Cardiac Magnetic Resonance Derived Left Ventricular Eccentricity Index and Right Ventricular Mass Measurements Predict Outcome in Children with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, affecting RV remodeling and RV performance, a major determinant of outcome in PAH-patients. In children with PAH, treatment strategy is guided by risk stratification where noninvasive prognosticators are highly needed. The prognostic value of RV characteristics derived by cardiac magnetic resonance (CMR) has been scarcely studied in pediatric PAH. We aimed to identify CMR-derived morphometric and functional RV characteristics prognostic for outcome in children with PAH. From the Dutch National cohort, thirty-eight children with either idiopathic/heritable PAH (IPAH/HPAH) or PAH associated with congenital heart disease (PAH-CHD), who underwent CMR, were included (median (interquartile range) [IQR] age 13.0 years (10.8–15.0), 66% females). Patients had severe PAH, characterized by their World Health Organization Functional Class, increased N-terminal pro-B-type natriuretic peptide and high pulmonary arterial pressure and pulmonary vascular resistance index at time of CMR. RV-ejection fraction (RVEF), indexed RV-mass (RVMi), the ratio between RV and LV mass (RVM/LVM-ratio) and left ventricular eccentricity index (LVEI) all correlated with transplant-free survival from time of CMR. These correlations could not be confirmed in the PAH-CHD group. This study shows that CMR-derived measures reflecting RV function and remodeling (LVEI, RVMi, RVM/LVM-ratio, RVEF) predict transplant-free survival in children with IPAH/HPAH and may be included in risk stratification scores in pediatric PAH.</p

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

RATIONALE &amp; OBJECTIVE: Prior studies report that the use of proton-pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients (KTR). Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population.STUDY DESIGN: Cross-sectional study.SETTING &amp; PARTICIPANTS: KTR (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study.EXPOSURE: PPI use, PPI type, PPI dosage, and duration of PPI use.OUTCOMES: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire.ANALYTICAL APPROACH: Logistic and linear regression.RESULTS: We included 937 KTR (mean age 56±13 years, 39% female) at a median of 3 [1-10] years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95%CI 2.18 to 5.85, p&lt;0.001), a higher risk of severe fatigue (OR 2.05, 95%CI 1.48 to 2.84, p&lt;0.001), lower physical HRQoL (regression coefficient -8.54, 95%CI -11.54 to -5.54, p&lt;0.001), and lower mental HRQoL (regression coefficient -4.66, 95%CI -7.15 to -2.17, p&lt;0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose-dependent. Duration of PPI exposure was only associated with fatigue severity.LIMITATIONS: Residual confounding and inability to assess causal relationships CONCLUSIONS: PPI use is independently associated with fatigue and lower HRQoL among KTR. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among KTR. Further studies examining the effect of PPI exposure in this population are warranted.</p

Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients

Background: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H2 and diarrhea in KTR, and explored potential clinical and dietary determinants. Methods: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H2 and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. Results: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m2) had a median exhaled H2 of 11 (5.0–25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H2 ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H2 was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07–2.14 per log2 ppm, p = 0.02). Polysaccharide intake was independently associated with higher H2 (std. β 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. β 0.16 p = 0.05). Conclusion: Higher exhaled H2 is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration.

The World Asthma Phenotypes (WASP) study started in 2016 and has been conducted in five centres, in the UK, New Zealand, Brazil, Ecuador and Uganda. The objectives of this study are to combine detailed biomarker and clinical information in order to 1) better understand and characterise asthma phenotypes in high-income countries (HICs) and low and middle-income countries (LMICs), and in high and low prevalence centres; 2) compare phenotype characteristics, including clinical severity; 3) assess the risk factors for each phenotype; and 4) assess how the distribution of phenotypes differs between high prevalence and low prevalence centres. Here we present the rationale and protocol for the WASP study to enable other centres around the world to carry out similar analyses using a standardised protocol. Large collaborative and integrative studies like this are essential to further our understanding of asthma phenotypes. The findings of this study will help elucidate the aetiological mechanisms of asthma and might potentially identify new causes and guide the development of new treatments, thereby enabling better management and prevention of asthma in both HICs and LMICs

Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients

BACKGROUND AND OBJECTIVES: Many kidney transplant recipients suffer from fatigue and poor health-related quality of life. Airflow limitation may be an underappreciated comorbidity among kidney transplant recipients, which could contribute to fatigue and lower health-related quality of life in this population. In this study, we compared the prevalence of airflow limitation between kidney transplant recipients and healthy controls and investigated associations of airflow limitation with fatigue and health-related quality of life in kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the ongoing TransplantLines Biobank and Cohort study were used. Airflow limitation was defined as forced exhaled volume in 1 second less than the fifth percentile of the general population. Fatigue and health-related quality of life were assessed using checklist individual strength 20 revised (CIS20-R) and Short Form-36 (SF-36) questionnaires. RESULTS: A total of 539 kidney transplant recipients (58% men; mean age 56±13 years) and 244 healthy controls (45% men; mean age 57±10 years) were included. Prevalence of airflow limitation was higher in kidney transplant recipients than in healthy controls (133 [25%] versus 25 [10%]). In multinomial regression models, airflow limitation was independently associated with fatigue severity (odds ratio moderate fatigue, 1.68; 95% confidence interval, 0.92 to 3.09 and odds ratio severe fatigue, 2.51; 95% confidence interval, 1.39 to 4.55; P=0.007) and lower physical health-related quality of life (-0.11 SDs; 95% confidence interval, -0.19 to -0.02; P=0.01) in kidney transplant recipients. In exploratory mediation analyses, fatigue accounted for 79% of the association of airflow limitation with physical health-related quality of life. CONCLUSIONS: Airflow limitation is common among kidney transplant recipients. Its occurrence is associated with more than two times higher risk of severe fatigue, and it is associated with lower physical health-related quality of life. Mediation analyses suggest that airflow limitation causes fatigue, which in turn, decreases physical health-related quality of life. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: TransplantLines: The Transplantation Biobank, NCT03272841 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN06600521.mp3

Pleural Mesothelioma in New Caledonia: Associations with Environmental Risk Factors

International audienceBackground: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. Objectives: We studied the spatial and temporal variation of MM and its association with environmental factors. Methods: We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. Results: The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Conclusions: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD