Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: A randomized, double-blind, placebo-controlled study (ADMIRE study)

AbstractObjectiveThis randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3mg/day) and flexible dose (3–15mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT).MethodDuring an 8-week prospective treatment phase, patients experiencing a major depressive episode received clinicians' choice of ADT. Subjects with inadequate response to ADT were randomized to receive adjunctive treatment with placebo (n=195), fixed dose aripiprazole (n=197) or flexible dose aripiprazole (n=194) for 6 weeks. The primary efficacy endpoint was mean change in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score from the end of prospective treatment (baseline) to the end of randomized treatment.ResultsMore than 90% of patients in all treatment groups completed the 6-week double-blind treatment phase. Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole (−10.5 and −9.6, respectively) than with placebo (−7.4). Aripiprazole was well tolerated. The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6*10 allele in Asian populations.LimitationsSix weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole. Exclusion of patients with established medical comorbidities does not reflect real-world practice.ConclusionsAripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT.Clinical trials registrationClinicalTrials.gov identifier NCT00876343

Not only Body Weight Perception but also Body Mass Index is Relevant to Suicidal Ideation and Self-Harming Behavior in Japanese Adolescents

Whether a low body mass index (BMI) is directly associated with a high risk of suicidal ideation or self-harming behavior in adolescents is still inconclusive. This study has, therefore, evaluated the relevance of BMI to suicidal ideation and self-harming behavior after controlling for body weight perception (BWP) and other potential confounding factors. BMI, BWP, suicidal ideation, and self-harming behavior were all assessed using a self-report questionnaire administered to 18,104 Japanese adolescents. Potential confounding factors were also evaluated. The data were then analyzed using bi-variate and multivariate logistic regression. Low BMI was associated with suicidal ideation and deliberate self-harm when controlling for sex, age, drug use, emotional distress, and BWP. Low BMI may be an independent risk factor for suicidal ideation and deliberate self-harming behavior in Japanese adolescents.ArticleJOURNAL OF NERVOUS AND MENTAL DISEASE. 200(4):305-309 (2012)journal articl

Guideline for Hereditary Angioedema (HAE) 2010 by the Japanese Association for Complement Research - Secondary Publication

ABSTRACTThis guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements

How many times can patients tolerate reoperation?

The frequency of resection for the recurrence of colorectal cancer has not been investigated in previous studies. Likewise, the related postoperative complications and the limit for indicating surgical resection has not been reported. Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three reoperations, based on our clinical experience. We included 15 cases exceeding two operations for the local recurrence of colorectal cancer from 2014 to 2019. We examined the postoperative complications classified as Clavien–Dindo IIIb. The positive rates of the complications were 0 (0.0%), 0 (0.0%), 2 (13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1st recurrent, 2nd recurrent, 3rd recurrent, and 4th recurrent operation group (p = 0.027), respectively. It is important to exercise caution in handling cases exceeding two reoperations (exceeding three reoperations including the primary operation)

東シナ海の流れ藻に蝟集する稚魚の摂餌生態と海洋環境

Many commercially important fishes associate with drifting seaweeds in their juvenile stage, however, the ecological significance of drifting seaweeds for juvenile fishes is still unclear. We postulated that the following two hypotheses may be applicable for juvenile fishes associate with drifting seaweeds, the “concentration of food supply” hypothesis: juvenile fishes are attracted by phytal animals on the drifting seaweeds and the “indicator-log” hypothesis: fish use accumulations of drifting seaweed as an indicator of productive areas (e.g. frontal areas) for food. We investigated the frontal areas, zooplankton abundance around the drifting seaweed, and the food availability of fish juveniles associated with drifting seaweed accumulations in the East China Sea in 2012 and 2013. A total of 14 drifting seaweed mass and 22 species (n = 408) of fish juveniles were collected. We found that 49.7 - 99.7 % of the individual fed on planktonic food and the feeding incidence on phytal animals was less than 50 %. Although drifting seaweeds were aggregated around the frontal areas of surface currents, the zooplankton abundance was not significantly different between these frontal areas and other areas. Our findings indicate that ecological significance of drifting seaweeds as feeding habit is relatively low for juvenile fishes associated with drifting seaweeds.流れ藻には多くの水産上重要種の稚魚が付随するが，流れ藻の稚魚にとっての生態学的意義は明らかにされていない。筆者らは次の2仮説のいずれかが流れ藻付随稚魚に当てはまると考え，“concentration of food supply hypothesis”（流れ藻葉上生物を摂餌するため）と“indicator log hypothesis”（流れ藻をフロント域のような餌豊度の高い海域の目印とするため）を検証するため，2012年と2013年に東シナ海の流れ藻周辺の海洋環境，フロント域，動物プランクトン豊度，流れ藻付随稚魚の摂餌個体率を調べた。流れ藻は表層流の収束帯に集積されていたが，収束帯のプランクトン豊度は高くなかった。合計14個の流れ藻を採集し，合計22種（408尾）の稚魚の胃内容物を調査した結果，稚魚の49.7 - 99.7 %の個体はプランクトンを選択的に摂餌していたが，葉上生物の摂餌個体率は高くなかった（50 %未満）。以上の結果から流れ藻の稚魚にとっての生態学的意義は摂餌場でないことが示唆された

Sapporo: A workflow execution service that encourages the reuse of workflows in various languages in bioinformatics [version 2; peer review: 1 approved, 2 approved with reservations]

The increased demand for efficient computation in data analysis encourages researchers in biomedical science to use workflow systems. Workflow systems, or so-called workflow languages, are used for the description and execution of a set of data analysis steps. Workflow systems increase the productivity of researchers, specifically in fields that use high-throughput DNA sequencing applications, where scalable computation is required. As systems have improved the portability of data analysis workflows, research communities are able to share workflows to reduce the cost of building ordinary analysis procedures. However, having multiple workflow systems in a research field has resulted in the distribution of efforts across different workflow system communities. As each workflow system has its unique characteristics, it is not feasible to learn every single system in order to use publicly shared workflows. Thus, we developed Sapporo, an application to provide a unified layer of workflow execution upon the differences of various workflow systems. Sapporo has two components: an application programming interface (API) that receives the request of a workflow run and a browser-based client for the API. The API follows the Workflow Execution Service API standard proposed by the Global Alliance for Genomics and Health. The current implementation supports the execution of workflows in four languages: Common Workflow Language, Workflow Description Language, Snakemake, and Nextflow. With its extensible and scalable design, Sapporo can support the research community in utilizing valuable resources for data analysis

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review

Background: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortality Case presentation: A 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital. Conclusion: The present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC