Complications and Their Resolution in Recipients of Deceased and Living Donor Liver Transplants: Findings From the A2ALL Cohort Study.

The purpose of this study was to explore long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). We analyzed 471 DDLTs and 565 LDLTs from 1998 to 2010 that were followed up to 10 years for 36 categories of complications. Probabilities of complications and their resolutions were estimated using the Kaplan-Meier method, and predictors were tested in Cox proportional hazards models. Median follow-up for DDLT and LDLT was 4.19 and 4.80 years, respectively. DDLT recipients were more likely to have hepatocellular carcinoma and higher disease severity, including Model for End-Stage Liver Disease score. Complications occurring with higher probability in LDLT included biliary-related complications and hepatic artery thrombosis. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and pulmonary edema were significantly more probable. Development of chronic kidney disease stage 4 or 5 was less likely in LDLT recipients (hazard ratio [HR] 0.41, p = 0.02). DDLT and LDLT had similar risk of grade 4 complications (HR 0.89, p = 0.60), adjusted for other risk factors. Once a complication occurred, the time to resolution did not differ between LDLT and DDLT. Future efforts should be directed toward reducing the occurrence of complications after liver transplantation.

Biological implications of extracellular adenosine in hepatic ischemia and reperfusion injury.

The purine nucleoside adenosine is clinically employed in the treatment of supraventricular tachycardia. In addition, it has direct coronary vasodilatory effects, and may influence platelet aggregation. Experimental observations mechanistically link extracellular adenosine to cellular adaptation to hypoxia. Adenosine generation has been implicated in several pathophysiologic processes including angiogenesis, tumor defenses and neurodegeneration. In solid organ transplantation, prolonged tissue ischemia and subsequent reperfusion injury may lead to profound graft dysfunction. Importantly, conditions of limited oxygen availability are associated with increased production of extracellular adenosine and subsequent tissue protection. Within the rapidly expanding field of adenosine biology, several enzymatic steps in adenosine production have been characterized and multiple receptor subtypes have been identified. In this review, we briefly examine the biologic steps involved in adenosine generation and chronicle the current state of adenosine signaling in hepatic ischemia and reperfusion injury.

Emerging Innovations in Liver Preservation and Resuscitation.

The availability of marginal liver grafts represents a potential resource of orthotopic liver transplantation (OLT) in the era of organ shortage. However, an increased susceptibility to ischemia-reperfusion injury results in the increased risk for primary nonfunction and biliary complications. Novel methods of organ preservation and resuscitation are under investigation to improve outcomes of OLT with the use of marginal grafts. Machine perfusion (MP) in OLT is categorized based on the temperature setting. Hypothermic MP minimizes oxygen demand and uses single- or dual-vessel infusion with or without oxygenation. Normothermic MP increases the metabolic rate to the physiologic level, and requires dual-vessel infusion with a higher blood flow rate with oxygenation typically by blood as an oxygen carrier. Midthermic or subnormothermic MP uses medium temperature settings to allow metabolic activity to maintain cellular integrity as well as decrease oxygen demand. Since 2010, a total of 9 clinical trials have investigated the safety and feasibility of hypothermic and normothermic MP. The results suggest that the incidence of primary nonfunction was minimal even when marginal grafts were used. Organ preservation time could be reasonably increased. MP offers an opportunity to assess the viability and time to apply therapeutic interventions. This review highlights the history of MP, mechanisms of different temperature settings in MP, and recent large animal studies and clinical trials in OLT.

A Specialized Transplantation Critical Care Model: Expanding Liver Transplantation Access to High-Acuity Patients.

The current organ crisis has led to prolonged waiting times for liver transplantation, the progression of liver disease, and the subsequent increase in severity of illness. High acuity patients in need of orthotopic liver transplantation (OLT) maybe denied access to life-saving transplantation due to perceived poor outcomes after OLT and severe comorbid conditions. Recent studies demonstrated the highest survival benefit and acceptable post-OLT outcomes in high-acuity patients. This article provides an overview of a transplantation critical care model to increase liver transplantation access and optimize post-OLT outcomes in high-acuity patients.

