Published papers

Although renin-angiotensin system (RAS) inhibitors reduce the risk of cardiovascular diseases and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) patients, they are often discontinued in clinical practice due to drug-related adverse events. However, limited evidence is available about the clinical impact of RAS inhibitor discontinuation in CKD patients. A comprehensive search of publications investigating the effect of discontinuing RAS inhibitors on clinical outcomes in CKD patients in PubMed, the Cochrane Library, and Web of Science was conducted (inception to November 7, 2022), and potentially relevant studies were searched by hand (through November 30, 2022). Two reviewers independently extracted data according to the PRISMA and MOOSE guidelines and assessed the quality of each study with risk-of-bias tools, RoB2 and ROBINS-I. The pooled hazard ratio (HR) for each outcome was integrated with a random-effect model. A total of 1 randomized clinical trial and 6 observational studies involving 248,963 patients were included in the systematic review. The meta-analysis of observational studies showed that discontinuation of RAS inhibitors was associated with a higher risk of all-cause mortality (HR, 1.41 [95% CI, 1.23-1.62]; I2 = 97%), ESKD (1.32 [95% CI, 1.10-1.57]; I2 = 94%) and MACE (1.20 [95% CI 1.15-1.25]; I2 = 38%), but not with hyperkalemia (0.79 [95% CI 0.55-1.15]; I2 = 90%). Overall risk of bias was moderate-to-serious, and quality of evidence (GRADE system) was low-to-very low. The present study suggests that CKD patients would benefit from continuing RAS inhibitors.

The use of artificial intelligence (AI) in the diagnosis of dry eye disease (DED) remains limited due to the lack of standardized image formats and analysis models. To overcome these issues, we used the Smart Eye Camera (SEC), a video-recordable slit-lamp device, and collected videos of the anterior segment of the eye. This study aimed to evaluate the accuracy of the AI algorithm in estimating the tear film breakup time and apply this model for the diagnosis of DED according to the Asia Dry Eye Society (ADES) DED diagnostic criteria. Using the retrospectively corrected DED videos of 158 eyes from 79 patients, 22,172 frames were annotated by the DED specialist to label whether or not the frame had breakup. The AI algorithm was developed using the training dataset and machine learning. The DED criteria of the ADES was used to determine the diagnostic performance. The accuracy of tear film breakup time estimation was 0.789 (95% confidence interval (CI) 0.769-0.809), and the area under the receiver operating characteristic curve of this AI model was 0.877 (95% CI 0.861-0.893). The sensitivity and specificity of this AI model for the diagnosis of DED was 0.778 (95% CI 0.572-0.912) and 0.857 (95% CI 0.564-0.866), respectively. We successfully developed a novel AI-based diagnostic model for DED. Our diagnostic model has the potential to enable ophthalmology examination outside hospitals and clinics.

INTRODUCTION: Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse CNS-progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. RESULTS: OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p<0.001) and JLGK0901. Hazard estimates for first CNS-progression favoring NSCLC were similar in both datasets but reached significance in the retrospective dataset only (MV-HR:0.82 [95%-CI:0.73-0.92], p=0.001). In the PSM cohorts, there were continued OS advantages for NSCLC (median-OS, 23.7 [EGFR/ALK-positive-NSCLC] vs 13.6 [mutation-negative-NSCLC] vs 10.4 months [SCLC], pairwise-p-values<0.001), but no significant differences in CNS-progression. Neurological mortality and number of lesions at CNS-progression were similar for NSCLC and SCLC patients. Leptomeningeal-progression was increased in NSCLC patients in the retrospective dataset only (MV-HR:1.61 [95%-CI:1.14-2.26], p=0.007). CONCLUSION: After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: To compare the surgical outcomes of anterior and posterior fusion surgeries in patients with K-line (-) cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although laminoplasty is effective for patients with K-line (+) OPLL, fusion surgery is recommended for those with K-line (-) OPLL. However, whether the anterior or posterior approach is preferable for this pathology has not been effectively determined. METHODS: A total of 478 patients with myelopathy due to cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the 478 patients, 45 and 46 with K-line (-) underwent anterior and posterior fusion surgeries, respectively. After adjusting for confounders in baseline characteristics using a propensity score-matched analysis, 54 patients in both the anterior and posterior groups (27 patients each) were evaluated. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. RESULTS: Both approaches showed comparable neurological and functional recovery. The cervical range of motion was significantly restricted in the posterior group because of the large number of fused vertebrae compared with the anterior group. The incidence of surgical complications was comparable between the cohorts, but the posterior group demonstrated a higher frequency of segmental motor paralysis, whereas the anterior group more frequently reported postoperative dysphagia. CONCLUSION: Clinical improvement was comparable between anterior and posterior fusion surgeries for patients with K-line (-) OPLL. The ideal surgical approach should be informed based on the balance between the surgeon's technical preference and the risk of complications.

