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            "text": "\n112798\nThe effect of platelet concentrates on graft maturation and graft-bone interface healing in anterior cruciate ligament reconstruction in human patients: a systematic review of controlled trials.\n\nVavken, P\n\nSadoghi, P\n\nMurray, MM\n\nBeiträge in Fachzeitschriften\nISI:000296580400019\n21862277.0\n10.1016/j.arthro.2011.06.003\nPMC3206130\nPURPOSE: To systematically review the current evidence for the effects of platelet concentrates on (1) graft maturation and (2) graft-bone interface healing in anterior cruciate ligament (ACL) reconstruction in human, controlled trials and for ensuing differences in clinical outcomes.                 METHODS: A systematic search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was performed for controlled trials of human ACL reconstruction with and without platelet concentrates. Data validity was assessed, and data were collected on graft maturation, graft-bone interface healing, and clinical outcome.                 RESULTS: Eight studies met the inclusion criteria. Seven studies reported on graft maturation with significantly better outcomes in the platelet groups in 4, and there were large differences in means in an additional 2 studies. Five studies reported on tunnel healing, and 4 found no difference between groups. Three studies assessed clinical outcome but found no differences, regardless of whether they had shown a beneficial effect (1 of 3) or no effect (2 of 3) of platelets on graft and tunnel healing.                 CONCLUSIONS: The current best evidence suggests that the addition of platelet concentrates to ACL reconstruction may have a beneficial effect on graft maturation and could improve it by 20% to 30% on average, but with substantial variability. The most likely mode of action is that treatment with platelets accelerates graft repopulation and remodeling, and this interpretation is supported by the existing data and is biologically plausible. However, the current evidence also shows only a very limited influence of platelet concentrates on graft-bone interface healing and no significant difference in clinical outcomes.                 LEVEL OF EVIDENCE: Level III, systematic review of Level I, II, and III studies.                 Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.\n\nSadoghi, Patrick\n\n\n"
        },
        {
            "text": "\n114419\nMinimal important differences for interpreting health-related quality of life scores from the EORTC QLQ-C30 in lung cancer patients participating in randomized controlled trials.\n\nMaringwa, JT\n\nQuinten, C\n\nKing, M\n\nRingash, J\n\nOsoba, D\n\nCoens, C\n\nMartinelli, F\n\nVercauteren, J\n\nCleeland, CS\n\nFlechtner, H\n\nGotay, C\n\nGreimel, E\n\nTaphoorn, MJ\n\nReeve, BB\n\nKoch, JS\n\nWeis, J\n\nSmit, EF\n\nvan Meerbeeck, JP\n\nBottomley, A\n\nEORTC PROBE project and the Lung Cancer Group\n\nBeiträge in Fachzeitschriften\nISI:000295528600010\n20886240.0\n10.1007/s00520-010-1016-5\nNone\nBACKGROUND: The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in a subset of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) scales, which could be considered as clinically meaningful in patients with non-small-cell lung cancer (NSCLC).                 METHODS: WHO performance status (PS) and weight change were used as clinical anchors to determine minimal important differences (MIDs) in HRQOL change scores (range, 0-100) in the EORTC QLQ-C30 scales. Selected distribution-based methods were used for comparison.                 FINDINGS: In a pooled dataset of 812 NSCLC patients undergoing treatment, the values determined to represent the MID depended on whether patients were improving or deteriorating. MID estimates for improvement (based on a one-category change in PS, 5 - <20% weight gain) were physical functioning (9, 5); role functioning (14, 7); social functioning (5, 7); global health status (9, 4); fatigue (14, 5); and pain (16, 2). The respective MID estimates for deterioration (based on PS, weight loss) were physical (4, 6); role (5, 5); social (7, 9); global health status (4, 4); fatigue (6, 11); and pain (3, 7).                 INTERPRETATION: Based on the selected QLQ-C30 scales, the MID may depend upon whether the patients' PS is improving or worsening, but our results are not definitive. The MID estimates for the specified scales can help clinicians and researchers evaluate the significance of changes in HRQOL and assess the value of a health care intervention or compare treatments. The estimates also can be useful in determining sample sizes in the design of future clinical trials.\n\nGreimel, Elfriede Renate\n\n\n"
        },
        {
            "text": "\n121196\nCombined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27.