Assessment of short-term survival after liver transplant by the Model for End-Stage Liver Disease

The Model for End-Stage Liver Disease (MELD) score has demonstrated the ability to predict mortality among patients with chronic liver disease on the liver waiting list. The aim of this study was to assess the capability of the MELD score to correctly predict posttransplantation survival in Spain and to determine specific thresholds of MELD above which liver transplantation should be discouraged and the patient removed from the waiting list. METHODS: In this study, we retrospectively applied the MELD score to 168 patients at time of transplantation to estimate 1-month and 3-month posttransplant survivals by stratifying them into four groups: group A, MELD score < 10; group B, MELD score 10-18; group C, MELD score 19-24; group D, MELD score > 24. RESULTS: One-, 2-, and 3-month survivals were 84.3%, 80% and 79.5%, respectively. One-, 2-, and 3-month survivals in group A (18 patients) were identical (77.8%). In group B (80 patients), 1-month survival was 84.8%, and 2- and 3-month survivals were 78.4%. In group C (42 patients) 1-month survival was 90.5% and 2- and 3-month survivals were 88%. One-, 2-, and 3-month survivals in group D (28 patients) were 77.9%, 74%, and 70%, respectively. We defined a new group (group E) formed by patients with MELD score < or =24. When we compared 1-, 2-, and 3-month survival rates in group E (85.6%, 81.25%, and 81.25%, respectively) with survival rates in group D, the difference was not significant (P > .05). CONCLUSIONS: Although overall outcomes of patients whose MELD scores were high at the time of liver transplantation were inferior to those of patients whose MELD scores were lower, there was no significant difference for specific thresholds of MELD above which liver transplantation should be discouraged and the patient removed from the waiting list.     

Sonovue improves endocardial border detection and variability in assessing wall motion score and ejection fraction during stress echocardiography

Background Stress echocardiography is useful for assessing patients with coronary artery disease unable to undergo formal exercise testing. Considerable skill is required to avoid large intra- and inter-observer variability due to poor endocardial definition. Intravenous ultrasound contrast agents are now available which may improve this variability. Aim To study intravenous Sonovue in assessing wall motion score and ejection fraction (EF) during stress echocardiography. Methods Thirty-eight patients undergoing arbutamine stress echocardiography for known or suspected coronary artery disease were studied. Echocardiographic analysis of wall motion score index, endocardial border detection (EBD) and EF was performed at rest and at peak stress before and after intravenous injection of Sonovue, by experienced and inexperienced observers. Results All three observers noted an improvement in endocardial border definition following Sonovue (p=<0.001). At baseline, there was a significant difference in wall motion score index between experienced and inexperienced observers at rest (p=0.01) and at peak stress (p=0.001). Following Sonovue administration this was no longer significant (p=0.07, p=0.114). Intra-observer variability of end diastolic, end systolic volumes (ESV) and EF improved following contrast (p<0.05) at rest and during stress. Conclusion Sonovue significantly improved EBD and reduced intra-observer variability of EF at rest and during peak arbutamine infusion.     

Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement

The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complement-mediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung cancer. We also evaluate the potential effect of factor H/FHL-1 in the protection of lung cancer cells against the activation of the complement cascade. By Northern blot analysis we demonstrate a high expression of factor H and FHL-1 in most non-small cell lung cancer cell lines, although neuroendocrine pulmonary tumors (small cell lung carcinoma and carcinoid cell lines) had undetectable levels. Western blot analysis of conditioned medium showed the active secretion of factor H and FHL-1 by cells that were positive by Northern blot. Expression of factor H/FHL-1 mRNA was also shown in a series of non-small cell lung cancer biopsies by in situ hybridization. Interestingly, many cultured lung cancer cells were able to bind fluorescence-labeled factor H to their surfaces. Deposition of C3 fragments from normal human serum on H1264, a lung adenocarcinoma cell line, was more efficient when factor H/FHL-1 activity was blocked by specific antibodies. Blocking factor H/FHL-1 activity also enhanced the release of anaphylatoxin C5a and moderately increased the susceptibility of these cells to complement-mediated cytotoxicity. In summary, we demonstrate the expression of factor H and FHL-1 by some lung cancer cells and analyze the contribution of these proteins to the protection against complement activation.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

Fracture of ceramic/ceramic/polymer trilayers for biomechanical applications

Fracture damage in trilayers consisting of outer and inner brittle layers bonded to a compliant (polycarbonate) substrate and subjected to concentrated surface loading is analyzed. The principal mode of fracture is radial cracking at the undersurface of the inner (core) layer, even in the strongest of core ceramics--other damage modes, including radial cracking in the outer (veneer) layer, are less invasive in these all-brittle coating systems. Tests on simple trilayer structures fabricated from glasses, sapphire, and dental ceramics are used to examine the dependence of the critical load for radial fracture in terms of relative outer/inner layer thickness and modulus, and inner layer strength. An explicit relation for the critical load, based on a flexing plate model in which the outer/inner bilayer is reduced to an "equivalent" monolithic coating with "effective" composite modulus, is used to examine these dependencies. The theoretical relation describes all the major trends in the critical load data over a broad range of variables, thus providing a sound basis for trilayer design. Relevance of the analysis to dental crowns and other biomechanical applications is a central theme of the study.     

