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COVID-19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020-2021 were compared with those diagnosed in the pre-pandemic 2018-2019. The primary outcome was all-cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre-pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre-pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor-directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor-directed treatment or cancer screening, despite potential selection bias for follow-up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF., (© 2024. The Author(s).)

Background: Delirium management is crucial in palliative care. Morphine effectively relieves dyspnea due to heart failure. However, the effect of morphine, which is used to relieve dyspnea due to heart failure, on the incidence of delirium has not been examined to date. Objective: To evaluate the effect of morphine, which is used to relieve dyspnea due to heart failure, on delirium. Design: Retrospective observational study. Setting/Subjects: Subjects were identified from Osaka University Hospital records, located in Japan, from January 1, 2010, to September 30, 2021. The case group consisted of admissions for heart failure or cardiomyopathy registered in electronic medical records. Morphine was administered to relieve dyspnea due to heart failure, and no surgeries or procedures were performed. The control group consisted of admissions for heart failure or cardiomyopathy in the Diagnosis Procedure Combination (DPC) database, which did not include administration of morphine, oxycodone, or fentanyl during the hospitalization period and patients did not undergo surgery or any other procedure. Measurements: The incidence of delirium was assessed. Results: The odds ratios for morphine in the multivariate logistic regression analysis with propensity score and univariate logistic regression analysis after propensity score matching were 1.406 (95% confidence interval (CI) [0.249-7.957]) and 1.034 (95% CI [0.902-1.185]), respectively. Conclusions: Morphine, which is used to relieve dyspnea due to heart failure, had minimal effect on the incidence of delirium. This information is likely to be beneficial for the future use of morphine in the management of dyspnea in patients with heart failure.

Objective: To compare healthcare resource utilisation (HCRU) and direct costs between responders versus non-responders to advanced therapies for rheumatoid arthritis (RA)., Methods: Patients initiating ≥1 advanced therapy (October 2018 - September 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs [direct medical, emergency department (ED), laboratory, and pharmacy] were compared between responders and non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses., Results: Among 2446 patients [non-responders (n = 1817); responders (n = 629)], non-responders had significantly longer hospitalisation days [IRR: 1.8 (95% CI: 1.2 - 2.6)], and significantly more ED visits [2.5 (1.5 - 4.2)] and prescriptions [1.1 (1.1 - 1.2)]. Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders [1.4 (1.3 - 1.6), ¥530,895 versus ¥357,009 ($3992 versus $2684) for responders; ¥173,886 ($1307) difference]; RA-related medical costs showed a similar trend [¥351,306 vs ¥253,030 ($2641 vs $1902); ¥98,276 ($739) difference]. No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs., Conclusions: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough. They exhibit almost homogeneous clinical and histopathological features, indicating motor neuronopathy. Over 10 years of follow-up, painful intractable muscle cramps ascended from legs to trunks and hands, followed by amyotrophy and subsequent leg pyramidal signs. The disease course combined with the electrophysical and imagery data suggest initial and prolonged hyperexcitability and the ensuing spinal motor neuron loss, which may progress from the lumbar to the rostral anterior horns and later expand to the corticospinal tract. Genetically, heterozygous ACAGG expansions of similar length were transmitted in unaffected family members of three successive generations, and some of them experienced muscle cramps. Leukocyte telomere length assays revealed comparatively shorter telomeres in affected individuals. This comprehensive pedigree analysis demonstrated a non-anticipating ACAGG transmission and high penetrance of manifestations with a biallelic state, especially motor neuronopathy in which muscle cramps serve as a prodromal and disease progress marker. CANVAS and RFC1 spectrum disorder should be considered when diagnosing lower dominant motor neuron disease, idiopathic muscle cramps, or neuromuscular hyperexcitability syndromes., (© 2024. The Author(s).)

Aims/introduction: Diet directly affects glucose metabolism, and eating behavior is influenced by various daily life stressors. This study was conducted to investigate the relationship between common psychosomatic stressors on endocrine hormones and eating behavior in patients with type 2 diabetes., Materials and Methods: This cross-sectional study was performed in 40 patients with type 2 diabetes. Resting hormone blood sampling and four self-reported questionnaires were employed., Results: Patients who scored higher on the 'anger/hostility' (AH) subcategory of the profile of mood state (POMS) questionnaire had significantly higher serum cortisol (β = 0.40, P = 0.01 by least squares adjusted for age and sex). In the eating behavior questionnaire, the subcategories of 'feeling of hunger/satiation' (β = 0.49, P < 0.01) and 'eating as diversion' (β = 0.39, P = 0.03) were associated with higher serum cortisol. Resting morning cortisol levels were higher in participants who rated high on the POMS-AH and in those who reported 'irritated when hungry' and 'tend to eat when irritated or anxious'. Sleep quality showed no association with eating behavior., Conclusions: Mood state is associated with eating behavior. Anger increases cortisol levels and may lead to compulsive eating. Various forms of hostility are important factors in appetite control and increased cortisol secretion, and can be an impediment to successful dietary self-management in patients with type 2 diabetes. Thus, assessment of mood state and control of negative mood are important therapeutic targets in diabetes management., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC)., Methods: This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within 2 days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or haemodialysis dependence at discharge., Results: Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs 49.0%; odds ratio, 0.69; 95% CI: 0.48, 1.00; P = 0.049)., Conclusions: The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or haemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes., Methods: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses., Results: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort., Conclusion: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine., Trial Registration: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Invasive functional coronary angiography (FCA), an angiography-derived physiological index of the functional significance of coronary obstruction, is a novel physiological assessment tool for coronary obstruction that does not require the utilization of a pressure wire. This technology enables operators to rapidly evaluate the functional relevance of coronary stenoses during and even after angiography while reducing the burden of cost and complication risks related to the pressure wire. FCA can be used for treatment decision-making for revascularization, strategy planning for percutaneous coronary intervention, and procedure optimization. Currently, various software-computing FCAs are available worldwide, with unique features in their computation algorithms and functions. With the emerging application of this novel technology in various clinical scenarios, the Japanese Association of Cardiovascular Intervention and Therapeutics task force was created to outline expert consensus on the clinical use of FCA. This consensus document advocates optimal clinical applications of FCA according to currently available evidence while summarizing the concept, history, limitations, and future perspectives of FCA along with globally available software., (© 2024. The Author(s).)

