Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intenstities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathing. Young children are even more challenging because of higher cardiac and respiratory rates giving motion blurring. For these reasons, CT has often been preferred over MRI for chest pediatric imaging. Despite its drawbacks, MRI also has advantages over CT, which justifies its further development and clinical use. The most important advantage is the absence of ionizing radiation, which allows frequent scanning for short- and long-term follow-up studie

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective: To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants: Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures: Genetic variants associated with TIM. Main Outcomes and Measures: Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results: Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10-9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10-8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10-7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance: Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required

Methane emissions proportional to permafrost carbon thawed in Arctic lakes since the 1950s

Permafrost thaw exposes previously frozen soil organic matter to microbial decomposition. This process generates methane and carbon dioxide, and thereby fuels a positive feedback process that leads to further warming and thaw1. Despite widespread permafrost degradation during the past ~40 years2, 3, 4, the degree to which permafrost thaw may be contributing to a feedback between warming and thaw in recent decades is not well understood. Radiocarbon evidence of modern emissions of ancient permafrost carbon is also sparse5. Here we combine radiocarbon dating of lake bubble trace-gas methane (113 measurements) and soil organic carbon (289 measurements) for lakes in Alaska, Canada, Sweden and Siberia with numerical modelling of thaw and remote sensing of thermokarst shore expansion. Methane emissions from thermokarst areas of lakes that have expanded over the past 60 years were directly proportional to the mass of soil carbon inputs to the lakes from the erosion of thawing permafrost. Radiocarbon dating indicates that methane age from lakes is nearly identical to the age of permafrost soil carbon thawing around them. Based on this evidence of landscape-scale permafrost carbon feedback, we estimate that 0.2 to 2.5 Pg permafrost carbon was released as methane and carbon dioxide in thermokarst expansion zones of pan-Arctic lakes during the past 60 years