Impact of a Transplantation Critical Care Model on Short-Term Outcomes Following Liver Transplantation in High Acuity Patients: A Single-Center Experience.

BACKGROUND: Orthotopic liver transplantation (OLT) is the definitive treatment for end-stage liver disease (ESLD). Patients with high acuity ESLD are frequently denied life-saving OLT by transplant centers due to reported inferior outcomes. We sought to analyze the impact of a specialized transplant critical care model (TCCM) on patient access to OLT and survival outcomes in high acuity patients. METHODS: From January 2009 to December 2016, 122 adults were wait-listed at our transplant center with laboratory Model for ESLD ≥35 or Status I. Outcomes in Era I (prior to TCCM) were compared to Era II (TCCM established October 1, 2012). RESULTS: Era II (TCCM) led to a significant increase in patients' access to OLT. Frequency and need to seek OLT at another center dropped 4-fold in Era II. Compared to Era I, the majority of patients in Era II required intensive care unit management (22% vs 83%, P < .01) and renal replacement therapy (11% vs 70%, P < .01) prior to OLT. Despite a higher acuity of illness in Era II, 1-year patient survival was comparable (89% Era I, 80% Era II, P = .35). CONCLUSION: Implementation of a specialized TCCM expanded OLT access to high acuity patients, reduced the need to seek higher level of care elsewhere, and achieved excellent short-term post-transplant survival outcomes.

Transabdominal Intrapericardial Approach in Liver Transplantation for Unresectable Primary Hepatic Functioning Paraganglioma With Invasion Into Hepatic Veins and Suprahepatic Vena Cava: A Surgical and Anesthesia Management Challenge.

Primary hepatic functional paraganglioma is a rare form of extra-adrenal catecholamine-secreting tumor. Definitive treatment of functioning paraganglioma is challenging because of the critical location of the tumor frequently in close proximity to vital structures and risk of excessive catecholamine release during operative manipulation. We report the multidisciplinary management approach for a case of unresectable primary hepatic functional paraganglioma with invasion into the hepatic veins and suprahepatic vena cava. To our knowledge, this is the first report showing that orthotopic liver transplantation is curative for patients with unresectable primary hepatic paraganglioma. For locally advanced unresectable hepatic paraganglioma that involves the intrapericardial vena cava, a meticulous pre- and intraoperative medical management and transabdominal intrapericardial vascular control of the suprahepatic vena cava during orthotopic liver transplantation allows for complete extirpation of the tumor and achieves optimal outcome.

Antiviral prophylaxis and recurrence of hepatocellular carcinoma following liver transplantation in patients with hepatitis B.

BACKGROUND: Orthotopic liver transplantation (OLT) is a viable treatment option for patients with hepatitis B (HBV) and concomitant hepatocellular carcinoma (HCC). However, cancer recurrence following transplantation approaches 20%. This study sought to identify the clinical and pathological factors associated with post-OLT survival. METHODS: Univariate and multivariate analyses considered the following variables: combination viral prophylaxis, HBV recurrence, tumor stage, vascular invasion, distribution, nodularity, pre- and post-OLT tumor size, pre-OLT alpha-fetoprotein (AFP), Milan and UCSF criteria, and Asian race. RESULTS: Cumulatively, HCC recurrence-free survival was 77%, 62%, and 53% at 1, 3, and 5 years, respectively, and was significantly better in patients who were free of viral recurrence post-OLT. Similarly, patients treated with combination prophylaxis had a significantly lower mortality than those who were not. CONCLUSIONS: Multivariate analysis revealed that AFP>500 ng/mL, presence of vascular invasion by explant, HBV recurrence, and combination prophylaxis were independent predictors of HCC recurrence-free survival.

Split liver transplantation.

Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

Inhibitory processing in visuospatial attention in healthy adults and schizophrenic patients.

