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Background and Objectives: During its monthly morbidity and mortality conference (MMC), the University of Colorado Division of Cardiology reviewed a "near-miss" patient safety event involving the delayed completion of a Stat-priority (ie, statim, meaning high priority) electrocardiogram (ECG). Because critical and interprofessional stakeholders participated in the conference, we hypothesized that the MMC would be associated with reduced ECG completion times., Methods: Data were collected for in-hospital ECGs performed at the University of Colorado Hospital between January 1, 2017, and June 30, 2018. An interrupted time series analysis was used to estimate the immediate and ongoing impact of the MMC (held on February 28, 2018) on ECG completion times, stratified by order priority (Stat, Now, or Routine). The percentage of delayed Stat-priority ECGs was analyzed as a secondary outcome., Results: Before the MMC, ECG completion times were stable for all order priorities ( P > .2), but the proportion of delayed Stat-priority ECGs increased from 5% in January 2017 to 20% in February 2018 ( P < .01). The MMC was associated with an immediate reduction in average daily ECG completion times for Routine (-18.4 minutes, P = .03) and Now (-8 minutes, P = .024) priority ECGs. No reduction was seen for Stat ECGs ( P = .97), though the percentage of delayed Stat ECGs stopped increasing ( P = .63). In the post-MMC period, completion times for Routine-priority ECGs increased and approached pre-MMC levels., Conclusions: The MMC was associated with an immediate, but temporary, improvement in ECG completion times. Although the observed clinical benefit of the MMC is novel, these data support the need for more durable reforms to sustain initial improvements., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiovascular disease is the leading cause of death globally. While pharmacological advancements have improved the morbidity and mortality associated with cardiovascular disease, non-adherence to prescribed treatment remains a significant barrier to improved patient outcomes. A variety of strategies to improve medication adherence have been tested in clinical trials, and include the following categories: improving patient education, implementing medication reminders, testing cognitive behavioral interventions, reducing medication costs, utilizing healthcare team members, and streamlining medication dosing regimens. In this review, we describe specific trials within each of these categories and highlight the impact of each on medication adherence. We also examine ongoing trials and future lines of inquiry for improving medication adherence in patients with cardiovascular diseases., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: STS reports none, AEL reports none, VK reports unrelated research grants from the NIH and Greenwall Foundation, PMH reports research grants from Department of Veterans Affairs, NHLBI, and University of Colorado School of Medicine. His NHLBI grant is focused on medication adherence. He has a research agreement with Bristol Myers Squibb unrelated to medication adherence. He serves as a deputy editor for Circulation: Cardiovascular Quality and Outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Among Medicare value-based payment programs for acute myocardial infarction (AMI), the Hospital Readmissions Reduction Program uses International Classification of Diseases, Tenth Revision ( ICD-10 ) codes to identify the program denominator, while the Bundled Payments for Care Improvement Advanced program uses diagnosis-related groups (DRGs). The extent to which these programs target similar patients, whether they target the intended population (type 1 myocardial infarction), and whether outcomes are comparable between cohorts is not known., Methods: In a retrospective study of 2176 patients hospitalized in an integrated health system, a cohort of patients assigned a principal ICD-10 diagnosis of AMI and a cohort of patients assigned an AMI DRG were compared according to patient-level agreement and outcomes such as mortality and readmission., Results: One thousand nine hundred thirty-five patients were included in the ICD-10 cohort compared with 662 patients in the DRG cohort. Only 421 patients were included in both AMI cohorts (19.3% agreement). DRG cohort patients were older (70 versus 65 years, P <0.001), more often female (48% versus 30%, P <0.001), and had higher rates of heart failure (52% versus 33%, P <0.001) and kidney disease (42% versus 25%, P <0.001). Comparing outcomes, the DRG cohort had significantly higher unadjusted rates of 30-day mortality (6.6% versus 2.5%, P <0.001), 1-year mortality (21% versus 8%, P <0.001), and 90-day readmission (26% versus 19%, P =0.006) than the ICD-10 cohort. Two observations help explain these differences: 61% of ICD-10 cohort patients were assigned procedural DRGs for revascularization instead of an AMI DRG, and type 1 myocardial infarction patients made up a smaller proportion of the DRG cohort (34%) than the ICD-10 cohort (78%)., Conclusions: The method used to identify denominators for value-based payment programs has important implications for the patient characteristics and outcomes of the populations. As national and local quality initiatives mature, an emphasis on ICD-10 codes to define AMI cohorts would better represent type 1 myocardial infarction patients.

Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions. Although individual health systems are engaged in projects to improve the quality of care delivery, these efforts often lack a robust study design or implementation evaluation that can inform generalizability and further dissemination. Aligning the work of health care systems and health services and outcomes researchers could serve as a strategy to overcome persisting gaps in cardiovascular quality and outcomes. We describe the inception of the Cardiovascular Quality Improvement and Care Innovation Consortium that seeks to rapidly improve cardiovascular care by (1) developing, implementing, and evaluating multicenter quality improvement projects using innovative care designs; (2) serving as a resource for quality improvement and care innovation partners; and (3) establishing a presence within existing quality improvement and care innovation structures. Success of the collaborative will be defined by projects that result in changes to care delivery with demonstrable impacts on the quality and outcomes of care across multiple health systems. Furthermore, insights gained from implementation of these projects across sites in Cardiovascular Quality Improvement and Care Innovation Consortium will inform and promote broad dissemination for greater impact.

Introduction: Although the Accreditation Council for Graduate Medical Education requires quality improvement and patient safety (QIPS) training for fellow-level trainees, this experience is often insufficient due to lack of faculty time and expertise within fellowship training programs. We developed a centralized GME curriculum targeted to an integrated, multispecialty audience of fellow-level trainees with the goal of promoting leadership and scholarship in QIPS., Methods: The University of Colorado implemented the Fellows' Quality and Safety Academy, a three-seminar curriculum in patient safety and health systems improvement. As most participants had prior training in QIPS during medical school or residency, educational strategies emphasized application of QIPS concepts through focused didactic content review paired with small-group case-based exercises and coaching of experiential project work to promote content mastery as well as practice of leadership and scholarship strategies., Results: Since the curriculum's inception in 2017, there have been 106 participants in the Foundations in Patient Safety seminar, 49 participants in the Adverse Events Into Quality Improvement seminar, and 48 participants in the Quality in Academics seminar. These participants represented 44 separate fellowship disciplines from both adult and pediatric subspecialties. Learners reported improved attitudes and confidence and demonstrated objective knowledge acquisition across QIPS content domains., Discussion: Our pedagogical approach of centralizing QIPS training and harnessing faculty expertise to teach fellow-level trainees across specialties through interdisciplinary collaboration and interactive project-based work is an effective strategy to promote development of QIPS competencies during fellowship training., (© 2020 Neumeier et al.)

Background: Initiation of the antiarrhythmic medication dofetilide requires an FDA-mandated 3 days of telemetry monitoring due to heightened risk of toxicity within this time period. Although a recommended dose management algorithm for dofetilide exists, there is a range of real-world approaches to dosing the medication., Methods and Results: In this multicenter investigation, clinical data from the Antiarrhythmic Drug Genetic (AADGEN) study was examined for 354 patients undergoing dofetilide initiation. Univariate logistic regression identified a starting dofetilide dose of 500 mcg (OR 5.0, 95%CI 2.5-10.0, p<0.001) and sinus rhythm at the start of dofetilide loading (OR 2.8, 95%CI 1.8-4.2, p<0.001) as strong positive predictors of successful loading. Any dose-adjustment during loading (OR 0.19, 95%CI 0.12-0.31, p<0.001) and a history coronary artery disease (OR 0.33, 95%CI 0.19-0.59, p<0.001) were strong negative predictors of successful dofetilide loading. Based on the observation that any dose adjustment was a significant negative predictor of successful initiation, we applied multiple supervised approaches to attempt to predict the dose adjustment decision, but none of these approaches identified dose adjustments better than a probabilistic guess. Principal component analysis and cluster analysis identified 8 clusters as a reasonable data reduction method. These 8 clusters were then used to define patient states in a tabular reinforcement learning model trained on 80% of dosing decisions. Testing of this model on the remaining 20% of dosing decisions revealed good accuracy of the reinforcement learning model, with only 16/410 (3.9%) instances of disagreement., Conclusions: Dose adjustments are a strong determinant of whether patients are able to successfully initiate dofetilide. A reinforcement learning algorithm informed by unsupervised learning was able to predict dosing decisions with 96.1% accuracy. Future studies will apply this algorithm prospectively as a data-driven decision aid., Competing Interests: The authors have declared that no competing interests exist.

Background: Reporting standards promote clarity and consistency of stress myocardial perfusion imaging (MPI) reports, but do not require an assessment of post-test risk. Natural Language Processing (NLP) tools could potentially help estimate this risk, yet it is unknown whether reports contain adequate descriptive data to use NLP., Methods: Among VA patients who underwent stress MPI and coronary angiography between January 1, 2009 and December 31, 2011, 99 stress test reports were randomly selected for analysis. Two reviewers independently categorized each report for the presence of critical data elements essential to describing post-test ischemic risk., Results: Few stress MPI reports provided a formal assessment of post-test risk within the impression section (3%) or the entire document (4%). In most cases, risk was determinable by combining critical data elements (74% impression, 98% whole). If ischemic risk was not determinable (25% impression, 2% whole), inadequate description of systolic function (9% impression, 1% whole) and inadequate description of ischemia (5% impression, 1% whole) were most commonly implicated., Conclusions: Post-test ischemic risk was determinable but rarely reported in this sample of stress MPI reports. This supports the potential use of NLP to help clarify risk. Further study of NLP in this context is needed.

Objective: To identify the threshold of total body fat percentage (TBF%) required for the resumption of menses (ROM) in hospitalized female adolescents with anorexia nervosa (AN) using bioimpedance analysis (BIA)., Methods: All female adolescents hospitalized with AN in our medical center were evaluated in a longitudinal prospective study during the years of 2012-2017. Anthropometric data, body fat measured by BIA, and hormonal determinants were collected periodically, in addition to routine medical and gynecological assessments., Results: Sixty-two participants presented with secondary amenorrhea, of which 20 remained with amenorrhea and 42 had ROM during hospitalization. At discharge, participants with ROM regained significantly more weight, and had higher mean body mass index (BMI), BMI standard deviation scores, and TBF% than those who remained with amenorrhea. Receiver operating characteristic analysis identified that a TBF% of 21.2% had the highest discriminative ability for ROM (sensitivity = 88%, specificity = 85%, positive predictive value = 93%). Compared with the anthropometric parameters, TBF% had the highest area under curve (AUC = .895), which significantly differed from that of BMI standard deviation scores (AUC = .643, p = .007) and body weight (AUC = .678, p = .03)., Conclusions: BIA is a safe and relatively simple method to assess the TBF% required for the return of balanced menstrual cycles in female adolescents with AN. The TBF% with the highest discriminative ability for menstrual resumption as assessed by BIA is 21.2%., (Copyright © 2018. Published by Elsevier Inc.)

Purpose of Review: Non-adherence to medications for the secondary prevention of myocardial infarction (MI) is a major contributor to morbidity and mortality in these patients. This review describes recent advances in promoting adherence to therapies for coronary artery disease (CAD)., Recent Findings: Two large randomized controlled trials to "incentivize" adherence were somewhat disappointing; neither financial incentives nor "peer pressure" successfully increased rates of adherence in the post-MI population. Patient education and provider engagement appear to be critical aspects of improving adherence to CAD therapies, where the provider is a physician, pharmacist, or nurse and follow-up is performed in person or by telephone. Fixed-dose combinations of CAD medications, formulated as a so-called "polypill," have shown some early efficacy in increasing adherence. Technological advances that automate monitoring and/or encouragement of adherence are promising but seem universally dependent on patient engagement. For example, medication reminders via text message perform better if patients are required to respond. Multifaceted interventions, in which these and other interventions are combined together, appear to be most effective. There are several available types of proven interventions through which providers, and the health system at large, can advance patient adherence to CAD therapies. No single intervention to promote adherence will be successful in all patients. Further study of multifaceted interventions and the interactions between different interventions will be important to advancing the field. The goal is a learning healthcare system in which a network of interventions responds and adapts to patients' needs over time.

Problem: Medical education has been cited as both part of the problems facing, and part of the solution to reforming, the increasingly challenging U.S. health care system which is fraught with concerns regarding the quality and affordability of care. To teach value in ways that are impactful, sustainable, and scalable, the best and brightest ideas need to be shared such that educators can build on successful existing innovations., Approach: To identify the most promising innovations and bright ideas for teaching value to clinical trainees, the authors hosted the "Teaching Value and Choosing Wisely Challenge." The challenge used crowdsourcing methods to solicit scalable, pedagogical approaches from across North America, and then draw generalizable lessons., Outcomes: The authors received 74 submissions (28 innovations; 46 bright ideas) from 14 students, 20 residents/fellows, 38 faculty members (ranging from instructors to full professors), and 2 nonclinical administrators. Submissions represented 14 clinical disciplines including internal medicine, emergency medicine, surgery, pediatrics, obstetrics-gynecology, laboratory medicine, and pharmacy. Thirty-nine abstracts focused on graduate medical education, 15 addressed undergraduate medical education, and 20 applied to both., Next Steps: The authors have solicited, shared, and described solutions for teaching high-value care to medical trainees. Challenge participants demonstrated commitment to improving value and ingenuity in addressing professional barriers to change. Further success requires strong local faculty champions and willing trainee participants. Additionally, the use of data to demonstrate the collective positive impact of these ideas and programs will be critical for sustaining pedagogical changes in the health professions.

Normal atrial conduction requires similar abundances and homogeneous/overlapping distributions of two connexins (Cx40 and Cx43). The remodeling of myocyte connections and altered electrical conduction associated with atrial fibrillation (AF) likely involves perturbations of these connexins. We conducted a comprehensive series of experiments to examine the abundances and distributions of Cx40 and Cx43 in the atria of AF patients. Atrial appendage tissues were obtained from patients with lone AF (paroxysmal or chronic) or normal controls. Connexins were localized by double label immunofluorescence confocal microscopy, and their overlap was quantified. Connexin proteins and mRNAs were quantified by immunoblotting and qRT-PCR. PCR amplified genomic DNA was sequenced to screen for connexin gene mutations or polymorphisms. Immunoblotting showed reductions of Cx40 protein (to 77% or 49% of control values in samples from patients with paroxysmal and chronic AF, respectively), but no significant changes of Cx43 protein levels in samples from AF patients. The extent of Cx43 immunostaining and its distribution relative to N-cadherin were preserved in the AF patient samples. Although there was variability of Cx40 staining among paroxysmal AF patients, all had some fields with substantial Cx40 heterogeneity and reduced overlap with Cx43. Cx40 immunostaining was severely reduced in all chronic AF patients. qRT-PCR showed no change in Cx43 mRNA levels, but reductions in total Cx40 mRNA (to <50%) and Cx40 transcripts A (to ~50%) and B (to <25%) as compared to controls. No Cx40 coding region mutations were identified. The frequency of promoter polymorphisms did not differ between AF patient samples and controls. Our data suggest that reduced Cx40 levels and heterogeneity of its distribution (relative to Cx43) are common in AF. Multiple mechanisms likely lead to reductions of functional Cx40 in atrial gap junctions and contribute to the pathogenesis of AF in different patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: We evaluated the impact of expert instruction during laboratory-based basic surgical skills training on subsequent performance of more complex surgical tasks., Methods: Forty-five junior residents were randomized to learn basic surgical skills in either a self-directed or faculty-directed fashion. Residents returned to the laboratory 2 days later and were evaluated while performing 2 tasks: skin closure and bowel anastomosis. Outcome measures included Objective Structured Assessment of Technical Skill, time to completion, final product quality, and resident perceptions., Results: Objective Structured Assessment of Technical Skill, time to completion, and skin esthetic ratings were not better in the faculty-directed group, although isolated improvement in anastomotic leak pressure was seen. Residents perceived faculty-directed training to be superior., Conclusions: Our data provided minimal objective evidence that faculty-directed training improved transfer of learned skills to more complex tasks. Residents perceived that there was a benefit of faculty mentoring. Curriculum factors related to training of basic skills and subsequent transfer to more complex tasks may explain these contrasting results.

