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Prognostic Determinants (prognostic + determinant)
Selected AbstractsCellular senescence in pretransplant renal biopsies predicts postoperative organ functionAGING CELL, Issue 1 2009Liane M. McGlynn Summary Older and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post-transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of pre-implantation human renal allograft biopsies (n = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function post-transplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre-transplant CDKN2A levels (p = 0.001) and donor age (p = 0.004) at 6 months post-transplant. Both these markers correlated significantly with urinary protein to creatinine ratios (p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter (p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% (p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% (p = 0.001) at 1 year post-transplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome. [source] Evaluation of the prognostic significance of Eosinophilia and Basophilia in a larger cohort of patients with myelodysplastic syndromesCANCER, Issue 10 2010Friedrich Wimazal MD Abstract BACKGROUND: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils. METHODS: The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression. RESULTS: Eosinophilia (eosinophils >350/,L) and basophilia (basophils >250/,L) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition "eosinophilia and/or basophilia" was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup. CONCLUSIONS: The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS. Cancer 2010. © 2010 American Cancer Society. [source] The Poor Outcome of Ischemic Stroke in Very Old People: A Cohort Study of Its DeterminantsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2010Licia Denti MD OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants. DESIGN: Cohort, observational. SETTING: University hospital. PARTICIPANTS: One thousand five hundred fifty-five patients with first-ever ischemic stroke consecutively referred to an in-hospital Clinical Pathway program were studied. MEASUREMENTS: The relationship between age and 1-month outcome (death, disability (modified Rankin Scale 3,5), and poor outcome (modified Rankin Scale 3,6)) was assessed, with adjustment for several prognostic factors. RESULTS: Six hundred twelve patients aged 80 and older showed worse outcome after 1 month than those who were younger, in terms of mortality (19% vs 5%, hazard ratio (HR)=3.85, 95% confidence interval (CI)=2.8,5.4) and disability (51% vs 33%, odds ratio (OR)=3.16, 95% CI=2.5,4.0), although in multivariate models, the adjusted HR for mortality decreased to 1.47 (95% CI=1.0,2.16) and the ORs for disability and poor outcome decreased to 1.76 (95% CI=1.32,2.3.) and 1.83 (95% CI=137,2.43), respectively. Stroke severity, the occurrence of at least one medical complication, and premorbid disability explained most of the risk excess in the oldest-old. CONCLUSION: Stroke outcome is definitely worse in very old people, and most of the excess risk of death and disability is attributable to the higher occurrences of the most-severe clinical stroke syndromes and of medical complications in the acute phase. These represent potential targets for preventive and therapeutical strategies specifically for elderly people. [source] Long-Term Outcome of Adult-to-Adult Living Donor Liver Transplantation for Post-Kasai Biliary AtresiaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2006Y. Uchida Our objective was to analyze problems in the perioperative management and long-term outcome of living donor liver transplantation (LDLT) for biliary atresia (BA). Many reports have described the effectiveness of liver transplantation (LT) for BA, particularly in pediatric cases, but little information is available regarding LT in adults (,16 years old). Between June 1990 and December 2004, 464 patients with BA underwent LDLT at Kyoto University Hospital, of whom 47 (10.1%) were older than 16 years. In this study, we compared the outcomes between adult (,16 years old) and pediatric (<16 years old) patients. The incidence of post-transplant intestinal perforation, intra-abdominal bleeding necessitating repeat laparotomy and biliary leakage was significantly higher (p < 0.0001, <0.001 and <0.001, respectively) in adults. Overall cumulative 1-, 5- and 10-year survival rates in pediatric patients were significantly higher (p < 0.005) than in adults. Two independent prognostic determinants of survival were identified: a MELD score over 20 and post-transplant complications requiring repeat laparotomy. Outcome of LDLT in adult BA patients was poorer than in pediatric patients. It seems likely that LT will be the radical treatment of choice for BA and that LDLT should be considered proactively at the earliest possible stage. [source] New perspectives in retinal imaging: fundus autofluorescence and age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 2007F HOLZ Fundus Autofluorescence (FAF) imaging using confocal scanning laser ophthalmoscopy is a non-invasive method to to accurately record the topographic distribution of RPE lipofuscin in the human eye in vivo. Excessive lipofuscin accumkulation in the RPE is a common downstream pathogenetic pathway in various complex and monogenetic retinal diseases. Toxic compounds and molecular mechanisms of interference with normal cellular functions have been identified including the dominant fluorophore A2-E. Alterations in fundus autofluorescence (FAF) appearance in eyes with early and late age-related macular degeneration (AMD) can be striking. FAF patterns and distribution do not necessarily correlate with the features of interest in color or angiographic images of eyes with early or late AMD. In the prospective, multicenter FAM study distinct patterns of abnormal FAF were identified and classified in the junctional zone of geographic atrophy (GA). Areas of increased FAF outside GA were associated with variable degrees of loss of retinal sensitivity when tested with microperimetry which suggests a functional correlate of lipofuscin accumulation. Increased FAF preceded the development and enlargement of outer retinal atrophy associated with spread of absolute scotoma in eyes with AMD. Longitudinal examinations showed that the abnormal phenotypic FAF patterns serve as novel prognostic determinants which allows to distinguish fast vs. slow progressors. These findings are relevant and now used to design and carry out interventional trials with agents aimed at slowing down spread of atrophy, e.g. using visual cycle modulators to influence lipofuscinogenesis. Hereby FAF imaging also serves as a mean to accurately delineate and measure areas of GA over time in an automated fashion. A phenotype-genotype correlation was identified for a distinct FAF phenotype subset which was found to represent late-onset Stargardt macular dystrophy mimicking late-stage atrophic AMD. New imaging technologies were recently applied including simultaneous recordings of FAF images and high-resolution, spectral-domain optical coherence tomography (OCT) which allows to identify morphological correlates of abnormal FAF signals in optical biopsies. [source] | ||||||||||