Background: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC)., Methods: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide., Results: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients., Conclusions: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting., Methods: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified., Results: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041)., Conclusions: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

An inter-hospital heart team conference based collaborative follow-up (FU) may facilitate outpatient cardiac rehabilitation (CR) programs, especially in hospitals without an outpatient CR center. Consecutive 145 patients with cardiovascular disease who received inpatient treatment at Yamagata University Hospital were divided into collaborative (n = 76) and same-hospital (n = 69) FU groups. In the collaborative FU group, patients received outpatient care at a university hospital and outpatient CR at different hospitals. In the same-hospital FU group, patients received outpatient care and outpatient CR at the same hospital other than the university hospital. The collaborative FU group held monthly 60-minute inter-hospital heart team conferences with CR specialists. No cardiovascular accidents occurred during the outpatient CR program in either group. Peak oxygen uptake VO 2 , anaerobic threshold, brain natriuretic peptide level, and left ventricular ejection fraction significantly improved in both groups. Kaplan-Meier analysis revealed no significant difference in prognosis between the collaborative and same-hospital FU groups (P = 0.246). Of the patients who had collaborative CR programs, 29 (38.2%) patients (37 consultations) were discussed at an inter-hospital heart team conference. Eighteen (48.6%) consultations were for issues related to continuing outpatient CR programs. Collaborative FU was as useful as same-hospital FU in terms of safety, efficacy, and prognosis in patients with cardiovascular disease. We conclude that regular inter-hospital heart team conferences are useful for facilitating collaboration among outpatient CR programs.

Background: This retrospective cohort study aimed to evaluate the impact of the COVID-19 pandemic on colorectal cancer care and mortality using a large cancer registry in Hiroshima Prefecture, Japan. The study aimed to estimate the all-cause mortality rates within 1 year of diagnosis among colorectal cancer patients diagnosed during the pandemic period (2020 and 2021) compared to those diagnosed during the pre-pandemic period (2018 and 2019)., Methods: The day of diagnosis was set as Day 0 and Cox regression models were utilized to estimate crude hazard ratios (HRs) and adjusted HRs, accounting for age, sex, cancer stage, and treatment status. Two sensitivity analyses of overall survival were performed with different cutoffs of the pre-pandemic/pandemic periods and year-to-year comparisons. Subgroup analyses were performed using likelihood ratio tests., Results: A total of 15,085 colorectal cancer patients were included, with 6499 eligible for follow-up. A median age of included patients was 72 years old, of which 59% were male. The distribution of cancer stages showed little variation between the pre-pandemic and pandemic periods. With a median follow-up of 177 days, the number of events was 316/3111 (173 events per 1000 person-years [E/1000PY], 95% confidence interval [CI]: 154-192 E/1000PY) in the pre-pandemic period, and 326/2746 (245 E/1000PY, 95% CI: 220-274 E/1000PY) in the pandemic period (crude HR: 1.42, 95% CI: 1.22-1.66; adjusted HR: 1.25, 95% CI: 1.07-1.46). The two sensitivity analyses and subgroup analyses consistently supported these findings., Conclusions: The study revealed an increased colorectal cancer mortality during the pandemic period, suggesting a continuous impact of the COVID-19 pandemic on the known and unknown risk factors for colorectal cancer for several years. Further studies are necessary to mitigate the adverse effects on patient outcomes., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This study aimed to evaluate the efficacy and safety of dentin hypersensitivity (DH) treatment using a newly developed device based on a powder jet deposition (PJD) technique that creates a hydroxyapatite (HAP) layer on the dentin surface, thereby alleviating the hypersensitivity. The effect of the PJD treatment was compared with that of conventional treatment using Teethmate Desensitizer (TMD; calcium-phosphate containing material with TTCP (Ca 4 (PO 4 ) 2 O) and DCPA (CaHPO 4 )), which has been used clinically in Japan with well-confirmed effectiveness., Materials and Methods: A randomized controlled trial was conducted including 35 patients who had symptoms of DH in two or more quadrants. Two test teeth were selected per patient (70 teeth in total) and randomly assigned to PJD or TMD treatment. The efficacy was evaluated using the improvement rate for air and scratch pain according to the scores obtained via visual analog scale 12 weeks after treatment. The safety assessment was performed focusing on gingival index (GI) and spontaneous pain. The t-test was used to analyze the non-inferiority of PJD treatment compared to TMD treatment., Results: The improvement rate of air pain was 69.0% for PJD and 69.7% for TMD. The improvement rate of scratch pain was 80.8% for PJD and 81.7% for TMD. Non-inferiority with a margin of 10% was not observed for both air and scratch pain. No change was observed in GI from baseline and the improvement rate of spontaneous pain for PJD was higher than that for TMD., Conclusion: Non-inferiority of PJD to TMD treatment was not observed in this study; however, it was not statistically demonstrated, and the results were thus interpreted as inconclusive. PJD did improve the DH symptoms, as did TMD. PJD's therapeutic effect was most likely attributable to the deposition of a HAP layer on the tooth surface, which would alleviate hypersensitivity for at least 12 weeks without causing severe adverse events., Trial Registration: UMIN-CTR. ID: UMIN000025022. date: 02/12/2016., (© 2023. BioMed Central Ltd., part of Springer Nature.)

As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders. Through the efforts of HBD participants, US-Japanese clinical trials have been conducted and the resulting data have supported regulatory approval for marketing in both countries. Based on these experiences, this paper outlines some of the key factors to consider when developing a global clinical trial involving US and Japanese participation. These considerations include the mechanisms for consultation with regulatory authorities on clinical trial strategies, the regulatory framework for clinical trial notification and approval, recruitment and conduct of clinical sites, and lessons learned from specific US-Japanese clinical trial experiences. The goal of this paper is to promote global access to promising medical technologies by assisting potential clinical trial sponsors in understanding when an international strategy may be appropriate and successful., Competing Interests: Declaration of competing interest None., (Published by Elsevier Inc.)

