A Japanese Case of COVID-19 Caused by Omicron Strain with Y453F Substitution.

Frequent mutations of SARS-CoV-2 change the strain more transmissible, leading to the pandemic in worldwide. We detected Y453F substitution on Omicron strain, isolated from a Japanese patient in July 2022. While Y453F substitution was identified B1.1.298 lineage in Netherlands and Denmark in 2020, the substitution has not been reported in Omicron strain especially in Japan. Y453F substitution is associated with higher viral infectivity because it is sited in the receptor-binding domain (RBD), and Y453F substitution contributes to increase binding affinity to angiotensin converting enzyme 2 (ACE2). Additionally, Y453F substitution has been reported to escape human leukocyte antigen (HLA), which is known to recognize non-self-antigens in virus-infected cells as cellular immunity, so it should be closely monitored.

Rare toxin A-negative and toxin B-positive strain of Clostridioides difficile from Japan lacking a complete tcdA gene.

INTRODUCTION: Clostridioides difficile (C. difficile) produces three kinds of toxins: toxin A (enterotoxin), toxin B (cytotoxin), and C. difficile transferase (CDT), a binary toxin. Some strains show positivity only for toxin B. These strains reportedly possess a gene for toxin A, tcdA. However, toxin A production is inhibited due to a mutated stop codon and/or deletion within the tcdA gene. Here for the first case in Japan, we describe toxin genomes and proteins of a strain possessing only toxin B and lacking a complete tcdA gene, along with clinical manifestations. METHODS: C. difficile was isolated from the bloody stool of a 60-year-old female patient treated with meropenem. Although a rapid detection kit of toxins (C. DIFF QUIK CHEK COMPLETE®, TechLab, Blacksburg, VA, USA) showed positivity, Western blotting detected no toxins. Therefore, we explored the strain's toxin genes and their sequences to determine whether the strain possessed a toxin. RESULTS: Polymerase chain reaction did not identify toxin genes. Whole-genome sequencing analysis showed that a gene for toxin A, tcdA, was completely deleted in the strain. Moreover, 701 mutations and some deletions/insertions were identified on the tcdB gene. CONCLUSIONS: We isolated a rare strain of C. difficile producing only toxin B and lacking a complete tcdA gene herein Japan. The possibility of a false negative needs to be considered with a genetic method for a diagnose of C. difficile infection.

[Functional Residual Capacity Measurement Based on Lung Structure Model Analysis Using the Helium Gas Dilution Technique].

In the helium gas dilution method, functional residual capacity (FRC) is calculated from a helium concentra- tion equilibrium curve. In this study, we analyzed the helium concentration equilibrium curves of healthy patients, clarified the determinants of the equilibrium concentration, and studied the effects of an uneven lung distribution. We collected data from 200 patients (92 males and 108 females) whose FRC values had been measured at our institution over the past 6 years. Their FRC values ranged from 80% to 120%, and theit other pulmo- nary function values were within the normal range. In the compartmental model analysis, we discovered that the helium concentration equilibrium curve was composed of one compartment, and that it did not have a polyphasic structure. Each 0.25-minute (15-second) segment of the helium concentration equilibrium curve obtained from the patients was evaluated using univariate and multivariate regression analyses. The helium concentration equilibrium curve decreased exponentially over the time course of the analysis, and the multiple correlation coefficient for the relationship between the 0.25-minute to 0.75-minute segments and the 1.00-minute to 1.50-minute segments in the final model was 0.949. Finally, we examined the influence of an uneven peripheral lung distribution. A model based on the con- centration change seen between the initial and middle periods during at rest ventilation indicated that the latter parameter was not affected by the ventilation volume of the peripheral lung. [Original].

Impact of kidney function and urinary protein excretion on intima-media thickness in Japanese patients with type 2 diabetes.

BACKGROUND: Carotid echo indexes [intima-media thickness (IMT)] are commonly used surrogate markers for cardiovascular disease; however, the impacts of chronic kidney disease (CKD) on changes in IMT are unclear. We examined associations between CKD and IMT in participants with and without type 2 diabetes through longitudinal analysis. METHODS: In total, 424 subjects were enrolled in this study. IMT was measured as per carotid echo indexes. Relationships between IMT and risk factors were analyzed using multiple linear regression analysis, in which we defined IMT as the dependent variable and atherosclerosis-related factors (age, sex, systolic pressure, total cholesterol, body mass index, estimated glomerular filtration rate (eGFR), uric acid, smoking index, number of antihypertensive drugs, statin use, urinary protein levels, past cardiovascular event, glycated hemoglobin, and diabetes duration) as independent variables. RESULTS: The study population was composed of 70.3 % male subjects. Participants with diabetes accounted for 64.4 % of the total population. The mean follow-up duration was 2.2 ± 1.5 years. Alterations in IMT tended to be associated with systolic blood pressure (+10 mmHg) (ß = -0.0084, p = 0.09) and eGFR (+10 mL/min/1.73 m(2)) (ß = -0.0049, p = 0.06) in all participants. In participants without diabetes, alterations in IMT were associated with eGFR (+10 mL/min/1.73 m(2)) (ß = -0.0104, p = 0.03) and tended to be associated with systolic blood pressure (+10 mmHg) (ß = 0.0094, p = 0.06). No significant relationships were found in participants with diabetes. CONCLUSION: Low eGFR was associated with progression of carotid thickness independent of common cardiovascular risk factors in non-diabetic participants.

Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease.

BACKGROUND: Although the cardiorenal relationship in chronic kidney disease has been investigated, information about the lung-kidney relationship is limited. Here, we investigated the impact of kidney function and urinary protein excretion on pulmonary dysfunction. METHODS: The data from pulmonary function tests and kidney function (estimated glomerular filtration rate [eGFR] and urinary protein) between 1 April 2005 and 30 June 2010 were selected from our laboratory database. Data were classified into 4 categories according to eGFR and proteinuria. Category 1, eGFR ≥60 ml/min/1.73 m(2) and urinary protein <0.3 g/gCr; category 2, eGFR <60 ml/min/1.73 m(2) and urinary protein <0.3 g/gCr; category 3, eGFR ≥60 ml/min/1.73 m(2) and urinary protein ≥0.3 g/gCr; and category 4, eGFR <60 ml/min/1.73 m(2) and urinary protein ≥0.3 g/gCr. Pulmonary function data were evaluated according to these 4 categories. RESULTS: A total of 133 participants without major respiratory disease, abnormal computed tomography and smoking history were enrolled. Hemoglobin (Hb)-adjusted percentage carbon monoxide diffusing capacity (%DLCO) in category 4 (46.2 ± 7.5) and category 2 (63.6 ± 17.8) were significantly lower than in category 1 (75.8 ± 18.9) (P < 0.05). In addition, Hb-adjusted %DLCO was weakly correlated with eGFR in participants with urinary protein <0.3 g/gCr (R = 0.30, P = 0.001). Hb-adjusted %DLCO was strongly correlated with eGFR in participants with urinary protein ≥0.3 g/gCr (R = 0.81, P < 0.001). Other pulmonary function test markers (percentage (%) vital capacity, % forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, % total lung capacity, and % residual volume) were not significantly different between categories. CONCLUSION: This study suggests that decreased eGFR is associated with decreased %DLCO in proteinuric patients.

Motor-Evoked Potential Monitoring With Multi-train Electrical Stimulation During Thoracoabdominal Aortic Aneurysm Surgery: A Case Report.

Intraoperative motor-evoked potentials (MEPs) are measured for assessing motor function during surgery. MEP monitoring is often performed in thoracoabdominal aortic aneurysm (TAAA) surgery, but false positives are common and amplification methods are needed to obtain waveforms under severe conditions to assess proper spinal cord function. One method of amplitude amplification in transcranial-stimulated MEP monitoring is multitrain stimulation. There are few reports on multitrain-stimulated MEP monitoring for this surgery. A 57-year-old woman underwent open repair of the thoracoabdominal aorta due to a dissecting aortic aneurysm. After opening the chest, the aneurysm was incised proximally, and anastomosis with an artificial vessel was initiated. The lumbar artery leading to the Adam-Kiewicz artery was reconstructed at a body temperature of 25 °C. However, the single-train stimulation did not produce MEPs. When the measurement was switched to multitrain stimulation, MEPs were elicited in the lower extremity muscle groups and the waveforms were maintained until the end of the measurement. This case illustrates that MEP monitoring using multitrain stimulation during descending thoracic aortic aneurysm surgery can effectively elicit MEPs under challenging conditions, in which conventional single-train stimulation may be insufficient.

Prediction formula for interrupter respiratory resistance in healthy Japanese adults.

Interrupter respiratory resistance (Rint) measurement is useful for evaluating lung function in patients who cannot perform traditional pulmonary function tests. However, data on the prediction formulas for Rint in healthy Japanese adults are lacking. Our aims were to examine the relationship between Rint and sex, age, height, and weight, to establish prediction formulas, and to evaluate our new prediction formula (%Rint) in patients with asthma. Rint measurement was performed in 1,536 healthy adult subjects aged 21-80 years. This study was conducted according to ATS guidelines, which recommend obtaining 10 measurements to ensure a minimum of 5 technically acceptable interruptions (Am J Respir Crit Care Med 2007). Stepwise multiple linear regression analysis indicated that height was the most significant variable independently correlating with Rint. The Rint prediction formulas for our cohort based on height were: RintE = -0.03168 x height + 8.204084 and Rinti = -0.02985 x height + 7.920835. Both %RintE and %Rinti were significantly higher in patients with asthma than in normal subjects (%RintE; 135.2 +/- 26.4 vs. 98.6 +/- 25.5, %RintI; 142.4 +/- 30.4 vs. 98.6 +/- 27.4; p < 0.0001). We established prediction formulas of Rint for healthy Japanese adults. %Rint is useful in screening for asthma.

Relationships between kidney dysfunction and left ventricular diastolic dysfunction: a hospital-based retrospective study.

BACKGROUND: Preclinical left ventricular diastolic dysfunction (LVDD) is a high-risk state for heart failure. Kidney dysfunction is a known risk factor for heart failure, but its association with asymptomatic LVDD is not well-known. METHODS: A hospital-based retrospective cohort study was conducted on patients who underwent echocardiogram between 2006 and 2016 to assess the association between baseline kidney function and LVDD on echocardiogram. E/e' ratio was defined as the ratio of peak velocity of early diastolic left ventricular inflow (E) to mitral annular velocity (e'). The primary outcome was time to development of LVDD, which was defined as E/e' ratio > 14. The changes in the E/e' ratio and other echocardiographic parameters were assessed using a mixed effects model. RESULTS: Among 1167 patients, the mean age was 61 years, and the mean baseline E/e' ratio and ejection fraction were 9.6 and 69%, respectively. During a median follow-up of 3.2 years, 231 (19.8%) people developed LVDD. According to eGFR (mL/min/1.73 m2), the risk for LVDD based on hazard ratio [95% confidence interval (95% CI)] was 1.20 (0.82, 1.75) for 60 to < 90, 1.42 (0.87, 2.31) for 45 to < 60, and 2.57 (1.61, 4.09) for < 45 (P trend < 0.001). The adjusted risks (95% CI) for annual change in E/e' ratio was 0.09 (0.03, 0.14) overall and 0.28 (0.11, 0.45) in the lowest eGFR group; the trend in changes in annual E/e' ratio by baseline eGFR was significant (P trend = 0.01). CONCLUSIONS: Relatively low kidney function was related with the risks for LVDD. Long-term cohort studies are warranted to confirm the association between LVDD and symptomatic heart failure in patients with kidney dysfunction.

[A case of bronchiolitis obliterans caused by allogeneic hematopoietic stem cell transplantation diagnosed with a body plethysmograph].

A 19-year-old woman with acute myeloid leukemia (M1) was treated with allogeneic hematopoietic stem cell transplantation. She was diagnosed with skin graft-versus-host disease 27 days after the transplantation. She was admitted to the Dept. of Respiratory Medicine at Kanazawa University Hospital, because she complained of progressive obstructive ventilatory impairment. A high-resolution computed tomography (CT) scan showed centrilobular small nodules. A chest CT scan (inspiratory phase and expiratory phase) revealed hyperlucent areas forming a mosaic pattern. A ventilation-perfusion scan showed matched unequal distribution. The pathological diagnosis made using biopsied lung, obtained by a right lower partial lobectomy, was constrictive bronchiolitis. Pulmonary function tests on admission showed mixed ventilatory impairment. %Residual volume(RV)/total lung capacity(TLC) was measured by the closed-circuit helium dilution method and was within the upper limit of the normal range. However, %RV/TLC measured by a body plethysmograph indicated a value of 258.1%. We believe that the difference in the %RV/TLC values reflected air trapping caused by bronchiolitis obliterans. Thus, the lung volume fraction measured by body plethysmograph was useful for diagnosing bronchiolitis obliterans in this case. [Rinsho Byori 58 : 906'-911, 2010].