\n\nSalzer, E\n\nDaschkey, S\n\nChoo, S\n\nGombert, M\n\nSantos-Valente, E\n\nGinzel, S\n\nSchwendinger, M\n\nHaas, OA\n\nFritsch, G\n\nPickl, WF\n\nFörster-Waldl, E\n\nBorkhardt, A\n\nBoztug, K\n\nBienemann, K\n\nSeidel, MG\n\nBeiträge in Fachzeitschriften\nISI:000317530600027\n22801960.0\n10.3324/haematol.2012.068791\nPMC3659923\nCD27, a tumor necrosis factor receptor family member, interacts with CD70 and influences T-, B- and NK-cell functions. Disturbance of this axis impairs immunity and memory generation against viruses including Epstein Barr virus (EBV), influenza, and others. CD27 is commonly used as marker of memory B cells for the classification of B-cell deficiencies including common variable immune deficiency. Flow cytometric immunophenotyping including expression analysis of CD27 on lymphoid cells was followed by capillary sequencing of CD27 in index patients, their parents, and non-affected siblings. More comprehensive genetic analysis employed single nucleotide polymorphism-based homozygosity mapping and whole exome sequencing. Analysis of exome sequencing data was performed at two centers using slightly different data analysis pipelines, each based on the Genome Analysis ToolKit Best Practice version 3 recommendations. A comprehensive clinical characterization was correlated to genotype. We report the simultaneous confirmation of human CD27 deficiency in 3 independent families (8 patients) due to a homozygous mutation (p. Cys53Tyr) revealed by whole exome sequencing, leading to disruption of an evolutionarily conserved cystein knot motif of the transmembrane receptor. Phenotypes varied from asymptomatic memory B-cell deficiency (n=3) to EBV-associated hemophagocytosis and lymphoproliferative disorder (LPD; n=3) and malignant lymphoma (n=2; +1 after LPD). Following EBV infection, hypogammaglobulinemia developed in at least 3 of the affected individuals, while specific anti-viral and anti-polysaccharide antibodies and EBV-specific T-cell responses were detectable. In severely affected patients, numbers of iNKT cells and NK-cell function were reduced. Two of 8 patients died, 2 others underwent allogeneic hematopoietic stem cell transplantation successfully, and one received anti-CD20 (rituximab) therapy repeatedly. Since homozygosity mapping and exome sequencing did not reveal additional modifying factors, our findings suggest that lack of functional CD27 predisposes towards a combined immunodeficiency associated with potentially fatal EBV-driven hemo-phagocytosis, lymphoproliferation, and lymphoma development.\n\nSeidel, Markus\n\n\n"
        },
        {
            "text": "\n121403\nTei Index in Fabry Disease\n\nNiemann, M\n\nBreunig, F\n\nBeer, M\n\nHu, K\n\nLiu, D\n\nEmmert, A\n\nHerrmann, S\n\nErtl, G\n\nWanner, C\n\nTakenaka, T\n\nTei, C\n\nWeidemann, F\n\nBeiträge in Fachzeitschriften\nISI:000294204600010\n21719255.0\n10.1016/j.echo.2011.05.021\nNone\nBackground: Systolic and diastolic dysfunction of the left ventricle are present in patients with cardiac involvement in Fabry disease. The aim of this study was to investigate the diagnostic value of the Tei index, a marker for combined diastolic and systolic function, in patients with Fabry disease. Methods: A total of 66 consecutive patients with genetically confirmed Fabry disease were included in this study. Standard echocardiography, including the Tei index, and magnetic resonance imaging were performed. Patients were followed for 2.9 +/- 1.9 years; 56 patients received enzyme replacement therapy, and 10 patients had natural history follow-up. Patients were subdivided into three groups: (1) those without cardiac involvement, (2) those with left ventricular (LV) hypertrophy and without late enhancement on magnetic resonance imaging, and (3) those with late enhancement on magnetic resonance imaging. Results: The Tei index was significantly higher in the groups 2 (0.56 +/- 0.10) and 3 (0.60 +/- 0.16) compared with patients without cardiac involvement (0.44 +/- 0.10) (P < .001). All patients with Tei indexes > 0.64 showed signs of cardiomyopathy. In contrast, ejection fractions were normal in all three patient groups and therefore not useful for the detection of cardiac involvement. A significant positive correlation was observed between LV wall thickness and the Tei index in the complete patient cohort. Moreover, receiver operating characteristic analysis revealed a large area under the curve for Tei index and hypertrophy, while the area under the curve for fibrosis was small. The Tei index remained unchanged in the natural history and enzyme replacement therapy groups during follow-up. Conclusions: In this cohort, the Tei index was of limited value to detect myocardial fibrosis and monitor enzyme replacement therapy. However, the progression of cardiomyopathy toward LV hypertrophy seems to be paralleled by global functional impairment, which can be assessed by the Tei index but not by ejection fraction. Thus, the Tei index seems to be a global parameter that can detect LV functional reduction in patients with Fabry disease. (J Am Soc Echocardiogr 2011; 24: 1026-32.)\n\n\n"
        },
        {
            "text": "\n125833\nCan noninvasive imaging tools potentially predict the risk of ulceration in invasive melanomas showing blue and black colors?\n\nLongo, C\n\nFarnetani, F\n\nMoscarella, E\n\nde Pace, B\n\nCiardo, S\n\nPonti, G\n\nPiana, S\n\nCesinaro, AM\n\nCota, C\n\nArgenziano, G\n\nRosendahl, C\n\nPellacani, G\n\nZalaudek, I\n\nBeiträge in Fachzeitschriften\nISI:000315810300005\n23358425.0\n10.1097/CMR.0b013e32835d90b8\nNone\nThe aim of this study was to evaluate the reflectance microscopy and histopathologic correlates of dermoscopic blue and black color (BB) in a series of melanomas. We searched our database for dermoscopic images of histopathologically diagnosed pigmented nodular melanomas (pNM), superficial spreading melanomas with a nodular component (SSM+Nod), and melanoma metastasis (METs). All cases were assessed for the presence of dermoscopic BB. Confocal microscopy findings were then compared with those of histopathology. A total of 17 BB-positive tumors including eight pNMs, five SSM+Nod, and four METs were included in the study. We identified two different dermoscopic patterns associated with black color, namely, large black blotches and irregular black dots/globules, which corresponded to two different confocal and histopathologic