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA., (© 2023 Japanese Dermatological Association.)

Objectives: As disasters become more frequent because of global warming, countries across the world are seeking ways to protect vulnerable older populations. Although these conditions may increase nursing home admission (NHA) rates for older persons, we know of no studies that have directly tested this hypothesis., Design: This was a retrospective cohort study., Setting and Participants: We analyzed data from long-term care insurance (LTCI) users in 3 Japanese prefectures that incurred heavy damage from the 2018 Japan Floods, which is the largest recorded flooding disaster in national history. Specifically, we extracted NHA data from the LTCI comprehensive database, both for disaster-affected and unaffected individuals., Methods: We employed the Cox proportional hazards model to calculate multivariate-adjusted hazard ratios (HRs) for NHAs within a 6-month period following the 2018 Japan Floods, with adjustments for potential confounding factors., Results: Of the 187,861 individuals who used LTCI services during the investigated period, we identified 2156 (1.1%) as disaster affected. The HR for NHA was significantly higher for disaster-affected (vs unaffected) individuals (adjusted HR 3.23: 95% CI 2.88‒3.64), and also higher than the HRs for older age (90-94 years vs 65-69 years: 2.29, CI 1.93‒2.70), cognitive impairment (severe impairment vs normal: 1.40, CI 1.25‒1.57), and physical function (bedridden vs independent: 2.27, CI 1.83‒2.70). According to our subgroup analyses, the adjusted HR for disaster-affected individuals unable to feed themselves was 6.00 (CI 3.68‒9.79), with a significant interaction between the 2 variables (P = .01)., Conclusions and Implications: Natural disasters increase the risk of NHA for older persons, especially those who are unable to feed themselves. Health care providers and policymakers should understand and prepare for this emerging risk factor., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: During the coronavirus disease 2019 (COVID-19) pandemic, a change in the trend of infections was observed. However, there are few reports comprehensively assessing the impact of the early phase of COVID-19 on the trend of bacteria isolated., Methods: We extracted the number of positive cultures of hospitalized patients for approximately 200 institutions using the Japanese national database. The outcome was the ratio of 10 species isolated in comparison to the total isolates for each month. Interrupted time-series analyses were conducted between 13 (from Jan-2019 to Jan-2020) and 8 (from May-2020 to Dec-2020) monthly data points., Results: A total of 369,210 isolates were involved. Differences in the level change for Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes decreased significantly by 0.272 (95% confidence interval [CI]:0.192-0.352), 0.244 (95%CI:0.174-0.314), and 0.324 (95%CI:0.06-0.589), respectively. Bacteria transmitted by contact infection, such as Staphylococcus aureus, did not decrease. Differences in slope change were not significant in all species., Conclusions: The ratios of isolated bacteria transmitted by droplet infection decreased immediately after the early phase of COVID-19 and maintained the same level. The awareness and behavioral changes toward increased COVID-19 prevention might have a substantial impact on the prevention of bacterial infections, especially droplet infections., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Level of care-need (LOC) is an indicator of elderly person's disability level and is officially used to determine the care services provided in Japan's long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country's second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims., Methods: This is a retrospective cohort study, based on the Japanese long-term care insurance claims from two months before (May 2018) to five months after the disaster (December 2018) in Hiroshima, Okayama, and Ehime prefectures, which were the most severely damaged areas in the country. A code indicating victim status, certified by a residential municipality, was used to distinguish between victims and non-victims. Those aged 64 years or younger, those who had the most severe LOC before the disaster, and those whose LOC increased even before the disaster were excluded. The primary endpoint was the augmentation of pre-disaster LOC after the disaster, which was evaluated using the survival time analysis. Age, gender, and type of care service were used as covariates., Results: Of the total 193,723 participants, 1,407 (0.7%) were certified disaster victims. Five months after the disaster, 135 (9.6%) of victims and 14,817 (7.7%) of non-victims experienced the rise of LOC. The victim group was significantly more likely to experience an augmentation of LOC than the non-victim group (adjusted hazard ratio 1.24; 95% confidence interval 1.06-1.45)., Conclusions: Older people who were affected by the disaster needed more care than before and the degree of care-need increase was substantially more than non-victims. The result suggests that natural disasters generate more demand for care services among the older people, and incur more resources and cost for society than before.

Objectives: This study aims to examine the association between migraine and various psychiatric and somatic comorbidities in Japan., Design: Cross-sectional study using existing data of the 2017 Japan National Health and Wellness Survey (NHWS)., Setting: Nationally representative sample of persons (in terms of age and gender) living in the general community aged 18 years or older in Japan., Participants: Out of a sample of 30 001 NHWS respondents, 378 respondents were identified as migraine patients and 25 209 were identified as non-migraine patients. After propensity score (PS) matching (1:4), 1512 matched non-migraine respondents were identified., Primary and Secondary Outcome Measures: Prevalence and PS-matched prevalence ORs (PORs) were assessed for each psychiatric and somatic comorbidity among migraine patients and matched non-migraine respondents (including migraine patients with less than 15 monthly headache days (MHDs) and migraine patients with more than 15 MHDs)., Results: Migraine patients were predominately female and had significantly higher prevalence than matched non-migraine respondents to have psychiatric and somatic comorbidities. Psychiatric comorbidities with >5% prevalence among migraine patients included depression, post-traumatic stress disorder and anxiety disorders, while gastrointestinal disorders were the most prevalent somatic comorbidity category. Other somatic comorbidities included allergies, insomnia, premenstrual syndrome and anaemia. Migraine patients with more than 15 MHDs tended to have higher point estimates for POR., Conclusion: Psychiatric and somatic conditions were more prevalent in migraine patients than matched non-migraine respondents, some being novel associations not previously reported in Japan. This study provided insights on comorbidities, which could complicate care, clinical practice and outcomes among migraine patients., Competing Interests: Competing interests: SK and TT received consultation fee for this study. YC is an employee at Cerner Enviza, Singapore. Cerner Enviza received funding from Amgen K.K. for conduction of the analysis and manuscript development. MH and KI are employees at Amgen K.K., and KA is a former employee at Amgen K.K. and is currently an employee of IQVIA Solutions Japan, K.K. MH holds and KA held stocks of Amgen Inc., (© 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.)

