Search

Objective: This study aimed to determine the incidence of laryngeal penetration and aspiration in elderly patients who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer. Method: A retrospective analysis of dynamic videofluoroscopic swallowing studies was performed in patients who had received supracricoid laryngectomy with cricohyoidoepiglottopexy as a treatment for laryngeal cancers. Digital analysis of videofluoroscopic swallowing studies included measurements of displacement and timing related to swallowing safety. Results: Videofluoroscopic swallowing studies from 52 patients were analysed. All participants were male and over 65 years old. Studies were performed five years after surgery. Among 52 videofluoroscopic swallowing studies, analysis showed that elevated pharyngeal constriction ratio (pharyngeal constriction ratio more than 0.0875, odds ratio = 5.2, p = 0.016), reduced pharyngoesophageal sphincter opening time (pharyngoesophageal sphincter open less than 0.6 seconds, odds ratio = 11.6, p = 0.00018) and reduced airway closure time (airway close less than 0.6 seconds, odds ratio = 10.6, p = 0.00057) were significantly associated with aspiration. Conclusion: Deteriorated pharyngeal constriction, shortened airway closure and reduced pharyngoesophageal sphincter opening time are key factors for predicting laryngeal penetration or aspiration after supracricoid laryngectomy with cricohyoidoepiglottopexy. [ABSTRACT FROM AUTHOR]

Summary: We compared the effectiveness of promoting bone healing between two teriparatide preparations for atypical femoral fracture (AFF). A total of 45 AFFs were included in this study, and we compared the duration of bone union. Teriparatide administered by daily injection enhanced bone union more than weekly administration in complete AFFs.Introduction: The efficacy of teriparatide for atypical femoral fracture (AFF) has been recently reported. Although two different teriparatide preparations can be used to treat osteoporosis in Japan, daily or weekly injection, all previous reports on the effectiveness of teriparatide for AFF only examined daily injection formulations. Therefore, we compared the promotion of bone healing between the two teriparatide preparations for AFF.Methods: A total of 45 consecutive AFFs in 43 Japanese patients were included in this study. They received either a daily 20-μg teriparatide injection (daily group; n = 32) or a once-a-week 56.5-μg teriparatide injection (weekly group; n = 13). We compared the clinical background and duration of bone union between these two groups.Results: When all patents were included, the fracture healing time was not significantly different between the two groups. Only patients with complete AFFs had significantly fewer daily bisphosphonate or denosumab injections than the weekly group (P < 0.05). The fracture healing time in the daily group (6.1 ± 4.1 months) was significantly shorter than that in the weekly group (10.1 ± 4.2 months) (P < 0.05). Even if the influence of bisphosphonate or denosumab usage was excluded, a similar significant difference was observed in the fracture healing time (P < 0.05). There was no significant difference between the two groups among patients with incomplete AFFs.Conclusions: Daily teriparatide injections enhance bone union more than weekly injections in complete AFF patients. [ABSTRACT FROM AUTHOR]

Background: This study marks the first epidemiological evaluation of the prevalence and burden of chronic neuropathic pain (NeP) in an Asian population. The objective of this nationwide cross-sectional study was to identify the characteristics of individuals with NeP, detect the NeP features that affect their quality of life (QOL), and demonstrate the negative effects of NeP on social and daily living as well as comorbidities including depression, anxiety and sleep disorders.Methods: We mailed a cross-sectional, population-based epidemiological survey to a random nationwide sample of 10,000 Japanese adults over 20 years old.Results: The response rate was 54.4% (2445 men, 2992 women; mean age, 53.4 years). Prevalence of chronic pain was 16.6%, and prevalence of NeP was 3.2% as detected by the PainDETECT. Participants with NeP showed significantly lower quality of life according to scores on the EuroQol-5 Dimensions scale (p < 0.001), higher levels of psychological distress on the Kessler 6-item psychological distress scale (p < 0.001), poorer sleep quality (p < 0.001), and more workdays lost (p < 0.001) than did participants without NeP. Linear regression modelling showed that widespread pain, thermal hyperalgesia and pressure-induced pain had strong associations with lower QOL, with regression coefficients of -0.046 (p < 0.001), -0.038 (p < 0.001), and -0.040 (p < 0.001), respectively.Conclusions: This study is the first to report the prevalence of NeP in an Asian population using a validated questionnaire. This study provides compelling evidence that chronic NeP is more strongly associated with poorer QOL, mental health and social well-being than CP without a neuropathic component.Significance: This population-based nationwide epidemiological study revealed the prevalence, characteristics, and negative effects of chronic pain with neuropathic components in Asian society. The prevalence of neuropathic pain was 3.2% with PainDETECT. [ABSTRACT FROM AUTHOR]

Abnormal storm waves cause coastal disasters along the coasts of Korean Peninsula and Japan in the East/Japan Sea (EJS) in winter, arising due to developed low pressures during the East Asia winter monsoon. The generation of these abnormal storm waves during rough sea states were studied and hindcast using an atmosphere-wave coupled modelling system. Wind waves and swell due to developed low pressures were found to be the main components of abnormal storm waves. The meteorological conditions that generate these waves are classified into three patterns based on past literature that describes historical events as well as on numerical modelling. In hindcasting the abnormal storm waves, a bogussing scheme originally designed to simulate a tropical storm in a mesoscale meteorological model was introduced into the modelling system to enhance the resolution of developed low pressures. The modelling results with a bogussing scheme showed improvements in terms of resolved low pressure, surface wind field, and wave characteristics obtained with the wind field as an input. [ABSTRACT FROM AUTHOR]

To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II–IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration–time curve of the first administration remained at less than 1500 μmol min/l in 27 of the 29 patients (93%), and between 900 and 1350 μmol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.Bone Marrow Transplantation (2009) 43, 611–617; doi:10.1038/bmt.2008.372; published online 17 November 2008 [ABSTRACT FROM AUTHOR]

