Publications by authors named "Kazunari Yoshida"

358 Publications

Pharmacogenetics-guided advances in antipsychotic treatment.

Clin Pharmacol Ther 2021 Jun 15. Epub 2021 Jun 15.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.

Pharmacogenetics (PGx) research over the past two decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of these findings to optimize treatment outcomes for patients in clinical practice has been limited. This paper presents a meta-review of key PGx findings related to antipsychotic response and common adverse effects, including antipsychotic-induced weight gain (AIWG), tardive dyskinesia (TD) and clozapine-induced agranulocytosis (CIAG), and highlights advances and challenges in clinical implementation. Most robust findings from candidate gene and genome-wide association studies (GWAS) were reported for associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. As a result, product labels and guidelines from various PGx expert groups have provided selection and dosing recommendations based on CYP2D6 metabolizer phenotypes for commonly prescribed antipsychotics. Other interesting genetic targets include dopamine receptor D2 (DRD2) for antipsychotic response, solute carrier family 18 member A2 (SLC18A2) for TD, and the human leukocyte antigen (HLA) genes, HLA-DQB1 and HLA-B, for CIAG. Well-designed studies using large, well-characterized samples that leverages international collaborations are needed to validate previous findings, as well as discover new genetic variants involved in antipsychotic response and adverse effects.
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http://dx.doi.org/10.1002/cpt.2339DOI Listing
June 2021

Molecular investigation of brain tumors progressing during pregnancy or postpartum period: the association between tumor type, their receptors, and the timing of presentation.

Clin Neurol Neurosurg 2021 Jun 1;207:106720. Epub 2021 Jun 1.

Department of Neurosurgery, Keio University, School of Medicine, Tokyo, Japan. Electronic address:

Objective: Brain tumors often become clinically evident during pregnancy; however, the mechanism has not been well elucidated. Purpose of this study is to investigate the influence of molecular genetic factors on the progression of brain tumors during pregnancy or the postpartum period.

Methods: Twelve cases of brain tumors that presented during pregnancy or postpartum period were included: five gliomas, three meningiomas, two vestibular schwannomas, and two chordomas. Tumor samples were investigated by metaphase comparative genomic hybridization and immunohistochemistry, for chromosomal copy number aberration (CNA) and receptor expression of sex hormones and growth factors.

Results: The results were correlated with the timing of tumor presentation in relation to the stage of pregnancy. EGFR, VEGFR-1/2, AR, and c-Myc were expressed in gliomas, PgR, ER, HER-2, VEGFR-1, EGF and VEGFR2 in meningiomas, VEGFR-1 in vestibular schwannomas, and EGFR, VEGFR-1/2, and c-Myc in chordomas. The CNAs of the tumors varied. Four of the five gliomas presented in the 2nd trimester, all three meningiomas in the 3rd trimester or postpartum period, and both of the two schwannomas in the late 2nd trimester. Expression of VEGFR-1/2 and EGFR was observed regardless of the timing of tumor presentation, whereas female hormone receptors and HER-2 were exclusively found in meningiomas. Interestingly, one anaplastic astrocytoma (IDH mut, non-codeleted) that progressed from precedent grade 2 tumor harbored amplification of the MYC locus.

Conclusion: Progression of brain tumors during pregnancy is associated with various growth factors as well as sex hormones. The timing of presentation is likely dependent on molecular receptors specific to each tumor type.
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http://dx.doi.org/10.1016/j.clineuro.2021.106720DOI Listing
June 2021

TMS-EEG Research to Elucidate the Pathophysiological Neural Bases in Patients with Schizophrenia: A Systematic Review.

J Pers Med 2021 May 10;11(5). Epub 2021 May 10.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.

Schizophrenia (SCZ) is a serious mental disorder, and its pathogenesis is complex. Recently, the glutamate hypothesis and the excitatory/inhibitory (E/I) imbalance hypothesis have been proposed as new pathological hypotheses for SCZ. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a non-invasive novel method that enables us to investigate the cortical activity in humans, and this modality is a suitable approach to evaluate these hypotheses. In this study, we systematically reviewed TMS-EEG studies that investigated the cortical dysfunction of SCZ to examine the emerging hypotheses for SCZ. The following search terms were set in this systematic review: (TMS or 'transcranial magnetic stimulation') and (EEG or electroencephalog*) and (schizophrenia). We inspected the articles written in English that examined humans and were published by March 2020 via MEDLINE, Embase, PsycINFO, and PubMed. The initial search generated 379 studies, and 14 articles were finally identified. The current review noted that patients with SCZ demonstrated the E/I deficits in the prefrontal cortex, whose dysfunctions were also associated with cognitive impairment and clinical severity. Moreover, TMS-induced gamma activity in the prefrontal cortex was related to positive symptoms, while theta/delta band activities were associated with negative symptoms in SCZ. Thus, this systematic review discusses aspects of the pathophysiological neural basis of SCZ that are not explained by the traditional dopamine hypothesis exclusively, based on the findings of previous TMS-EEG research, mainly in terms of the E/I imbalance hypothesis. In conclusion, TMS-EEG neurophysiology can be applied to establish objective biomarkers for better diagnosis as well as to develop new therapeutic strategies for patients with SCZ.
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http://dx.doi.org/10.3390/jpm11050388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150818PMC
May 2021

Correcting anemia and native vitamin D supplementation in kidney transplant recipients: a multicenter, 2 × 2 factorial, open-label, randomized clinical trial.

