The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation

BackgroundSymptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce.ObjectiveWe compared the clinical course of SGH occurring with different energy sources.MethodsThis multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation.ResultsThe data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1–4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5–5) days; the total hospitalization duration was 11 [7–19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for >1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set.ConclusionsThe clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Three-dimensional electroanatomical mapping for atrioventricular nodal reentrant tachycardia associated with persistent left superior vena cava

AbstractBackgroundThe anatomical courses of the slow pathway and His bundle are altered in patients with atrioventricular nodal reentrant tachycardia (AVNRT) associated with persistent left superior vena cava (PLSVC). We report a case of successful catheter ablation in such a patient using an electroanatomical approach with a three-dimensional mapping system.CaseA 33-year-old woman underwent catheter ablation for AVNRT. The conventional approach for ablating the atrial end of the slow pathway was unsuccessful; therefore, a second attempt was made using a three-dimensional electroanatomical mapping system. The ablation was easily performed without damaging the His bundle because of a clear understanding of the anatomical relationships.ConclusionThe electroanatomical approach using a three-dimensional mapping system can be an alternative if conventional methods prove to be technically difficult because this new approach can provide precise spatial distribution of the pathways

Ozone profiles in the high-latitude stratosphere and lower mesosphere measured by the Improved Limb Atmospheric Spectrometer (ILAS)-II: Comparison with other satellite sensors and ozonesondes

A solar occultation sensor, the Improved Limb Atmospheric Spectrometer (ILAS)-II, measured 5890 vertical profiles of ozone concentrations in the stratosphere and lower mesosphere and of other species from January to October 2003. The measurement latitude coverage was 54–71°N and 64–88°S, which is similar to the coverage of ILAS (November 1996 to June 1997). One purpose of the ILAS-II measurements was to continue such high-latitude measurements of ozone and its related chemical species in order to help accurately determine their trends. The present paper assesses the quality of ozone data in the version 1.4 retrieval algorithm, through comparisons with results obtained from comprehensive ozonesonde measurements and four satellite-borne solar occultation sensors. In the Northern Hemisphere (NH), the ILAS-II ozone data agree with the other data within ±10% (in terms of the absolute difference divided by its mean value) at altitudes between 11 and 40 km, with the median coincident ILAS-II profiles being systematically up to 10% higher below 20 km and up to 10% lower between 21 and 40 km after screening possible suspicious retrievals. Above 41 km, the negative bias between the NH ILAS-II ozone data and the other data increases with increasing altitude and reaches 30% at 61–65 km. In the Southern Hemisphere, the ILAS-II ozone data agree with the other data within ±10% in the altitude range of 11–60 km, with the median coincident profiles being on average up to 10% higher below 20 km and up to 10% lower above 20 km. Considering the accuracy of the other data used for this comparative study, the version 1.4 ozone data are suitably used for quantitative analyses in the high-latitude stratosphere in both the Northern and Southern Hemisphere and in the lower mesosphere in the Southern Hemisphere

MAP3K19 Affects TWEAK-Induced Response in Cultured Bronchial Epithelial Cells and Regulates Allergic Airway Inflammation in an Asthma Murine Model

The mitogen-activated protein kinase (MAPK) signaling pathway is involved in the epithelial–mesenchymal transition (EMT) and asthma; however, the role of mitogen-activated protein kinase kinase kinase 19 (MAP3K19) remains uncertain. Therefore, we investigated the involvement of MAP3K19 in in vitro EMT and ovalbumin (OVA)-induced asthma murine models. The involvement of MAP3K19 in the EMT and the production of cytokines and chemokines were analyzed using a cultured bronchial epithelial cell line, BEAS-2B, in which MAP3K19 was knocked down using small interfering RNA. We also evaluated the involvement of MAP3K19 in the OVA-induced asthma murine model using Map3k19-deficient (MAP3K19−/−) mice. Transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) induced the MAP3K19 messenger RNA (mRNA) expression in the BEAS-2B cells. The knockdown of MAP3K19 enhanced the reduction in E-cadherin mRNA and the production of regulated upon activation normal T cell express sequence (RANTES) via stimulation with TWEAK alone or with the combination of TGF-β1 and TWEAK. Furthermore, the expression of MAP3K19 mRNA was upregulated in both the lungs and tracheas of the mice in the OVA-induced asthma murine model. The MAP3K19−/− mice exhibited worsened eosinophilic inflammation and an increased production of RANTES in the airway epithelium compared with the wild-type mice. These findings indicate that MAP3K19 suppressed the TWEAK-stimulated airway epithelial response, including adhesion factor attenuation and RANTES production, and suppressed allergic airway inflammation in an asthma mouse model, suggesting that MAP3K19 regulates allergic airway inflammation in patients with asthma