Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and Hepatobiliary–Pancreatic Cancers

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary–pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m2 for men and 15 kg/m2 for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival

Impact of phase angle on postoperative prognosis

Objective Phase angle (PhA), by bioelectrical impedance analysis, has been used in patients with several diseases; however, its prognostic value in patients with gastrointestinal and hepatobiliary–pancreatic (HBP) cancer is unclear. The present study aimed to investigate the impact of PhA on postoperative short-term outcomes and long-term survival in these patients. Research Methods & Procedures This retrospective study reviewed data of 501 patients with gastrointestinal and HBP cancers who underwent first resection surgery and divided the data into the following groups according to the preoperative PhA quartile values by sex: high-PhA group with the highest quartile (Q4), normal-PhA group with middle quartiles (Q3 and Q2), and low-PhA group with the lowest quartile (Q1). Preoperative nutritional statuses, postoperative short-term outcomes during hospitalization, and 5-year survival between three groups were compared. Cox proportional hazard models were used to evaluate the prognostic effect of PhA. Results PhA positively correlated with body weight, skeletal muscle mass, and handgrip strength, and negatively correlated with age and C-reactive protein levels. The low-PhA group showed a high prevalence of malnutrition (48%) than normal-PhA (25%), and high-PhA (9%) (P < 0.001). The incidence of postoperative severe complications was 10% in all patients [14% in low-PhA, 12% in normal-PhA, and 4% in high-PhA (P = 0.018)]. The incidence of prolonged postoperative high care unit or/and intensive care unit stays was 8% in all patients [16% in low-PhA, 8% in normal-PhA, and 2% in high-PhA (P < 0.001)]. The 5-year survival rate was 74% in all patients [68% in low-PhA, 74% in normal-PhA, and 79% in high-PhA (P < 0.001)]. The multivariate analysis demonstrated that a low-PhA group was an independent risk factor for mortality (hazard ratio, 1.99; 95% confidence interval 1.05–3.90; P = 0.034). Conclusion PhA is a useful short-term and long-term postoperative prognostic marker for patients with gastrointestinal and HBP cancers

Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary–pancreatic cancer

Background & Aims: The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary–pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. Methods: A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. Results: The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08–2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m2 was an independent poor prognostic factor. Conclusions: EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m2 is most associated with prognosis in patients with preoperative GI and HBP cancers

Muscle mass, quality, and strength; physical function and activity; and metabolic status in cachectic patients with head and neck cancer

Background & aims: Cancer cachexia is commonly associated with poor prognosis in patients with head and neck cancer (HNC). However, its pathophysiology and treatment are not well established. The current study aimed to assess the muscle mass/quality/strength, physical function and activity, resting energy expenditure (REE), and respiratory quotient (RQ) in cachectic patients with HNC. Methods: This prospective cross-sectional study analyzed 64 patients with HNC. Body composition was measured via direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity on ultrasonography images. Muscle strength was investigated utilizing handgrip strength and isometric knee extension force (IKEF). Physical function was evaluated using the 10-mwalking speed test and the five times sit-to-stand (5-STS) test. Physical activity was examined using a wearable triaxial accelerometer. REE and RQ were measured via indirect calorimetry. These parameters were compared between the cachectic and noncachectic groups. Results: In total, 23 (36%) patients were diagnosed with cachexia. The cachectic group had a significantly lower muscle mass than the noncachectic group. Nevertheless, there was no significant difference in terms of fat between the two groups. The cachectic group had a higher quadriceps echo intensity and a lower handgrip strength and IKEF than the noncachectic group. Moreover, they had a significantly slower normal and maximum walking speed and 5 STS speed. The number of steps, total activity time, and time of activity (<3 Mets) did not significantly differ between the two groups. The cachectic group had a shorter time of activity (≥3 Mets) than the noncachectic group. Furthermore, the cachectic group had a significantly higher REE/body weight and REE/fat free mass and a significantly lower RQ than the noncachectic group. Conclusions: The cachectic group had a lower muscle mass/quality/strength and physical function and activity and a higher REE than the noncachectic group. Thus, REE and physical activity should be evaluated to determine energy requirements. The RQ was lower in the cachectic group than that in the noncachectic group, indicating changes in energy substrate. Further studies must be conducted to examine effective nutritional and exercise interventions for patients with cancer cachexia

ショチュウトウ キョウイク ニホンゴ キョウシ ケンシュウ ニ オケル キョウジュホウ ジュギョウ ニ ツイテ

初・中等教育段階の日本語教育は、各国・地域の外国語教育政策に基づいて展開されており、シラバス、カリキュラム、教材もそれぞれの国・地域で統一されている場合が多く、学習者の発達段階など多くの要因を考慮しながら授業を組み立てていく必要がある。初・中等教育の教師を対象とした研修の教授法授業では、このような背景を考慮した実践的な教授活動を取り入れていくことが重要である。2003年度海外日本語教師短期研修(春期)(以下、春短期研修)における教授法授業では以下の試みを行った。できる限り教授環境を共有する国・地域別のクラス編成を重視し、多国籍のクラスの人数を少数になるようにした。さらに、それぞれの教授環境を重視し、その一方で国・地域を超えた初・中等教育に共通する課題をその枠組みの中で取り上げることとした。 共通に扱う項目としては、それぞれの教師が普段行っているであろう教授活動の流れ、「教授目標設定→授業設計→授業準備・教材作成→授業実施→授業に対する評価」の流れを教授法授業で経験させること、コンピュータの利用、高校訪問という要素を、それぞれの教師の望む程度に応じて教授活動の中に織り込ませることであった。 本稿では、5クラスそれぞれの教授法授業の実際を報告し、コンピュータ利用、高校訪問については全体について報告した。研修に参加したほとんどの教師は、教授法授業のクラス分け、扱った内容について役立ったとしているが、違う国・地域の教師との情報交流の機会をより増やすことを望む声が多かった。さらに、コンピュータ利用を勧めたことについては、IT普及の如何に関わらず好評であった。高校訪問については、半数程度が役立つとしているが、問題があったとする意見もあり、教授法授業への取り入れ方については検討を要する。今後も、初・中等教育に携わる日本語教師への研修を改善していくためには、実践に根ざした情報の蓄積が必要である

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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