Transpl Int 2021 07 15;34(7):1212-1225. Epub 2021 Jun 15.

Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.
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http://dx.doi.org/10.1111/tri.13885DOI Listing
July 2021

A case of central nervous system lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates: a case report and literature review.

Brain Tumor Pathol 2021 Jul 30;38(3):263-270. Epub 2021 Mar 30.

Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, Japan.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disease with angiocentric and angiodestructive infiltrates, and by definition, Epstein-Barr virus (EBV)-associated B-cell malignancy. It most frequently involves the lung, and in some cases, the lesions are confined to the central nervous system (isolated CNS-LYG). However, it remains a controversial disease in terms of pathophysiology, especially in those confined to the CNS. We report the case of a 37-year-old man with CNS lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates that resembled CNS-LYG. The lesion was clinically aggressive with subacute onset and irregular ring-like enhancement on MRI. The resected specimen showed no cytological atypia, EBV-infected cells, or monoclonality for IgH and TCR gene rearrangements. Considering the possibility of latent malignancy, the patient was successfully treated with corticosteroid and chemoradiotherapy with high-dose methotrexate. The present case and the literature suggest that EBV-negative CNS lesions with angiocentric lymphoid infiltrates are probably heterogeneous in their pathogenesis, including those that could fit into the so-called CNS-LYG and those with T-cell predominance. The accumulation of similar cases is warranted for the classification and appropriate treatment of these lesions.
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http://dx.doi.org/10.1007/s10014-021-00398-yDOI Listing
July 2021

Endoscopic Endonasal Transinfraturbinate Approach With Nasoseptal Window for Removal of the Pterygopalatine Fossa Tumor.

J Craniofac Surg 2021 Mar-Apr 01;32(2):716-718

Department of Neurosurgery.

Abstract: Recent advances in endoscopic intranasal technology have allowed for a safe approach to the pterygopalatine fossa lesion. However, we consider that there is still scope of improvement to approach a broader area with better operability and minimal invasiveness. A 51-year-old man underwent endoscopic endonasal surgery due to the recurrence of chordoma at the left pterygopalatine fossa. To access the lower and lateral part of the pterygopalatine fossa, we performed endoscopic endonasal transmaxillary removal via an inferior turbinate incision. During surgery, a wide operative field and good operability could be secured by inserting an endoscope from the right nostril through a window of the nasal septum. Subtotal removal of the tumor was achieved without any complication during the surgery. Endoscopic endonasal transinfraturbinate approach with nasoseptal window was effective in the removal of the pterygopalatine fossa tumor because it is less invasive and provides a good surgical view with better operability.
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http://dx.doi.org/10.1097/SCS.0000000000006979DOI Listing
June 2021

In-Hospital Complications After Surgery in Elderly Patients with Asymptomatic or Minor Symptom Meningioma: A Nationwide Registry Study.

World Neurosurg 2021 04 11;148:e459-e470. Epub 2021 Jan 11.

Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: Asymptomatic or minor symptom meningiomas (AMSMs) in the elderly are incidental findings, with no consensus reached on the optimal management strategy. In the present study, we aimed to determine the surgical risk factors for elderly patients with AMSMs using a nationwide registry database in Japan.

Methods: We identified patients with surgically treated AMSMs using the Diagnosis Procedure Combination database from 2010 to 2015 and reviewed the medical records for age (<65 years; pre-elderly, 65-74 years; and elderly, ≥75 years), sex, Barthel index (BI) score, medical history, tumor location, and complications. An AMSM was defined by a BI score of 100 points at admission. The risk factors for all stroke complications, BI deterioration at discharge, and in-hospital mortality were determined using multivariate logistic regression analyses.

Results: From a total of 10,535 patients with meningioma, 6628 were included. Advanced age was a significant risk factor (odds ratio, 3.54; 95% confidence interval, 2.80-4.46) for BI deterioration but not for all-stroke complications or in-hospital mortality. Midline and posterior fossa tumors, diabetes mellitus, and chronic heart disease were significant risk factors for in-hospital mortality.

Conclusions: For elderly patients with surgically treated AMSMs, advanced age was a prominent risk factor for functional decline at discharge. Our study identified several factors that should be evaluated before proceeding with surgery for AMSMs in elderly and pre-elderly patients. These findings could, not only improve decision-making among clinicians treating patients with AMSMs, but also help in predicting the results of surgery for elderly patients with AMSMs.
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http://dx.doi.org/10.1016/j.wneu.2021.01.001DOI Listing
April 2021

Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia.

Behav Brain Res 2021 03 5;402:113098. Epub 2021 Jan 5.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address:

Background: Antipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia.

Methods: This narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia.