Introduction: Vaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections., Methods: The subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination., Results: AS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360-896). AS-ab titer had then increased to 22471 U/mL (15761-32622) three weeks after booster vaccination. There were no significant differences among age groups. A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20-29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5-5.6) and those aged 20-49 years (aOR:9.7, 95%CI 1.3-71.2) were risk factors for SARS-CoV-2 infection., Conclusions: Booster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20-49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection., Competing Interests: Declaration of competing interest The authors whose names are listed in the manuscript have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method., Patients and Methods: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities., Results: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%., Conclusion: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)-located on the gene encoding for pleiotrophin on chromosome 7-that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To describe the real-world prescription and treatment retention of molecular-targeted drugs for rheumatoid arthritis (RA) in Japan., Methods: A total of 204,416 patients with RA were prescribed at least one of the eight molecular-targeted drugs in 7 years from the National Database of Health Insurance Claims and Specific Health Checkups of Japan covering 98.3% of the Japanese population. The retention rates of each drug as well as head-to-head comparisons were estimated by Kaplan-Meier method., Results: A total of 121,131 RA patients were prescribed any molecular-targeted drug for the first time, while 36,633 uses of molecular-targeted drug were switched from another (switch use). The overall retention rates of molecular-targeted drugs at 12, 36, and 60 months were 0.64, 0.42, and 0.32 for the naïve use and 0.59, 0.40, and 0.31 for the switch use, respectively. Non-tumour necrosis factor (TNF)-inhibitor molecular-targeted drugs, particularly tocilizumab and tofacitinib, had higher retention rates than TNF inhibitors for both naïve and switch uses regardless of the previous drug and showed higher retention rates in head-to-head comparisons between eight molecular-targeted drugs., Conclusions: Our data reveal that the real-world drug retention is overall lower than previously reported and higher with non-TNF inhibitors than with TNF inhibitors., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

Background: Apalutamide-associated skin adverse events are more common in the Japanese than in the global population. However, limited clinical data have hampered further understanding. This real-world study investigated the clinical characteristics of skin adverse events in patients with advanced prostate cancer., Methods: We retrospectively reviewed 119 patient records from 16 institutions in Japan. Skin adverse events were graded according to the Common Terminology Criteria for Adverse Events (v5.0). The incidence and characteristics of skin adverse events (along with the clinical risk factors for their incidence, worsening, and recurrence) were evaluated., Results: Fifty-five patients (46.2%) experienced skin adverse events. The median times to the incidence and remission of skin adverse events were 62 and 30 days, respectively. Grade 3 skin adverse events were observed in 15 patients (12.6%). The median time from the first incidence to apalutamide interruption was significantly longer in patients with progression to grade 3 skin adverse events than in those without such a progression (8 vs. 0 days, p = 0.005). Skin adverse events were observed in 45.2% of patients who resumed apalutamide treatment (median treatment interruption time: 31.5 days). Sixteen patients (13.4%) permanently discontinued apalutamide due to skin adverse events. No significant clinical risk factors for the incidence, worsening and recurrence of apalutamide-associated skin adverse events were observed., Conclusions: Nearly half of the Japanese patients in this study experienced skin adverse events following apalutamide administration. The time to apalutamide discontinuation after the incidence of skin adverse events was positively correlated with the worsening of these events., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Chronic wasting disease (CWD) is a prion disease affecting cervid species primarily in the United States of America and Canada; however, it is now emerging in Scandinavian countries. Although CWD cases have not been reported in Japan, in case of a CWD outbreak occuring, it is critical to prepare for testing a large number of specimens. The present study showed that a rapid post-mortem test kit, which is used for bovine spongiform encephalopathy surveillance in Japan, is valid for the detection of CWD prion., (© 2022 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: To assess the current status of shared decision making (SDM) in rheumatoid arthritis (RA) clinical practice in Japan from the perspectives of physicians and patients., Methods: A web-based survey was conducted to recruit patients with RA who were prescribed, for the first time, a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or a biological drug/Janus kinase (JAK) inhibitor, and physicians who prescribed these treatments to patients with RA. The SDM Questionnaire-Physician version (SDM-Q-Doc) and the 9-item SDM Questionnaire (SDM-Q-9) were used to assess the SDM levels of physicians and patients, respectively. The scale ranged from 0 to 100, and higher scores indicated better SDM status., Results: The responses from 107 physicians who treat patients with RA, 107 patients prescribed a csDMARD, and 110 patients prescribed a biological drug/JAK inhibitor were collected. The mean SDM score for SDM-Q-Doc was 74.5 when physicians decided to prescribe a csDMARD and 77.2 when they decided to prescribe a biological drug/JAK inhibitor. However, the mean SDM score for SDM-Q-9 was 62.3 when patients were prescribed csDMARDs and 72.6 when they were prescribed biological drugs/JAK inhibitors., Conclusions: The results showed differences in SDM level between patients and physicians and, from the patient perspective, between treatment types.

