Search

BACKGROUND Clazosentan is an endothelin receptor antagonist approved in Japan for preventing cerebral vasospasm and vasospasm-associated cerebral ischemia and infarction. This study included elderly patients aged ≥75 years with aneurysmal subarachnoid hemorrhage (SAH) and aimed to evaluate the factors associated with discontinuing anti-vasospasm therapy with clazosentan. MATERIAL AND METHODS In this single-center retrospective observational study, we extracted diagnostic and therapeutic work-up data of consecutive 40 patients with SAH treated with clazosentan infusion (10 mg/h) as first-line anti-vasospasm therapy between May 2022 and August 2023. Patient data were compared between the discontinued and completed groups, and related factors for the discontinuation were further analyzed. RESULTS Clazosentan was discontinued in 22% (n=9) of patients due to intolerable dyspnea accompanied by hypoxemia at 5±3 days after therapy initiation, in which 44% (n=4) were elderly (≥75 years). Patients who discontinued clazosentan therapy showed significantly lower urine volumes compared with those who completed the therapy (P<0.05). Multivariate regression analysis revealed that day-to-day urine volume variance and older age were independent risk factors for drug cessation (P<0.05). The cut-off value for predicting clazosentan discontinuation was -0.7 mL/kg/h with sensitivity of 86% and specificity of 75% (area under the curve: 0.76±0.10; 95% confidence interval: 0.56-0.96; P=0.035). CONCLUSIONS Our results suggest that approximately 20% of SAH patients suffered from intolerable respiratory symptoms attributable to hypoxemia. We found that both reduced day-to-day urine volume variation and older age are independent risk factors for drug discontinuation.

Objectives: The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis., Methods: PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach., Results: For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively., Conclusions: This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: To investigate 6-year drug survival (median: 48.5 months) of golimumab and predictors for lack of efficacy leading to golimumab discontinuation in Japanese patients with rheumatoid arthritis (RA) in routine practice., Methods: This retrospective single-center study included 60 patients with RA treated with golimumab from November 2011 to August 2020. Patients were divided into 2 groups (retention, n = 28; withdrawal due to lack of efficacy, n = 24). The retention rate was assessed using the Kaplan-Meier method, and variables associated with golimumab discontinuation were identified using the Cox proportional hazard model., Results: The prevalence of concomitant methotrexate and no biologics use was significantly higher in the retention than in the withdrawal group. Overall drug survival of golimumab was 66.3%, 48.3%, and 24.5% at 12, 36, and 72 months, respectively. There were statistical differences in retention rates among groups stratified by initiation dose, methotrexate, and biologics use. Multivariate analysis revealed the factor associated with golimumab discontinuation as history of 1 (hazards ratio: 4.42, 95% CI: 1.35-19.93, P = .012) and ≥2 biologics use (7.49, 1.97-36.27, P = .003)., Conclusions: Prior exposure of increasing number of biologics was identified as the most important factor negatively affecting long-term golimumab retention in Japanese patients with RA., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Japanese industries have struggled with stagnation after the collapse of bubble economy in the 1990s. Such a financial crisis has led to overseas business expansion of Japanese industries. This study empirically examines Japanese general contractors' overseas operations over the post-bubble period in relation to their financial status. The result shows that general contractors facing financial distress expand overseas business aggressively, when the domestic market shrinks. This result is opposite to conventional wisdom that stronger entities expand their territories of operations, thus "overseas business paradox." However, it can be considered a new scenario of industries' evolution when a country's economy matures., Competing Interests: We do not have any conflict of interests concerning this research. While the first author, Taichi Mutoh, belongs to a private company of Taisei corporation, it does not alter our adherence to all PLoS ONE policies on sharing data and materials.

Background and Objectives: When children accidentally ingest foreign bodies, they may be unable to communicate adequately; it is often difficult to identify the causative foreign body unless someone is watching over them. In such instances, to identify the causative foreign body during clinical practice, we aimed to determine if it varies according to age. Materials and Methods: From April 2013 to June 2018, 252 records of pediatric patients with a confirmed diagnosis of foreign-body ingestion were retrospectively examined in a Japanese university hospital. Comparisons among multiple age groups, according to type of ingested foreign body, were analyzed using Kruskal‒Wallis tests. The differences between the individual data were tested using the Steel‒Dwass test. Results: The median age of the patients was 15 months, and of the total patients, 140 were boys (55.5%). The types of foreign bodies ingested were as follows, in order of frequency: cigarettes ( n = 44, 17%, median age: 12 months), plastics ( n = 43, 17%, median age: 11 months), chemicals ( n = 27, 11%, median age: 13 months), internal medicines ( n = 26, 10%, median age: 33 months), and metals ( n = 26, 10%, median age: 35 months). The median age was significantly different among the types of causative foreign bodies ( p < 0.01). The patient age for the ingestion of cigarettes was significantly younger than that for ingesting metals or coins. The age for ingesting internal medicines was significantly older than that for ingesting plastics, cigarettes, paper, or chemicals ( p < 0.01). Conclusions: The causative foreign body ingested differed according to age. This will be valuable information for physicians that encounter pediatric patients who may have ingested an unknown foreign body in Japanese pediatric emergency or general practice settings.