findings. Black blotches resulted from a total filling of the epidermis by an upward migration of melanocyte nests and pagetoid melanocytes as single cells and clusters, whereas black dots/globules also corresponded to the upward migration of melanocyte nests in the epidermis and pagetoid spread, but with sparing of intervening areas of epidermis. Interestingly, two pNM and two METs showing black color lacked any epidermal involvement and, instead, they were characterized by upward-bulging dermal masses of atypical melanocytes covered by an highly attenuated epidermis. In both cases, black color corresponded to pigment-containing melanocytes in close proximity to the surface of the skin. Our study suggests that black color results not only from epidermal melanin but also from a dense dermal proliferation of pigmented melanocytes under a thinned epidermis. It seems reasonable to suggest that a bulging proliferation of dermal melanocytes beneath a thin epidermal layer could precede ulceration. As ulceration is a very significant prognostic factor, speculation arising from this study that dermoscopic black color may in some cases indicate incipient ulceration is worthy of further study.\n\nZalaudek, Iris\n\n\n"
        },
        {
            "text": "\n127439\nThermometry of red blood cell concentrate: magnetic resonance decoding warm up process.\n\nReiter, G\n\nReiter, U\n\nWagner, T\n\nKozma, N\n\nRoland, J\n\nSchöllnast, H\n\nEbner, F\n\nLanzer, G\n\nBeiträge in Fachzeitschriften\nISI:000315524900203\n23469108.0\n10.1371/journal.pone.0057931\nPMC3585280\nPurpose: Temperature is a key measure in human red blood cell concentrate (RBC) quality control. A precise description of transient temperature distributions in RBC units removed from steady storage exposed to ambient temperature is at present unknown. Magnetic resonance thermometry was employed to visualize and analyse RBC warm up processes, to describe time courses of RBC mean, surface and core temperatures by an analytical model, and to determine and investigate corresponding model parameters. Methods: Warm-up processes of 47 RBC units stored at 1-6 degrees C and exposed to 21.25 degrees C ambient temperature were investigated by proton resonance frequency thermometry. Temperature distributions were visualized and analysed with dedicated software allowing derivation of RBC mean, surface and core temperature-time courses during warm up. Time-dependence of mean temperature was assumed to fulfil a lumped capacitive model of heat transfer. Time courses of relative surface and core temperature changes to ambient temperature were similarly assumed to follow shifted exponential decays characterized by a time constant and a relative time shift, respectively. Results: The lumped capacitive model of heat transfer and shifted exponential decays described time-dependence of mean, surface and core temperatures close to perfect (mean R-2 were 0.999 +/- 0.001, 0.996 +/- 0.004 and 0.998 +/- 0.002, respectively). Mean time constants were tau(mean) = 55.3 +/- 3.7 min, tau(surface) = 41.4 +/- 2.9 min and tau(core) = 76.8 +/- 7.1 min, mean relative time shifts were Delta(surface) = 0.07 +/- 0.02 and Delta(core) = 0.04 +/- 0.01. None of the constants correlated significantly with temperature differences between ambient and storage temperature. Conclusion: Lumped capacitive model of heat transfer and shifted exponential decays represent simple analytical formulas to describe transient mean, surface and core temperatures of RBC during warm up, which might be a helpful tool in RBC temperature monitoring and quality control. Independence of constants on differences between ambient and storage temperature suggests validity of models for arbitrary storage and ambient temperatures.\n\nLanzer, Gerhard\n\nReiter, Ursula\n\nSchoellnast, Helmut\n\nWagner, Thomas\n\n\n"
        },
        {
            "text": "\n127809\nVisualization of Intrapulmonary Lymph Vessels in Healthy and Inflamed Murine Lung Using CD90/Thy-1 as a Marker.\n\nKretschmer, S\n\nDethlefsen, I\n\nHagner-Benes, S\n\nMarsh, LM\n\nGarn, H\n\nKonig, P\n\n\n\nBeiträge in Fachzeitschriften\nISI:000314660300007\n23408960.0\n10.1371/journal.pone.0055201\nPMC3568125\nBackground: Lymphatic vessels play a pivotal role in fluid drainage and egress of immune cells from the lung. However, examining murine lung lymphatics is hampered by the expression of classical lymph endothelial markers on other cell types, which hinders the unambiguous identification of lymphatics. The expression of CD90/Thy-1 on lymph endothelium was recently described and we therefore examined its suitability to identify murine pulmonary lymph vessels under healthy and inflammatory conditions. Methodology/Principal Findings: Immunohistochemistry with a monoclonal antibody against CD90.2/Thy-1.2 on 200 mu thick precision cut lung slices labeled a vascular network that was distinct from blood vessels. Preembedding immunostaining and electron microscopy verified that the anti-CD90.2/Thy-1.2 antibody labeled lymphatic endothelium. Absence of staining in CD90.1/Thy-1.1 expressing FVB mice indicated that CD90/Thy-1 was expressed on lymph endothelium and labeling was not due to antibody cross reactivity. Double-labeling immunohistochemistry for CD90/Thy-1 and alpha-smooth muscle actin identified two routes for lymph vessel exit from the murine lung. One started in the parenchyma or around veins and left via venous blood vessels. The other began in the space around airways or in the space between airways and pulmonary arteries and left via the main bronchi. As expected from the pulmonary distribution of lymph vessels, intranasal application of house dust mite led to accumulation of T cells around veins and in the connective tissue between airways and pulmonary arteries. Surprisingly, increased numbers of T cells were also detected around intraacinar arteries that lack lymph vessels. This arterial T cell sheath extended to the pulmonary arteries where lymph vessels were located. Conclusions/Significance: These results indicate that CD90/Thy-1 is expressed on lymphatic endothelial cells and represents a suitable marker for murine lung lymph vessels. Combining CD90/Thy-1 labeling with precision cut lung slices allows visualizing the anatomy of the lymphatic system in normal and inflamed conditions.\n\nMarsh, Leigh\n\n\n"