Objectives: We aimed to investigate the impact of the first and second waves of the COVID-19 pandemic on healthcare service use by non-COVID-19 patients., Design: Retrospective cohort study., Setting: Hospital-based claims database from anonymised hospitals in Japan., Participants: Patients (n=785 495) who visited and/or were hospitalised in 26 anonymised hospitals in Japan between January 2017 and November 2020., Outcome Measures: We compared changes in the monthly number of hospitalisations (overall or by diagnosis), outpatient visits, endoscopic fibrescopies (EFs), rehabilitations, outpatient chemotherapy treatments, maintenance haemodialysis treatments and outpatient prescriptions between pre-COVID-19 years and the same period in 2020., Results: The overall number of hospitalisations and outpatient visits decreased by 27% and 22%, respectively, in May 2020, of which the most substantial decrease was observed in the paediatrics department (65% and 51%, respectively). The number of hospitalisations for respiratory diseases, circulatory diseases, malignant neoplasms and digestive diseases decreased by a maximum of 55%, 32%, 10% and 26%, respectively, in 2020. The number of hospitalisations for non-COVID-19 pneumonia in patients aged <16 years, patients aged ≥16 years and patients with asthma decreased by 93%, 43% and 80%, respectively, in May 2020. EFs and outpatient rehabilitations decreased by >30%. In contrast, outpatient chemotherapy and maintenance haemodialysis treatments decreased by <10%, if at all. Outpatient prescriptions decreased by a maximum of 20% in 2020, with the largest decrease observed in drugs for obstructive airway diseases and cough and cold preparations., Conclusions: The use of healthcare services by non-COVID-19 patients was most affected during the first wave of the COVID-19 pandemic in May 2020. The number of hospitalisations for respiratory diseases, particularly non-COVID-19 pneumonia and asthma, drastically decreased, while the number of hospitalisations and outpatient chemotherapies for malignant neoplasms or maintenance haemodialysis was less affected., Competing Interests: Competing interests: SY, AO, KIK and TK are members of the Department of Prevention of Diabetes and Lifestyle-related Diseases, which is a cooperative programme between The University of Tokyo and Asahi Mutual Life Insurance Company. KIK was previously employed by Asahi Mutual Life Insurance Company., (© 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: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders., Methods: A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public., Results: The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP's scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data., Conclusion: The recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation., (© 2021. The Author(s).)

Objective: The aim of this study was to determine the prognosis, clinical course, and current management of severe interstitial lung disease (ILD) associated with myositis in Japan., Methods: We conducted a retrospective descriptive study using a nationwide database for inpatient care of acute illness in Japan. Among a total of ~66 million inpatient admissions, we identified patients with severe ILD associated with polymyositis (PM) or dermatomyositis (DM) who required mechanical ventilation and methylprednisolone pulse therapy (≥1 gm/day of methylprednisolone) from July 2010 to March 2018., Results: We identified 155 patients with PM and 394 with DM who fulfilled the above criteria. The median age of patients was 65 years; DM patients were significantly younger than PM patients (64 versus 68 years; P < 0.001). The numbers of patients who were treated with calcineurin inhibitors, intravenous cyclophosphamide, and polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) were 403 (73.4%), 318 (57.9%), and 78 (14.2%), respectively. All these treatments were given significantly more frequently to the patients with DM compared with those with PM. The uses of other treatment options were much less frequent. The median periods after hospitalization when methylprednisolone pulse therapy, calcineurin inhibitors, mechanical ventilation, intravenous cyclophosphamide, and PMX-DHP were initiated and in-hospital death occurred among patients with DM were 2, 4, 7, 8, 17, and 36 days, respectively. In-hospital mortality was significantly higher in patients with DM than in those with PM (76.6% versus 56.8%; P < 0.001)., Conclusion: The mortality of patients with myositis-associated severe ILD who require mechanical ventilation is extremely high despite aggressive and prompt interventions., (© 2021 American College of Rheumatology.)