Reclaimed wastewater (RWW) will be introduced to the first large-scale irrigation project for dry-farming on Okinawa Island, Japan. The wastewater reclamation for agricultural use sounds attractive to the water resource management. Since there are no specific standards for the RWW irrigation, the monitoring and other demonstrative experiments have been conducted using the experimental reclamation facility, which is based on the criteria "Title22". The experiments showed that the existing system is sufficient to meet the above criteria of pathogens, protozoa and viruses, and the concentrations of hazardous chemicals are lower than the environmental standards in Japan. In addition, several laboratory soil column experiments were conducted to address the environmental issues. An increase of denitrification due to the continuous irrigation was observed. Salt and nitrate accumulation in the surface soil was observed as well. We can conclude that the RWW of the above facility assures the safety for human health, and further research based on environmental issues is needed in addition to an integrated risk assessment and communication. [ABSTRACT FROM AUTHOR]

Study design:Analysis of answers to a new questionnaire.Objective:To examine current practice patterns of physicians in the urological surveillance and management of spinal cord injury (SCI) patients in Japan.Setting:Nationwide questionnaire survey to physicians in Japan.Methods:A Japanese version of the 14-item questionnaire survey carried out in US was mailed to 770 members of the Japanese Neurogenic Bladder Society (JNBS).Results:We received answers to our questionnaire from 333 (43.2%) members of JNBS. The responders were all urologists. For surveillance of the upper urinary tract (UUT), 239 (71.8%) respondents preferred abdominal ultrasound. Cystometry was performed routinely by 174 (52.3%) respondents for the evaluation of vesicourethral function. Cystoscopy was carried out in cases of hematuria (88.0%) and bladder stone (55.3%). Surveillance of the urinary tract was performed every year in 154 (46.2%). For detection of bladder cancer, which 119 (37.9%) respondents have experienced, 94.9% physicians perform cystoscopy, 76.3% urinary cytology, and 60.4% ultrasound. For initial treatment of detrusor-sphincter dyssynergia (DSD), 225 (69.2%) respondents chose α-blocker, and 94 (28.9%) chose clean intermittent catheterization (CIC) with/without anticholinergic agent(s). For initial treatment of overactive bladder, 245 (74.7%) chose anticholinergic agent(s) only and 63 (19.2%) chose anticholinergic agent(s) with CIC. For initial treatment of areflexic bladder, 233 (73.7%) chose CIC and 63 (19.9%) chose Credé maneuver or tapping.Conclusions:This survey shows that there are some differences in urological surveillance and management of SCI patients between Japan and the US. Reasons for the discrepancy should be examined.Spinal Cord (2006) 44, 362–368. doi:10.1038/sj.sc.3101854; published online 6 December 2005 [ABSTRACT FROM AUTHOR]

Abstract: We present a retrospective study of 82 patients with intraoral minor salivary gland tumors which were diagnosed from 1979 to 2003 in Gifu University Hospital. The histological diagnoses were reevaluated according to the 1991 WHO classification. A total of 82 tumors, consisting of 55 benign and 27 malignant tumors, were found in 28 male and 54 female Japanese patients; the male-to-female ratio was 1:1.9. The mean age of the patients was 51.4±18.1 years. The tumors affected the palate (n =64), the buccal region (n =10), the upper lip (n =6), the floor of the mouth (n =1), and the retromolar region (n =1). Histologically, the tumors were classified as pleomorphic adenoma (n =54), papillary cystadenoma (n =1), adenoid cystic carcinoma (n =10), mucoepidermoid carcinoma (n =8), acinic cell carcinoma (n =3), adenocarcinoma (n =2), basal cell adenocarcinoma (n =1), papillary cystadenocarcinoma (n =1), and carcinoma in pleomorphic adenoma (n =2). From the results of the present study and review of the literature, it is suggested that the minor salivary gland tumors in Japan may be characterized by a higher incidence of benign tumors, especially of pleomorphic adenoma; a more marked tendency for female predominance; a higher incidence of palatal involvement; and a rarer occurrence of polymorphous low grade adenocarcinoma, in comparison with those reported in the literature from outside of Japan. [Copyright &y& Elsevier]

Type 1 diabetes is a multifactorial disease in which the genes of the major histocompatibility complex (MHC) play a key role. Recently, non-human leukocyte antigen (non-HLA) genes in the class III region of this complex have been presumed to be associated with type 1 diabetes by linkage analyses. We investigated the possibility of the inhibitor of κB-like ( IKBL, also known as ‘ NFKBIL1’) gene as one of these candidates. We carried out a case-control study of 124 patients with type 1 diabetes and 330 healthy control subjects. The haplotypes of the IKBL promoter, i.e., PA (−263A, −63T), PB (−263A, −63A), PC (−263G, −63T), were assigned by the single-nucleotide polymorphisms at positions −263 and −63 from the transcription start site. The frequency of the wild-type haplotype, PA, was elevated, while that of the variant-type haplotype, PC, was lower in patients than controls. In two-locus analyses with HLA-DRB1 alleles, the PA haplotype showed linkage disequilibrium with the DRB1* 0405 allele and the PC haplotype with the DRB1* 1502 allele. A notable observation was that the PC haplotype was significantly associated with protection in the DRB1* 1502-negative population. Our study indicates the first evidence of a possible independent association between type 1 diabetes and polymorphisms in the promoter of the IKBL gene. [ABSTRACT FROM AUTHOR]

We performed a 5 year longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren from 6 to 11 years of age in a rural area of southwestern Japan. The spherical refraction was measured under cycloplegia with an infrared autorefractometer. The grouped data from 350 right eyes showed leptokurtic frequency distributions, and the median was +0.91 D at age 6 yrs, shifted towards emmetropia with increasing age and reached +0.34 D at age 11 years. The prevalence of myopia of -1.0 D or more was 0.3%, 0.6%, 2.0%, 2.6%, 2.9%, and 4.9% from age 6 to 11 years. and the prevalence of myopia of more than -2.0 D was less than 1% at age 6-9 years and thereafter increased up to 6.0% at age 11 years. Linear regression analysis for the longitudinal refractive data revealed that 247 (70.6%) of the 350 eyes exhibited first-order linear decrease in hyperopia or increase in myopia with an average annual change of -0.15 D/year, 14 (4%) showed second-order curvilinear change. and 89 (25.4%) remained unchanged. In the eyes with linear change, there was a significant relationship between the refraction at age 6 years and the rate of subsequent change such that the less hyperopic or emmetropic at age 6 years, the larger the change. The refraction at birth was estimated by extrapolation of the linear regression analysis results, implying that 88% of newborns have hyperopia of +1.0 D or greater and myopia is rare. These results indicate the current state of refraction in Japanese schoolchildren of a rural area. [ABSTRACT FROM AUTHOR]