        },
        {
            "text": "\n130252\nmRNA levels of alpha1(VI) collagen, alpha1(XII) collagen, and beta ig in rabbit cornea during normal development and healing.\n\nEl-Shabrawi, Y\n\nKublin, CL\n\nCintron, C\n\nBeiträge in Fachzeitschriften\nISI:000071410800005\n9430543.0\nNone\nNone\nType VI and XII collagens and beta ig, major components of the interfibrillar matrix, may maintain proper spacing among collagen fibrils, necessary for corneal transparency. During normal corneal stroma development and healing, changes in mRNA levels of these proteins were measured to determine whether differences in steady state levels are indicative of the unique structure produced by each corneal tissue.\n                A full-thickness excision wound was made in each cornea of six adult rabbits and allowed to heal for 1, 2, or 4 weeks. Scar tissue from two rabbits (four scars) were used from each time period and processed for RNA extraction. Total RNA from 23-day-old fetal rabbit corneas (equivalent to approximately 1 week of stromal development) and 8-day-old neonate corneas (equivalent to approximately 3.5 weeks of stromal development) was also extracted. Relative quantities of alpha1(VI) collagen, alpha1(XII) collagen, beta ig, and beta-actin mRNAs were determined by competitive reverse transcriptase-polymerase chain reaction. Glyceraldehyde-3-phosphate dehydrogenase was used as a housekeeping gene.\n                Increased mRNA levels for alpha1(VI) and alpha1(XII) collagens, beta ig, and beta-actin were seen during the first 2 weeks of healing and were followed by a decrease in 4-week-old scars. Similar increases were seen in fetal corneas with a further increase in the neonate. Differences in the beta ig mRNA levels relative to that of alpha1(XII) collagen in fetal stroma and in comparison with 1-week-old wounds suggest a higher production of beta ig in early healing tissue.\n                Alterations of mRNA levels during healing and development are consistent with the cellular events and deposition of extracellular matrices in these corneal tissues. Assuming that extracellular matrix protein production is regulated at the transcriptional level, relative changes in beta ig and collagen mRNA levels reflect differences in protein deposition in early fetal and healing tissues. This is consistent with differences in the organization of the interfibrillar matrices of these tissues and their transparency.\n\nEl-Shabrawi, Yosuf\n\n\n"
        },
        {
            "text": "\n151902\nLow cerebral activity and cerebral oxygenation during immediate transition in term neonates-A prospective observational study.\n\nTamussino, A\n\nUrlesberger, B\n\nBaik, N\n\nSchwaberger, B\n\nBinder-Heschl, C\n\nSchmölzer, GM\n\nAvian, A\n\nPichler, G\n\nBeiträge in Fachzeitschriften\nISI:000375898600021\n27039154.0\n10.1016/j.resuscitation.2016.03.011\nNone\nTo analyze whether in term neonates during immediate transition after birth low cerebral activity measured by amplitude-integrated EEG (aEEG) is linked to cerebral regional oxygen saturation (crSO2) measured by near-infrared spectroscopy (NIRS). Additionally, the cerebral fractional tissue oxygen extraction (cFTOE) was calculated to analyze whether cerebral activity is linked to cFTOE.\n                A total of 244 term neonates delivered by primary cesarean section were studied. In addition to routine monitoring with pulse oximetry, aEEG and NIRS measurements were performed during the first 15min after birth. The mean minimum (Vmin) and maximum (Vmax) amplitude of the cerebral activity as well as crSO2 and cFTOE for each minute was determined. Neonates with initial Vmin<5μV or Vmax<10μV, which normalized during transition (study group) were compared to neonates with normal aEEG values throughout the whole monitoring period (control group).\n                9 neonates fulfilled inclusion criteria to the study group and were compared to 50 neonates in the control group. Vmin, Vmax, crSO2, SpO2 and cFTOE were compared from the 4th to 15thmin after birth. During our study period, Vmin and Vmax were significantly lower in the study group than in the control group. crSO2 was significantly lower in the study group until minute 11, dropping below the 10th centile in minute 8. cFTOE was significantly higher in the study group until minute 10, rising above the 90th centile in minutes 8 and 9. SpO2 was within normal ranges in both groups. crSO2 and cFTOE were within normal ranges in the control group.\n                The present study demonstrates that neonates with initially low cerebral activity during immediate transition after birth concurrently showed low crSO2 (<10th percentile), but increased cerebral oxygen extraction (cFTOE>90th percentile). Cerebral monitoring with aEEG and NIRS might provide useful information on the neonates' condition during immediate transition.\n                Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.\n\nAvian, Alexander\n\nBaik-Schneditz, Nariae\n\nBinder-Heschl, Corinna\n\nPichler, Gerhard\n\nSchwaberger, Bernhard Christian\n\nUrlesberger, Berndt\n\n\n"
