菅原 斉

Background The coronavirus disease 2019 (COVID-19) pandemic has put a strain on the healthcare system, and sudden changes in disease status during home treatment have become a serious issue. Therefore, prediction of disease severity and allocation of sufficient medical resources, including high-flow nasal cannula (HFNC), to patients in need are important. We aimed to determine risk factors for the need of HFNC use in COVID-19. Methods This was a single-center retrospective observational cohort study including all eligible hospitalized adult patients aged ≥18 years diagnosed with COVID-19 between April 14, 2020 and August 5, 2021 who were treated in the study hospital. The primary outcome is the need for HFNC. Nineteen potential predictive variables, including patient characteristics at hospital admission, were screened using least absolute shrinkage and selection operator and logistic regression to construct a predictive risk score. Accuracy of the risk score was determined using area under the receiver operating characteristic curve. Results The study cohort included 148 patients. The rate of the need for HFNC was 22.9%. Among the 19 potential variables, percutaneous oxygen saturation (SpO₂) <92% (odds ratio [OR] 7.50, 95% confidence interval [CI] 2.806–20.82) and IL-6 (OR 1.021, 95% CI 1.010–1.033) were included in developing the risk score, which was termed interleukin (IL)-6-based COVID-19 severity (IBC-S) score. Conclusions The IBC-S score, an easy-to-use risk score based on parameters available at the time of hospital admission, predicted the need for HFNC in patients with COVID-19. The IBC-S score based on interleukin-6 and SpO₂ might aid in determining patients who should be transported to a tertiary medical institution or an isolation facility.

<sec id="sec001"> <title>Background</title> Coronavirus disease (COVID-19) is associated with a high mortality rate in older adults; therefore, it is important for medical institutions to take measures to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. This study aimed to assess the risk of SARS-CoV-2 infection among healthcare workers (HCWs) and the effectiveness of infection control measures. </sec> <sec id="sec002"> <title>Methods</title> This study had a cross-sectional component and a prospective cohort component. The cross-sectional component comprised an anti-SARS-CoV-2 antibody survey among HCWs at a medical center in Saitama City, Japan. In the prospective cohort component, HCWs at the same medical center were tested for anti-SARS-CoV-2 antibodies monthly over a 3-month period (May to July 2020) to assess the effectiveness of infection prevention measures, including personal protective equipment use. All participants in the cohort study also participated in the antibody survey. The primary outcome was anti-SARS-CoV-2 antibody (measured using Elecsys^® Anti-SARS-CoV-2) positivity based on whether participants were engaged in COVID-19-related medical care. Other risk factors considered included occupational category, age, and sex. </sec> <sec id="sec003"> <title>Results</title> In total, 607 HCWs participated in the antibody survey and 116 doctors and nurses participated in the cohort study. Only one of the 607 participants in the survey tested positive for anti-SARS-CoV-2 antibodies. All participants in the cohort study were anti-SARS-CoV-2 antibody negative at baseline and remained antibody negative. Engaging in the care of COVID-19 patients did not increase the risk of antibody positivity. During the study period, a total of 30 COVID-19 in-patients were treated in the hospital. </sec> <sec id="sec004"> <title>Conclusions</title> The infection control measures in the hospital protected HCWs from nosocomially acquired SARS-CoV-2 infection; thus, HCWs should engage in COVID-19-related medical care with confidence provided that they adhere to infectious disease precautions. </sec>

