Doris Wagner

Low 25-Hydroxyvitamin D Is Associated with Increased Mortality in Female Nursing Home Residents

CONTEXT Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients. Whether low 25-hydroxyvitamin D (25[OH]D) concentrations are an independent risk factor for mortality in these patients is, however, unclear. OBJECTIVE We aimed to evaluate whether 25(OH)D concentrations are associated with mortality. DESIGN, SETTING, AND PARTICIPANTS This is a prospective cohort study among elderly female patients (age >70 yr) recruited from 95 nursing homes in Austria. MAIN OUTCOME MEASURES We calculated Cox proportional hazard ratios (HR) for all-cause mortality according to 25(OH)D quartiles. RESULTS We examined 961 study participants (age 83.7 ± 6.1 yr). Median 25(OH)D concentration was 17.5 (interquartile range 13.7-25.5) nmol/liter, and 93% of our cohort had 25(OH)D levels below 50 nmol/liter. During a mean follow-up time of 27 ± 8 months, 284 patients died. Compared with the fourth quartile (25[OH]D >25.5 nmol/liter), the age-adjusted HR (with 95% confidence interval) was 1.49 (1.07-2.10) in the first 25(OH)D quartile (25[OH]D <14.0 nmol/liter), and this association remained significant after multivariate adjustments (HR = 1.56; 95% confidence interval = 1.01-2.40). CONCLUSIONS This Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality. These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency, in particular in the setting of nursing homes.

Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery.

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation - equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on PubMed and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia - the loss of muscle mass - is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patients peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the pre-operative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and long-term outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepato-pancreatico-biliary resections.

The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation.

Kniepeiss D, Renner W, Trummer O, Wagner D, Wasler A, Khoschsorur GAli, Truschnig‐Wilders M, Tscheliessnigg K‐H. The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation. 
Clin Transplant 2011: 25: 146–150.

Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates.

There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.

Levels of osteoprotegerin (OPG) and receptor activator for nuclear factor kappa B ligand (RANKL) in serum: Are they of any help?

ZusammenfassungDer Knochen unterliegt einem ständigen Umbauprozess, wobei das Zusammenspiel zwischen Knochenneubildung durch die Osteoblasten und Knochenresorption durch die Osteoklasten über das OPG/RANKL/RANK-System streng geregelt ist. OPG wird von Osteoblasten und deren Vorläuferzellen produziert, kommt jedoch nahezu ubiquitär im Organismus vor. RANKL wird in erster Linie von Osteoklasten und immunkompetenten Zellen produziert, und bewirkt durch die Bindung an seinen Rezeptor RANK die Aktivierung, Proliferation und Verringerung der Apoptoserate von Osteoklasten. Seit Assays zur Bestimmung der OPG und RANKL Serumspiegel am Markt erhältlich sind, steht die Evaluierung der möglichen Zusammenhänge von Serumkonzentrationen dieser Key-Regulatoren in Relation zu Aktivität von metabolischen Knochenstoffwechselstörungen, Alter, Geschlecht, Knochendichte und Frakturrisiko im Fokus des wissenschaftlichen Interesses. Inhalt des aktuellen Review Artikels ist es, eine Zusammenfassung der derzeit vorliegenden publizierten Daten von Serum OPG und RANKL Spiegeln und deren Zusammenhang mit Veränderung des Knochenstoffwechsels zu geben.SummaryThe coupling of bone formation and resorption is mediated through the OPG/RANK/RANKL system. OPG and RANKL are mainly produced by osteoblasts but also a variety of other tissues. The binding of RANKL to RANK, its natural receptor which is expressed by osteoclasts, accelerates bone resorption. OPG acts as decoy receptor and prevents the interaction of RANKL with RANK and therefore leads to a decrease in activity, survival and proliferation of osteoclasts. Since assays for measurements of serum OPG and RANKL have become commercially available, intense research focused on serum OPG/RANKL levels in context with underlying disease, age, co-morbidities, bone density, and fractures has derived. This review aims to provide an overview if and to which extent serum OPG and RANKL levels may reflect bone metabolism in patients with osteoporosis and metabolic bone disease.

Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis

Background: Indocyanine green (ICG) clearance has been proposed as a quantitative liver function test several decades ago. Interest in this method has been renewed following the development of finger pulse densitometry for noninvasive estimation of the ICG plasma disappearance rate (PDR). On the other hand, the model for end‐stage liver disease (MELD), which is based on routine laboratory parameters, is widely used for estimation of short‐term survival in cirrhosis, but its prognostic value in critically ill cirrhotic patients is unclear.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

Wagner D, Adunka C, Kniepeiss D, Jakoby E, Schaffellner S, Kandlbauer M, Fahrleitner‐Pammer A, Roller RE, Kornprat P, Müller H, Iberer F, Tscheliessnigg KH. Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.
Clin Transplant 2011: 25: E396–E3400.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine‐based equations

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr‐ and CysC‐based equations including the Chronic kidney disease (CKD)‐EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft‐Gault, Hoek, Larsson, and the CKD‐EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty‐five percent had a GFR < 60 ml/min/1.73 m2 according to the IC. The Larsson, the Hoek and the CKD‐EPI‐CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr‐based equations showed less bias than CysC‐based formulas with a similar precision. All CysC‐based equations were superior as compared with sCr‐based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m2.

Glomerular Filtration Rate (GFR) determination via individual kinetics of the inulin-like polyfructosan sinistrin versus creatinine-based population-derived regression formulae

BackgroundIn renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae.MethodsIn 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses.ResultsReasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m2]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods.ConclusionsFor routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73 m2] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination.Consorthttp://www.consort-statement.org/index.aspx?o=1190

Long-term quality of life of liver transplant recipients beyond 60 years of age

Due to ameliorated surgery as well as better immunosuppression, the recipient age after liver transplantation has been extended over the past years. This study aimed to investigate the health related quality of life after liver transplantation in recipients beyond 60 years of age. The SF-36 was used to evaluate the recipients’ health-related quality of life as standardized tool. It comprises 36 items that are attributed to 8 subscales attributed to 2 components: the physical component score and the mental component score. Differences in the health-related quality of life between the included aged recipients and age-matched general population as well as among female and male recipients. Aged recipients showed significantly lower scores in physical functioning (29 vs. 76, p = 0.001), role physical (42 vs. 73, p = 0.003), bodily pain (34 vs. 71, p = 0.003), general health (28 vs. 59, p = 0.001), vitality (25 vs. 61, p = 0.001), social functioning (36 vs. 87, p = 0.001), role emotional (46 vs. 89, p = 0.001) as well as the physical component score (28 vs. 76, p = 0.001). Aged female recipients showed lower results as compared to males in social functioning, physical functioning, role physical, and social functioning (p = 0.03 respectively) but comparable results in the remaining. Quality of life seems to be an issue among aged recipients and should be assessed on a regular basis.