Relapsing upper bleeding in non-Hodgkin's oesophageal lymphoma associated with achalasia

Achalasia is a disease of unknown origin in which there is a denervation of the myenteric plexus on the smooth muscle of the lower oesophageal sphincter, causing a cardial stenosis and a loss of efficacy of oesophageal peristalsis. The predominant symptoms are dysphagia for solids and liquids and regurgitation of the retained food. Occasionally, there may be oesophageal haemorrhage as a consequence of oesophagitis and stasis ulcers. An important but uncommon complication is the development of oesophageal cancer, which is typically squamous cell carcinoma. We report an exceptional case of a 77-year-old woman with a long-term achalasia and mega-oesophagus who presented four episodes of upper gastrointestinal bleeding in a 2 month period. The patient underwent surgical resection of the 10 cm of distal oesophagus, performing a partial fundoplication, and the pathological study revealed an oesophageal infiltration by a low-grade non-Hodgkin's lymphoma. After an insidious outcome, she died on the 47th day after admission.     

Is there an optimal therapeutic regimen for antimitochondrial antibody‐negative primary biliary cirrhosis (autoimmune cholangitis)?

Testing for antimitochondrial antibodies is the most useful laboratory procedure in the diagnosis of primary biliary cirrhosis; nevertheless, 5-10% of patients with typical features of primary biliary cirrhosis do not have detectable antimitochondrial antibodies, their condition being referred to as antimitochondrial antibody-negative primary biliary cirrhosis or "autoimmune cholangitis". Uncertainty exists whether antimitochondrial antibody-positive and -negative primary biliary cirrhosis represent distinct entities. We reviewed studies that compared: (i) the clinical, laboratory and histological characteristics of antimitochondrial antibody-positive and -negative primary biliary cirrhosis; (ii) the response to treatment of both conditions; and (iii) the response of autoimmune cholangitis to ursodeoxycholic acid and immunosuppressive therapy. Antimitochondrial antibody-positive and -negative primary biliary cirrhosis were characterized by similar clinical, laboratory and histological abnormalities, clinical course and survival. Antimitochondrial antibody status did not seem to affect the response to ursodeoxycholic acid. At present, the efficacy of therapies for autoimmune cholangitis has not been established in controlled trials. Of 52 patients with autoimmune cholangitis treated with ursodeoxycholic acid in 13 uncontrolled studies, 83% had serum biochemical improvement. Also, a favourable effect of immunosuppressive drugs occurred in 57% of 54 patients with autoimmune cholangitis in 17 uncontrolled studies. Each of these trials included very few patients and most evaluated the effects of treatment on surrogate markers of disease only. No marker that consistently distinguished patients who would respond favourably to ursodeoxycholic acid or immunosuppression was apparent. Consequently, treatment is, at present, empirical. However, ursodeoxycholic acid may be given when histology reveals bile duct lesions, whereas immunosuppressive therapy should probably be reserved for patients exhibiting interface hepatitis.     

Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis

BACKGROUND/AIMS: To conduct a systematic review and meta-analysis on the prevalence of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT). METHODS: Studies evaluating prevalence of HCV infection in patients with PCT were considered. Bibliographical searches were conducted in several electronic databases. Studies comparing HCV prevalence in PCT (cases) and in a reference group (controls) were included in the meta-analysis, combining the Odds Ratios (OR) of the individual studies. RESULTS: Fifty studies including 2,167 patients were identified. Mean HCV prevalence by serology was 47%, and 50% with polymerase chain reaction (PCR). HCV prevalence markedly varied depending on the country and the type of PCT (57% in the sporadic and 26% in the familial form). Eight case-control studies were identified. Seven studies compared HCV prevalence in PCT vs. healthy controls: 40% vs. 0.24%, respectively (OR=275; 95% confidence interval=104-725). Heterogeneity disappeared when only studies evaluating HCV infection by PCR were included. CONCLUSIONS: HCV prevalence in patients with PCT is approximately 50%, much higher than that reported in general population, suggesting a possible etiopathogenic role of HCV in PCT. The striking geographical variation in this association suggests that genetic and/or environmental factors may also be involved in the pathogenesis of this disorder.