        },
        {
            "text": "\n152588\nClinical impact of interleukin 6 as a predictive biomarker in the early diagnosis of postoperative systemic inflammatory response syndrome after major thoracic surgery: A prospective clinical trial.\n\nFink-Neuboeck, N\n\nLindenmann, J\n\nBajric, S\n\nMaier, A\n\nRiedl, R\n\nWeinberg, AM\n\nSmolle-Juettner, FM\n\nBeiträge in Fachzeitschriften\nISI:000379888000022\n27206334.0\n10.1016/j.surg.2016.04.004\nNone\nPostoperative systemic inflammatory response syndrome and sepsis are associated with high morbidity and mortality rates. Early detection of postoperative systemic inflammatory response syndrome improves the outcome. The aim of this study was to evaluate the feasibility of interleukin 6 as a predictive biomarker in the early diagnosis of postoperative systemic inflammatory response syndrome after a major thoracic operation.\n                A total of 94 patients were enrolled in this prospective, clinical, single-center study. The enrolled subjects underwent either lung resection or esophageal operation. Interleukin 6, procalcitonin, C-reactive protein, and leucocytes were measured sequentially before, during, and after the operation. These levels were compared between patients who developed postoperative systemic inflammatory response syndrome and those who did not.\n                The enrollees who completed the study included of 55 males (79.7%) and 14 females (20.3%) with a mean age of 60.9 years. Twenty patients (29.0%) developed systemic inflammatory response syndrome at a median time of 33.0 hours postoperatively. In cases of postoperative systemic inflammatory response syndrome, interleukin 6 was the most predictive biomarker, showing a striking increase on the day of operation and preceding the median onset of postoperative systemic inflammatory response syndrome, which occurred the next day (P ≤ .001). Peak procalcitonin and C-reactive protein occurrence were significantly delayed at 24 hours (P = .012) and 48 hours (P = .012). There was no mortality 30 days postoperatively.\n                Interleukin 6 is a reliable predictor of postoperative systemic inflammatory response syndrome, and it is able to detect postoperative system inflammatory response syndrome before the onset of related clinical symptoms. When identifying patients at high risk, it would be beneficial to include interleukin 6 in conventional postoperative monitoring, particularly after extended surgical resection.\n                Copyright © 2016 Elsevier Inc. All rights reserved.\n\nFink-Neuböck, Nicole\n\nLindenmann, Jörg\n\nMaier, Alfred\n\nRiedl, Regina\n\nSmolle-Juettner, Freyja-Maria\n\nWeinberg, Annelie-Martina\n\n\n"
        },
        {
            "text": "\n157049\nAnti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis.\n\nJendrek, ST\n\nGotthardt, D\n\nNitzsche, T\n\nWidmann, L\n\nKorf, T\n\nMichaels, MA\n\nWeiss, KH\n\nLiaskou, E\n\nVesterhus, M\n\nKarlsen, TH\n\nMindorf, S\n\nSchemmer, P\n\nBär, F\n\nTeegen, B\n\nSchröder, T\n\nEhlers, M\n\nHammers, CM\n\nKomorowski, L\n\nLehnert, H\n\nFellermann, K\n\nDerer, S\n\nHov, JR\n\nSina, C\n\nBeiträge in Fachzeitschriften\nISI:000392282900017\n27406039.0\n10.1136/gutjnl-2016-311739\nNone\nPancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC. In a previous study, we observed a high frequency of primary sclerosing cholangitis (PSC) in patients with anti-GP2-positive UC. We therefore aimed to characterise the role of anti-GP2 in PSC.\n                In an evaluation phase, sera from 138 well-characterised Norwegian patients with PSC were compared with healthy controls (n=52), and patients with UC without PSC (n=62) for the presence of PABs by indirect immunofluorescence. Further, 180 German patients with PSC served as a validation cohort together with 56 cases of cholangiocarcinoma without PSC, 20 of secondary sclerosing cholangitis (SSC) and 18 of autoimmune hepatitis.\n                Anti-GP2 IgA specifically occurred at considerable rates in large bile duct diseases (cholangiocarcinoma=36%, PSC and SSC about 50%). In PSC, anti-GP2 IgA consistently identified patients with poor survival during follow-up (Norwegian/German cohort: p Log Rank=0.016/0.018). Anti-GP2 IgA was associated with the development of cholangiocarcinoma in both PSC cohorts, yielding an overall OR of cholangiocarcinoma in patients with anti-GP2 IgA-positive PSC of 5.0 (p=0.001). Importantly, this association remained independent of disease duration, bilirubin level and age.\n                Anti-GP2 IgA can be hypothesised as a novel marker in large bile duct diseases. In particular, in PSC, anti-GP2 IgA identified a subgroup of patients with severe phenotype and poor survival due to cholangiocarcinoma. Anti-GP2 IgA may therefore be a clinically valuable tool for risk stratification in PSC.\n                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.\n\nSchemmer, Peter\n\n\n"
        },
        {