Hypothesis: Multimedia delivery of cognitive content paired with faculty-supervised partial task simulation for both excision of a simulated skin lesion with subsequent wound closure and hand-sewn bowel anastomosis would be an effective method for developing appropriate procedural skills among junior residents., Design: Prospective cohort study., Setting: University-based surgical residency., Participants: First- and second-year surgical residents (n = 45)., Interventions: Surgical residents were given comprehensive instructional materials, including structured curricula with goals and objectives, text, figures, and narrated expert digital video, before the training session. A 4-hour, standardized, laboratory-based instruction session was then performed in small groups, which emphasized faculty-supervised practice. Residents were asked to (1) excise a skin lesion and close the wound and (2) perform hand-sewn bowel anastomosis. These 2 tasks were assessed before and after supervised practice. Performances were video recorded. Residents were surveyed before and after training., Main Outcome Measures: Time to completion and Objective Structured Assessment of Technical Skill global rating scale score based on video recordings were evaluated by blinded reviewers. Final product quality was measured by anastomotic leak pressure and by wound closure aesthetic quality., Results: Residents perceived the laboratory training to be equal to training in the operating room for skin closure and superior to training in the operating room for bowel anastomosis. Residents perceived time spent on both tasks to be "perfect." Mean objective scores improved significantly on 5 of 6 outcome measures., Conclusions: Junior resident surgical performance improved substantially with 4 hours of laboratory-based, faculty-supervised practice. Both first- and second-year residents benefited from this training. These data show that curriculum-driven, faculty-supervised instruction in a laboratory setting is beneficial in the training of junior surgical residents.

The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We conducted a retrospective review of 834 consecutive liver transplants from 1/1/1996 to 12/31/2005 (mean follow-up 1303 +/- 1069 days) at one institution and 352 consecutive transplants from 1/2/2002 to 12/31/2005 (mean follow-up 836 +/- 402 days) at a second institution. The test cohort comprised patients identified with HCC in their explanted livers from 1/1/2001 to 12/31/2005 at the first institution. Explant pathology and donor and recipient characteristics were reviewed to determine factors associated with HCC recurrence. These predictors were validated in the remaining liver transplant recipients. The test cohort had 116 patients with findings of HCC in their explanted livers. Twelve patients developed recurrent HCC. Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (>4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from -3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. In conclusion, patients transplanted for HCC with a PCRS of < or =0 have a low risk of recurrence. Patients with a PCRS of 1 or 2 have a moderate risk of recurrence, and those with a PCRS of > or =3 have a high risk for recurrence.

The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1-year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times > or =9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts.

Background: Antiviral prophylaxis has been shown to decrease the incidence of cytomegalovirus (CMV) disease in organ transplant recipients, but whether CMV disease that occurs despite prophylaxis is associated with mortality remains unknown., Methods: The clinical features and risk factors for CMV disease in a cohort of liver transplant recipients who received antiviral prophylaxis were assessed retrospectively. Cox proportional hazard regression was used to assess the relationship of CMV to mortality during the first posttransplant year., Results: CMV disease developed in 37 of 437 (8.5%) recipients at a median of 4.5 (range, 2.5 to 12) months posttransplant and was associated only with donor-seropositive/recipient-seronegative serostatus in multivariate analysis (P<0.0001). Mortality at 1 year was 12% (51 of 437) and was infection-associated in 49% of cases. In multivariate analysis, CMV disease was independently associated with overall mortality at 1 year (HR, 5.1, P=0.002) and even more strongly with infection-associated mortality (HR 11, P=0.002). There was no association of CMV with noninfection-associated mortality (P>0.05)., Conclusions: Late CMV disease is an important clinical problem in liver transplant recipients who receive antiviral prophylaxis, and is strongly and independently associated with mortality. Strategies to prevent late CMV disease are warranted.