Results: The efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent: akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infarction, stroke, thromboembolism, QT interval prolongation, anticholinergic adverse effects, somnolence, pneumonia, hip fracture, and neuroleptic malignant syndrome. In contrast, the relationships of antipsychotic dose with dyslipidemia, hypotension, seizure, sialorrhea, and neutropenia and agranulocytosis remained unclear due to mixed findings and/or limited data. Although a higher lifetime cumulative antipsychotic dose might contribute to higher mortality, it is still difficult to conclude whether mortality increases in a dose-dependent manner.

Conclusion: These findings could help clinicians to optimize antipsychotic treatment in patients with schizophrenia by balancing risks and benefits in clinical practice. However, further investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.
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http://dx.doi.org/10.1016/j.bbr.2020.113098DOI Listing
March 2021

Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients With Meningiomas.

Front Oncol 2020 24;10:592470. Epub 2020 Nov 24.

Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.

Background: Meningiomas are the most common benign intracranial tumors. However, even WHO grade I meningiomas occasionally show local tumor recurrence. Prognostic factors for meningiomas have not been fully established. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor for several solid tumors. The prognostic value of NLR in meningiomas has been analyzed in few studies.

Materials And Methods: This retrospective study included 160 patients who underwent surgery for meningiomas between October 2010 and September 2017. We analyzed the associations between patients' clinical data (sex, age, primary/recurrent, WHO grade, extent of removal, tumor location, peritumoral brain edema, and preoperative laboratory data) and clinical outcomes, including recurrence and progression-free survival (PFS).

Results: Forty-four meningiomas recurred within the follow-up period of 3.8 years. WHO grade II, III, subtotal removal, history of recurrence, Ki-67 labeling index ≥3.0, and preoperative NLR value ≥2.6 were significantly associated with shorter PFS ( < 0.001, < 0.001, 0.002, < 0.001, and 0.015, respectively). Furthermore, NLR ≥ 2.6 was also significantly associated with shorter PFS in a subgroup analysis of WHO grade I meningiomas ( = 0.003). In univariate and multivariate analyses, NLR ≥2.6 remained as a significant predictive factor for shorter PFS in patients with meningioma ( = 0.014).

Conclusions: NLR may be a cost-effective and novel preoperatively usable biomarker in patients with meningiomas.
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http://dx.doi.org/10.3389/fonc.2020.592470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732694PMC
November 2020

Quiescent and Activated Fibroblasts in Lateral Ventricular Meningioma With a Dura-like Membrane.

World Neurosurg 2021 03 11;147:e215-e224. Epub 2020 Dec 11.

Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Background: Lateral ventricular meningioma (LVM) is a rare entity, accounting for 0.5%-5% of all intracranial meningiomas. This type of meningioma arises from meningothelial inclusion bodies in the tela choroidea and/or mesenchymal stroma of the choroid plexus. Although not yet fully characterized, a membranous structure is frequently observed around LVMs. This study analyzed quiescent and activated fibroblast phenotypes in LVMs with focus on the relationship between tumor growth and development of the membranous structure.

Methods: This retrospective study analyzed 9 LVM cases for which gross total removal was achieved. Expression of the ependymal cell marker (Forkhead Box J1 [FoxJ1]) was histopathologically evaluated. The distribution of quiescent and activated fibroblasts was also analyzed using anti-fibroblast-specific protein-1 (FSP1)/S100A4 antibody and anti-α-smooth muscle actin (αSMA) antibody, respectively. The control group was 5 cases with primary convexity meningioma for which Simpson grade I removal was achieved.

Results: Small LVMs (≤30 mm) were covered by a FoxJ1-positive(+) ependymal cell monolayer; no αSMA(+) cells were detected in the tumor; and a thick membrane capsule was not observed. None of the convexity meningiomas showed FoxJ1(+) cells. Large LVMs (>30 mm) had thick membrane capsules without an ependymal cell monolayer, which resembled dura mater. The FSP1/S100A4(+) and αSM(+) cells were clearly concentrated in the peripheral area just below the thick dura mater-like membrane capsules.

Conclusions: This study found an association between activated fibroblasts and dura mater-like membrane capsules in LVMs. The characteristics of membranous structure in LVMs may differ depending on tumor size.
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http://dx.doi.org/10.1016/j.wneu.2020.12.025DOI Listing
March 2021

Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.

Neurosci Biobehav Rev 2021 02 8;121:47-59. Epub 2020 Dec 8.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with AD, mild cognitive impairment (MCI), and healthy controls (HC). Our meta-analyses indicated that RMT, SAI, SICI, and LICI were significantly lower in patients with AD, while ICF did not show a difference in patients with AD compared with HC. In patients with MCI, RMT and SAI were significantly lower than in HC. In conclusion, motor cortical excitability was increased, while cholinergic function was decreased in AD and MCI in comparison with HC and patients with AD had decreased GABAergic and glutamatergic functions compared with HC. Our results warrant further studies to differentiate AD, MCI, and HC, employing multimodal TMS neurophysiology.
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http://dx.doi.org/10.1016/j.neubiorev.2020.12.003DOI Listing
February 2021

Activation of ventral CA1 hippocampal neurons projecting to the lateral septum during feeding.

Hippocampus 2021 Mar 9;31(3):294-304. Epub 2020 Dec 9.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.

