Monitoring of muscle mass in critically ill patients : comparison of ultrasound and two bioelectrical impedance analysis devices

Background: Skeletal muscle atrophy commonly occurs in critically ill patients, and decreased muscle mass is associated with worse clinical outcomes. Muscle mass can be assessed using various tools, including ultrasound and bioelectrical impedance analysis (BIA). However, the effectiveness of muscle mass monitoring is unclear in critically ill patients. This study was conducted to compare ultrasound and BIA for the monitoring of muscle mass in critically ill patients. Methods: We recruited adult patients who were expected to undergo mechanical ventilation for > 48 h and to remain in the intensive care unit (ICU) for > 5 days. On days 1, 3, 5, 7, and 10, muscle mass was evaluated using an ultrasound and two BIA devices (Bioscan: Malton International, England; Physion: Nippon Shooter, Japan). The influence of fluid balance was also evaluated between each measurement day. Results: We analyzed 93 images in 21 patients. The age of the patients was 69 (interquartile range, IQR, 59–74) years, with 16 men and 5 women. The length of ICU stay was 11 days (IQR, 9–25 days). The muscle mass, monitored by ultrasound, decreased progressively by 9.2% (95% confidence interval (CI), 5.9–12.5%), 12.7% (95% CI, 9.3–16.1%), 18.2% (95% CI, 14.7–21.6%), and 21.8% (95% CI, 17.9–25.7%) on days 3, 5, 7, and 10 (p < 0.01), respectively, with no influence of fluid balance (r = 0.04, p = 0.74). The muscle mass did not decrease significantly in both the BIA devices (Bioscan, p = 0.14; Physion, p = 0.60), and an influence of fluid balance was observed (Bioscan, r = 0.37, p < 0.01; Physion, r = 0.51, p < 0.01). The muscle mass assessment at one point between ultrasound and BIA was moderately correlated (Bioscan, r = 0.51, p < 0.01; Physion, r = 0.37, p < 0.01), but the change of muscle mass in the same patient did not correlate between these two devices (Bioscan, r = − 0.05, p = 0.69; Physion, r = 0.23, p = 0.07). Conclusions: Ultrasound is suitable for sequential monitoring of muscle atrophy in critically ill patients. Monitoring by BIA should be carefully interpreted owing to the influence of fluid change

Unveiling the RNA virosphere associated with marine microorganisms

The study of extracellular DNA viral particles in the ocean is currently one of the most advanced fields of research in viral metagenomic analysis. However, even though the intracellular viruses of marine microorganisms might be the major source of extracellular virus particles in the ocean, the diversity of these intracellular viruses is not well understood. Here, our newly developed method, referred to herein as fragmented and primer ligated dsRNA sequencing (flds) version 2, identified considerable genetic diversity of marine RNA viruses in cell fractions obtained from surface seawater. The RNA virus community appears to cover genome sequences related to more than half of the established positive‐sense ssRNA and dsRNA virus families, in addition to a number of unidentified viral lineages, and such diversity had not been previously observed in floating viral particles. In this study, more dsRNA viral contigs were detected in host cells than in extracellular viral particles. This illustrates the magnitude of the previously unknown marine RNA virus population in cell fractions, which has only been partially assessed by cellular metatranscriptomics and not by contemporary viral metagenomic studies. These results reveal the importance of studying cell fractions to illuminate the full spectrum of viral diversity on Earth

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Clinical benefits of adjuvant chemotherapy with carboplatin and gemcitabine in patients with non-small cell lung cancer: A single-center retrospective study

Purpose: In cases of non-small cell lung cancer (NSCLC), surgery remains the best option for cure, but surgery is of benefit only when the disease is localized. Although adjuvant chemotherapy reportedly has a significant beneficial effect on survival, the benefit of a carboplatin (CBDCA) regimen is unclear. We therefore investigated the efficacy and tolerability of CBDCA (area under the curve 5) plus gemcitabine (GEM, 1000 mg/m2) as adjuvant chemotherapy. Methods: A total of 82 pStage IB-IIIA NSCLC patients who had undergone complete resection and received adjuvant chemotherapy were analyzed retrospectively. Among them, 65 patients received CBDCA + GEM and 17 received CDDP + VNR. Propensity score analysis generated 17 matched pairs of both groups. Results: Sixty-five patients received CBDCA + GEM. Their 5-year relapse-free survival (RFS) and overall survival were 47.8% (median, 52.5 months) and 76.9% (median, 90.1 months), respectively. Toxicities, which included neutropenia, nausea/ anorexia, fatigue, and vasculitis, were significantly milder than with CDDP + VNR. There were no significant differences in RFS between CBDCA + GEM and CDDP + VNR (p = 0.079) after matching for age, performance status, and pStage. Conclusion: CBDCA + GEM was effective and well tolerated as adjuvant chemotherapy, with a manageable toxicity profile