Background: The International Transanal Total Mesorectal Excision Registry group showed that transanal total mesorectal excision included clinical issues regarding anastomosis-related complications., Objective: This study evaluated anastomotic complications in patients whose anastomoses were created with the stapler plus reinforced sutures procedure after transanal total mesorectal excision for low rectal cancer., Design: This was a retrospective single-center study., Setting: The study was conducted at the National Cancer Center Hospital East, Japan., Patients: Between June 2016 and December 2019, 150 patients underwent transanal total mesorectal excision for low rectal cancer. Stapled anastomosis was performed for 55 patients, and coloanal handsewn anastomosis was performed for 95 patients. Blood perfusion of the colon was routinely evaluated with intraoperative indocyanine green fluorescence angiography. All patients who underwent stapled anastomosis received additional handsewn sutures on all rounds of the stapled line. Patients who underwent intersphincteric resection were excluded., Main Outcome Measures: The anastomosis-related complications were compared between the groups., Results: Early anastomotic leakage was found in one (1.8%) and eight (8.4%) patients in the stapled group and handsewn group. Overall anastomosis-related complications, pelvic abscess, and anastomotic stenosis were significantly less frequent in the stapled group (p < 0.001, p < 0.048, and p < 0.032). Incomplete donuts after the stapled anastomosis were observed in 9 patients (16.4%); however, we reinforced all around the stapled line in these patients, and this reduced the subsequent occurrence of anastomotic leakage., Limitations: First, this was a retrospective single-center study that was not randomized or controlled. Second, there were chronological differences regarding the anastomotic method between the two groups. Third, our study included a relatively small number of patients who received preoperative chemoradiotherapy., Conclusions: Stapled anastomosis with reinforced handsewn sutures resulted in fewer anastomosis-related complications than did coloanal handsewn anastomosis after transanal total mesorectal excision for low rectal cancer; thus, the former may be superior and should be the preferred method, when technically possible. See Video Abstract at http://links.lww.com/DCR/B749.COMPLICACIONES RELACIONADAS CON LAS ANASTOMOSIS ENGRAMPADAS Y REFORZADAS CON SUTURAS EN LA EXCISIÓN TOTAL DEL MESORRECTO POR VÍA TRANSANAL EN CASOS DE CÁNCER DE RECTO BAJO: ESTUDIO RETROSPECTIVO UNICÉNTRICO., Antecedentes: El grupo del Registro Internacional de Excisión Total del Mesorrecto por vía Transanal mostró que la excisión total mesorrectal transanal incluía problemas clínicos relacionados a las complicaciones involucradas con la anastomosis., Objetivo: Se evaluaron las complicaciones anastomóticas en pacientes cuyas anastomosis se realizaron con engrampadora reforzada de suturas después de la excisión total de l mesorrecto por vía transanal en casos de cáncer de recto bajo., Diseo: Estudio retrospectivo unicéntrico., Ajuste: El Hospital del Centro Nacional del Cáncer del Este, Japón., Pacientes: Entre junio de 2016 y diciembre de 2019, 150 pacientes se sometieron a excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo. Se realizó anastomosis con engrampadora en 55 y anastomosis coloanal suturada a mano en 95 pacientes. La perfusión tisular sanguínea del colon operado se evaluó de forma rutinaria con angiografía de fluorescencia con verde de indocianina intraoperatoria. Todos los pacientes que se sometieron a anastomosis con grapas recibieron suturas realizadas a mano adicionales sobre la totalidad de la línea de grapas. Se excluyeron los pacientes sometidos a resección interesfintérica., Principales Medidas De Resultado: Las complicaciones relacionadas con la anastomosis se compararon entre los grupos., Resultados: Se encontró fuga anastomótica temprana en 1 (1.8%) y 8 (8.4%) pacientes en el grupo de engrampado y en el grupo suturado a mano, respectivamente. En general, las complicaciones relacionadas con la anastomosis, el absceso pélvico y la estenosis anastomótica fueron significativamente menos frecuentes en el grupo con grapas (p < 0.001, p < 0.048, p < 0.032, respectivamente). Se observaron donas incompletas después de la anastomosis grapada en 9 pacientes (16,4%); sin embargo, reforzamos todo alrededor de la línea de grapas en estos pacientes, y esto redujo la aparición posterior de fugas anastomóticas., Limitaciones: Inicialmente, este fue un estudio retrospectivo de un solo centro que no fue aleatorizado ni controlado. En segundo lugar, hubo diferencias cronológicas con respecto al método anastomótico entre los dos grupos. En tercer lugar, nuestro estudio incluyó un número relativamente pequeño de pacientes que recibieron quimiorradioterapia preoperatoria., Conclusiones: La anastomosis engrapada reforzada con suturas realizadas a mano dio como resultado menos complicaciones relacionadas con la anastomosis que la anastomosis coloanal suturada a mano después de la excisión total del mesorrecto por vía transanal en casos de cáncer de recto bajo; por tanto, el primero puede ser superior y debería ser el método preferido, cuando sea técnicamente posible. Consulte Video Resumen en http://links.lww.com/DCR/B749. (Traducción-Dr. Xavier Delgadillo)., (Copyright © The ASCRS 2021.)

We characterised the bioavailability, safety, and tolerability of brivaracetam 100 mg intravenous bolus and 15-min infusion versus oral reference tablet in 24 healthy Japanese participants.In this randomised, open-label, three-period crossover study, participants received three 100 mg single doses of brivaracetam, intravenous bolus, infusion, and oral tablets. Maximum plasma concentration (C max ), area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUC t ), and area under the plasma concentration-time curve extrapolated to infinity (AUC inf ), were compared using analysis of variance following logarithmic transformation. Bioavailability comparisons were based on the 90% confidence intervals (CIs) around the geometric least squares means ratios (intravenous:oral). Safety and tolerability were monitored throughout the study.The 90% CIs around AUC t and AUC inf ratios were entirely contained within the bioequivalence limits (0.80-1.25), but C max was outside the limits (90% CI: 1.77-2.08 and 1.44-1.70 for intravenous bolus and infusion, respectively). All participants completed the study. Brivaracetam was well tolerated.Because response to brivaracetam in epilepsy is related to exposure (AUC), no dose adjustment is warranted when switching from oral to intravenous dosing. However, investigations are needed to assess the safety and tolerability of intravenous administration in Japanese patients with epilepsy.

Objective: A single-nucleotide polymorphism 538G>A in the human ABCC11 gene is a determinant of the earwax morphotype. ABCC11 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the ABCC11 genotypes and acquired middle ear cholesteatoma., Study Design: Case-control study., Setting: Single-center academic hospital., Methods: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the ABCC11 genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used., Results: The proportion of participants with ABCC11 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population ( P < .001). The ABCC11 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population ( P < .001). Multivariate logistic regression analyses revealed a significant association between the ABCC11 genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; P < .001)., Conclusion: Our results suggest that the ABCC11 genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.

Background: The treatment guidelines for acute Kawasaki disease (KD) have been revised several times. Moreover, the criterion used to define coronary artery abnormalities (CAAs) has changed from the coronary artery's internal diameter to the Z-score. Treatment for KD and methods for evaluating CAAs vary between hospitals, so we investigated the actual status of acute KD treatment and development of CAAs under the 2012 Japanese treatment guidelines for acute KD., Methods: The 24th Japanese Nationwide Survey on Kawasaki Disease yielded 2618 patients who developed KD in the Kinki area in 2016. We sent a secondary questionnaire to each participating hospital and used the resulting data to investigate the frequency of CAAs according to Z-score, treatment by KD treatment stage, and predictors of CAAs., Results: The response rate was 80.0%. The data for 1426 patients without major data deficiencies were examined. The frequency of CAAs was 3.0% when based on coronary artery internal diameters and 8.8% when based on Z-scores. Intravenous immunoglobulins combined with corticosteroids were administered as an initial treatment in 12.8% of cases and as a second-line treatment in 16.8% of cases. Corticosteroids, cyclosporine A, infliximab, and plasma exchange were used at similar frequencies for third-line treatment. A pretreatment maximum coronary artery Z-score of ≥1.9 and age <1 year were associated with significantly higher incidences of CAAs., Conclusions: Using the Z-score resulted in a threefold increase in the number of patients diagnosed with CAAs. A pretreatment maximum coronary artery Z-score of ≥1.9 and age <1 year are useful predictors of CAAs., (© 2022 Japan Pediatric Society.)