Development of reliable non-contact unrestrained respiratory monitoring is capable of augmenting the safety of hospitalized patients in the recovery phase. We previously discovered respiratory-related centroid shifts along the long axis of the bed with load cells under the bed legs (bed sensor system: BSS). This prospective exploratory observational study examined whether non-contact measurements of respiratory-related tidal centroid shift amplitude (TA-BSS: primary variable) and respiratory rate (RR-BSS: secondary variable) were correlated with tidal volume (TV-PN) and respiratory rate (RR-PN), respectively measured by pneumotachograph in 14 ICU patients under mechanical ventilation. Among the 10-minute average data automatically obtained for a 48-hour period, 14 data were randomly selected from each patient. Successfully and evenly selected 196 data points for each variable were used for the purpose of this study. A good agreement between TA-BSS and TV-PN (Pearson's r = 0.669) and an excellent agreement between RR-BSS and RR-PN (r = 0.982) were observed. Estimated minute ventilatory volume as 3.86*TA-BSS*RR-BSS (MV-BSS) was found to be in very good agreement with true minute volume (MV-PN) (r = 0.836). Although Bland-Altman analysis evidenced accuracy of MV-BSS by a small insignificant fixed bias (-0.02 liter/min), a significant proportional bias of MV-BSS (r = -0.664) appeared to produce larger precision (1.9 liter/min) of MV-BSS. We conclude that contact-free unconstraint respiratory monitoring with load cells under the bed legs may serve as a new clinical monitoring system, when improved.

PURPOSE: Major depression is a heterogeneous disorder. Therefore, careful evaluation and comprehensive assessment are crucial elements for achieving remission. Personality traits influence prognosis and treatment outcomes, but there is not enough evidence on the association between personality traits and sustained remission (SR). Hence, the present study aimed to evaluate the relationship between personality traits and SR among patients with major depression. PATIENTS AND METHODS: The 12-month prospective study evaluated 77 patients diagnosed with major depressive disorder. All patients underwent a comprehensive assessment, including the Temperament and Personality Questionnaire (T&P) at baseline, and depression severity was measured at baseline as well as six and 12 months. SR was defined as remission (the GRID-Hamilton Depression Rating Scale [GRID-HAMD17] score ≦ 7) at both the 6- and 12-month follow-up. We compared eight T&P construct scores at baseline between the SR and non-SR groups. Multivariable logistic regression analyses were performed to determine the T&P personality traits related to SR. RESULTS: Patients who achieved SR had a lower T&P personal reserve and lower T&P rejection sensitivity. Further, lower scores on the T&P personal reserve trait were independently associated with higher rates of SR among patients with major depression. Patients who achieved SR had a shorter duration of the current depressive episode and milder severity of depression at baseline. CONCLUSION: A lower level of personal reserve predicted a higher probability of SR in the treatment of depression. Extended observations in naturalistic follow-up settings with larger sample sizes are required to better understand the personality traits affecting SR in patients with depression.

