric LI allografts with and without macrosteatosis at 90 days (p = .11) or 1 year (p = .14) post-transplant in Kaplan-Meier analysis or a Cox proportional hazards model (p > .05). CONCLUSION: Obese pediatric LI donors have increased over time and were more likely to have hepatic macrosteatosis; however, pediatric macrosteatosis did not appear to adversely affect recipient outcomes.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

The Influence of an Acting or Subintern on Third-Year Medical School Surgery Clerkship Students.

BACKGROUND: Previous reports demonstrated a positive relationship between the surgical clerkship and student likelihood of pursuing a surgical career, but no studies have examined the influence a peer has on comfort during a surgical clerkship. We hypothesized that a fourth-year acting intern (AI) would positively impact third-year medical students' experience during their surgical clerkship. METHODS: All third-year medical students at our institution who completed their surgical clerkship in 2019 were surveyed regarding the preclerkship and postclerkship perceptions. RESULTS: Of the 110 students surveyed, 52 responded (47.3% response rate), and 25 students (48.1%) reported having an AI during their clerkship rotation, and 27 did not (51.9%). Presence of an AI had no significant effect on the postclerkship perception of surgery, likelihood of pursuing general surgery, or comfort in the OR. Analysis of all responses demonstrated the surgery clerkship had no significant impact on students' perception of surgery or likelihood of pursuing general surgery but did statistically increase students' comfort in the OR. CONCLUSIONS: The results of this study suggest that AI presence did not significantly influence a student's clerkship experience or comfort in the OR. Further studies are needed to determine what, if any effect, an AI could have on third-year clerkship students.

Influence of Pennsylvania liquor store closures during the COVID-19 pandemic on alcohol withdrawal consultations.

INTRODUCTION: Alcohol withdrawal syndrome (AWS) is a serious consequence of alcohol use disorder (AUD). Due to the current COVID-19 pandemic there was a closure of Pennsylvania (PA) liquor stores on March 17, 2020. METHODS: This is a retrospective, observational study of AWS patients presenting to a tertiary care hospital. We used descriptive statistics for continuous and categorical variables and compared AWS consults placed to the medical toxicology service for six months preceding liquor store closure to those placed between March 17, 2020 and August 31, 2020. We compared this to consults placed to the medical toxicology service placed from October 1, 2019 through March 16, 2020. Charts were identified based on consults placed to the medical toxicology service, and alcohol withdrawal was determined via chart review by a medical toxicologist. This study did not require IRB approval. We evaluated Emergency Department (ED) length of stay (LOS), weekly and monthly consultation rate, rate of admission and ED recidivism, both pre- and post-liquor store closure. RESULTS: A total of 324 AWS consults were placed during the ten month period. 142 (43.8%) and 182 (56.2%) consults were pre- and post-liquor store closure. The number of consults was not statistically significant comparing these two time frames. There was no significant difference by patient age, gender, or race or by weekly or monthly consultation rate when comparing pre- and post-liquor store periods. The median ED LOS was 7 h (95% Confidence Interval (CI) Larson et al. (2012), Pollard et al. (2020) [5, 11]) and did not significantly differ between pre- and post-liquor store periods (p = 0.78). 92.9% of AWS patients required admission without significant difference between the pre- and post-liquor store closure periods (94.4% vs. 91.8%, p = 0.36). There was a significant increase in the number of AWS patients requiring a return ED visit (Odds Ratio 2.49; 95% CI [1.38, 4.49]) post closure. CONCLUSION: There were nearly 2.5 times greater odds of ED recidivism among post-liquor store closure AWS patients compared with pre-closure AWS patients.

Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench.

Alcoholic liver disease (ALD) is a major cause of liver-related mortality. There is still no US Food and Drug Administration-approved therapy for ALD, and therefore, identifying therapeutic targets is needed. Our previous work demonstrated that ethanol exposure leads to up-regulation of cAMP-degrading phosphodiesterase 4 (PDE4) expression, which compromises normal cAMP signaling in monocytes/macrophages and hepatocytes. This effect of ethanol on cAMP signaling contributes to dysregulated inflammatory response and altered lipid metabolism. It is unknown whether chronic alcohol consumption in humans alters hepatic PDE4 expression and cAMP signaling and whether inadequate cAMP signaling plays a pathogenic role in alcohol-induced liver injury. Our present work shows that expression of the PDE4 subfamily of enzymes is significantly up-regulated and cAMP levels are markedly decreased in hepatic tissues of patients with severe ALD. We also demonstrate the anti-inflammatory efficacy of roflumilast, a clinically available PDE4 inhibitor, on endotoxin-inducible proinflammatory cytokine production ex vivo in whole blood of patients with alcoholic hepatitis. Moreover, we demonstrate that ethanol-mediated changes in hepatic PDE4 and cAMP levels play a causal role in liver injury in in vivo and in vitro models of ALD. This study employs a drug delivery system that specifically delivers the PDE4 inhibitor rolipram to the liver to avoid central nervous system side effects associated with this drug. Our results show that PDE4 inhibition significantly attenuates ethanol-induced hepatic steatosis and injury through multiple mechanisms, including reduced oxidative and endoplasmic reticulum stress both in vivo and in vitro. Conclusion: Increased PDE4 plays a pathogenic role in the development of ALD; hence, directed interventions aimed at inhibiting PDE4 might be an effective treatment for ALD.

Sex differences in patients with suicidal intent that are managed by toxicologists: An analysis of the Toxicology Investigators' Consortium (ToxIC) Registry.

INTRODUCTION: The Toxicology Investigator's Consortium (ToxIC) maintains a prospective case registry of all patients that have been managed at the bedside by medical toxicologists. We set out to characterize the differences in toxicological suicide attempts between men and women among adult patients with poisonings managed by medical toxicologists. METHODS: ToxIC database consults for adults aged 19-65 whose primary reasons for encounter were classified as suicide attempt were used for this study (1/2010-12/2016). Data used for analysis included primary agents of toxic exposure, routes of administration, and complications. The statistical analysis was limited to descriptive methods. RESULTS: Out of 51,440 registry cases, 33,259 cases remained for analysis after applying the ages 19-65 and removing those without complete data. Of these, there were 4827 suicide attempts (14.5% of toxicological exposures) which were sub classified by gender. There were more females (F) than males (M) whose toxicology consults were due to suicidal attempts (57.6% versus 42.4%). We also found that more males used alcohol as their primary agent (2.8%M v 1.5%F) or a nonpharmaceutical (%7.4 M v %2.3 F). CONCLUSIONS: In our study, we found that there were more females than males who attempted suicide by self-poisoning; and more of them used pharmaceuticals than males. In contrast, a greater number of males used nonpharmaceuticals such as alcohol. We did not find large sex-differences in suicide completion rates, routes of administration, or subsequent symptomologies. In summary, sex-based differences were observed between adult patients with suicidal-intent exposures/ingestions managed at the bedside by medical toxicologists.

Patterns of geographic variability in mortality and eligible deaths between organ procurement organizations.

Eligible deaths are currently used as the denominator of the donor conversion ratio to mitigate the effect of varying mortality patterns in the populations served by different organ procurement organizations (OPOs). Eligible death is an OPO-reported metric rather than a product of formal epidemiological analysis, however, and may be confounded with OPO performance. Using Scientific Registry of Transplant Recipients and Centers for Disease Control and Prevention data, patterns of mortality and eligible deaths within each OPO were analyzed with the use of formal geostatistical analysis to determine whether eligible deaths truly reflect the geographic patterns they are intended to mitigate. There was a 2.1-fold difference in mortality between the OPOs with the highest and lowest rates, with significant positive spatial autocorrelation evident in mortality rates (Moran I = .110; P < .001), meaning geographically proximate OPOs tended to have similar mortality rates. The eligible death ratio demonstrated greater variability, with a 4.5-fold difference between the OPOs with the highest and lowest rates. Contrary to the pattern of mortality rates, the geographic distribution of eligible deaths among OPOs was random (Moran I = -.002; P = .410). This finding suggests geographic patterns do not play a significant role in eligible deaths, thus questioning its continuing use in OPO performance comparisons.

Thoracic Aortic Dissection Associated with Marijuana Use.

BACKGROUND: Acute aortic dissection (AD) is a life-threatening condition most frequently seen in men with an average age >60 years. Risk factors include family history, hypertension and cigarette smoking. AD has been associated with methamephatamine and cocaine use but has not previously been associated with the use of marijuana. CASE REPORT: We report a case of an aortic dissection in a 56-year-old male that occurred while smoking marijuana. The patient had a family history significant for both aortic aneurysm and dissection. He developed crushing chest pain, shortness of breath, and diaphoresis shortly after smoking marijuana from a glass pipe called a "bubbler". His ECG was unremarkable as was his chest x-ray and initial labs. CT scan revealed an Aortic dissection from the aortic root to the internal iliac artery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The role of cannabis in cardiovascular disorders is complex and not completely understood. Acute chest pain associated with marijuana use typically raises concern for pneumothorax or pneumomediastinum. Marijuana has also been associated with hypertension and arrhythmias and has also been associated with an increased risk of myocardial infarction. However a link between marijuana and acute aortic dissection has not been previously reported. As more states legalize medical and recreational marijuana use this is a timely and important consideration for Emergency physicians evaluating chest pain. Our goal is to document the temporal relationship of cannabis use and acute aortic dissection in a recent ED patient.

Brief Motivational Interviewing for Substance Use by Medical Students Is Effective in the Emergency Department.

