Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome

Better characterization of the potential kidney transplant recipient using novel biomarkers, for example, pretransplant plasma endotrophin, will lead to improved outcome after transplantation. This mini-review will focus on current knowledge about pretransplant recipients’ characteristics, biomarkers, and immunology. Clinical characteristics of recipients including age, obesity, blood pressure, comorbidities, and estimated survival scores have been introduced for prediction of recipient and allograft survival. The pretransplant immunologic risk assessment include histocompatibility leukocyte antigens (HLAs), anti-HLA donor-specific antibodies, HLA-DQ mismatch, and non-HLA antibodies. Recently, there has been the hope that pretransplant determination of markers can further improve the prediction of posttransplant complications, both short-term and long-term outcomes including rejections, allograft loss, and mortality. Higher pretransplant plasma endotrophin levels were independently associated with posttransplant acute allograft injury in three prospective European cohorts. Elevated numbers of non-synonymous single-nucleotide polymorphism mismatch have been associated with increased allograft loss in a multivariable analysis. It is concluded that there is a need for integration of clinical characteristics and novel molecular and immunological markers to improve future transplant medicine to reach better diagnostic decisions tailored to the individual patient

Determining a healthy reference range and factors potentially influencing PRO-C3 – A biomarker of liver fibrosis

Background & AimsProgressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay.MethodsPRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis.ResultsRobustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1–14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77–0.88], p <0.0001), and AUC = 0.79 (95% CI [0.73–0.85], p <0.0001), respectively).ConclusionsThe assay proved to be robust and sample stability was found to comply with hospital sample handling requirements. PRO-C3 measured in samples from patients with NAFLD/NASH was diagnostic for significant and advanced liver fibrosis

Two-Point Functions and Boundary States in Boundary Logarithmic Conformal Field Theories

Our main aim in this thesis is to address the results and prospects of boundary logarithmic conformal field theories: theories with boundaries that contain the above Jordan cell structure. We have investigated c_{p,q} boundary theory in search of logarithmic theories and have found logarithmic solutions of two-point functions in the context of the Coulomb gas picture. Other two-point functions have also been studied in the free boson construction of BCFT with SU(2)_k symmetry. In addition, we have analyzed and obtained the boundary Ishibashi state for a rank-2 Jordan cell structure [hep-th/0103064]. We have also examined the (generalised) Ishibashi state construction and the symplectic fermion construction at c=-2 for boundary states in the context of the c=-2 triplet model. The differences between two constructions are interpreted, resolved and extended beyond each case.Comment: Ph.D. Thesis (University of Oxford), 96 pages, the layout is modified from the origina

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Anamnesemethode: snel en doelmatig? : geautomatiseerde voedingsanamnese voor het vaststellen van energie-inname

Doel van dit onderzoek was: meten van de reproduceerbaarheid van een bestaande voedselfrequentievragenlijst (VVL) bij een groep patiënten met ongewijzigd dieetadvies; meten van verandering in energie-inname bij een groep patiënten met gewijzigde dieetadvies; en evalueren van de bruikbaarheid van VVL bij patiënt en diëtis

Anamnesemethode: snel en doelmatig? : geautomatiseerde voedingsanamnese voor het vaststellen van energie-inname

Doel van dit onderzoek was: meten van de reproduceerbaarheid van een bestaande voedselfrequentievragenlijst (VVL) bij een groep patiënten met ongewijzigd dieetadvies; meten van verandering in energie-inname bij een groep patiënten met gewijzigde dieetadvies; en evalueren van de bruikbaarheid van VVL bij patiënt en diëtis

Collagen turnover is associated with cardiovascular autonomic and peripheral neuropathy in type 1 diabetes: novel pathophysiological mechanism?

Background: Diabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D). Methods: In a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry. Symmetrical vibration sensation threshold above 25 V constituted DSPN. Results: Participants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio &gt; 2 for CAN and &gt; 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations. Conclusions: Results show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D.</div