Guillain-Barré syndrome (GBS) is an acute monophasic neuropathy. Prognostic tools include the modified Erasmus GBS outcome score (mEGOS), Erasmus GBS respiratory insufficiency score (EGRIS), and the increase in serum IgG levels (ΔIgG) 2 weeks after intravenous immunoglobulin (IVIg) treatment. Given that proportions of GBS subtypes differ between Western countries and Japan, the usefulness of these tools in Japan or other countries remains unknown. We enrolled 177 Japanese patients with GBS from 15 university hospitals and retrospectively obtained mEGOS and EGRIS for all and ΔIgG status for 79 of them. High mEGOS scores on admission or on day 7 were significantly associated with poorer outcomes (unable to walk independently at 6 months). High EGRIS scores (≥5 points) were associated with an increased risk for mechanical ventilation. Patients with ΔIgG <1,108 mg/dl had significantly poorer outcomes. We suggest that mEGOS, EGRIS, and ΔIgG in GBS are clinically relevant in Japan., (© 2017 Peripheral Nerve Society.)

Introduction: Takotsubo cardiomyopathy (TCM) is a life-threatening systemic consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics and related outcome have not been studied. The purpose of this study was to investigate the TCM-induced cardiac function by transpulmonary thermodilution and its impact on clinical outcome of SAH., Methods: We retrospectively analyzed 46 consecutive postoperative SAH patients who developed TCM. Patients were divided into two groups of echocardiographic left ventricular ejection fraction (LVEF) < 40% (TCM with left ventricular (LV) dysfunction) and LVEF ≥40% (TCM without LV dysfunction). Cardiac function index (CFI) and extravascular lung water index (ELWI) were monitored by transpulmonary thermodilution, in parallel with serial measurements of echocardiographic parameters and blood biochemical markers., Results: Transpulmonary thermodilution-derived cardiac function index (CFI) was significantly correlated with (LVEF) (r = 0.82, P < 0.0001). The CFI between day 0 to day 7 was significantly lower in patients with LV dysfunction (LVEF <40%) than in patients with LVEF ≥40% (P < 0.05). CFI had a better ability than cardiac output to detect cardiac dysfunction (LVEF < 40%) (area under the curve: 0.85 ± 0.02; P < 0.001). A CFI value of < 4.2 min-1 had a sensitivity of 82% and specificity of 84% for detecting LVEF <40%. The CFI < 4.2 min-1 was associated with delayed cerebral ischemia (DCI) (odds ratio (OR), 2.14; 95% confidence interval (CI), 1.33-2.86; P = 0.004) and poor 3-month functional outcome on modified Rankin Scale of 4-6 (OR, 1.87; 95% CI, 1.06-3.29; P = 0.02). An extravascular lung water index (ELWI) > 14 mL/kg after day 4 increased the risk of poor functional outcome at 3-month follow-up (OR, 2.10; 95% CI, 1.11-3.97; P = 0.04)., Conclusions: Prolonged cardiac dysfunction and pulmonary edema increased the risk of DCI and poor 3-month functional outcome in patients with SAH suffering from TCM. Serial measurements of CFI and ELWI by transpulmonary thermodilution may provide an easy bedside method of detecting early changes of the cardiopulmonary function in directing proper post-SAH treatment.

Autosomal dominant spinocerebellar ataxias (AD-SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, a single nucleotide substitution in the 5'-untranslated region of the puratrophin-1 gene was found to be associated with one type of AD-SCA linked to chromosome 16q (16q-SCA). To obtain further insight into the contribution of the C-to-T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16q-SCA, we analyzed 686 families with 719 individuals diagnosed with progressive ataxia. We found C-to-T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals. The mean age at onset in the patients with 16q-SCA was 59.1 (range, 46-77). Ataxia is the most common initial symptom. The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes, involuntary movements, and reduced vibration sense. We also examined the frequency of the AD-SCA subtype, considering the effects of age at onset. In the 686 AD-SCA families, SCA6 and Machado-Joseph disease/SCA3 are frequent subtypes, followed by dentatorubral-pallidoluysian atrophy and 16q-SCA. 16q-SCA is not a rare subtype of Japanese AD-SCA, particularly in patients with ages at onset over 60.

Breast conserving operations have become the standard operation for early breast cancer. They were performed in about 40% of all breast cancer patients in Japan in 2000, and the percentage is still increasing. Ductal carcinoma in situ (DCIS) accounts for about 7% of all breast cancers and breast conserving operations for DCIS have been followed by a low in-breast recurrence rate, leading to wider indications for breast conserving operations as screening mammography has come to be used in Japan. In-breast recurrence is correlated to surgical margin status. It is important to evaluate the surgical margin for volume of cancer cell nests as well as for positivity. Neoadjuvant chemotherapy has become popular as an in vivo sensitivity test and as a means of down-staging to increase the possibility of performing a breast conserving operation. There are two patterns of shrinkage when neoadjuvant chemotherapy is effective: cocentric and honeycomb, and the pattern of residual cancer cell nests must be determined before surgery. MRI is an effective method of evaluating residual cancer cell nests. The in-breast recurrence rate after down-staging to perform breast conserving operations is reported to be higher than among candidates for breast conserving operation at the start. Sentinel node biopsy techniques and endoscopic operations are now being assessed in conjunction with breast conserving operations. The current status of breast conserving operations in Japan is reviewed in comparison with their status in Western countries.

Purpose: We evaluated the safety of indocyanine green for use in fundus angiography., Methods: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera., Results: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock., Conclusions: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.

Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns.