Clinical Evaluation and Metabolism of Sevoflurane in Patients

Sevoflurane was submitted to Phase II studies in patients following Phase I studies. Sevoflurane, 2% inspired during maintenance, was administered with 50% N2O in oxygen to produce surgical anesthesia in 9 orthopedic patients of ASA Physical Status I. Under controlled ventilation, endotracheal concentration of sevoflurane was recorded. The blood concentration of sevoflurane was measured during and after the inhalation. Serum, urinary inorganic fluoride, and glucuronide of hexafluoroisopropanol were analysed with ion chromatographic analyzer. The patient inhaled sevoflurane for 3.5 ± 1.6 hr. All the patients were anesthetized and operated uneventfully. Postoperative laboratory findings showed no unexplainable abnormality. The end expiratory concentration of sevoflurane reached a plateau in 4.0 ± 0.8 min and fell rapidly after discontinuation of sevoflurane. Blood concentration of sevoflurane was about 500 μM during inhalation. It decreased promptly after termination of sevoflurane and was not correlated with anesthetic time. The time for verbal response after discontinuation was 11.8 ± 4.2 min. The serum concentration of inorganic fluoride increased after inhalation and reached a plateau (13.7 ± 8.2 μM) in 120 min. The level lasted for 120 min after anesthesia and fell by half at 12 hr after anesthesia. Urinary fluoride concentration varied from 20 to 3,000 μM during the first 12 hr urine, and showed its maximum in the first postoperative 12 or 24 hr urine. The findings that sevoflurane with nitrous oxide and oxygen produced surgical anesthesia without any sequelae and that the serum fluoride level did not exceed the nephrotoxic level warrent the further clinical evaluation in a wider range of subjects.A part of this work was supported by a Research Grant from the Japanese Ministry of Education, Science and Culture and presented at the 8th European Congress of Anaesthesiology, Vienna, Austria, in September, 1986

糖尿病患者における足部関節可動域と動脈硬化指標の関係

Foot ulcers cause gait disturbances, decreased quality of life, and high rates of mortality in diabetic patients. High plantar pressure and failure of peripheral circulation dynamics have been mentioned as risk factors for diabetic foot ulcers. It has been reported that plantar pressure is affected by the limited joint mobility （LJM） of foot joints. Therefore, preventing LJM of foot joints is important for prevention of diabetic foot ulcers. Failure of peripheral circulation dynamics can be evaluated by measuring brachial-ankle pulse wave velocity （baPWV）. The LJM of foot joints and arteriosclerosis are involved in the etiology of diabetic foot ulcers, but there have been no studies regarding the relationship between these two factors. We investigated the relationship between the range of motion （ROM） of foot joints and baPWV in diabetic patients.The study population consisted of 48 diabetic patients admitted to hospital for glycemic control and diabetes education. The LJM parameters measured were passive ROM of plantar flexion and dorsiflexion of the ankle joint, flexion and extension of the first metatarsophalangeal joint, and pronation and supination of the subtalar joint. baPWV was measured using an automated device. Pearsonʼs and partial correlation coefficients of patientsʼ baPWV and ROM values were calculated. The control conditions were age, gender, diabetes condition （diabetes duration, HbA1c levels, and diabetic polyneuropathy）, and arteriosclerosis status （systolic and diastolic blood pressure）.The mean age of the subjects was 57.4±11.8 years. ROM values for ankle, first metatarsophalangeal, and subtalar joints were 56.9°±8.8°, 89.7°±11.8°, and 27.0°±7.1°, respectively. Partial correlation analysis revealed a negative correlation between baPWV and ankle ROM （r=－0.35, p=0.03） after controlling for age, sex, systolic and diastolic blood pressure, diabetes duration, HbA1c level, and diabetic polyneuropathy. No significant associations of these outcomes were found in other joints.In diabetic patients, baPWV and ankle ROM were significantly negatively correlated when controlling for factors such as age, systolic and diastolic blood pressure, diabetes duration, HbA1c level, and diabetic polyneuropathy. However, additional studies are needed to draw clinical conclusions.糖尿病性足部潰瘍は歩行障害、QOL の低下、死亡率の上昇を引き起こす。糖尿病性足部潰瘍の危険因子として高すぎる足底圧と末梢循環動態の障害が報告されている。足底圧は、足部関節の可動域制限の影響を受けることが示されている。従って、足部関節の関節可動域制限を予防することは、糖尿病性足部潰瘍の予防において重要である。末梢循環動態は、上腕 ‐ 足首脈波速度（baPWV）で評価できる。足部関節の可動域制限および動脈硬化は糖尿病性足部潰瘍に個々に関与しているが、両者の関係は不明である。そこで本研究の目的は、糖尿病患者の足部関節の関節可動域と baPWV の関係を調べることとした。対象は、血糖コントロールと糖尿病教育のために入院した 48 人の糖尿病患者とした。測定された関節可動域は、足関節の背屈および底屈、第1中足趾節間関節の屈曲および伸展、および距骨下関節の回内および回外方向の他動関節可動域とした。baPWV は専用の自動計測装置で測定した。対象の baPWV および各関節の関節可動域のピアソンおよび偏相関係数を計算した。偏相関係数の統制条件は、年齢、性別、糖尿病の状態（糖尿病罹病期間、 HbA1c 値および糖尿病性多発性神経障害）および動脈硬化に関連する値（収縮期血圧および拡張期血圧）とした。対象の平均年齢は 57.4 ± 11.8 歳であった。足関節、第 1 中足趾節間関節、距骨下関節の関節可動域は、それぞれ 56.9 ± 8.8°、89.7 ± 11.8°、27.0 ± 7.1°であった。偏相関分析は、年齢、性別、収縮期血圧および拡張期血圧、糖尿病期間、HbA1c 値および糖尿病性多発性神経障害の有無で制御した後、baPWV と足関節の関節可動域との間に負の相関を示した（r = -0.35、p = 0.03）。他の関節では有意な関連は認められなかった。糖尿病患者では、年齢、収縮期および拡張期血圧、糖尿病期間、HbA1c 値および糖尿病性多発性神経障害の因子で統制しても、baPWV および足関節の関節可動域は有意に負の相関関係を認めた。しかしながら、臨床的結論を引き出すためにはさらなる研究が必要である

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors

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

Changes in the Respiratory Quotient during Surgery with or without Carbohydrate Loading

Usually glucose is used as an energy source intraoperatively, and recently maltose containing fluids was introduced as intraoperative fluid supply. However, the optimal dosage and form of intraoperative carbohydrate have not yet been known. The authors compared changes in the RQ during surgery without any energy source supply, and with administration of glucose or maltose in twenty eight males and females to know the effects of carbohydrates administration on RQ during surgery and to estimate the optimal dosage and form of intraoperative carbohydrates. Patients in group 1 received no carbohydrates during the operation; in groups 2 and 3, patients were given 0.25g glucose/kg and 0.5g glucose/kg/hr respectively, and patients in groups 4 and 5 received maltose at the speed of 0.25g/kg/hr, respectively. No differences in RQ were observed before the beginning of surgery among groups. In group 1, the RQ decreased from 0.85 ± 0.08 (X ± S.D.) to 0.72 ± 0.04 at 150 min after the beginning of the operation. In groups 2 and 3 (the glucose groups) and group 4 (the maltose group), the RQ also had fallen at 150 min, from 0.86 ± 0.06 to 0.74 ± 0.06 (group 2), 0.86 ± 0.05 to 0.80 ± 0.05 (group 3), 0.86 ± 0.03 to 0.81 ± 0.03 (group 4). Group 5 was the only group in which we could not observe any significant change of RQ during surgery (0.85 ± 0.06 to 0.84 ± 0.03). Without carbohydrates administration, the RQ decreased to nearly 0.7, indicating that the main energy source of the patients changed from carbohydrates to lipids. This reduction of RQ during operation can be inhibited with administration of carbohydrates, which suggests that the administered carbohydrates were utilized as the energy source during the time of surgery, and maltose 0.5g/kg/hr is thought to be suitable for intraoperative use as an energy source.This study was supported by a Research Grant from the Japanese Ministry of Education, Science and Culture (No. 61771129), and was presented at the 7th European Congress of Anesthesiologists held in Vienna, 1986.【Hiroshima J. Med. Sci.Vol.37, No.3, p149に掲載】 ERRATUM Page 83 In the Abstract section, 0.25g glucose/kg on line 8 should be read 0.25g glucose/kg/hr; and 0.25g/kg/hr on line 9 should be corrected to be 0.25g/kg/hr and 0.5g/kg/hr