            "text": "\n164857\nNonvascularized Cartilage Grafts Versus Vascularized Cartilage Flaps: Comparison of Cartilage Quality 6 Months After Transfer.\n\nHiggins, JP\n\nBorumandi, F\n\nBürger, HK\n\nBenlidayı, ME\n\nVasilyeva, A\n\nSencar, L\n\nPolat, S\n\nGaggl, AJ\n\nBeiträge in Fachzeitschriften\nISI:000425107500016\n29033290.0\n10.1016/j.jhsa.2017.09.014\nNone\nSubchondral perfusion of osteochondral grafts has been shown to be important in preventing long-term cartilage degeneration. In carpal reconstruction, subchondral perfusion from the graft bed is limited. This study's purpose was to compare the histological characteristics of cartilage in osteochondral grafts supported by synovial imbibition alone to cartilage of vascularized osteochondral flaps that have both synovial and vascular pedicle perfusion.\n                Two adjacent osteochondral segments were harvested on the medial femoral trochlea in domestic 6- to 8-month-old pigs. Each segment measured approximately 12 mm × 15 mm × 17 mm. One segment was maintained on the descending geniculate artery vascular pedicle. The adjacent segment was separated from the pedicle to serve as a nonvascularized graft. A thin layer of methylmethacrylate cement was used to line the harvest site defect to prevent vascular ingrowth to the subsequently replaced specimens. The pigs were maintained on a high-calorie feed and returned to ambulation and full weight-bearing on the surgical legs. The animals were sacrificed after 6 months and the specimens were reharvested, sectioned, and examined. The cartilage was graded by 2 pathologists blinded to the origin of specimens as vascularized flaps or nonvascularized grafts.\n                All specimens were assigned scores utilizing the International Cartilage Repair Society grading system. Scoring for chondrocyte viability, cartilage surface morphology, and cell and matrix appearance was significantly higher in the vascularized osteochondral group than in the graft group.\n                When deprived of subchondral perfusion from underlying bone, osteochondral vascularized flaps in an intrasynovial environment demonstrate superior cartilage quality and survival compared with nonvascularized grafts.\n                In locations in which perfusion from surrounding bone may be limited (ie, proximal scaphoid or proximal lunate reconstruction), articular reconstruction using vascularized osteochondral flaps will yield superior cartilage organization and architecture than nonvascularized osteochondral grafts. The clinical and functional relevance of this finding requires further study.\n                Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.\n\n\n"
        },
        {
            "text": "\n181921\nRivaroxaban for treatment of pediatric venous thromboembolism. An Einstein-Jr phase 3 dose-exposure-response evaluation.\n\nYoung, G\n\nLensing, AWA\n\nMonagle, P\n\nMale, C\n\nThelen, K\n\nWillmann, S\n\nPalumbo, JS\n\nKumar, R\n\nNurmeev, I\n\nHege, K\n\nBajolle, F\n\nConnor, P\n\nHooimeijer, HL\n\nTorres, M\n\nChan, AKC\n\nKenet, G\n\nHolzhauer, S\n\nSantamaría, A\n\nAmedro, P\n\nBeyer-Westendorf, J\n\nMartinelli, I\n\nMassicotte, MP\n\nSmith, WT\n\nBerkowitz, SD\n\nSchmidt, S\n\nPrice, V\n\nPrins, MH\n\nKubitza, D\n\nEINSTEIN-Jr. Phase 3 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000537554300001\n32246743.0\n10.1111/jth.14813\nNone\nRecently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling.\n                Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to <30, and <12 kg, respectively. Previously, these regimens were confirmed for children weighing ≥20 kg but only predicted in those <20 kg. Based on sparse blood sampling, the daily area under the plasma concentration-time curve [AUC(0-24)ss ] and trough [Ctrough, s ] and maximum [Cmax, s ] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients.\n                Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable.\n                Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.\n                © 2020 International Society on Thrombosis and Haemostasis.\n\nGrangl, Gernot\n\n\n"
        },
        {
            "text": "\n183346\nInterleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.\n\nReiter, A\n\nBengesser, SA\n\nHauschild, AC\n\nBirkl-Töglhofer, AM\n\nFellendorf, FT\n\nPlatzer, M\n\nFärber, T\n\nSeidl, M\n\nMendel, LM\n\nUnterweger, R\n\nLenger, M\n\nMörkl, S\n\nDalkner, N\n\nBirner, A\n\nQueissner, R\n\nHamm, C\n\nMaget, A\n\nPilz, R\n\nKohlhammer-Dohr, A\n\nWagner-Skacel, J\n\nKreuzer, K\n\nSchöggl, H\n\nAmberger-Otti, D\n\nLahousen, T\n\nLeitner-Afschar, B\n\nHaybäck, J\n\nKapfhammer, HP\n\nReininghaus, E\n\nBeiträge in Fachzeitschriften\nISI:000580179900001\n32858844.0\n10.3390/nu12092575\nPMC7551871\nMajor depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1, 4) = 1.33, p = ns) nor time (F(1, 4) = 0.00, p = ns), but interaction was significant (F(1, 4) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nHamm, Carlo\n\nHaybäck, Johannes\n\nKapfhammer, Hans-Peter\n\nKohlhammer-Dohr, Alexandra\n\nLahousen-Luxenberger, Theresa\n\nLenger, Melanie\n\nMaget, Alexander\n\nMörkl, Sabrina\n\nPilz, Rene\n\nPlatzer, Martina\n\nQueissner, Robert\n\nReininghaus, Eva\n\nSeidl, Matthias\n\nUnterweger, Renate\n\nWagner-Skacel, Jolana\n\n\n"
        },
        {