When breast-conserving therapy was introduced at the Cancer Institute Hospital (CIH) in Tokyo in 1986, we instituted our own strategy as follows: 1) every effort is to be made for complete tumor resection while avoiding deformity of the breast, and 2) radiotherapy (RT) is applied only to the patients with positive surgical margins. This is, in turn, to clarify the group of patients in whom postoperative RT can be safely spared. Among 9670 patients operated on for primary breast cancer during the 16.5 year period from 1986 to 2002 at CIH, there were 2449 patients who underwent breast-conserving surgery (BCS). During the 6.5 years mean follow-up period, ipsilateral intrabreast tumor recurrence (IBTR) developed in 99 of the 2449 patients, with an overall rate of 4.0% and an annual rate of 0.62%. These 2449 patients were categorized into four subgroups according to either negative or positive margins and with or without radiotherapy. The IBTR rates and the number of patients in each subgroup were 5.5% in 1351 margin(–)RT(–) patients, 1.0% in 307 margin(–)RT(+) patients, 2.4% in 680 margin(+)RT(+) patients, and 4.5% in 111 margin(+)RT(–) patients. These results either with or without RT seem to be quite comparable to or even better than the results of BCS with RT reported from Western countries, where less emphasis seems to be placed on completeness of the local tumor resection with BCS, while RT is administered to basically all patients following BCS. IBTR was categorized into true recurrence (TR) and second primary lesion (SP) according to the margin status at the time of BCS, the former being lesions developed in patients with positive margins and the latter being those in patients with negative margins. It was demonstrated that in patients with positive margins, TR was much more common than SP, whereas in patients with negative margins, these incidences were just the opposite (i.e., TR was 60% less common than SP) and postoperative RT was effective in preventing both TR and SP, the effect on the latter being much more striking. With RT, the incidence of developing TR in patients who had positive margins was reduced to almost equal to that in margin(–) patients treated with no RT. Our method of IBTR categorization is based on biological consideration and detailed histopathologic examination, and appears to be the only biologically reasonable means so far that has been proposed for distinction between these two biologically different entities. TR and SP can be further reduced to exceptionally low levels in patients who received RT despite negative margins, though it would not seem reasonable to administer RT to all of these patients because the actual number of patients who would benefit is comparatively small. From these observations, it seems that our imaging, pathologic examination, and surgical approaches for patients who are candidates for BCS have been highly valid, and our criteria for sparing postoperative RT as well as categorization of IBTR into TR and SP are quite appropriate. Although our results with BCS seem to deserve wide recognition, they are not from randomized clinical trials, so the findings must be confirmed by a study in order to investigate whether the results at CIH can be applied generally at other institutions. [ABSTRACT FROM AUTHOR]

Background:  We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk., Methods:  This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies., Results:  The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 ( n  = 427) and 93.3 ± 57.8 ng/mL ( n  = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 ( n  = 79; 12.4 ± 12.1 and n  = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group ( n  = 83; 25.1 ± 36.6 and n  = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study ( n  = 39; 18.4 ± 11.2 and n  = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not., Conclusion:  PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight., Competing Interests: T.Y. received personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; grants and personal fees from Daiichi Sankyo Co., Ltd., Bayer Yakuhin, Ltd., and Bristol Myers Squibb K.K.; personal fees from Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Toa Eiyo Ltd., Novartis Pharma K.K., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work. Y.I., M.F., and T.H. are employees of Daiichi Sankyo Co., Ltd. S.H. is an employee of Certara, Inc. K.O. received grants and personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; personal fees from Daiichi Sankyo Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., Medtronic Japan Co., Ltd., Johnson and Johnson K.K., and Bayer Yakuhin, Ltd. outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

The 88 th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8 th to Sunday, March 10 th in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

Background: This prospective ANAFIE Registry substudy investigated the relationship between the echocardiographic parameters of left atrial (LA) structure and function and clinical outcomes at 2 years among atrial fibrillation (AF) patients aged ≥75 years., Methods and results: Outcomes of 1,474 elderly non-valvular AF (NVAF) patients who underwent transthoracic echocardiography at baseline were analyzed by categories of maximum LA volume index (max. LAVi) and LA emptying fraction (LAEF) total. Baseline mean±standard deviation LAEF total and max. LAVi were 28.2±14.9% and 54.2±25.9 mL/m 2 , respectively. Proportions of oral anticoagulant (OAC), direct OAC, and warfarin use were 92.7%, 68.7%, and 24.0%, respectively. Patients with LAEF total ≤45.0% (n=1,213) vs. >45.0% (n=224) were at higher risk of cardiovascular events (hazard ratio [HR]: 2.19, P=0.021) and heart failure (HF) hospitalization (HR: 2.25, P=0.045). Risk of all-cause death was higher with max. LAVi >48.0 mL/m 2 (n=656) vs. ≤48.0 mL/m 2 (n=621) (HR: 1.69, P=0.048). Subgroups with abnormal LA function and structure had increased incidence of cardiac/cardiovascular events and HF hospitalization. No significant interaction was observed between echocardiographic parameters and OAC type., Conclusions: Elderly Japanese patients with NVAF and LAEF total ≤45.0% were at higher risk of cardiovascular events and HF hospitalization, and those with max. LAVi >48.0 mL/m 2 were at higher risk of all-cause death.