Background: With the advent of programs such as the American College of Surgeons-National Surgical Quality Improvement Program, surgical services will be compared with their peers across the United States. At times, many programs will experience lower-than-expected outcomes. During July 1, 1998, to June 30, 2000 our 1-year graft (76.86%, P = 0.23) and patient (80.61%, P = 0.016) survivals after liver transplantation were lower than our expected rates (graft 81.89% and patient 88.3%), according to the U.S. Scientific Registry of Transplant Recipients (SRTR)., Methods: We used aggregate root cause analysis to determine underlying reasons for our patient deaths. Two of our surgeons performed a systematic review of all our center's liver transplant patient deaths from January 1, 1995, to December 31, 2000. Each phase of the transplant process was reviewed., Results: Of 355 patients receiving their first transplant, there were 90 deaths, with 188 root causes identified. The apportionment according to phase of the transplant process was patient selection, 50%; transplant procedure, 17%; donor selection, 15%; post-transplant care, 8%, and psychosocial issues, 10%. Risk reduction action plans were developed, and several important changes made in our care protocol. In April 2004, SRTR data revealed that for patients transplanted between January 1, 2001 and June 30, 2003, our 1-year liver graft survival of 90.73% (P = 0.018) was significantly higher than the national expected rate of 84.48%. Our 1-year patient survival rate of 92.66% (P = 0.285) was higher than the expected rate of 89.29%., Conclusions: Lower-than-expected outcomes can provide an impetus for improving patient care and raising the quality of a surgical service. Aggregate root cause analysis of adverse events is a valuable method for program improvement.

Background: Bladder drainage of the exocrine secretions of pancreas transplants has been the standard of practice as it affords the ability to monitor for rejection and is thought to be associated with decreased morbidity. Recently, there has been renewed interest in avoiding the urinary tract complications and metabolic derangements that accompany bladder drainage by draining pancreatic exocrine secretions into the jejunum (enteric drainage). We sought to determine whether enteric drainage of pancreas transplants is safe and offers advantages without compromise in graft function or longevity., Methods: We retrospectively reviewed all pancreas transplants performed at the University of Washington between 2000 and 2003. Selection of the exocrine drainage method was based on the length of cold ischemia time and whether the pancreas was transplanted alone or in combination with a kidney. Pearson's chi-square and Fisher's Exact tests were used for statistical comparisons in complications or rejections between the groups., Results: Thirty-four pancreas transplants were performed with exocrine drainage into the bladder used in 17 and enteric drainage in 17. The complication rate was 53% in the bladder-drained group and 41% (P=.49) in the enteric-drained group. The incidence of pancreas rejection was 24% in the bladder-drained versus 29% in the enteric-drained patients (P=.50). One graft failed, which was in the bladder cohort., Conclusions: We found comparable rejection and complication rates between groups. We conclude that enteric drainage is safe when used selectively, and entails no increased risks compared with bladder drainage.

Hypothesis: Treatment of hepatocellular carcinoma before liver transplantation can curb local tumor progression and thereby prolong patients' transplantation eligibility., Design: Retrospective case-control pilot study. Twelve of 39 patients receiving liver transplantation for hepatocellular carcinoma had treatment before transplantation. Pretreatment included radiofrequency ablation (n = 8), percutaneous ethanol injection (n = 2), both modalities (n = 1), and tumor resection (n = 1). Twelve control subjects without pretreatment who were age-, sex-, and score-matched on the Model for End-stage Liver Disease and Child-Turcotte-Pugh classification were selected. The primary outcome measure was the waiting period for transplantation., Results: Patients with pretreatment waited on the transplant list significantly longer than their counterparts without pretreatment (median, 484 vs 253 days; P =.03)., Conclusions: Treatment before transplantation with tumor ablation or resection is associated with a longer waiting period on the transplant list. This enables patients who might otherwise be removed from the list because of tumor progression to receive transplantation.