            "text": "\n185016\nSkin lesions of face and scalp - Classification by a market-approved convolutional neural network in comparison with 64 dermatologists.\n\nHaenssle, HA\n\nWinkler, JK\n\nFink, C\n\nToberer, F\n\nEnk, A\n\nStolz, W\n\nDeinlein, T\n\nHofmann-Wellenhof, R\n\nKittler, H\n\nTschandl, P\n\nRosendahl, C\n\nLallas, A\n\nBlum, A\n\nAbassi, MS\n\nThomas, L\n\nTromme, I\n\nRosenberger, A\n\nReader study level-I and level-II Groups Christina Alt\n\nBeiträge in Fachzeitschriften\nISI:000610215700019\n33370644.0\n10.1016/j.ejca.2020.11.034\nNone\nThe clinical differentiation of face and scalp lesions (FSLs) is challenging even for trained dermatologists. Studies comparing the diagnostic performance of a convolutional neural network (CNN) with dermatologists in FSL are lacking.\n                A market-approved CNN (Moleanalyzer-Pro, FotoFinder Systems) was used for binary classifications of 100 dermoscopic images of FSL. The same lesions were used in a two-level reader study including 64 dermatologists (level I: dermoscopy only; level II: dermoscopy, clinical close-up images, textual information). Primary endpoints were the CNN's sensitivity and specificity in comparison with the dermatologists' management decisions in level II. Generalizability of the CNN results was tested by using four additional external data sets.\n                The CNN's sensitivity, specificity and ROC AUC were 96.2% [87.0%-98.9%], 68.8% [54.7%-80.1%] and 0.929 [0.880-0.978], respectively. In level II, the dermatologists' management decisions showed a mean sensitivity of 84.2% [82.2%-86.2%] and specificity of 69.4% [66.0%-72.8%]. When fixing the CNN's specificity at the dermatologists' mean specificity (69.4%), the CNN's sensitivity (96.2% [87.0%-98.9%]) was significantly higher than that of dermatologists (84.2% [82.2%-86.2%]; p < 0.001). Dermatologists of all training levels were outperformed by the CNN (all p < 0.001). In confirmation, the CNN's accuracy (83.0%) was significantly higher than dermatologists' accuracies in level II management decisions (all p < 0.001). The CNN's performance was largely confirmed in three additional external data sets but particularly showed a reduced specificity in one Australian data set including FSL on severely sun-damaged skin.\n                When applied as an assistant system, the CNN's higher sensitivity at an equivalent specificity may result in an improved early detection of face and scalp skin cancers.\n                Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nDeinlein, Teresa Maria\n\nHofmann-Wellenhof, Rainer\n\n\n"
        },
        {
            "text": "\n4785\n[The impact of the Multicenter Automatic Defibrillator Implantation Trial II in a university hospital--do all patients with myocardial infarction and reduced left ventricular function need an implantable cardioverter-defibrillator?].\n\nLercher, P\n\nRotman, B\n\nScherr, D\n\nKraxner, W\n\nLuha, O\n\nKlein, W\n\nBeiträge in Fachzeitschriften\nISI:000182186900007\n12741076.0\n10.1007/BF03040304\nNone\nPatients with coronary artery disease (CAD) and severely compromised left ventricular ejection fraction are at high risk to die from sudden cardiac death. The Multicenter Automatic Defibrillator implantation Trial II (MADIT II) shows a significant benefit of a cardioverter-defibrillator (ICD) therapy compared to standard treatment alone in this selected group of patients. The objective of the present study was to investigate the number of patients who will fulfil the MADIT II criteria and are candidates for prophylactic ICD implantation.\n                From January to December 2001 a total of 2653 patients underwent coronary angiography at our institution due to angina pectoris, positive exercise stress testing, pathological SPECT myocardial perfusion images, suspected dilated cardiomyopathy or ventricular arrhythmias. According to the MADIT II inclusion criteria patients with significant coronary artery disease (diameter stenosis > 50%), ejection fraction < 0.31% and previous myocardial infarction were included. Exclusion criteria were acute coronary syndromes, patients with ventricular tachyarrhythmias or an existing indication for ICD therapy, and patients with coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty within the past or following three months.\n                Out of 2653 patients 185 (7%) had an ejection fraction less than 0.31, 149 (5.6%) showed significant coronary artery stenosis and 70 (2.6%) patients fulfilled the MADIT II criteria. The mean age of these patients was 68 +/- 9 years, the left ventricular ejection fraction 24 +/- 6. In 37 patients an ICD system was implanted according to the existing guidelines. 70 patients met the MADIT II inclusion criteria, resulting in an increase of 189% of ICD implantations per year.\n                2.6% out of 2653 patients who were referred to coronary angiography fulfilled the criteria of MADIT II. The expanding indication for ICD therapy will result in an annual increase of 70 (189%) prophylactic ICD implantations in our study population.\n\nLercher, Peter\n\nScherr, Daniel\n\n\n"
        },
        {
            "text": "\n52359\nRegulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells.\n\nStepan, V\n\nRamamoorthy, S\n\nNitsche, H\n\nZavros, Y\n\nMerchant, JL\n\nTodisco, A\n\nBeiträge in Fachzeitschriften\nISI:000228444800031\n15691835.0\n10.1074/jbc.M413037200\nNone\nShh (Sonic hedgehog) regulates gastric epithelial cell differentiation. We reported that incubation of purified canine parietal cells with epidermal growth factor (EGF) for 6-16 h, stimulates H(+)/K(+)-ATPase alpha-subunit gene expression through the activation of Akt. We explored if Shh mediates some of the actions of EGF in the parietal cells. EGF induced a 6-fold increase in Shh expression, measured by Western blots, after 5 h of incubation. This effect was inhibited by both the phosphatidylinositol 3-kinase inhibitor LY294002 and by transduction of the cells with an adenoviral vector expressing dominant negative Akt. EGF stimulated the release of Shh-like immunoreactivity from the parietal cells, after 16 h of incubation. Shh induced H(+)/K(+)-ATPase alpha-subunit gene expression, assessed by Northern blots, it stimulated a luciferase reporter plasmid containing the EGF-responsive sequence (ERE) of the canine