BACKGROUND: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. OBJECTIVE: We examined the epidemiology and clinical features of MOGAD in Japan. METHODS: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan. RESULTS: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483-1907] and 487 (95% CI: 414-560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18-1.51) and 0.39/100,000 (95% CI: 0.32-0.44), respectively. The median age at onset was 28 years (range: 0-84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective. CONCLUSION: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

BACKGROUND & AIMS: Sarcopenia, resulting from skeletal muscle loss, is a serious concern in children, for whom nutrition and physical activity are essential for growth. In sarcopenia research, the skeletal muscle mass is often obtained from computed tomography (CT) cross-sectional images in both adults and children; however, the method of evaluating skeletal muscle using CT, especially the area range to be measured, has not yet been validated in children. The aim of this study is to establish reference values for three compartments of the abdominal skeletal muscle area (aSMA) obtained from cross-sectional CT images, and to validate the differences among them by assessing correlations with physical development. METHODS: We conducted a single-centre, retrospective, cross-sectional study and included patients aged 1-17 years who underwent abdominal CT at Chiba University Hospital from 2007 to 2020. Patients with chronic diseases such as malignant tumours and inflammatory bowel disease were excluded from the analysis. aSMA was obtained from CT cross-sections at the lumbar L3-L4 intervertebral disc level by dividing it into three compartments: the psoas muscle area (PMA), paraspinal muscle area (PSMA), and total skeletal muscle area (TSMA). Quartile regression curves by sex and muscle compartment were generated using non-crossover and nonparametric regression quantile estimation. The correlation between each compartment of aSMA with height and weight was assessed using Spearman's rank correlation coefficient. RESULTS: We analysed the abdominal CT images of 593 children (male: n = 335, female: n = 258) and generated curves predictive for the 5th, 25th, 50th, 75th, and 95th percentiles for each compartment of aSMA by sex. In patients aged 13 years and older, boys had significantly larger aSMA areas than girls in all three compartments. Among the three compartments, PSMA had the strongest correlation coefficient with height and weight for both boys and girls. CONCLUSIONS: We generated quantile regression curves for three aSMA compartments obtained from cross-sectional CT images and established reference values in children. PSMA values were most strongly correlated with height and weight among the three aSMA compartments.

Abstract Tools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.

PURPOSE: To evaluate the 5-year performance of a bioresorbable vascular scaffold, the Remedy stent, for the treatment of iliac artery atherosclerotic disease. MATERIALS AND METHODS: This prospective, multicenter, single-arm clinical study evaluated 97 patients (97 lesions) with symptomatic TransAtlantic Inter-Society Consensus II A/B iliac artery lesions for 5 years after stent placement. The primary efficacy end point was 12-month primary patency compared with the prespecified standard derived from historical data with metallic stents, and the primary safety end point was the occurrence of major adverse clinical events within 5 years. All angiographic and computed tomography angiographic findings were evaluated by an independent core laboratory for quantitative vessel analysis. RESULTS: The 12-month primary patency rate was 88.6% (95% CI, 80.1%-94.4%), which was lower than the prespecified standard. No significant difference was noted between the diameter stenosis at 9 and 12 months. There were no device- or procedure-related deaths, major amputation, or distal embolization during the follow-up period. The ankle-brachial index maintained significant improvement through the 5-year period compared with that at baseline. The Kaplan-Meier estimates of freedom from target lesion revascularization (TLR), major adverse cardiovascular events, and major adverse cardiovascular and limb events were 95.8%, 91.7%, and 87.5% at 12 months and 85.4%, 72.1%, and 62.5% at 5 years, respectively. CONCLUSIONS: The 5-year follow-up outcomes, including freedom from TLR, of the Remedy stent in iliac artery lesions were satisfactory, with a good safety profile. Nevertheless, the 12-month primary patency did not meet the expected standard compared with that of contemporary metallic stents.

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose. UMIN Clinical Trials Registry ID: UMIN000043340.