A number of studies have reported the involvement of the ventral hippocampus (vHip) and the lateral septum (LS) in negative emotional responses. Besides these well-documented functions, they are also thought to control feeding behavior. In particular, optogenetic and pharmacogenetic interventions to LS-projecting vHip neurons have demonstrated that the vHip neural circuit exerts an inhibition on feeding behavior. However, there have been no reports of vHip neuronal activity during feeding. Here, we focused on LS-projecting vCA1 neurons (vCA1 ) and monitored their activity during feeding behaviors in mice. vCA1 neurons were retrogradely labeled with adeno-associated virus carrying a ratiometric Ca indicator and measured compound Ca dynamics by fiber photometry. We first examined vCA1 activity in random food-exploring behavior and found that vCA1 activation seemed to coincide with food intake; however, our ability to visually confirm this during freely moving behaviors was not sufficiently reliable. We next examined vCA1 activity in a goal-directed, food-seeking lever-press task which temporally divided the mouse state into preparatory, effort, and consummatory phases. We observed vCA1 activation in the postprandial period during the consummatory phase. Such timing- and pathway-specific activation was not observed from pan-vCA1 neurons. In contrast, reward omission eliminated this activity, indicating that vCA1 activation is contingent on the food reward. Sated mice pressed the lever significantly fewer times but still ate food; however, vCA1 neurons were not activated, suggesting that vCA1 neurons did not respond to habitual behavior. Combined, these results suggest that gastrointestinal interoception rather than food-intake motions or external sensations are likely to coincide with vCA1 activity. Accordingly, we propose that vCA1 neurons discriminate between matched or unmatched predictive bodily states in which incoming food will satisfy an appetite. We also demonstrate that vCA1 neurons are activated in aversive/anxious situations in an elevated plus maze and tail suspension test. Future behavioral tests utilizing anxious conflict and food intake may reconcile the multiple functions of vCA1 neurons.
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http://dx.doi.org/10.1002/hipo.23289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984357PMC
March 2021

Changes in telepsychiatry regulations during the COVID-19 pandemic: 17 countries and regions' approaches to an evolving healthcare landscape.

Psychol Med 2020 Nov 27:1-8. Epub 2020 Nov 27.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.

Background: During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.

Methods: We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.

Results: Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.

Conclusions: Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.
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http://dx.doi.org/10.1017/S0033291720004584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750654PMC
November 2020

Pharmacogenomic Studies in Intellectual Disabilities and Autism Spectrum Disorder: A Systematic Review: Études Pharmacogénomiques en Déficiences Intellectuelles et Trouble du Spectre de L'autisme: Une Revue Systématique.

Can J Psychiatry 2020 Nov 23:706743720971950. Epub 2020 Nov 23.

Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Background: Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to treat aberrant behaviors and mood symptoms, frequently resulting in polypharmacy and drug-related adverse effects. Pharmacogenomic (PGx) studies with ASD and/or ID (ASD/ID) have been scarce despite the promise of optimizing treatment outcomes. We reviewed the literature on PGx studies with antipsychotics and antidepressants (e.g., treatment response and adverse effects) in ASD/ID.

Methods: We performed a systematic review using MEDLINE, Embase, and PsycINFO, including peer-reviewed original articles in English referring to PGx in the treatment of ASD/ID in any age groups (e.g., treatment response and adverse effects).

Results: A total of 28 PGx studies using mostly candidate gene approaches were identified across age groups. Notably, only 3 studies included adults with ASD/ID while the other 25 studies focused specifically on children/adolescents with ASD/ID. Twelve studies primarily investigated treatment response, of which 5 and 6 studies included patients treated with antipsychotics and antidepressants, respectively. Most interesting results for response were reported for 2 sets of candidate gene studies, namely: (1) The (rs6280) polymorphism was examined in patients treated with risperidone in 3 studies, 2 of which reported an association with risperidone treatment response and (2) the 5-HTTLPR polymorphism and treatment response to antidepressants which was investigated in 4 studies, 3 of which reported significant associations. In regard to side effects, 9 of 15 studies focused on hyperprolactinemia in patients treated with risperidone. Among them, 7 and 5 studies examined the impact of and polymorphisms, respectively, yielding mostly negative study findings.

Conclusions: There is limited data available on PGx in individuals with ASD/ID and in particular in adults. Given the potential for PGx testing in improving treatment outcomes, additional PGx studies for psychotropic treatment in ASD/ID across age groups are warranted.
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http://dx.doi.org/10.1177/0706743720971950DOI Listing
November 2020

Towards safer risperidone prescribing in Alzheimer's disease.

Br J Psychiatry 2020 Nov 12:1-8. Epub 2020 Nov 12.

Division of Psychiatry, University College London, UK.

Background: In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to 'use the lowest possible dose' of antipsychotic drugs, but provide no information on optimal dosing.

Aims: This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).

Method: A statistical model, which described the concentration-time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and 'active moiety' (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.

Results: The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann-Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.

Conclusions: Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.
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http://dx.doi.org/10.1192/bjp.2020.225DOI Listing
November 2020

Renal functional outcome after laparoscopic partial nephrectomy using dynamic renal scintigraphy.