This study assessed visuospatial attention in healthy adults and medicated schizophrenic patients. Participants performed a visual orientation task in which a peripheral cue was followed. at different intervals, by a target presented either at valid or invalid locations. When the long stimulus onset asynchrony (SOA) was used, participants were presented with either a single peripheral cue (single-cue condition) or two cues, the peripheral cue followed by a central cue (the double-cue condition). Healthy adults showed marginal facilitation effects with the short SOA and similar inhibition of return effects with the long SOA in both single-cue and double-cue conditions. Schizophrenic individuals showed a big facilitation effect with the short SOA and normal inhibition of return with the long SOA in both cue conditions. Results with the short SOA replicated previous findings (Huey, E.D., Wexler, B.E., 1994. Schizophrenia Research 14, 57-63) but, in contrast, we did not observe blunted inhibition of return with the long SOA. An inspection of the differences in the procedures used in both studies may help both to account for the discrepancies and to reveal what processes involved in visuospatial attention are affected in schizophrenia.

Vascular cell adhesion molecule--1 expression is obligatory for endotoxin-induced myocardial neutrophil accumulation and contractile dysfunction.

BACKGROUND: Sepsis-induced cardiac dysfunction occurs commonly in critically ill patients and is associated with high mortality rates. Neutrophils play a central role in sepsis-induced lung and liver injury; however, the mechanism of sepsis-induced cardiac dysfunction remains unclear. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in neutrophil-mediated liver injury during endotoxemia and is also expressed in myocardium. The purposes of this study were to examine the temporal relationship of myocardial VCAM-1 expression with neutrophil accumulation during endotoxemia and to determine whether VCAM-1 mediates neutrophil accumulation and cardiac dysfunction during endotoxemia. METHODS: Mice were subjected to lipopolysaccharide (LPS; 0.5 mg/kg, intraperitoneally). Myocardial VCAM-1 expression and neutrophil accumulation were determined by immunofluorescence staining. Cardiac performance with or without VCAM-1 blocking antibody (5 mg/kg, intravenously) was determined by the Langendorff technique. RESULTS: LPS caused a time-dependent increase in both myocardial VCAM-1 expression and neutrophil accumulation. At 6 hours after LPS, the immunofluorescent intensity for VCAM-1 increased from 2.5 +/- 0.6 x 10(6) in saline solution controls to 19.9 +/- 3.5 x 10(6) (P <.05, analysis of variance), and neutrophil count increased from 2.4 +/- 1.7/mm(2) in saline solution controls to 13.0 +/- 2.5/mm(2) (P <.05). Left ventricular developed pressure was decreased maximally at 6 hours after LPS compared with saline solution controls (29.1 +/- 1.1 mm Hg vs 53.1 +/- 3.9 mm Hg; P <.05). Treatment with VCAM-1 monoclonal antibody abrogated both myocardial neutrophil accumulation and cardiac dysfunction during endotoxemia. CONCLUSIONS: LPS-induced myocardial dysfunction is associated with increased expression of VCAM-1 and with neutrophil accumulation. Blockade of VCAM-1 abrogates myocardial neutrophil accumulation and preserves cardiac function during endotoxemia, which supports a role for VCAM-1 as a therapeutic target for myocardial protection during sepsis.

The case for beta-adrenergic blockade as prophylaxis against perioperative cardiovascular morbidity and mortality.

Perioperative morbidity and mortality are frequently cardiac in origin. Many studies have prospectively attempted to define risk factors for cardiac ischemic events. Although we can now identify high-risk patients, optimal cardioprotective management strategies remain unclear. Treatment with beta-adrenergic antagonists decreases myocardial oxygen consumption and is generally well tolerated. This article reviews the physiologic and clinical basis for using these agents as prophylaxis against cardiovascular events in high-risk surgical patients.

Organ preconditioning.

The initial discovery of cardiac preconditioning has evolved into an exciting series of practical surgical applications. An enormous amount of evidence demonstrating both the safety and efficacy of ischemic preconditioning is available from animal studies. The challenging premise of intentionally subjecting patients and their organs to transient ischemia has acted as a formidable psychological and ethical impediment to the widespread clinical application of organ preconditioning. A more palatable alternative to ischemic preconditioning now involves approved medications designed to manipulate the cellular machinery mediating ischemic preconditioning. Pharmacologically induced preconditioning seems to confer equal organ protection. The relatively brief (but surgically relevant) window of protection provided by strategies such as ischemic preconditioning or adenosine agonists and potassium-adenosine triphosphate channel openers may, in the future, be extended. We have developed and reported the feasibility of liposomal delivery of heat shock protein to cardiac myocytes with subsequent protection against sepsis-induced dysfunction. Targeted strategies will ultimately broaden the therapeutic potential of organ preconditioning.

Inhibitory tagging in inhibition of return is affected in schizophrenia: evidence from the stroop task.

L. J. Fuentes, A. B. Vivas, and G. W. Humphreys (1999b) showed that stimulus processing is affected when stimuli are presented to locations subject to inhibition of return. They argued that activated representations of stimuli presented at inhibited locations are disconnected from their associated responses through an "inhibitory tagging" mechanism occurring in inhibition of return. In the present research, the authors asked whether such a mechanism is affected in people with schizophrenia. Healthy adults and patients with schizophrenia performed a Stroop task in an inhibition of return paradigm. Healthy adults showed a reduction in the Stroop interference when stimuli were presented at inhibited locations, a result that agrees with the inhibitory tagging mechanism hypothesis and replicates previous findings. However, patients with schizophrenia did not show such a reduction, a result suggesting that they have a deficit in inhibitory processing occurring in inhibition of return.

Citizen participation in rural health: a promising resource.

The role of consumers in rural health care is explored in this review of the literature. A brief history of public, private, and grassroots efforts to involve consumers in health care is presented. A more in-depth analysis of two primary areas where consumers can be useful resources for addressing rural health care problems--personnel shortages and improving community acceptance of health care innovations--is discussed. Emergency medical services, care for medically disabled persons, and prenatal care are specifically addressed. Barriers to effective citizen participation and policy recommendations are also presented.

Revisiting health and mental health linkages: a policy whose time has come ... again.

This review and policy analysis examines the connection between physical and mental health. The review includes an analysis of individual diagnoses of physical and mental illness and training issues for both health and mental health professionals. A summary of earlier efforts to link health and mental health services includes a brief history of federal involvement and evaluation of linkage efforts. Linkage examples from a rural context are described briefly. Barriers to successful linkages are discussed with some suggestions for overcoming these obstacles. Policy recommendations for encouraging and establishing health and mental health linkages are presented.

Gender differences in HIV-related sexual risk behavior among urban African American youth: a multivariate approach.

Alcohol and other drug (AOD) use during sexual encounters, sexual partner's age, perceived HIV risk and perceived condom effectiveness were studied among 388 sexually active African American youth. Cluster analysis of condom use, number of partners, and frequency of sexual intercourse identified four groups: low risk, monogamy strategy, condom strategy, and high risk. Low-risk youth used condoms consistently and had few partners. High-risk youth used condoms inconsistently with many partners. Monogamy strategy youth used condoms inconsistently but had few partners. Condom strategy youth used condoms consistently with a moderate number of partners. The high-risk group included more males and the monogamy group included more females. High-risk males reported more AOD use during sexual activity than all females, and low-risk or condom strategy males. Females had older partners, rated condoms as less effective and perceived lower HIV/AIDS risk than males. Results suggest differential HIV risk mechanisms by gender. Implications for gender-specific HIV prevention are discussed.

AIDS knowledge and sexual behavior among Mexican gay and bisexual men.

Little knowledge exists about AIDS and Human Immunodeficiency Virus (HIV) infection among Latin American gay males. In Latin America, sexual transmission from man to man is the leading cause of HIV infection. In Mexico, which ranks third in number of AIDS cases in the Americas, more than three-quarters of the cases are due to sexual transmission; among these cases, 35% and 23.7% are due to homosexual and bisexual male practices, respectively. A sample of 200 individuals from Juarez, Mexico, a city on the U.S. border, was interviewed. Information about their AIDS knowledge, sexual behavior, and condom use was obtained. Factory workers and individuals who meet sexual partners in the streets reported more sexual partners than workers in service or professional occupations and those who meet their partners in bars and discos. Number of sexual partners and respondents' age were inversely associated with condom use. Implications for HIV prevention are discussed.