Introduction: It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD)., Methods: This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years., Results: The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios <0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios <0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates., Conclusions: Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Objectives: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response., Methods: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses., Results: Two thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 - 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 - 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers., Conclusions: Our data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The effect of treatment with paclitaxel-containing devices (PTXD) on mortality in patients with peripheral artery disease remains controversial., Methods and results: An independent patient-level meta-analysis of 12 clinical trials (1,389 PTXD patients and 1,192 non-PTXD patients) was conducted. This study included 7 pivotal trials and 5 post-marketing surveillance studies on endovascular treatment for femoropopliteal artery by 6 companies. The primary endpoint was all-cause death, and 5-year cumulative mortality was estimated by a Kaplan-Meier curve. Cox proportional hazard model was used to calculate the hazard ratio (HR) and confidential interval (CI). During the median follow up of 3.0 years, 459 patients died. The cumulative 5-year mortality for the entire cohort was significantly lower in the PTXD than in the non-PTXD group (24.4% vs. 27.4%, respectively; HR, 0.81; 95% CI, 0.67-0.97; P=0.023), but this difference was no longer significant after adjustment for relevant covariates (HR, 1.01; 95% CI, 0.39-2.58; P=0.987). The Cox proportional hazard model revealed that sex, hyperlipidemia, Type 2 diabetes, hemodialysis, Rutherford category, and age above 75 years were significantly associated with 5-year mortality, but treatment with PTXD was not., Conclusions: This large individual meta-analysis of patients with femoropopliteal artery disease found that the use of PTXD does not have a negative effect on 5-year mortality.

Background: Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined., Methods: We retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors., Results: A score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%., Conclusions: Our results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients., (© 2021. The Author(s).)

Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99-18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA., (© 2021. The Author(s).)

Background: Patients' perceptions and beliefs of disease could be influenced by their lifestyle and culture. Although it is important to understand their perceptions and beliefs toward disease to prevent and manage osteoarthritis (OA) through conservative care, this topic has not been investigated in Japanese people with knee OA. Therefore, this qualitative study aims to clarify how Japanese patients with knee OA experience and perceive their symptoms and disabilities, and how they face them during conservative care., Methods: Participants were recruited by purposive sampling. Face-to-face, semi-structured interviews were conducted with nine patients (2 men and 7 women; mean age, 74.3 ± 5.5 years) with knee OA until data saturation was reached. Interview data comprised participants' accounts of particular personal experiences of living with knee OA, including their perceptions and attitudes toward knee OA-related symptoms and disabilities. Two physiotherapists (one with extensive experience conducting qualitative studies) and four physiotherapy students conducted the interviews. Recorded interview data were transcribed verbatim in Japanese. Data analysis, including developing a coding scheme, was conducted based on a grounded theory approach., Results: Two core categories were extracted from the data: 'Negative experiences' and 'Coping with difficulties'. 'Negative experiences' included three main categories: 'Self-analysis on the cause of knee OA', 'Difficulties in daily life due to knee symptoms', and 'Psychological barrier'. 'Coping with difficulties' included three main categories: 'How to deal with knee pain and difficulty in moving', 'Information considered useful to cope with knee OA' and 'Importance of connecting with others'. Japanese patients with knee OA desired evidence-based information and to connect with other people in the same situation to solve problems related to their condition., Conclusions: To address patients' concerns, medical professionals should conduct careful interviews and obtain information regarding patients' past experiences, and understand their experiences related to knee OA. Symptoms and difficulties experienced by patients with knee OA should be managed by evidence-based information integrating their perceptions and beliefs toward knee OA., (© 2021. The Author(s).)

Objectives: This study examined the association between intensive rehabilitation for subacute stroke patients and medical costs and readmission ratio during the year after discharge., Design: This was a natural experiment study., Setting and Participants: We identified individuals with a diagnosis of cerebrovascular disorder (ICD-10: I60-I69 cerebrovascular disease) in an insurance claims database in Japan from January 2005 to December 2017. From the database, 980 patients who were admitted to a convalescent rehabilitation unit with stroke were identified. After excluding 575 patients, 405 were eligible for the study., Methods: In Japan, from April 2011, a new policy was established that allows special costs to be added as rehabilitation time increases. This policy provides an additional medical fee for inpatients in a convalescent rehabilitation unit who receive more than 120 minutes of rehabilitation therapy. We defined high-intensity rehabilitation as transfer from hospitalization to a convalescent rehabilitation unit after April 2011. Outcomes were total direct medical costs and readmission ratio during the year after discharge from the convalescent rehabilitation unit., Results: Daily rehabilitation time, total rehabilitation time, and total medical costs of the high-intensity rehabilitation group were significantly higher than those of the low-intensity rehabilitation group (P < .001, P < .001, P = .011, respectively). However, there was no significant difference in the medical costs during the year after discharge (P = .653) or in the readmission ratio (hazard ratio: 1.09, 95% confidence interval: 0.55-2.18, P = .804)., Conclusions and Implications: Intensive rehabilitation did not reduce medical costs or the readmission ratio during the first year after discharge. Future studies should consider the necessary rehabilitation intensity given the severity of the patient's condition, using large sample sizes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Transfusion-associated circulatory overload (TACO) is an adverse reaction associated with a high risk of mortality. The actual incidence of TACO and hypertension associated with transfusion in Japan is unknown., Methods: A multicentre retrospective observational study was conducted across 23 institutions during the 1-year period of 2016. Patients were included if they developed TACO or their blood pressure (either systolic or diastolic) increased by at least 30 mmHg during the transfusion. TACO was confirmed by the primary physicians and transfusion medicine teams and recorded in the data on passive surveillance, and additional data were extracted from electronic medical records., Results: In our patient cohort of 31 384 patients who underwent transfusion, the incidence of TACO and hypertension was 0·03% and 0·2%, respectively. However, 43% of the participating institutions didn't report any cases. When comparing risk factors between the TACO and hypertension groups, there were significant differences in comorbidities, such as abnormal findings on chest x-ray. Significant differences between the two groups were observed post-transfusion pulse rate, body temperature and oxygen saturation (P < 0·01). In the group of patients with hypertension, the level of BNP increased significantly after transfusion in 45% (5/11) of the patients. We identified 4 patients in the hypertension group who met the new ISBT's TACO criteria., Conclusion: Our study suggests that more attention should be given to TACO in Japan, particularly in terms of improving surveillance systems. For the early diagnosis of TACO, it is crucial to carefully monitor vital signs including blood pressure., (© 2020 International Society of Blood Transfusion.)