Can J Urol 2020 10;27(5):10402-10406

Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.

INTRODUCTION To explore postoperative operation-side renal functional outcome after laparoscopic partial nephrectomy (LPN) using dynamic renal scintigraphy.

Materials And Methods: Between July 2006 and December 2014, 62 patients with localized renal tumor received ischemic LPN at our institution. Preoperative, 6 months postoperative, and 12 months postoperative split renal functions were evaluated by dynamic renal scintigraphy using radionuclide technetium-99m-mercaptoacetyltriglycine. Postoperative operation-side renal function was calculated. To assess the significant factors affecting postoperative operation-side renal functional decrease, simple regression and multiple regression analyses were carried out.

Results: Postoperative operation-side renal functions were significantly decreased to 86.6% at 6 months and 86.9% at 12 months postoperatively (p < 0.0001). Simple regression analyses revealed that postoperative operation-side renal functions were significantly decreased with prolonged warm ischemia time at 6 months and 12 months postoperatively (p = 0.0058 and 0.0032, respectively). Multiple regression analysis identified warm ischemia time as an independent predictive factor for operation-side renal functional decreases at 6 months and 12 months postoperatively (p = 0.0158 and 0.0109, respectively).

Conclusions: Irreversible renal damage using dynamic renal scintigraphy after LPN was observed. With prolongation of warm ischemia time during LPN, postoperative operation-side renal function was significantly decreased.
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October 2020

Posture-induced changes in the vessels of the head and neck: evaluation using conventional supine CT and upright CT.

Sci Rep 2020 10 6;10(1):16623. Epub 2020 Oct 6.

Department of Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Since the venous system is affected by gravity, upright computed tomography (CT) in addition to conventional supine CT has great potential for evaluating postural changes in the venous system. We evaluated the morphological differences in the head and neck vessels by performing a contrast CT study in both the supine and the sitting positions. In this study, the 20 included participants (10 men and 10 women) were healthy adults aged 30 to 55 years. The cross-sectional area of the cervical vessels, craniocervical junction veins, and intracranial vessels were obtained quantitatively. Venous sinuses and venous plexuses that were difficult to measure were evaluated qualitatively. The average change in areas from a supine to an upright posture was - 77.87 ± 15.99% (P < 0.0001) in the right internal jugular vein (IJV), - 69.42 ± 23.15% (P < 0.0001) in the left IJV, - 61.52 ± 12.81% (P < 0.0001) in the right external jugular vein (EJV), and - 58.91 ± 17.37% (P < 0.0001) in the left EJV. In contrast, the change in the anterior condylar vein (ACV) from a supine to an upright posture was approximately + 144% (P < 0.005) on the right side and + 110% (P < 0.05) on the left side. In addition, according to the qualitative analysis, the posterior venous structures including the anterior condylar confluence (ACC) of the craniocervical junction became more prominent in an upright posture. Despite these changes, the intracranial vessels showed almost no change between postures. From a supine to an upright position, the IJVs and EJVs above the heart collapsed, and venous channels including the ACCs and ACVs opened, switching the main cerebral venous drainage from the IJVs to the vertebral venous system. Upright head CT angiography can be useful for investigating physiological and pathophysiological hemodynamics of the venous system accompanying postural changes.
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http://dx.doi.org/10.1038/s41598-020-73658-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538893PMC
October 2020

A Pilot Study of the Adverse Events Caused by the Combined Use of Bevacizumab and Vascular Endothelial Growth Factor Receptor-Targeted Vaccination for Patients with a Malignant Glioma.

Vaccines (Basel) 2020 Sep 2;8(3). Epub 2020 Sep 2.

Department of Neurosurgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.
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http://dx.doi.org/10.3390/vaccines8030498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564945PMC
September 2020

Delayed reopening of a superficial temporal artery to middle cerebral artery bypass graft occluded by a white thrombus during surgery.

Surg Neurol Int 2020 1;11:220. Epub 2020 Aug 1.

Department of Neurosurgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.

Background: To the authors' knowledge, reopening of a superficial temporal artery to middle cerebral artery (STA-MCA) bypass graft occluded by a white thrombus during the procedure and was observed several months after the surgery is relatively rare.

Case Description: The authors encountered a case of moyamoya disease in an Asian female in her third decade of life, in whom a bypass recipient vessel was occluded by a white thrombus during surgery and remained occluded on magnetic resonance angiography (MRA) performed up to 6 weeks after the procedure. However, recanalization was confirmed by MRA performed 4 months after surgery. MRA performed 10 and 19 months after surgery revealed that the bypass vessel had grown thicker, and the ischemic symptoms experienced by the patient also improved.

Conclusion: Whether this lesion is explained by reopening or angiogenesis, its pathophysiology remains controversial. The uninterrupted connection of occluded bypass vessel in STA-MCA bypass surgery in conjunction with surgical strategy of single bypass using only parietal branch of STA as donor and preserving blood flow of frontal branch to scalp may have made a positive impact on promoting the development of extracranial-intracranial bypass anastomosis in the chronic phase and should be considered.
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http://dx.doi.org/10.25259/SNI_235_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451180PMC
August 2020

Antifungal Agent Luliconazole Inhibits the Growth of Mouse Glioma-initiating Cells in Brain Explants.