Background and Objectives: Acetaminophen (INN, paracetamol) is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), a hepatotoxic metabolite, predominantly by cytochrome P450 (CYP) 2E1. Alterations in drug metabolism occur after organ transplantation. This study was designed to characterize acetaminophen disposition during the first 6 months after liver transplantation., Methods: Thirteen liver transplant patients received an oral dose of acetaminophen (500 mg) on days 2, 10, 90, and 180 after transplantation. Serial blood samples were collected for 8 hours, and urine was collected for 24 hours. Liver biopsy specimens were obtained from the donor liver during transplantation (day 0) and on days 10, 90, and 180 after transplantation., Results: There were significant time-dependent changes in acetaminophen metabolism after liver transplantation. When day 2 and day 10 were compared with day 180, the respective mean urinary recovery was 137% and 81% higher for thioether conjugates derived from NAPQI (P =.0002 and P =.01, respectively); 31% and 22% lower for acetaminophen sulfate (P =.0006 and P =.008, respectively); and 22% and 27% lower for acetaminophen glucuronide (P =.05 and P =.004, respectively). Metabolite formation clearances changed in concordance with the fractional urinary recovery. It was surprising that hepatic CYP2E1 content on day 10 after transplantation was only 20% higher, on average, than that found on day 180 (not significant). In contrast, hepatic CYP3A4 content was 984% higher, on average, when tissue from days 10 and 180 was compared after transplantation (P =.007)., Conclusions: Increased recovery of acetaminophen thioether conjugates during the first 10 days after liver transplantation was a result of impaired glucuronidation and sulfation and enhanced NAPQI formation.

Background: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options., Methods: We successfully re-transplanted a 46-year-old female patient who developed acute portal vein thrombosis 19 d after orthotopic liver transplantation. Vascular reconstruction included a cavoportal shunt to augment portal blood flow., Results: Twelve months after re-transplantation this patient lives independently and enjoys excellent liver allograft function., Conclusions: Cavoportal shunt can augment portal blood flow in adult recipients of orthotopic liver transplants. This technique can be successfully employed during re-transplantation when portal blood flow is inadequate to maintain patency.

Objective: We describe the imaging findings of venous thrombosis and occlusion after pancreatic transplantation in five patients who underwent multiphasic breath-hold gadolinium-enhanced three-dimensional MR imaging., Conclusion: Venous thrombus appeared as serpetine voids within the graft parenchyma or at the venous anastomosis during the venous phase of MR imaging. Nonenhancement or heterogeneous enhancement of graft parenchyma corresponded to glandular necrosis at pancreatectomy in two patients. Initial sonographic evaluation was nondiagnostic of venous thrombosis in two of five patients. Multiphasic breath-hold gadolinium-enhanced three-dimensional MR imaging of pancreatic transplants can provide information to make the specific diagnosis of venous thrombosis or occlusion.

While the existence of chimeric cells in host tissue following organ transplantation is well documented, its distribution, temporal evolution and relationship to allograft survival is less clear. To explore this phenomenon, Lewis recipients of ACI cardiac allografts representing a wide range of immunosuppressive protocols and graft survival times were examined for the presence of chimerism using a sensitive polymerase chain reaction assay. Four groups of animals were examined: untransplanted animals receiving donor specific transfusion (DST)/cyclosporine A (CsA); allograft recipients with no treatment; recipients treated with DST/CsA/supplementary immunosuppression with rejection at 21-183 days; and recipients sacrificed with functioning allografts, treated with DST/CsA/supplementary immunosuppression and surviving > 200 days. To elucidate variations in the tissue distribution of chimeric cells, bone marrow, skin, liver, spleen, and thymus were examined in each animal. Untransplanted animals receiving DST/CsA displayed no evidence of chimerism. In animals receiving a cardiac allograft but no treatment, there was extensive evidence of chimerism in four of five animals. Chimerism was also detected in seven of nine animals with intermediate graft survival at the time of rejection. In animals with long-term graft survival, only four of eight displayed chimerism. These results suggest that, without immunosuppression, early chimerism does not lead to prolonged graft survival and that, even when graft survival is moderately prolonged, these cells are not sufficient to prevent rejection. In conclusion, chimerism appears to be a common phenomenon following transplantation, is not a result of DST, and may not be necessary for maintenance of long-term graft survival.