Pericardial effusion (PE) presentation varies from an incidental finding to a life-threatening situation; thus, its etiology and clinical course remain unknown. The aim of the present study was to retrospectively investigate these factors.We analyzed 171 patients (0.4%) who presented with PE among 34,873 patients who underwent echocardiography between 2011 and 2021 at our hospital. Clinical and prognostic information was retrieved from electronic medical records. The primary endpoints were all-cause death, hospitalization due to heart failure (HF), and other cardiovascular events such as cardiovascular death, acute coronary syndrome, elective percutaneous coronary intervention, and stroke.The etiologies of PE were as follows: idiopathic (32%), HF-related (18%), iatrogenic (11%), cardiac surgery-related (10%), radiation therapy-related (9%), malignancy (8%), pericarditis/myocarditis (8%), myocardial infarction-related (2%), and acute aortic dissection (2%). Patients with idiopathic/HF etiology were more likely to be older than the others.During a mean follow-up period of 2.5 years, all-cause death occurred in 21 patients (12.3%), cardiovascular events in 10 patients (5.8%), and hospitalization for HF in 24 patients (14.0%). All-cause death was frequently observed in patients with malignancy (44% per person-year). Cardiovascular events were mostly observed in patients with radiation therapy-related and malignancy (8.6% and 7.3% per person-year, respectively).The annual incidence of hospitalization for HF was the highest in patients with HF-related (25.1% per person-year), followed by radiation therapy-related (10.4% per person-year).This retrospective study is the first, to the best of our knowledge, to reveal the contemporary prevalence of PE, its cause, and outcome in patients who visited a cardiovascular hospital in an urban area of Japan.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Patient profiles suitable for long-term lenvatinib treatment for unresectable hepatocellular carcinoma (uHCC) are yet to be fully understood. This post-hoc analysis aimed to identify such patient characteristics and explore the impact of treatment duration and relative dose intensity (RDI) on treatment outcomes. The data were obtained from 703 patients in a multicenter, prospective cohort study in Japan. Lenvatinib-naïve patients with uHCC were enrolled between July 2018 and January 2019 and were followed up for 12 months. Moreover, patients were dichotomized using the median treatment duration into the longer- (≥177 days; n = 352) or shorter-treatment (<177 days; n = 351) groups. The longer-treatment group often had better performance status, lower Child-Pugh score and better modified albumin-bilirubin grade than the shorter treatment group (p<0.05 for all). The objective response rate (47.6% vs. 28.2%; p<0.001) and disease control rate (92.4% vs. 60.2%; p<0.001) were both significantly higher in the longer-treatment groups than in the shorter-treatment groups. The proportion of patients with any adverse drug reactions was generally similar between the two treatment groups. Within the longer-treatment group, the disease control rate was high regardless of dose modification (i.e., RDI <100% vs. ≥100% during the initial 177 days) (91.2% vs. 98.0%). In conclusion, patients with longer treatment tended to have better overall conditions. Lenvatinib dose modifications at the physician's discretion, considering the balance between effectiveness and safety, may contribute to the long-term treatment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Tatsuya Yamashita has received travel grants and honoraria for speaking or participation at meetings from Chugai Pharma, Eli Lilly Japan, and Eisai. Natsumi Suzuki, Katsuaki Motoyoshi, and Wanjun Zhu are employees of Eisai Co., Ltd. Junji Furuse received research grants from Astellas, Astra Zeneca, Incyte Biosciences Japan, Eisai, MSD, Ono Pharmaceutical, Sanofi, J-Pharma, Daiichi Sankyo, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, Delta-Fly-Pharma, Chugai Pharma. He has received travel grants and honoraria for speaking or participation at meetings from Ono Pharmaceutical, Chugai Pharma, Incyte Biosciences Japan, Eisai, Eli Lilly Japan, Astra Zeneca, Yakult Honsha, Servier Japan, MSD, Novartis Pharma, Takeda, Bayer, Taiho Pharmaceutical, EA Pharma, Teijin pharma, Daiichi Sankyo, Terumo, Fuji film, Astellas, Onco Therapy Science, Delta-Fly-Pharma, Merck Bio, Incyte Biosciences Japan, J-Pharma. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yamashita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Here, we aimed to provide an overview of Japan Council for the Implementation of the Maternal Emergency Life-Saving System (J-CIMELS) and its simulation program, which has reduced maternal mortality due to direct causes in Japan. The Japan Association of Obstetricians and Gynecologists (JAOG), Japan Association of Obstetricians and Gynecologists, and Maternal Death Exploratory Committee (JMDEC) launched the Maternal Death Reporting Project in 2010. The project analyzed obstetricians' tendency to delay their initial response to sudden maternal deterioration. Obstetricians can predict small changes before deterioration by monitoring vital signs. In 2015, the J-CIMELS was established to provide practical education. J-CIMELS developed a simulation program (J-MELS; Japan Maternal Emergency Life Support) to ensure that the obstetricians acquire the latest knowledge of emergency physicians, anesthesiologists, and other general practitioners and apply it in clinical situations. In the last 7 years, the J-MELS basic course has been conducted 1000 times with a total attendance of 19 890 people. As a result, the incidence of obstetric hemorrhage progressively decreased from 29% in 2010 to 7% in 2020. We believe that the activities of J-CIMELS are improving obstetric care providers' medical practices in Japan., (© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Aim: Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross-sectional questionnaire survey to ascertain the status of MIS for endometrial cancer., Methods: The survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed., Results: The total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board-certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan., Conclusion: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra-fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS., (© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Background: Several epidemiological studies have been conducted to understand the relationship between environmental factors (including chronic sun exposure) and clinical signs of pigmented spots. However, no quantitative analysis has focused on the adverse effects of the detailed features of pigmented spots, including their color intensity, size, and number on the cheek. This study was performed to elucidate the adverse effects of environmental factors on clinical signs of pigmented spots., Methods: We conducted an epidemiological survey of 102 Japanese women in 2 regions of high and low sun exposure (southern and northern regions, respectively). Using image analysis of high-resolution digital facial photographs, individual pigmented spots were quantified according to color, size, and total number on the cheek. Each indicator was then compared between the groups., Results: For the number of pigmented spots on the cheek, the age-related increase curve showed a large slope in the southern group. For the size of pigmented spots, no significant difference was found between the two groups, and large pigmented spots were observed on the cheek even in the northern group. For the color intensity of the spots, the southern group showed a marked age-related change; among older subjects, the pigmented spots were significantly darker in the southern than northern group., Conclusion: Our results may indicate that environmental factors, including chronic exposure to sunlight, mainly increase the number of pigmented spots and darkening of these spots. However, the occurrence of large pigmented spots may be related to intrinsic factors represented by heredity rather than environmental factors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Two novel actinobacteria, designated IFM 12276 T and IFM 12275, were isolated from clinical specimens in Japan, and their taxonomic positions were investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strains IFM 12276 T and IFM 12275 have completely identical 16S rRNA gene sequences and were closely related to members of the genus Nocardia . The highest 16S rRNA gene sequence similarity was observed to Nocardia beijingensis (99.6 %) and Nocarida sputi (99.6 %), followed by Nocardia niwae (99.3 %) and Nocardia araoensis (99.3 %). The whole-cell hydrolysates of strains IFM 12276 T and IFM 12275 contained meso -diaminopimelic acid, arabinose and galactose. The acyl type of muramic acid was N -glycolyl. The predominant isoprenoid quinone was MK-8(H 4 , ω -cycl.) and the principal polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. Strains IFM 12276 T and IFM 12275 contained mycolic acids that co-migrated with those from the type strain of N. niwae . These chemotaxonomic features corresponded to those of the genus Nocardia . Meanwhile, the differences in some phenotypic characteristics, along with the results of average nucleotide identity and digital DNA-DNA hybridization analyses, indicated that strains IFM 12276 T and IFM 12275 should be distinguished from the recognized species of the genus Nocardia . Therefore, these strains represent a novel species of the genus Nocardia , for which the name Nocardia sputorum sp. nov. is proposed. The type strain is IFM 12276 T (=NBRC 115477 T =TBRC 17096 T ).

Background/aim: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC)., Patients and Methods: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined., Results: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival., Conclusion: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT)., Methods: Symptomatic venous thromboembolism (VTE) and major bleeding were assessed., Results: Of 1016 patients with acute symptomatic/asymptomatic DVT and/or pulmonary embolism treated with rivaroxaban, 288 had IDDVT and 294 had proximal DVT (pDVT). The IDDVT group had fewer patients on the higher rivaroxaban dose (30 mg/day) (42.7% vs. 66.0%) and a shorter treatment duration (135.5 vs 369.5 days) than the pDVT group. VTE recurrence occurred in 14 and 11 patients with IDDVT and pDVT, respectively (2.89% vs. 2.29% per patient-year; p = 0.534). Major bleeding was less frequent in the IDDVT group (1.55% vs. 4.53% per patient-year; p = 0.044). Comparable effectiveness and safety were observed with 15 and 30 mg/day rivaroxaban in the IDDVT group., Conclusions: Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment.

The perinatal resuscitation history in Japan is short, with the earliest efforts in the field of neonatology. In contrast, the standardization and dissemination of maternal resuscitation is lagging. With the establishment of the Maternal Death Reporting Project and the Maternal Death Case Review and Evaluation Committee in 2010, with the aim of reducing maternal deaths, the true situation of maternal deaths came to light. Subsequently, in 2015, the Japan Council for the Dissemination of Maternal Emergency Life Support Systems (J-CIMELS) was established to educate and disseminate simulations in maternal emergency care; training sessions on maternal resuscitation are now conducted in all prefectures. Since the launch of the project and council, the maternal mortality rate in Japan (especially due to obstetric critical hemorrhage) has gradually decreased. This has been probably achieved due to the tireless efforts of medical personnel involved in perinatal care, as well as the various activities conducted so far. However, there are no standardized guidelines for maternal resuscitation yet. Therefore, a committee was set up within the Japan Resuscitation Council to develop a maternal resuscitation protocol, and the Guidelines for Maternal Resuscitation 2020 was created in 2021. These guidelines are expected to make the use of high-quality resuscitation methods more widespread than ever before. This presentation will provide an overview of the Guidelines for Maternal Resuscitation 2020., (© 2022 Japan Society of Obstetrics and Gynecology.)

Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination dataset over time (2012-2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (< 18.5 kg/m 2 ), normal (18.5-22.9 kg/m 2 ), overweight at risk (23.0-24.9 kg/m 2 ), obese I (25.0-29.9 kg/m 2 ), and obese II (≥ 30.0 kg/m 2 ). Age was significantly and inversely related to high BMI for all diseases (P < 0.001). The proportion of BMI categories significantly altered over time; annual BMI trends showed a significant and gradual increase, except AAD. In adjusted mixed models, underweight was significantly associated with a high risk of in-hospital mortality in all CVD patients (AHF, OR 1.41, 95% CI 1.35-1.48, P < 0.001; AMI, OR 1.27, 95% CI 1.20-1.35, P < 0.001; AAD, OR 1.23, 95% CI 1.16-1.32, P < 0.001; IS, OR 1.45, 95% CI 1.41-1.50, P < 0.001; ICH, OR 1.18, 95% CI 1.13-1.22, P < 0.001; SAH, OR 1.17, 95% CI 1.10-1.26, P < 0.001). Moreover, obese I and II groups were significantly associated with a higher incidence of in-hospital mortality, except AHF and IS. Age was associated with in-hospital mortality for all BMI categories in six CVD patients. BMI increased annually in patients with six types of CVDs. Although underweight BMI was associated with high mortality rates, the impact of obesity on in-hospital mortality differs among CVD types., (© 2022. The Author(s).)

Background: Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer., Methods: In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment)., Results: Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths., Conclusions: In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs., Gov Identifier: NCT03343054., (© 2022. The Author(s).)