BACKGROUND: Efficacy of medical student substance use interventions in the emergency department (ED) setting remains unstudied. OBJECTIVE: In this pilot study, we set out to determine whether medical students could perform a brief motivational interview for substance use in the ED. METHODS: At two hospitals, medical students utilized motivational interviewing skills taught by their medical school curriculum and administered a substance use intervention to ED patients who met the study definition of unhealthy substance use. RESULTS: In 6 weeks, medical students gave a brief intervention to 102 subjects. The mean age of the subjects was 46.9 (standard deviation 15.6) years. The majority, 86 (86.3%) identified as white. Fifty-four (52.9%) identified as male. Eighty of 102 (78.4%) participants completed a phone follow-up assessment. Of the 69 smokers, 11 (15.9%) reported attempting to quit or quitting completely. Of the 33 with high-risk alcohol use, 11 (33.3%) were abstaining completely from alcohol use and an additional 12 (36.4%) reported a decrease in alcohol daily consumption (measured in drinks per day). Warm hand-off success for street drugs or at-risk alcohol use was 13.6% for those who received an intervention. CONCLUSIONS: It is feasible for medical students to perform a substance use intervention in the ED setting. Medical student contributions as a part of the team response to this public health crisis provide an opportunity for further discussion and research.

A cost analysis of early biliary strictures following orthotopic liver transplantation in the United States.

INTRODUCTION: To date, the financial burden of biliary strictures (BS) after orthotopic liver transplantation (OLT) has remained largely unassessed. This study sought to approximate perioperative costs associated with early BS and delineate where in the hospital these costs are incurred. METHODS: The Premier Healthcare Database was queried for patients undergoing OLT between 2010 and 2016. Patients who did and did not develop early BS were compared with respect to perioperative costs and outcome variables. Multivariable regression models were used to estimate differences between groups. RESULTS: Patients who developed early BS had a longer length of stay (LOS) (35.3 days vs 17.8 days, P < 0.001) and were less likely to be discharged home (odds ratio = 0.45, P = 0.003). Development of early BS was associated with an incremental cost increase of $81 881 (45.8%, P < 0.001). The greatest relative cost increases were in radiology (+163.5%) and respiratory therapy (+157.1%), while the greatest absolute increase was in room and board (+$27 589). CONCLUSIONS: Early BS after OLT result in higher costs stemming from longer LOS and increased need for various diagnostic studies and therapies. In addition to incentivizing measures that may prevent early BS, hospitals should account for these factors when developing payment schemes for OLT with payors.

Assessing relative cost of complications following orthotopic liver transplant.

INTRODUCTION: Perioperative complications impose both a clinical and financial burden on patients and the healthcare system. This study sought to identify the frequency and economic impact of complications following orthotopic liver transplantation (OLT). METHODS: The Premier Perspective® Hospital Database was queried for patients undergoing OLT between 2008 and 2015. Complications were identified by ICD-9 code and grouped by complication type. Complication frequency as well as impact on clinical and economic outcomes was calculated. Complication frequency and effect on cost were combined to determine the annual impact of each complication type on perioperative OLT cost. RESULTS: Among 2747 OLT patients, the most common groups of complications following OLT were pulmonary, bleeding, and infectious. The complications with the greatest average effect on treatment-related costs were infectious, neurologic, deep vein thrombosis/pulmonary embolus, and hepatic arterial thrombosis. Infectious, pulmonary, and bleeding complications had the greatest annual effect on perioperative OLT cost. CONCLUSIONS: Efforts focused on preventing coagulopathic bleeding, improving post-operative pulmonary toilet, and minimizing sources of infection can help improve the cost-effectiveness of OLT. Additionally, the combination of these cost data and systematized protocols can help insurers construct bundled payments for OLT that more accurately reflect the cost of perioperative transplant care.

Loperamide-Induced Torsades de Pointes: A Case Series.

BACKGROUND: Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations. CASE REPORT 1: A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered intravenous sodium bicarbonate and magnesium sulfate and admitted to the intensive care unit, eventually developing Torsades de Pointes (TdP). He was given lidocaine and isoproterenol infusions, and an external pacemaker was placed. He was discharged in stable condition on hospital day (HD) 16. CASE REPORT 2: A 39-year-old woman with a history of hepatitis C, depression, and SUD was transported to the ED after reported seizure-like activity. The patient experienced TdP in the ED and admitted to ingesting large amount of loperamide daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208 ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit admission, the patient experienced no further TdP and was discharged on HD 6. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should proceed with caution when treating patients with loperamide toxicity. Even in asymptomatic patients and drug discontinuance, obtain consultation with a medical toxicologist, promptly treat ECG abnormalities aggressively, and admit all patients for further monitoring.

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.

Recipient obesity and outcomes after kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation. METHODS: A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated. RESULTS: Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847). CONCLUSIONS: Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.