EEG harmonic responses to photic stimulation in normal aging and Alzheimer's disease: differences in interhemispheric coherence.

OBJECTIVES: The distinction between electroencephalogram (EEG) driving responses in normal aging and Alzheimer's disease (AD) is unclear. This study was conducted to explore the structure of harmonic responses of EEG coherence during photic stimulation (PS) in AD. METHODS: EEG interhemispheric coherence was analyzed for each harmonic responses during PS (white flickers at 5, 10 and 15 flashes/sec) in younger subjects (20-25 years), non-demented elderly subjects (50-67 years) and AD patients (43-66 years). RESULTS: The elderly subjects had higher interhemispheric coherence during PS than the younger subjects, with significant differences found in the 6th (30Hz) and 8th (40Hz) harmonic responses to 5Hz PS. The AD patients had significantly smaller coherence than the elderly subjects in the 2nd (10Hz) and 4th (20Hz) harmonic responses to 5Hz PS, and in the fundamental (10Hz) and 2nd (20Hz) harmonic responses to 10Hz PS. These coherence values did not correlate with duration of the disease or with cognitive functioning as evaluated by MMSE score. CONCLUSIONS: A failure of stimulation-related brain activation in AD patients was observed in alpha-related frequencies, suggesting that AD is not the end result of normal aging of the brain, at least in terms of the mechanisms which are involved in PS-related functional organization.

Reversibility of the pulmonary function based on the partial flow-volume curve predicts the efficacy of bronchodilator therapy for treating chronic cough.

OBJECTIVE: Partial expiratory flow-volume curves have the potential to detect mild bronchoconstriction because they are not affected by the modulatory effects of deep inspiration. The aim of this study was to investigate the relationship between the efficacy of bronchodilator therapy (BDT) in treating the cough and to assess the increase in the expiratory flow of the partial flow-volume curve at 40% above the residual volume level (PEF40) caused by treatment with a short-acting beta-2 agonist (SABA) in patients with chronic nonproductive cough. METHODS: We measured the reversibility of PEF40 caused by a SABA in 42 patients with chronic nonproductive cough at visit 1 (day 0). The patients received BDT for six days. The visual analogue scale (VAS) was used to assess the efficacy of BDT in treating coughing at visit 2 (day 7) (0 mm, 'no cough;' 100 mm, 'no change in coughing'). RESULTS: Reversibility of the PEF40 was correlated (r=0.690, p<0.001) with the VAS score determined at visit 2 and was higher in the patients with cough variant asthma (CVA) (44.9 ± 18.3%) than in those with atopic cough (13.4 ± 10.4%) (p<0.01). CONCLUSION: Reversibility of the PEF40 predicted the efficacy of BDT in patients with chronic nonproductive cough and helped to identify patients with CVA.

Association between coefficients of variation of the R-R intervals on electrocardiograms and post-challenge hyperglycemia in patients with newly diagnosed type 2 diabetes.

The aim of the present study was to examine whether there is a relationship between autonomic function and post-challenge hyperglycemia in patients with type 2 diabetes. Subjects included 122 Japanese patients newly diagnosed with type 2 diabetes. Autonomic nerve function was assessed using coefficients of variation of the R-R intervals on electrocardiograms (CVRR). Unlike anthropometry, insulin secretion and insulin resistance, age (r = -0.209, P < 0.021) and post-challenge plasma glucose at 120 min (PG120; r = -0.219, P < 0.015) were the only variables significantly correlated with CVRR. Age was not significantly correlated with PG120. In multiple regression analyses, CVRR Z-score, but not age, was significantly correlated with PG120. The present results suggest that autonomic function affects post-challenge blood glucose levels independently of age. (J Diabetes Invest,doi: 10.1111/j.2040-1124.2010.00098.x, 2011).