Recently, oral hypoglycemic agents with newer glucose lowering mechanisms have been on release. This is mostly to meet the diabetic patient's need to avoid hypoglycemia, which is profoundly important for better long-term outcome of the treatment. In this study, we quantified the annual number of patients with type 2 diabetes who experienced hypoglycemia needing the third-party assistance who had random sample plasma glucose<59.4 mg/dl (3.3 mmol/l) on the one hand and analyzed the prescription trend of hypoglycemic agents all over Japan on the other. Analysis of the annual number of hypoglycemic patients visited ER was performed at Aizawa Hospital, a medical center located in the midst of a city. The study duration was over 10 years from 2008 to 2019. We found a clear-cut decreasing trend of hypoglycemia over the 10 years, ca. 61/year to 39/year. Immediately after the release of sodium-glucose co-transporter-2 inhibitors, since 2013 to 2017, the decrease was rather sharp as 81/year to 31/year, and the change of the national number of its prescription inversely correlated with the change of the number of the patients with hypoglycemia. This was not the case immediately after the introduction of dipeptidyl peptidase-4 inhibitors in the Japanese market since 2008 to 2012. There was no significant correlation between its prescription and the number of patients with hypoglycemia. The data strongly suggested that there was a causal relationship exclusively between the introduction of sodium-glucose cotransporter-2 inhibitor, and the reduction of hypoglycemic events among patients with type 2 diabetes., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study, which included serological and cellular immunity tests, evaluated whether coronavirus disease 2019 (COVID-19) vaccination adequately protected healthcare workers (HCWs) from COVID-19. Serological investigations were conducted among 1600 HCWs (mean ± standard deviation, 7.4 ± 1.4 months after the last COVID-19 vaccination). Anti-SARS-CoV-2 antibodies N-Ig, Spike-Ig (Roche), N-IgG, Spike-IgM, and -IgG (Abbott), were evaluated using a questionnaire of health condition. 161 HCWs were analyzed for cellular immunity using T-SPOT ® SARS-CoV-2 kit before, and 52 HCWs were followed up until 138.3 ± 15.7 days after their third vaccination. Spike-IgG value was 954.4 ± 2282.6 AU/mL. Forty-nine of the 1600 HCWs (3.06%) had pre-existing SARS-CoV-2 infection. None of the infectious seropositive HCWs required hospitalization. T-SPOT value was 85.0 ± 84.2 SFU/10 6 cells before the third vaccination, which increased to 219.4 ± 230.4 SFU/10 6 cells immediately after, but attenuated later (to 111.1 ± 133.6 SFU/10 6 cells). Poor counts (< 40 SFU/10 6 cells) were present in 34.8% and 38.5% of HCWs before and after the third vaccination, respectively. Our findings provide insights into humoral and cellular immune responses to repeated COVID-19 vaccinations. COVID-19 vaccination was effective in protecting HCWs from serious illness during the original Wuhan-1, Alpha, Delta and also ongoing Omicron-predominance periods. However, repeated vaccinations using current vaccine versions may not induce sufficient cellular immunity in all HCWs., (© 2022. The Author(s).)

Background: In the global phase III IMpassion031 study, neoadjuvant atezolizumab plus nab-paclitaxel/anthracycline-based chemotherapy improved pathological complete response in patients with early stage triple-negative breast cancer. Here, we report primary analysis results from a subgroup of Japanese patients., Methods: Patients with histologically documented, previously untreated, stage cT2-cT4, cN0-cN3, cM0 triple-negative breast cancer were randomized 1:1 to receive intravenous atezolizumab 840 mg or placebo every 2 weeks in combination with chemotherapy consisting of nab-paclitaxel intravenous 125 mg/m2 once a week, followed by doxorubicin intravenous 60 mg/m2 and cyclophosphamide intravenous 600 mg/m2 every 2 weeks. Patients then underwent surgery. Pathological complete response (ypT0/is ypN0) in the intention-to-treat and PD-L1-positive (≥1% PD-L1-expressing tumor-infiltrating immune cells) populations were co-primary endpoints., Results: This subanalysis (data cutoff: 3 April 2020) included 36 patients from Japan (intention-to-treat; atezolizumab arm, n = 17; placebo arm, n = 19). Pathological complete response occurred in 41% (n = 7; 95% confidence interval, 18-67) of patients in the atezolizumab arm and 37% (n = 7; 95% confidence interval, 16-62) in the placebo arm. In the PD-L1-positive population, pathological complete response occurred in 50% (n = 5; 95% confidence interval, 19-81) of patients in the atezolizumab arm and 45% (n = 5; 95% confidence interval, 17-77) in the placebo arm. Treatment-related grade 3-4 adverse events occurred in 71% and 68% of patients in the respective arms., Conclusion: Atezolizumab added to neoadjuvant chemotherapy numerically improved pathological complete response versus placebo in this small exploratory analysis of Japanese patients with early stage triple-negative breast cancer, a trend directionally consistent with the global study results. No new safety signals were identified., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity., Materials and Methods: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically., Results: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05)., Conclusions: Early detection and radical treatment are essential for improving the prognosis of oral MM patients., Clinical Relevance: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population., Methods: Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively., Results: A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed., Conclusions: The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan., (© 2022. The Author(s).)

Background: Idarucizumab, a dabigatran-specific reversal agent, was launched in Japan in 2016. The J-Dabigatran Surveillance 2 study was designed to assess the characteristics and outcomes of dabigatran-treated patients after the launch of idarucizumab., Methods: Patient characteristics and outcomes, including thromboembolic and bleeding events, of dabigatran-naïve patients with non-valvular atrial fibrillation (NVAF) who received dabigatran etexilate [110 mg or 150 mg twice-daily (b.i.d.)] for the prevention of ischemic stroke and systemic embolism were investigated and presented descriptively. Absolute standardized differences (ASD) in baseline characteristics compared with the first J-Dabigatran Surveillance (J-Dabi1; 2011-2013) study were included., Results: In total, 5660 patients were enrolled and 5436 were analyzed in this study; 3516 and 1898 received 110 mg b.i.d. and 150 mg b.i.d. dabigatran, respectively; 22 received other doses. The overall duration of follow-up (mean ± standard deviation) was 287 ± 179 days. Baseline characteristics, including stroke/bleeding-risk scores, were typical of this patient population. Overall, paroxysmal, persistent, permanent, and symptomatic atrial fibrillation were observed for 53.2%, 27.1%, 13.7%, and 53.9% of patients, respectively (J-Dabi1 ASD: 0.2, 0.0, 0.3, and 0.2, respectively). Catheter ablation was selected in 27.9% of patients (J-Dabi1 ASD: 0.6). Rates of clinical outcomes were low in the study (mostly <2%/year). The incidence rate of major bleeding was 1.1%/year (n = 46) and stroke/transient ischemic attack/systemic embolism was 1.7%/year (n = 71). Twelve (0.2%) patients received idarucizumab, commonly for serious bleeding events, and most recovered., Conclusions: Dabigatran continues to be safe and well tolerated in patients with NVAF for stroke and systemic embolism prevention and continues to be prescribed appropriately. Treatment outcomes have not changed since the availability of idarucizumab. Since the J-Dabi1 study, treatment guidelines for anticoagulation use in NVAF have been updated based on emerging clinical evidence, accounting for differences in patient characteristics, and making dabigatran a preference for distinct patient populations., Competing Interests: Declaration of competing interest Takeshi Yamashita has received remuneration from Boehringer Ingelheim, Daiichi Sankyo, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Novartis, Otsuka Pharmaceutical, Ono Pharmaceutical, and Toa Eiyo, and research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Bayer Healthcare, and Daiichi Sankyo; Shinichiro Uchiyama has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Sanofi; Hirotsugu Atarashi has received remuneration from Boehringer Ingelheim and Daiichi Sankyo; Ken Okumura has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Pfizer; Yukihiro Koretsune has received remuneration from Daiichi Sankyo, Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, and Pfizer; Masahiro Yasaka has received remuneration from Boehringer Ingelheim, Bayer Healthcare, and Daiichi Sankyo, and research funding from Boehringer Ingelheim; Junichi Wakayama is an employee of EPS Corporation; Taku Fukaya is an employee of Nippon Boehringer Ingelheim; Hiroshi Inoue has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Bristol-Myers Squibb., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . 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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

Background/aims: To compare the effects of silicone oil tamponade (SOT) to that of gas tamponade (GT) on the best-corrected visual acuity (BCVA) after successful vitrectomy for retinal detachment (RD)., Methods: A retrospective, multicentre, nationwide study with RD who were registered in the Japan-RD Registry. All cases with RD treated with successful vitrectomy between February 2016 and March 2017 were studied. A propensity score matching was performed using the preoperative findings as covariates to adjust the relevant confounders. The primary outcome was the estimated mean difference of the postoperative BCVA in 6 months between eyes treated with SOT to those treated with GT., Results: Of the 3446 cases registered, 2097 cases met the entry criteria. There were 2042 eyes that had GT and 55 eyes that had SOT. Primary success was defined as a reattached retina with no tamponade at 6 months. After propensity score matching, each group contained 40 cases. The preoperative BCVA was 0.966±0.738 logMAR units in the GT group and 1.270±0.945 logMAR units in the SOT group (p=0.177). Six months postoperatively, the BCVA in the GT group was significantly better at 0.309 logMAR units in the GT group than the 0.671 logMAR units in the SOT group (p=0.002)., Conclusions: Even after successful surgery for RD, eyes that experienced SOT had poorer BCVA than eyes treated with GOT. SOT should be considered cautiously., Precis: Propensity score analysis of eyes with rhegmatogenous RD showed that postoperative vision was worse in eyes treated once with silicone oil than with gas even after completely successful surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Catheter ablation is widely used as first-line therapy for patients with impaired quality of life; however, whether catheter ablation improves survival and other outcomes in atrial fibrillation (AF) cases remains unclear., Objective: The purpose of this study was to evaluate whether catheter ablation reduces adverse clinical outcomes and improves patients' quality of life using data from a contemporary Japanese multicenter registry of patients with early-stage AF., Methods: The Keio Interhospital Cardiovascular Studies-Atrial Fibrillation registered 3318 patients with AF newly diagnosed at or referred to participating hospitals between 2014 and 2018. Propensity score matching based on 47 demographic variables was performed. We extracted 823 pairs who underwent catheter ablation or medical therapy alone. The primary outcome was the composite of all-cause death, stroke, bleeding events, and heart failure hospitalization during a 2-year follow-up period. Additionally, the Atrial Fibrillation Effect on QualiΤy-of-Life scores at baseline and 1-year follow-up were evaluated., Results: Within the matched cohort, the median time since AF diagnosis was 0.3 years (interquartile range [IQR] 0.1‒2.3 years), age was 67.0 years (IQR 59.0‒73.0 years), and the CHA 2 DS 2 -VASc score was 2.0 (IQR 1.0‒2.0). During a median follow-up period of 730 days (IQR 366‒731 days), patients who underwent catheter ablation had a lower risk of primary outcomes (hazard ratio 0.49; 95% confidence interval 0.30‒0.79; P = .004), with a significantly lower risk of heart failure hospitalization (hazard ratio 0.33; 95% confidence interval 0.14-0.77; P = .010) and improved Atrial Fibrillation Effect on QualiΤy-of-Life scores, than did those who received medical therapy., Conclusion: In patients with propensity score-matched, early-stage, real-world AF, catheter ablation was associated with a lower risk of adverse clinical events and improved quality of life as compared with medical therapy., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Mutations in neurofilament genes have been linked to several neuromuscular disorders. The neurofilament heavy (NEFH) gene was identified as the causative gene of Charcot-Marie-Tooth disease type 2CC (CMT2CC) in 2016, with a toxic gain of function mechanism caused by the translation and aggregation of cryptic amyloidogenic element (CAE) in the 3' untranslated region (UTR). But the NEFH-related clinical and genetic spectrums are still unclear in Japan., Methods: We analyzed all variants in the NEFH gene from our in-house whole-exome sequencing data, established from Japanese nationwide patients with neuromuscular disorders, including Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA)., Results: We identified a c.3017dup (p.Pro1007Alafs*56) variant in NEFH from three families clinically diagnosed with CMT, and one family with SMA. In addition to the patients presented with typical peripheral neuropathies, pyramidal signs were observed from one CMT patient. Whereas the SMA patients showed severe characteristic weakness of triceps brachii and quadriceps femoris. All of these four families reside in Kagoshima Prefecture of Japan, and a following haplotype analysis strongly suggests a founder effect., Interpretation: This is the original report referring to a founder mutation in NEFH. The clinical diversity in our study, comprising CMT, with or without pyramidal signs, and SMA, suggest an extensive involvement of peripheral nerve, anterior horn cells, or both. Our findings broaden the phenotypic spectrum of NEFH-related disorders., (© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Objective: Rivaroxaban is commonly prescribed to prevent venous thromboembolism (VTE). Although lower than standard dosages (under-dosing) may be administered in the real-world setting, data on subsequent clinical outcomes in Japanese patients are lacking., Methods: The prospective, multicenter, observational J'xactly study enrolled patients with acute symptomatic/asymptomatic deep vein thromboses (DVT), pulmonary embolism (PE), or both, who were prescribed rivaroxaban. This subanalysis investigated patient characteristics and outcomes associated with rivaroxaban under-dosing., Results: Among 1016 evaluable patients, 667 (65.6%) received an initial standard dosage of rivaroxaban (30 mg/day) and 349 (34.4%) received an initial under-dosage (20 mg/day, n  = 22; 15 mg/day, n  = 282; and 10 mg/day, n  = 45). Those receiving an under-dose had significantly lower body weight and slower pulse rate compared with the standard-dose group regardless of DVT or PE status. Under-dosing was common for distal DVTs, but less frequent for massive/submassive PEs. There were no differences between under-dose and standard-dose groups in the incidences of recurring symptomatic VTEs (DVT: 1.77% vs. 3.35% per patient-year, p  = .138; PE: 0.84% vs. 2.84% per patient-year, p  = .208) or major bleeding (DVT: 3.55% vs. 3.41% per patient-year, p  = .960; PE: not observed vs. 2.83% per patient-year, p  = .132)., Conclusions: In the real-world setting, rivaroxaban under-dosing for patients with VTE occurred in those with lower body weight, slower pulse rate, distal DVT, or non-massive PEs. There were no statistically significant differences in the clinical outcomes for patients received under-dose of rivaroxaban at the discretion of the physicians in the clinical practice compared with those received standard dose of rivaroxaban.