The risk factors associated with mortality in patients with extremely high serum C-reactive protein (CRP) levels are controversial. In this retrospective single-center cross-sectional study, the clinical and laboratory data of patients with CRP levels ≥40 mg/dL treated in Saitama Medical Center, Japan from 2004 to 2017 were retrieved from medical records. The primary outcome was defined as 72-hour mortality after the final CRP test. Forty-four mortal cases were identified from the 275 enrolled cases. Multivariate logistic regression analysis (MLRA) was performed to explore the parameters relevant for predicting mortality. As an alternative method of prediction, we devised a novel risk predictor, “weighted average of risk scores” (WARS). WARS features the following: (1) selection of candidate risk variables for 72-hour mortality by univariate analyses, (2) determination of C-statistics and cutoff value for each variable in predicting mortality, (3) 0–1 scoring of each risk variable at the cutoff value, and (4) calculation of WARS by weighted addition of the scores with weights assigned according to the C-statistic of each variable. MLRA revealed four risk variables associated with 72-hour mortality—age, albumin, inorganic phosphate, and cardiovascular disease—with a predictability of 0.829 in C-statistics. However, validation by repeated resampling of the 275 records showed that a set of predictive variables selected by MLRA fluctuated occasionally because of the presence of closely associated risk variables and missing data regarding some variables. WARS attained a comparable level of predictability (0.837) by combining the scores for 10 risk variables, including age, albumin, electrolytes, urea, lactate dehydrogenase, and fibrinogen. Several mutually related risk variables are relevant in predicting 72-hour mortality in patients with extremely high CRP levels. Compared to conventional MLRA, WARS exhibited a favorable performance with flexible coverage of many risk variables while allowing for missing data.

The risk factors associated with 72-hours mortality in patients with extremely high levels of random plasma glucose (RPG) remain unclear. To explore the risk factors predictive of 72-hours mortality in patients with extremely high RPG under heterogenos pathophysiological conditions. Retrospective, single-center, case-controlled cross-sectional study. University teaching hospital. Adults over age 18 were selected from the medical records of patients at the Saitama Medical Center, Japan, from 2004 to 2013. Extremely high RPG (≥500 mg/dl). Mortality at 72 hours following the RPG test, regardless of hospitalization or in an outpatient setting. Multivariate logistic regression analysis was performed with adjustment for age, sex, body mass index (BMI), and RPG level. The final prediction model was built using the logistic regression model with a higher C-statistic, specificity, and sensitivity. A total of 351 patients with RPG ≥500 mg/dl were identified within the 10-year period. The 72-hours mortality rate was 16/351 (4.6%). The C-statistics of the 72-hours mortality prediction model with serum albumin (ALB) and creatine kinase (CK) was 0.856. The probability of 72-hours mortality was calculated as follows: 1/[1 + exp (−5.142 + 0.901log (CK) −1.087 (ALB) + 0.293 (presence (1) or absence (0) of metastatic solid tumor)]. The sensitivity and specificity of this model was 75.5%. The independent risk factors associated with 72-hours mortality in patients with RPG ≥500 mg/dl are hypoalbuminemia, elevated CK, and presence of a metastatic solid tumour. Further research is needed to understand the mechanisms and possible interventions to prevent mortality associated with extremely high RPG.

<title>Abstract</title>Risk factors associated with 72-h mortality in patients with extremely high serum aspartate aminotransferase levels (AST; ≥ 3000 U/L) are unknown. This single-centre, retrospective, case-controlled, cross-sectional study obtained data from medical records of adult patients treated at Saitama Medical Center, Japan, from 2005 to 2019. We conducted a multivariate logistic after adjusting for age, sex, height, weight, body mass index, Brinkman Index, vital signs, biochemical values, updated Charlson Comorbidity Index (CCI) score, CCI components, and underlying causes. A logistic regression model with selected validity risks and higher C-statistic for predicting 72-h mortality was established. During the 15-year period, 428 patients (133 non-survivors and 295 survivors [cases and controls by survival &lt; 72 and ≥ 72 h, respectively]) with AST levels ≥ 3000 U/L were identified. The 72-h mortality rate was 133/428 (31.1%). The model used for predicting 72-h mortality through the assessment of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus levels had a C-statistic value of 0.852 (sensitivity and specificity, 76.6%). The main independent risk factors associated with 72-h mortality among patients with AST levels ≥ 3000 U/L included higher serum values of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus.