H(+)/K(+)-ATPase alpha-subunit gene promoter, and it induced parietal cell nuclear protein binding to the ERE. Gli transcription factors mediate the intracellular actions of Shh. Co-transfection of the parietal cells with the H(+)/K(+)-luc plasmid together with one expressing Gli2, induced H(+)/K(+)-luciferase activity 5-fold, whereas co-transfection of the cells with the H(+)/K(+)-luc plasmid together with one expressing dominant negative Gli2, inhibited EGF induction of H(+)/K(+)-luciferase activity. Identical results were observed in the presence of the Shh signal transduction pathway inhibitor, cyclopamine. Transfection of the cells with dominant negative Akt inhibited EGF, but not Shh stimulation of H(+)/K(+)-ATPase-luciferase activity. Thus, EGF but not Shh signals through Akt. Preincubation of the cells for 16 h with either Shh or EGF enhanced histamine-stimulated [(14)C]aminopyrine uptake by 50%. In conclusions, some of the actions of EGF in the parietal cells are mediated by the sequential activation of the Akt and the Shh signal transduction pathways. These effects might represent novel mechanisms mediating the actions of growth factors on gastric epithelial cell differentiation.\n\nJasser-Nitsche, Hildegard\n\nStepan, Vinzenz\n\n\n"
        },
        {
            "text": "\n52388\nMolecular mechanisms for the growth factor action of gastrin.\n\nTodisco, A\n\nTakeuchi, Y\n\nUrumov, A\n\nYamada, J\n\nStepan, VM\n\nYamada, T\n\nBeiträge in Fachzeitschriften\nISI:A1997YC06800018\n9357832.0\nNone\nNone\nWe have previously observed that gastrin has a cholecystokinin B (CCK-B) receptor-mediated growth-promoting effect on the AR42J rat pancreatic acinar cell line and that this effect is paralleled by induction of expression of the early response gene c-fos. We undertook these experiments to elucidate the mechanism for induction of c-fos and the linkage of this action to the trophic effects of gastrin. Gastrin (0.1-10 nM) dose dependently induced luciferase activity in AR42J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element (SRE) of the c-fos promoter. This effect was blocked by the specific CCK-B receptor antagonist D2 but not by the specific CCK-A receptor antagonist L-364, 18 or by pertussis toxin, indicating that gastrin targets the SRE via specific CCK-B receptors through a mechanism independent of Gi. Inhibition of protein kinase C (PKC) either by prolonged (24 h) exposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (100 nM) or by incubation with the selective inhibitor GF-109203X (3.5 microM) resulted in an 80% reduction in luciferase activity. Similar results were observed in the presence of the specific extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor PD-98059 (50 microM). We measured ERK2 activity in AR42J cells via in-gel kinase assays and observed that gastrin (1 pM-100 nM) induced ERK2 enzyme activity in a dose-dependent manner. Addition of GF-109203X and PD-98059, either alone or in combination, produced, respectively, partial and total inhibition of gastrin-induced ERK2 activity. Gastrin induction of ERK2 activity also resulted in a threefold increase in the transcriptional activity of Elk-1, a factor known to bind to the c-fos SRE and to be phosphorylated and activated by ERK2. PD-98059 blocked the growth-promoting effect of gastrin on the AR42J cells, demonstrating that this effect depends on activation of MEK. Our data lead us to conclude that the trophic actions of gastrin are mediated by ERK2-induced c-fos gene expression via PKC-dependent and -independent pathways.\n\nStepan, Vinzenz\n\n\n"
        },
        {
            "text": "\n52820\nAPOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.\n\nBurwick, RM\n\nRamsay, PP\n\nHaines, JL\n\nHauser, SL\n\nOksenberg, JR\n\nPericak-Vance, MA\n\nSchmidt, S\n\nCompston, A\n\nSawcer, S\n\nCittadella, R\n\nSavettieri, G\n\nQuattrone, A\n\nPolman, CH\n\nUitdehaag, BM\n\nZwemmer, JN\n\nHawkins, CP\n\nOllier, WE\n\nWeatherby, S\n\nEnzinger, C\n\nFazekas, F\n\nSchmidt, H\n\nSchmidt, R\n\nHillert, J\n\nMasterman, T\n\nHogh, P\n\nNiino, M\n\nKikuchi, S\n\nMaciel, P\n\nSantos, M\n\nRio, ME\n\nKwiecinski, H\n\nZakrzewska-Pniewska, B\n\nEvangelou, N\n\nPalace, J\n\nBarcellos, LF\n\nBeiträge in Fachzeitschriften\nISI:000237365000017\n16682670.0\n10.1212/01.wnl.0000210531.19498.3f\nNone\nBACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3, 99 MS cases and 2, 32 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1, 79 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4, 48 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.\n\nEnzinger, Christian\n\nFazekas, Franz\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
        },
        {
            "text": "\n81966\nIndependent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality.\n\nDobnig, H\n\nPilz, S\n\nScharnagl, H\n\nRenner, W\n\nSeelhorst, U\n\nWellnitz, B\n\nKinkeldei, J\n\nBoehm, BO\n\nWeihrauch, G\n\nMaerz, W\n\nBeiträge in Fachzeitschriften\nISI:000256916600019\n18574092.0\n10.1001/archinte.168.12.1340\nNone\nBACKGROUND: In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1, 5-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. METHODS: Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1, 5-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. RESULTS: During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1, 5-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). CONCLUSIONS: Low 25-hydroxyvitamin D and 1, 5-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.\n\nMärz, Winfried\n\nPilz, Stefan\n\nRenner, Wilfried\n\nScharnagl, Hubert\n\n\n"
        }
    ]
}