PIP: Two hundred gay and bisexual men of mean age 26.4 years from Juarez, Mexico, were interviewed by the Mexican Federation of PRivate Associations for Community Development (FEMAP) about their AIDS knowledge, sexual behavior, and condom use. 88% were single and never married. 66% self-identified as being gay, 29% as bisexual, and 2% as transvestites; 10% reported having sex for money. 14% had had at least one sexually transmitted disease and 57% were negative about condom use. Having an average 4.46 sex partner/month, most respondents were knowledgeable about HIV transmission routes, AIDS symptoms, and HIV antibody tests. 75% and 77.5%, respectively, reported practicing receptive anal intercourse and insertive anal intercourse. They used condoms an average of 6.47 times in their most recent ten sexual encounters. By profession and social behavior, factory workers and individuals who recruit sex partners from the street reported having more sex partners than service and professional workers and those who meet their partners in bars and discos. Further, the number of sex partners and respondents' age were inversely associated with condom use. These findings clearly highlight the failure of knowledge about HIV to bring about change in sexual behavior among certain subpopulations in the study area. Since homosexuality remains unaccepted in Mexican society, the author suggests targeted peer education and small-group session prevention efforts which do not confront mainstream social structure and values.

Preventing the spread of AIDS in youth: principles of practice from 11 diverse projects.

PURPOSE: The purpose of this study was to identify the factors that contributed to intervention effectiveness in acquired immunodeficiency syndrome (AIDS) prevention projects targeting youth. METHODS: Eleven AIDS prevention projects funded by the Robert Wood Johnson Foundation whose target populations consisted of at least 60% youth were studied. A blended methodology resulted in quantitative data (i.e., survey responses) from all 11 projects supplemented with qualitative data (i.e., open-ended interviews) drawn from in-depth site visits to six projects. RESULTS: Projects reported using a mean of 16.6 intervention activities (selected from a list of 30). Six activities were used by all 11 projects. Small group discussions were rated as one of three most effective activities by 72.7% of the projects that used them. Project staff identified three elements of effective interventions: involvement of peer educators, recognition of the role of adults (e.g., parents, teachers), and use of structured settings to gain access to the target population (e.g., schools, clubs). CONCLUSIONS: The most powerful strategies described by project staff for reaching adolescents at risk for human immunodeficiency virus (HIV) transmission also bring considerable challenges. Opportunity costs associated with using peer educators, gatekeeper support, and structured settings may include limited control of the message, impaired credibility, and failure to reach those youth at greatest risk of HIV infection, respectively. Health educators will do well to consider the advantages and disadvantages of these factors when developing, implementing, and evaluating AIDS prevention programs for youth.

Patient and physician perceptions of their relationship and patient satisfaction: a study of chronic disease management.

This study investigated patient and physician perceptions of their relationship and examined how their perceptions related to patient satisfaction. Data are based on 134 patient-physician interactions. Study participants included 12 physicians (five women and seven men) and 134 male patients with a diagnosis of diabetes mellitus being seen on an outpatient basis. Information on patient and physician demographics, patient's metabolic control and functional status and time spent in the interaction were also collected. Results revealed that patients with lower levels of education were most satisfied and that physicians who viewed the relationship as a patient-physician partnership had more satisfied patients than those who viewed the relationship as physician controlled. Findings also indicated that physicians' gender and number of years in practice were not related to patient satisfaction. Practical implications include: (1) increasing attention to physician's perceptions of his or her relationship with individual patients and (2) exposing newly trained physicians to partnership types of relationships, if future research confirms these findings in chronic disease management.

An HIV/AIDS prevention project for Mexican homosexual men: an empowerment approach.

In this intervention, participants design and implement an HIV/AIDS prevention project for Mexican homosexual men. The intervention is consistent with, and contributes to, empowerment theory because it enhances collective action, provides opportunities to develop knowledge and skills, creates needed resources, and includes shared control with professional and among participants. The intervention described provides an illustration of an empowering process and distinguishes itself from empowerment outcomes. An evaluation of the project is also described, but the outcomes were HIV/AIDS-related behaviors rather than psychological empowerment of the participants. The results suggest that the participants' HIV/AIDS knowledge and preventive behavior improved when compared to individuals who did not participate in the intervention. In addition, the intervention generated community change initiated by participants. Implications for designing interventions using an empowerment approach are discussed.