Variation in PTX3 Is Associated with Primary Graft Dysfunction after Lung Transplantation

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.     

Quels marqueurs osseux chez les patients hémodialysés : phosphatases alcalines osseuses ou ß-CrossLaps ?

BackgroundBone turnover (BT) abnormalities are frequently observed in patients with chronic kidney disease. Bone biopsy remains the gold standard for diagnosis; however, its invasive nature has led to its decreased utilisation. The serum parathyroid hormone (PTH) level is not a reliable bone marker (BM) for BT assessment. The latest international recommendations suggest the use of total alkaline phosphatase (t-ALP) or bone-specific alkaline phosphatase (b-ALP), but not ß-CrossLaps (CTX). We compared b-ALP, t-ALP, and CTX levels in patients on haemodialysis (HD).MethodsAll HD patients at a single institution following a standard 3 × 4 to 3 × 5 hours schedule were included in the study, provided they were free from liver disease. Serum intact PTH, t-ALP, b-ALP, and CTX values were compared at baseline and after 18 months of treatment. A kinetic study was performed for pre- and postdialysis CTX values over a 2-week period. We described the longitudinal evolution of these BMs in two typical patients.ResultsA total of 98 patients on HD (46% female) were evaluated. The mean age was 69.8 ± 11 years and the mean duration of dialysis was 54.4 ± 61 months. At baseline, CTX (2.1 ± 1 μg/L) correlated well with b-ALP (18 ± 11 μg/L; r = 0.64; P < 0.001) and PTH (221 ± 165 pg/mL; r = 0.62; P < 0.001). The changes in these values at 18 months were also correlated (ΔCTX compared with Δb-ALP: r = 0.51; P < 0.001; Δb-ALP compared with ΔPTH: r = 0.37, P < 0.01). b-ALP and t-ALP (245 ± 132 U/L) were closely correlated (r = 0.78), as was their variation over 18 months (r = 0.67), but t-ALP did not correlate with PTH, and correlated poorly with CTX (r = 0.38). The CTX reduction ratio during standard dialysis was approximately 70 to 75% over each session, although predialysis values remained stable.ConclusionIn HD patients, mean CTX values are five times higher than the normal range. CTX appears to be an alternative to b-ALP for assessing BT. b-ALP remains the standard BM, despite being expensive, infrequently available in many laboratories, and not useful for patients with liver disease.     

Muscle strengthening exercises during pregnancy are associated with increased energy and reduced fatigue

Introduction: Physical inactivity likely contributes to fatigue and low energy during pregnancy but whether acute resistance exercise attenuates these symptoms is unknown.

Methods: Twenty-six women performed six low-to-moderate intensity resistance exercises twice per week from weeks 23 to 35 of pregnancy and measurements were made before and after each workout using the Mental and Physical State Energy and Fatigue Scales.

Results: Acute resistance exercise usually increased perceived physical and mental energy (92% to 96% of workouts, respectively). These increases did not differ significantly across the 24 exercise sessions for feelings of physical energy or mental energy, even after adjusting for variations in attendance (median?=?22/24 workouts). Acute resistance exercise usually decreased perceived physical and mental fatigue (79% to 88% of workouts, respectively), and ANCOVA showed these decreases did not differ significantly across the 24 exercise sessions for feelings of physical fatigue or mental fatigue even after adjusting for variations in attendance.

Discussion: The results suggest acute, low-to-moderate intensity muscle strengthening exercise during pregnancy is effective for transiently improving feelings of energy and fatigue.