Background: Long-term care (LTC) prevention is a pressing concern in ageing societies. To understand the risk factors of LTC, it is vital to consider psychological and social factors in addition to physical factors. Owing to a lack of relevant data, we aimed to investigate the social, physical and psychological factors associated with LTC using large-scale, nationally representative data to identify a high-risk population for LTC in terms of multidimensional frailty., Methods: We performed a cross-sectional study using anonymised data from the 2013 Comprehensive Survey of Living Conditions conducted by the Ministry of Health, Labour and Welfare of Japan. Among the 23,730 eligible people aged 65 years or older and those who were not in hospitals or care facilities during the survey, 1718 stated that they had LTC certification. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with LTC certification., Results: Factors positively associated with LTC certification in the multivariate analyses included older age, the interaction term between sex and age group at age 85-89 years, limb movement difficulties, swollen/heavy feet, incontinence, severe psychological distress (indicated by a Kessler Psychological Distress Scale [K6] score ≥ 13), regular hospital visits for dementia, stroke, Parkinson's disease, chronic obstructive pulmonary disease, fracture, rheumatoid arthritis, kidney disease, diabetes and osteoporosis. Factors negatively associated with LTC certification included the presence of a spouse, regular hospital visits for hypertension and consulting with friends or acquaintances about worries and stress., Conclusions: In summary, we identified the physical, psychological and social factors associated with LTC certification using nationally representative data. Our findings highlight the importance of the establishment of multidimensional approaches for LTC prevention in older adults.

Addiction has become a major worldwide medical, public health, and social problem. Because the prevalence of addiction varies widely geographically, due to differences in ethnicity, culture, education, social environment, and regulation, each country or region needs to understand its current state of addiction and to take appropriate measures, in multidisciplinary collaboration. In order to understand the direction of addiction research in Japan, we analyzed 50 research and development topics and their characteristics, based on an expert questionnaire survey. The topics were placed in five categories, as follows. Category 1: Basic science; all 10 topics were of the Long-term project and International cooperation types. Category 2: Translational and clinical research; 6 out of 10 topics were of the Long-term project. Category 3: Fact-finding surveys; 8 out of 10 topics were of the Japan-specific type. Category 4: Health system and service; 8 out of 10 topics were of the Japan-specific type and Short-term project. Category 5: Study on society, culture, environment, education, and regulation; 7 out of 10 topics were of the Short-term project (similar to Category 4). As far as we know, this is the first systematic questionnaire survey on the direction of addiction research. The results of this study might support developing a strategy for addiction research, not only in Japan, but also in other countries., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background: Hepatitis C virus is the leading cause of liver cirrhosis and hepatocellular carcinoma in Japan. We aimed to examine the long-term (> 20 years) mortality and hepatocellular carcinoma rates and associated risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis (Child-Pugh B or C)., Methods: Cumulative survival and hepatocellular carcinoma rates were determined using Kaplan-Meier analysis. Independent risk factors were identified by multivariate analysis. A two-tailed P-value of < 0.05 was considered significant., Results: The patients were followed up for a median of 2 years (range 0.5-24.2 years). In total, 62.3%, 41.7%, 4.7%, and 68.3% of the patients had a history of hepatocellular carcinoma, ascites, hepatic encephalopathy, and esophageal varices, respectively. The 1-, 5-, 10-, and 20-year cumulative overall survival rates in the total cohort was 74.9%, 29.0%, 9.1%, and 1.4%, respectively. The 1-, 3-, 5-, and 10-year cumulative survival rates for patients without hepatocellular carcinoma were 93.1%, 54.4%, 18.2%, and 4.0%, respectively, and the corresponding cumulative post-decompensation hepatocellular carcinoma rates were 14.0%, 31.6%, 46.1%, and 66.2%, respectively. The independent risk factors for mortality were older age, Child-Pugh C cirrhosis, the presence of hepatocellular carcinoma, low estimated glomerular filtration rate, low serum sodium level, low platelet count, and high γ-glutamyl transferase and α-fetoprotein levels for all patients and older age, Child-Pugh C cirrhosis, and low estimated glomerular filtration rate for patients without hepatocellular carcinoma. Overall, 1035 patients (73.3%) died; the causes of death were liver failure with/without hepatocellular carcinoma, pneumonia, sepsis, cardiovascular disease, and non-hepatocellular carcinoma malignancies. The corresponding morality rates per person-year were 133.4, 59.9, 10.9, 10.6, 9.0, and 5.2, respectively., Conclusions: Among Japanese patients with decompensated hepatitis C virus-related cirrhosis, hepatocellular carcinoma is associated with poor prognosis. Our results highlight the importance of managing liver-related events, including hepatocellular carcinoma, in these patients.

Handwriting is thought to impede vocabulary learning in sighted adults because the motor execution of writing interferes with efficient audiovisual processing during encoding. However, the motor memory of writing may facilitate adult word learning when visual sensory inputs are severely restricted. Using functional MRI, we show that late-blind participants, but not sighted participants, learned novel words by recruiting the left dorsal premotor cortex known as Exner's writing area and its functional coupling with the left hippocampus. During later recall, the phonological and semantic contents of these words are represented in the activation patterns of the left hippocampus as well as in those of left frontotemporal language areas. These findings suggest that motor codes of handwriting help blind participants maintain word-form representations during learning and retrieval. We propose that such reliance on the motor system reflects a broad architecture of the cerebral language network which encompasses the limb motor system as a hardwired component.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7-14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS., Competing Interests: The authors have declared that no competing interests exist.