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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.
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PMID:Effect modification in liver allografts with prolonged cold ischemic time. 1826 Nov 67

Accumulation of unfolded or malfolded proteins induces endoplasmic reticulum (ER) stress which elicits a complex network of interacting and parallel responses that dampen the stress. The ER stress response in the liver is controlled by intrinsic feedback effectors and is initially protective. However, delayed or insufficient responses or interplay with mitochondrial dysfunction may turn physiological mechanisms into pathological consequences including apoptosis, fat accumulation and inflammation all of which have an important role in the pathogenesis of liver disorders such as genetic mutations, viral hepatitis, insulin resistance, ischemia/reperfusion injury, and alcoholic and non-alcoholic steatosis. In both alcohol and non-alcohol-induced ER stress, a common candidate is hyperhomocysteinemia. Betaine supplementation and/or expression of betaine-homocysteine methyltransferase (BHMT) promote removal of homocysteine and alleviate ER stress, fatty accumulation and apoptosis in cultured hepatocytes and mouse models. The rapidity and magnitude of homocysteine-induced activation of each of the main ER resident transmembrane sensors including inositol requiring enzyme 1 (IRE-l alpha), activating transcription factor 6 (ATF-6) and RNA-activated protein kinase (PKR)-like ER kinase (PERK) appear different in different experimental models. Dissection and differentiation of ER stress signaling may reveal clues on the specific importance of the ER stress response in contributing to liver injury and thus provide better strategies on prevention and treatment of liver disease.
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PMID:Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury. 1833 57

Evaluation and management of medical comorbidities in the perioperative period can help improve surgical morbidity and mortality. Perioperative evaluation essentially is risk assessment and minimization. Patients undergoing orthopaedic treatment may benefit from temporizing measures to reduce systemic complications associated with some procedures. Patients at increased risk of cardiac ischemia should undergo risk stratification to determine possible perioperative interventions. Use of perioperative medications and/or consultation with specialists can help to address heart murmurs, bacterial endocarditis, prior stenting, heart failure, and hypertension. Patients with severe or unstable chronic obstructive pulmonary disease require the involvement of pulmonary care specialists. Renal failure can require nephrology consultation, particularly in cases of worsening renal function or urinary outflow obstruction. Hematologic considerations include bleeding and clotting. Prophylaxis should be used in patients with risk factors for peptic ulcer, as well as respiratory failure and hypotension. Nutritional status and liver disease also must be monitored and treated preoperatively. Orthopaedic diabetic patients should be placed on modified oral hypoglycemic or insulin regimens; recalcitrant cases merit consultation. Effective communication among all members of the patient's caregiving team is paramount.
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PMID:Perioperative medical comorbidities in the orthopaedic patient. 1839 Apr 84

Portal hypertension and its complications account for the majority of morbidity and mortality that occurs in patients with cirrhosis. In addition to portal hypertension, a number of other vascular syndromes are also of great importance, especially the ischemia-reperfusion (IR) injury. With the identification of major vascular defects that could account for many of the clinical sequelae of these syndromes, the liver vasculature field has now integrated very closely with the broader vascular biology discipline. In that spirit, the Henry and Lillian Stratton Basic Research Single Topic Conference was held on the topic of Vascular Biology and Pathobiology of the Liver. The course took place approximately 10 years after the first American Association for the Study of Liver Disease (AASLD)-sponsored conference on this topic that occurred in Reston, Virginia. The conference initiated with an introduction to basic vascular cell signaling and then explored vascular biology specifically as it relates to liver cells. Subsequently, specific disease syndromes were discussed in more detail including portal hypertension and IR injury. Finally, clinical and translational sessions focused on emerging therapies and technologies to treat vascular diseases of the liver.
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PMID:Vascular biology and pathobiology of the liver: Report of a single-topic symposium. 1839 22

Advanced donor age is a risk factor for poor outcome in liver transplantation (LT). We reviewed 553 consecutive transplants according to donor age categories [group 1 (n = 173): <50 years; group 2 (n = 96): 50-59 years; group 3 (n = 132): 60-69 years; group 4 (n = 111): 70-79 years; group 5 (n = 41): > or =80 years]. Clinical parameters were comparable between groups. Group 5 had the highest proportion of pretransplant liver biopsy (85%), with only 1 graft showing macrovesicular steatosis > 30%, and the lowest ischemia time. Five-year graft survival was significantly higher in group 1 (75%) versus groups 3 (60%) and 4 (62%; P = 0.01 and P = 0.001, respectively) and in group 5 (81%) versus groups 3 and 4 (P = 0.04 and P = 0.01, respectively). Donor age of 60-79 years, recipient hepatitis C virus-positive status, Model for End-Stage Liver Disease score > or = 25, and emergency LT were predictors of poor survival. In hepatitis C virus-positive patients, 5-year graft survival was 72% in group 1, 85% in group 2, 52% in group 3, 65% in group 4, and 71% in group 5 (group 1 versus group 3, P = 0.04; group 2 versus group 3, P = 0.03). In conclusion, older donor grafts managed with routine graft biopsy and short ischemia time may work effectively, regardless of the severity of the recipient's liver disease.
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PMID:Improving the outcome of liver transplantation with very old donors with updated selection and management criteria. 1843 35

Patients undergoing liver transplantation often experience coagulopathy and massive intraoperative blood loss that can lead to morbidity and reduced survival. The aim of this study was to verify the survival rate and discover predictive factors for death among liver transplant patients who received massive intraoperative blood transfusions. This cohort study was based on prospective data collected retrospectively from January 2004 to July 2006. The 232 patients were distributed according to their blood requirements, (namely, more or less than 6 units), including red blood cell saver. The statistical analyses were performed using Student t test, Cox hazard regression, and the Kaplan-Meier method (log-rank test). The massively transfused cohort displayed higher Child-Pugh classifications (10.2 vs 9.6; P = .03); model for end-stage liver disease (MELD) scores (19 vs 17; P = .02); recipient weights (75.4 vs 71 kg; P = .03); as well as warm ischemia times (70.7 vs 56.4 minutes; P < .001) and surgery times (584.6 vs 503.4 minutes; P < .05). The proportional hazard (Cox) regression analysis showed that the risk of death increased 2.1% for each unit of donor sodium and 1.6% for each additional year of donors age over 50. The survival rates at 6, 12, 60, and 120 months for > or = 6 vs <6 U of blood transfusion of 63.8% vs 83.3%; 53.9% vs 76.3%; 40% vs 60%; 34.5% vs 49.2%. In conclusion, we observed that patients receiving over 6 red blood cell units intraoperatively displayed reduced survival. Predictive factors for this risk factor were high donor level of sodium and of age.
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PMID:Intraoperative massive transfusion decreases survival after liver transplantation. 1845 18

Derangements in apoptosis of liver cells are mechanistically important in the pathogenesis of end-stage liver disease. Vulnerable hepatocytes can undergo apoptosis via an extrinsic, death receptor-mediated pathway, or alternatively intracellular stress can activate the intrinsic pathway of apoptosis. Both pathways converge on mitochondria, and mitochondrial dysfunction is a prerequisite for hepatocyte apoptosis. Persistent apoptosis is a feature of chronic liver diseases, and massive apoptosis is a feature of acute liver diseases. Fibrogenesis is stimulated by ongoing hepatocyte apoptosis, eventually resulting in cirrhosis of the liver in chronic liver diseases. Endothelial cell apoptosis occurs in ischemia-reperfusion injury. Natural killer and natural killer T cells remove virus-infected hepatocytes by death receptor-mediated fibrosis. Lastly, activated stellate cell apoptosis leads to slowing and resolution of apoptosis. This review summarizes recent cellular and molecular advances in the understanding of the injury mechanisms leading to end-stage liver disease.
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PMID:Cellular and molecular mechanisms of liver injury. 1847 44

Polyarteritis nodosa (PAN) is a necrotizing, focal segmental vasculitis that affects predominantly medium-sized arteries in many different organ systems. It is associated with hepatitis B virus (HBV) in about 7% of cases, a decline from about 30% before the mandatory testing of blood products and the widespread vaccination programs. HBV PAN is an early postinfectious process. The hepatitis is silent in most cases, with mild transaminase level increases in 50% of patients. Gastrointestinal involvement occurs in 14% to 65% of patients with PAN. Postprandial abdominal pain from ischemia is the most common symptom. When transmural ischemia develops, there may be necrosis of the bowel wall with perforation, associated with a poor prognosis. Liver involvement occurs in 16% to 56% of patients, although clinical manifestations related to liver disease are quite rare. Acalculous gangrenous cholecystitis may develop owing to arteritis involving the wall of the gallbladder. Microaneurysms on arteriography or computed tomography angiography are characteristic of PAN, but are seen in other conditions. Tissue biopsy may confirm the diagnosis, although involvement is segmental. Corticosteroids are used for non-HBV PAN with cyclophosphamide added for severe disease. For PAN related to HBV, a 2-week course of corticosteroids is begun, with plasma exchanges and an antiviral agent. Corticosteroids and cyclophosphamide have improved patient outcome so that the 1-year survival rate is now about 85%.
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PMID:Gastrointestinal involvement in polyarteritis nodosa. 1858 77

It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21,673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30,321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.
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PMID:Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation. 2222 77

Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them.Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis.It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process - although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.
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PMID:Experimental obstructive cholestasis: the wound-like inflammatory liver response. 1901 18


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