Stimulation of B-cell antigen receptor (BCR) induces a rapid increase in cytoplasmic free calcium due to its release from intracellular stores and influx from the extracellular environment. Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are ligand-gated channels that release intracellular calcium stores in response to the second messenger, inositol 1,4,5-trisphosphate. Most hematopoietic cells, including B cells, express at least two of the three different types of IP3R. We demonstrate here that B cells in which a single type of IP3R has been deleted still mobilize calcium in response to BCR stimulation, whereas this calcium mobilization is abrogated hi B cells lacking all three types of IP3R. Calcium mobilization by a transfected G protein-coupled receptor (muscarinic M1 receptor) was also abolished in only triple-deficient cells, Capacitative Ca2+ entry, stimulated by thapsigargin, remains unaffected by loss of all three types of IP3R. These data establish that IP(3)Rs are essential and functionally redundant mediators for both BCR- and muscarinic receptor-induced calcium mobilization, but not for thapsigargin-induced Ca2+ influx. We further show that the BCR-induced apoptosis is significantly inhibited by loss of all three types of IP3R, suggesting an important role for Ca2+ in the process of apoptosis.

We studied the antioxidant effects of nine calcium antagonists (nisoldipine, benidipine, nilvadipine, felodipine, nicardipine, nitrendipine, nifedipine, verapamil, and diltiazem) by means of rat myocardial membrane lipid peroxidation with a nonenzymatic active oxygen-generating system (DHF/FeCl3-ADP). The order of antioxidant potency of these agents was nilvadipine &gt; nisoldipine &gt; felodipine &gt; nicardipine &gt; verapamil &gt; benidipine. Their IC50 values (microM) were 25.1, 28.2, 42.0, 150.0, 266.1, and 420.0, respectively. In contrast, nitrendipine, nifedipine, and diltiazem had little inhibitory effect on lipid peroxidation. These six calcium antagonists could be divided into four types on the basis of their antioxidant mechanisms. Nilvadipine, nisoldipine, and verapamil, which showed antioxidant effects both before and after the addition of active oxygen, and reduced the dihydroxyfumarate (DHF) auto-oxidation rate, were chain-breaking and preventive antioxidants. Felodipine, which showed antioxidant effects both before and after exposure to active oxygen and increased the DHF auto-oxidation rate, was only a chain-breaking antioxidant. Nicardipine, which showed an antioxidant effect only before exposure to active oxygen and reduced the DHF auto-oxidation rate, was mainly a preventive antioxidant. Benidipine, which showed an antioxidant effect only before exposure to active oxygen and had no appreciable effect on the DHF auto-oxidation rate, could interrupt the chain reaction of lipid peroxidation at the initial step alone. Although these results suggest that the antioxidant properties of some calcium antagonists may be beneficial clinically in protecting against cellular damage caused by lipid peroxidation, further studies are required to establish the antioxidant effects of these agents in vivo.

Both the production of active oxygen species and cellular damage due to concurrent lipid peroxidation are believed to be important factors in the pathogenesis of cardiovascular diseases and the ageing process. Since cardiovascular drugs are often administered over a long term, it might be advantageous if they reduced lipid peroxidation. There have been conflicting reports concerning the antiperoxidant effect of nifedipine. Therefore, we investigated whether nifedipine could inhibit lipid peroxidation in a nonenzymatic active oxygen-generating system, utilizing rat crude myocardial membranes, and compared its effect with those of propranolol, nisoldipine, and diltiazem. Nifedipine and diltiazem had no inhibitory effects on the lipid peroxidation of myocardial membranes. In contrast, nisoldipine and propranolol had a concentration-dependent antiperoxidant effect, with IC50 values of 28.2 and 50.1 mu M, respectively. In addition, nisoldipine appeared to possess dual antiperoxidant mechanisms, involving both preventive and chain-breaking properties.