scholarly journals Metabolomics and Whole-Exome Sequencing in Patients with Differential Sensitivity to Sevoflurane: A Protocol for a Prospective Observational Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiyong Wei ◽  
Donghang Zhang ◽  
Yunxia Zuo

Introduction: Different sensitivity to volatile anesthetics in Drosophila, nematodes and mice is related to mutation of energy metabolism genes. In clinical practice, we find that the end-tidal sevoflurane concentration (ETsevo) differs among patients at the same depth of anesthesia, indicating that the sensitivity to sevoflurane varies among patients. However, the underlying mechanism remains unclear. The sensitivity of an anesthetic is associated with the postoperative outcomes of patients and the mechanism of action of volatile anesthetics. We therefore propose this protocol to determine whether differences in metabolite profile and genetic variations contribute to patients’ sensitivity to volatile anesthetics.Methods and Analysis: This is a single-centre, prospective observational study. 720 patients undergoing abdominal surgery were included. General anesthesia was induced with inhaled sevoflurane, a bolus of sufentanil (0.2–0.4 μg/kg) and cis-atracurium (0.2–0.3 mg/kg). The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain a BIS (bispectral index) value between 40–60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery (steady state) was calculated for each patient. Patients were further divided into a high-sensitivity group (mean ETsevo – SD) and a low-sensitivity group (mean ETsevo + SD) to investigate the sensitivity to sevoflurane. Cases were paired from the high-sensitivity group (group H) and low-sensitivity group (group L) according to age, sex, body mass index (BMI), ASA physical status classification, vital signs, BIS, ephedrine use, sufentanildose, and cis-atracurium dose at anesthesia induction and steady state. Differences in metabolite levels, single nucleotide polymorphisms (SNPs) and protein-coding gene sequence variations between group H and group L will be determined through plasma metabolomics, whole-exome sequencing (WES), genome-wide association study (GWAS), and bioinformatics analyses. These results will be analysed to determine the reasons for the differential sensitivity to sevoflurane in humans.Ethics and Dissemination: This prospective observational study protocol has received ethical approval from the Ethical Committee of West China Hospital of Sichuan University on May 19, 2017 (Approval No. 78). Informed consent will be obtained before patient enrolment. The results will be submitted to international peer-review journals.Trial Registration Number: ChiCTR1800014327.

2021 ◽  
Vol 22 (19) ◽  
pp. 10400
Author(s):  
H. Busra Cagirici ◽  
Bala Ani Akpinar ◽  
Taner Z. Sen ◽  
Hikmet Budak

The highly challenging hexaploid wheat (Triticum aestivum) genome is becoming ever more accessible due to the continued development of multiple reference genomes, a factor which aids in the plight to better understand variation in important traits. Although the process of variant calling is relatively straightforward, selection of the best combination of the computational tools for read alignment and variant calling stages of the analysis and efficient filtering of the false variant calls are not always easy tasks. Previous studies have analyzed the impact of methods on the quality metrics in diploid organisms. Given that variant identification in wheat largely relies on accurate mining of exome data, there is a critical need to better understand how different methods affect the analysis of whole exome sequencing (WES) data in polyploid species. This study aims to address this by performing whole exome sequencing of 48 wheat cultivars and assessing the performance of various variant calling pipelines at their suggested settings. The results show that all the pipelines require filtering to eliminate false-positive calls. The high consensus among the reference SNPs called by the best-performing pipelines suggests that filtering provides accurate and reproducible results. This study also provides detailed comparisons for high sensitivity and precision at individual and population levels for the raw and filtered SNP calls.


Author(s):  
Yutaka Kondo ◽  
Toru Hifumi ◽  
Junya Shimazaki ◽  
Yasutaka Oda ◽  
Shin-ichiro Shiraishi ◽  
...  

Background: This study aims to compare the Bouchama heatstroke (B-HS) and Japanese Association for Acute Medicine heatstroke (JAAM-HS) criteria with regard to the diagnosis and prediction of mortality and neurological status of heatstroke patients. Methods: This multicenter observational study recruited eligible patients from the emergency departments of 110 major hospitals in Japan from 1 July to 30 September, 2014. Results: A total of 317 patients (median age, 65 years; interquartile range, 39–80 years) were included and divided into the B-HS, JAAM-HS, and non-HS groups, with each group consisting of 97, 302, and 15 patients, respectively. The JAAM-HS (1.0; 95% confidence interval [CI], 0.87–1.0) and B-HS (0.29; 95% CI, 0.14–0.49) criteria showed high and low sensitivity to mortality, respectively. Similarly, the JAAM-HS (1.0; 95% CI, 0.93–1.0) and B-HS (0.35; 95% CI, 0.23–0.49) criteria showed high and low sensitivity to poor neurological status, respectively. Meanwhile, the sequential organ failure assessment (SOFA) scores demonstrated good accuracy in predicting mortality among heat-related illness (HRI) patients. However, both JAAM-HS and B-HS criteria could not predict in-hospital mortality. The AUC of the SOFA score for mortality was 0.83 (day 3) among the HRI patients. The patients’ neurological status was difficult to predict using the JAAM-HS and B-HS criteria. Concurrently, the total bilirubin level could relatively predict the central nervous system function at discharge. Conclusions: The JAAM-HS criteria showed high sensitivity to mortality and could include all HRI patients who died. The JAAM-HS criterion was considered a useful tool for judgement of admission at ED. Further investigations are necessary to determine the accuracy of both B-HS and JAAM-HS criteria in predicting mortality and neurological status at discharge.


2014 ◽  
Vol 39 (6) ◽  
pp. 636-647 ◽  
Author(s):  
Luminita Voroneanu ◽  
Dimitrie Siriopol ◽  
Ionut Nistor ◽  
Mugurel Apetrii ◽  
Simona Hogas ◽  
...  

Author(s):  
Sadhana Joshi ◽  
Gaurav Parashar

Background: Tonsillitis is a frequent condition noticed in the ENT department of every hospital. One out of every 10 children visiting the ENT OPD, suffer from acute tonsillitis. Methods: This was a prospective observational study conducted on patients coming with a history of throat pain, pain on swallowing, fever, body ache and other constitutional symptoms. Results: Antibiotic resistance was seen in case of the commonly used antibiotics like ampicillin, amoxicillin, Amoxicillin+Clavulanic acid. Cephalosporins were less commonly used antibiotics and showed resistance in 78.00% cases. Cotrimoxazole showed about 16.00% resistant cases. The less commonly used antibiotic was vancomycin however, showed high sensitivity (100%) followed by Linezolid (92.00%) and Clindamycin (82.00%). Erythromycin showed 76% sensitivity while ciprofloxacin showed a low sensitivity of 40.00% followed by Cephalosporins (22.0%). Conclusion: The antibiotic sensitivity pattern could revolutionize the management of chronic tonsillitis. Keywords: Acute tonsillitis, Antibiotics, Sensitivity


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