Healthcare workers (HCWs), especially frontline workers against coronavirus disease 2019 (COVID-19), are considered to be risky because of occupational exposure to infected patients. This study evaluated the correlation between seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among HCWs and the implementation of personal protective equipment (PPE) & infection prevention and control (IPC). We recruited 1237 HCWs from nine public COVID-19-designated hospitals in Shiga Prefecture, central Japan, between 15-26 February 2021. All participants answered a self-administered questionnaire and provided blood samples to evaluate SARS-CoV-2 antibodies. A total of 22 cases (1·78%) were seropositive among the 1237 study participants. An unavoidable outbreak of SARS-CoV-2 had occurred at the terminal care unit of one hospital, before identifying and securely isolating this cluster of cases. Excluding with this cluster, 0·68% of HCWs were suspected to have had previous SARS-CoV-2 infections. Binomial logistic regression from individual questionnaires and seropositivity predicted a significant correlation with N95 mask implementation under aerosol conditions (p = 8.63e-06, aOR = 2.47) and work duration in a red zone (p = 2.61e-04, aOR = 1.99). The institutional questionnaire suggested that IPC education was correlated with reduced seropositivity at hospitals. Seroprevalence and questionnaire analyses among HCWs indicated that secure implementation of PPE and re-education of IPC are essential to prevent SARS-CoV-2 infection within healthcare facilities. Occupational infections from SARS-CoV-2 in healthcare settings could be prevented by adhering to adequate measures and appropriate use of PPE. With these measures securely implemented, HCWs should not be considered against as significantly risky or dirty by local communities., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Myopia is a known risk factor of pigmentary glaucoma (PG), and the increased prevalence of myopia in Asian countries indicates that more cases of PG will likely develop soon. However, there are no diagnostic criteria for PG for Asians. Therefore, the purpose of this study is to determine the characteristics of PG in Japanese individuals and establish three diagnostic signs for PG., Methods: This was a single-center, retrospective, case series study of glaucoma patients who visited the Kagoshima University Hospital between January 2015 and January 2020. The inclusion criteria were age <50 years at time of diagnosis and presence of pigmentation in the anterior chamber (AC) angle including a Sampaolesi line. Eyes with pigmentation of the AC angle caused by other types of glaucoma such as uveitis, trauma, exfoliation, or childhood glaucoma were excluded. We investigated the classic diagnostic triad of signs of PG; posterior corneal pigmentation, mid peripheral iris transillumination defect, and pigmentation of the trabecular meshwork. We also examined the Sampaolesi line, iris concavity, and midperipheral iris depigmentation in eyes with PG., Results: Ten eyes of 5 Japanese men and 10 eyes of 5 Japanese women were studied. Their age ranged from 13 to 46 years at the time of diagnosis. One eye had posterior corneal pigmentation and 6 eyes had pigmentation of the trabecular meshwork. None had mid peripheral iris transillumination defect. The Sampaolesi line, iris concavity, and midperipheral iris depigmentation were found in all patients except one patient who lacked the mid peripheral depigmentation. Two eyes had the pigment reversal sign, none had lens pigmentation, and 2 eyes had peripheral retinal degeneration., Conclusion: The presence of the Sampaolesi line, iris concavity, and midperipheral iris depigmentation may be appropriate signs for the diagnosis of PG in Asians., Competing Interests: The authors have declared that no competing interests exist.

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases., (© 2021. Springer Japan KK, part of Springer Nature.)

Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI., (© 2021. Springer Japan KK, part of Springer Nature.)

Clinical screening using the National Comprehensive Cancer Network (NCCN) testing criteria may fail to identify all patients with hereditary breast and ovarian cancers. Thus, this study aimed to evaluate the strategy of expanding target patients for genetic testing among Japanese patients. We reviewed the medical records of 91 breast cancer patients who underwent genetic testing. Among 91 patients, eight were diagnosed with pathogenic or likely pathogenic variants: BRCA1 (n = 4) and BRCA2 (n = 4). Among 50 patients meeting the testing criteria of the guidelines, 6 (12%) were diagnosed with pathogenic or likely pathogenic variants. The sensitivity and specificity of screening using the testing criteria were 75% and 47%, respectively. Expanding the NCCN criteria to include all women diagnosed with breast cancer aged ≤65 years achieved 88% sensitivity but 8% specificity. The expansion of the NCCN criteria could benefit Japanese patients; however, larger studies are necessary to change clinical practice.

Objectives: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH)., Methods: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review., Results: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence., Conclusions: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The association between fruit and vegetable consumption before and during pregnancy and offspring's physical growth has been well reported, but no study has focused on offspring's neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23 406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption was calculated using FFQ, and offspring's developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10 420 women and 10 543 infants were included in the analysis. Totally, 14·9 % of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·74; 95 % CI 0·63, 0·89 and OR 0·70; 95 % CI 0·59, 0·84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·78; 95 % CI 0·66, 0·92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.

Background: The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain., Methods: This retrospective study, conducted across 10 Japanese institutions, included patients aged 5-15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student's t-test was used to compare the associations between the lesion size and spontaneous pain., Results: A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4-102 mm) and 13.2 mm (range: 5-21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (p = 0.67 and p = 0.27, respectively)., Conclusion: The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain., (© 2022. The Author(s).)