Keio J Med 2020 Dec 31;69(4):97-104. Epub 2020 Jul 31.

Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.

Imidazole antifungal compounds exert their antipathogenic effects through inhibition of sterol biosynthesis. These drugs have also recently been identified as candidate anticancer agents for several solid tumors including glioblastoma. However, their effects on glioma-initiating cells (GICs), i.e., glioma cells with stemlike properties that are able to initiate tumors, remain unclear. Consequently, we examined the effects of the optically active imidazole compound luliconazole on mouse GICs and GIC-based tumors. Luliconazole impaired in a concentration-dependent manner the growth of spheres formed by GICs in vitro. In contrast to the inhibitory effects of ionizing radiation and temozolomide on sphere growth, that of luliconazole was attenuated by the addition of exogenous cholesterol. Exposure to luliconazole of brain slices derived from mice with orthotopic GIC implants for 4 days in culture resulted in a marked increase in the number of tumor cells positive for cleaved caspase-3, but without a similar effect on normal cells. Furthermore, in brain slices, luliconazole inhibited the expansion of GIC-based tumors and the parenchymal infiltration of tumor cells. Our findings therefore indicate that luliconazole effectively targets GICs, thereby providing further support for the antitumorigenic effects of imidazole antifungal compounds.
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http://dx.doi.org/10.2302/kjm.2020-0001-OADOI Listing
December 2020

Exchange Cranioplasty Using Bioabsorbable Hydroxyapatite and Collagen Complex After Removal of an Extensive Frontal Bone Tumor in an Infant.

World Neurosurg 2020 10 20;142:375-378. Epub 2020 Jul 20.

Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.

Background: Forehead reconstruction is challenging. Reconstruction of the innate curvature of the forehead is difficult, and the forehead is an esthetically important part of the face. Although synthetic implants and autologous split bone grafts are useful, these cannot be used in infants.

Case Description: A 4-month-old girl was presented with a right frontal bone Ewing sarcoma. The tumor was removed, and the defect was reconstructed with an autologous contralateral parietal bone graft. The parietal bone defect was repaired with a bioabsorbable hydroxyapatite and collagen complex. Good reconstruction of the forehead and ossification of the donor site was achieved within 3 years after surgery.

Conclusions: After removal of an extensive frontal bone tumor in an infant, exchange cranioplasty with an autograft using a bioabsorbable hydroxyapatite and collagen complex at the donor site yielded good results.
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http://dx.doi.org/10.1016/j.wneu.2020.07.085DOI Listing
October 2020

Sinking skin flap syndrome visualized by upright computed tomography.

Acta Neurochir (Wien) 2020 08 22;162(8):1825-1828. Epub 2020 Jun 22.

Department of Radiology, Keio University School of Medicine, Tokyo, Japan.

Sinking skin flap syndrome is a craniectomy complication characterized by new neurological dysfunction that typically worsens in the upright position and improves after cranioplasty. We present a 33-year-old man who experienced hemiparesis in the upright position after craniectomy. Upright computed tomography (CT) before cranioplasty showed a remarkable shift of the brain compared to supine CT. After cranioplasty, both symptoms and brain shift on CT resolved. Upright CT enables detection and objective evaluation of paradoxical herniation and midline shift that is not obvious on supine imaging modalities. Clinicians need to be aware of positional brain shift in postcraniectomy patients.
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http://dx.doi.org/10.1007/s00701-020-04459-7DOI Listing
August 2020

Novel histopathological classification of meningiomas based on dural invasion.

J Clin Pathol 2021 Apr 16;74(4):238-243. Epub 2020 Jun 16.

Department of Neurosurgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan

Aims: Histological invasion into the adjacent brain parenchyma is frequently investigated in meningioma because it is an important morphological criterion for grade II meningioma according to the 2016 WHO classification. However, few studies have focused on dural invasion of meningiomas. Herein, we propose a novel histopathological classification based on dural invasion of meningiomas.

Methods: Forty-nine cases with WHO grade I meningiomas who underwent Simpson grade I removal were collected. After the meningeal layer (ML) and periosteal layer (PL) of dura mater were visualised by Masson's trichrome stain, we evaluated the depth (to the ML and PL) and the patterns (1, expanding; 2, infiltrating) of dural invasion of meningiomas using serial paraffin sections. Invasion-associated markers, including Ki-67, matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13, aquaporin 1 and Na-K-2Cl cotransporter, were quantitatively analysed by immunohistochemistry.

Results: Thirty-five cases (71.4%) showed the dural invasion. In 27 of these 35 cases (77.1%), dural invasion was localised in ML. Type 1 (expanding type) and type 2 (infiltrating type) invasions were observed in 23 and 12 cases, respectively. The recurrence rate in cases with type 2 invasion was significantly higher than that in cases with type 1 invasion. The percentage of MMP-1-positive tumour cells was also significantly higher in cases with dural invasion than those without, suggesting involvement of MMP-1 in dural invasion.

Conclusions: We quantitatively evaluated the depth and patterns of dural invasion in meningiomas. The patterns of dural invasion were associated with meningioma recurrence.
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http://dx.doi.org/10.1136/jclinpath-2020-206592DOI Listing
April 2021

Efficacy of Exercise Therapy Initiated in the Early Phase After Kidney Transplantation: A Pilot Study.

J Ren Nutr 2020 11 2;30(6):518-525. Epub 2020 Jun 2.

Department of Organ Transplant Medicine, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address:

Objective: In patients with kidney transplant (KT), frailty is a predictor of adverse outcomes. Outcomes of exercise therapy in patients with KT, particularly the efficacy of early exercise after KT, have not been evaluated. We investigated the effect of exercise intervention beginning early after KT on physical performance, physical activity, quality of life, and kidney function in patients with KT.

Methods: KT recipients who underwent surgery with usual care plus exercise training from a prospective cohort (exercise group; n = 10) and those with usual care alone from a historical cohort (control group; n = 14) were included in this study. Early exercise comprised supervised aerobic training and physical activity instruction from day 6 to 2 months after KT. The following outcomes were measured: 6-minute walking distance, isometric knee extensor strength, gait speed, physical activity, quality of life, and estimated glomerular filtration rate.

Results: Analyses of covariance, adjusted for baseline values, revealed significant mean differences between exercise and control groups at 2 months after KT in 6-minute walking distance (+44.4 m, P = .03) and isometric knee extensor strength (+8.1%body weight, P = .03). No significant between-group differences were found in gait speed, physical activity, and quality of life. The analysis of variance for comparison of the area under the recovery curves of estimated glomerular filtration rate after KT revealed no significant difference between groups.

Conclusion: Supervised aerobic training and physical activity instruction initiated in the early phase after KT can improve physical performance without adversely affecting kidney function.
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http://dx.doi.org/10.1053/j.jrn.2019.11.005DOI Listing
November 2020

Cerebrospinal fluid leakage due to nasoseptal flap partial necrosis: A pitfall for skull base reconstruction of endoscopic endonasal surgery.

Surg Neurol Int 2020 23;11:121. Epub 2020 May 23.

Departments of Neurosurgery, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, Japan.

Background: Vascularized nasoseptal flaps allow for the reconstruction of large dural defects and have remarkably reduced the incidence of postoperative complications during endoscopic endonasal skull base surgery. Nevertheless, some complications related to nasoseptal flap have been reported. Flap necrosis is a rare, but serious issue is associated with meningitis and cerebrospinal fluid (CSF) leak.

Case Description: We performed endoscopic endonasal removal of the tuberculum sella meningioma in a 39-year-old woman with a history of Turner syndrome using abdominal fat, fascia, and a vascularized nasoseptal flap for dural and skull base defect reconstruction. After surgery, she developed CSF leak, and reoperation revealed partial necrosis of the septal flap that caused leakage. At this time, with a concern that removal of the necrotic part may lead to the insufficient size of the flap, we filled the gap tightly with fat pieces. However, the CSF leak recurred, and thus, we performed debridement of the necrotic region and reformed the multilayered reconstruction, following which she no longer experienced CSF leakage.

Conclusion: Our case suggested that partial rather than total flap necrosis could occur, possibly due to variances of vascular anatomy, leading to focal ischemia. Debridement of the necrotic region may be an important solution for recurrent cerebrospinal leakage secondary to partial necrosis of a nasoseptal flap.
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http://dx.doi.org/10.25259/SNI_117_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265470PMC
May 2020

Pharmacogenetics of Antipsychotic Drug Treatment: Update and Clinical Implications.

Mol Neuropsychiatry 2020 Apr 26;5(Suppl 1):1-26. Epub 2018 Sep 26.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Numerous genetic variants have been shown to be associated with antipsychotic response and adverse effects of schizophrenia treatment. However, the clinical application of these findings is limited. The aim of this narrative review is to summarize the most recent publications and recommendations related to the genetics of antipsychotic treatment and shed light on the clinical utility of pharmacogenetics/pharmacogenomics (PGx). We reviewed the literature on PGx studies with antipsychotic drugs (i.e., antipsychotic response and adverse effects) and commonly used commercial PGx tools for clinical practice. Publications and reviews were included with emphasis on articles published between January 2015 and April 2018. We found 44 studies focusing on antipsychotic response and 45 studies on adverse effects (e.g., antipsychotic-induced weight gain, movement disorders, hormonal abnormality, and clozapine-induced agranulocytosis/granulocytopenia), albeit with mixed results. Overall, several gene variants related to antipsychotic response and adverse effects in the treatment of patients with schizophrenia have been reported, and several commercial pharmacogenomic tests have become available. However, further well-designed investigations and replication studies in large and well-characterized samples are needed to facilitate the application of PGx findings to clinical practice.
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http://dx.doi.org/10.1159/000492332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206586PMC
April 2020

Alterations of the tumor microenvironment in glioblastoma following radiation and temozolomide with or without bevacizumab.

Ann Transl Med 2020 Mar;8(6):297

Department of Neurosurgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Background: The immunosuppressive tumor microenvironment (TME) contributes to the tumor progression and treatment failure. Our previous study demonstrated alterations in the TME during bevacizumab (Bev) therapy in human glioblastoma (GB) specimens obtained from patients who underwent surgical resection. Continuous Bev administration downregulates the expression of programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), suppresses the infiltration of tumor associated macrophages (TAMs) and regulatory T cells (Tregs), and increases cytotoxic T lymphocytes (CTLs) infiltration. However, one may argue that these immunosupportive effects might also be induced by radiation therapy (RT) or temozolomide (TMZ), and they cannot necessarily be attributed to Bev alone.

Methods: In the present study, changes in the molecules relevant to the TME were analyzed by immunohistochemistry using paired pre- and post-treatment samples of malignant glioma specimens from 15 patients who received RT and TMZ therapy without Bev.

Results: The expression levels of CD34, vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (VEGFR2), HIF-1α, CA9, nestin, CD4, CD8, CD163, PD-1, and PD-L1 were not significantly changed after the treatment with RT and TMZ. However, VEGFR1 expression and the number of Foxp3-positive cells tended to be upregulated and increased after the treatment (P=0.058, P=0.082, respectively).

Conclusions: This was the first study to show the alterations of TME following RT and TMZ therapy using paired pre- and post-treatment malignant glioma samples. Long-term treatment of RT and TMZ might worsen immunosuppressive TME in malignant gliomas.
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http://dx.doi.org/10.21037/atm.2020.03.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186631PMC
March 2020

Association between the -2548G/A polymorphism of the leptin gene and antipsychotic-induced weight gain: Analysis of the CATIE sample and meta-analysis.

Prog Neuropsychopharmacol Biol Psychiatry 2020 08 23;102:109952. Epub 2020 Apr 23.

Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Antipsychotics, especially most of the second-generation antipsychotics, have a high risk for metabolic syndrome and antipsychotic-induced weight gain (AIWG). A promoter variant of the leptin (LEP) gene, -2548G/A (rs7799039), has been associated with AIWG in several studies. The aim of this study was to evaluate this association in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sample, followed by meta-analysis.

Methods: We investigated the association between rs7799039 and AIWG in a sub-sample of European (N = 164) individuals from the CATIE study. Body mass index (BMI) change and weight gain (presence or absence) was analyzed using ANCOVA and logistic regression, respectively. For the meta-analysis, a literature search was conducted using MEDLINE, Embase, and PsycINFO up to October 2019. The pooled odds ratio was calculated for presence or absence of weight gain (≥7% weight change) using a random effects model.

Results: We did not detect an association between rs7799039 and BMI change or weight gain (presence or absence) in the CATIE sample. As for the meta-analysis, we included 12 studies. No significant associations between the LEP rs7799039 polymorphism and AIWG were observed under the allelic genetic model (allele A vs. allele G) (OR = 1.10 [0.71, 1.70], p = .68). In the subgroup analyses of first-episode schizophrenia patients, a significant association between the A-allele and weight gain was observed, respectively (OR = 2.32 [1.41, 3.82], p = .0009).

Conclusions: The present meta-analysis showed no significant effect of rs7799039 on AIWG. However, this variant may influence AIWG in first-episode schizophrenia patients. Further investigation of a larger and more homogenous sample is required to elucidate the role of the LEP gene in AIWG.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109952DOI Listing
August 2020

Author Correction: A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2.

Nat Commun 2020 04 21;11(1):2028. Epub 2020 Apr 21.

Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-16007-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174327PMC
April 2020

Novel method to evaluate the risk of tumor adhesions and post-operative hemorrhage of meningiomas using 320 row CT-DSA: A clinical research study.

Acta Neurochir (Wien) 2020 09 16;162(9):2145-2153. Epub 2020 Apr 16.

Department of Neurosurgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, Japan.

Objective: Meningioma is an extra-axial tumor that forms adhesions toward the brain surface in the course of its growth. Predicting adhesions between the tumor and the brain surface leads to better predictions of surgical results. There are few studies on brain-tumor adhesions or postoperative hemorrhage. This study aimed to assess tumor vascularity of the dura and cerebral surface, and predict surgical outcomes using four-dimensional computed tomography angiography (4D CTA).

Patients And Methods: Using a dynamic contrast CT, we conducted a retrospective study of 27 patients with convexity (n = 15), falx (n = 6), and parasagittal (n = 6) meningiomas treated in our hospital from January 2016 to September 2018. We set the region of interest on the dural layer and cerebral surface side of meningiomas and calculated the mean CT value in each region. Distribution of blood flow in the tumor was classified into two groups: A, which has a higher CT value of the dural side than that of the brain surface side at every timing, and B, which meets the criteria other than those in group A. Demographic data, preoperative characteristic images, and postoperative complications were compared between the groups.

Results: Twelve and 15 patients were classified into groups A and B, respectively. The extent of adhesions against the cerebral cortex in group A was significantly less severe compared with that in group B (p = 0.038). The rate of postoperative hemorrhage occurrence in group B (53%) was significantly higher than that in group A (8%) (p = 0.04). There were no significant differences in the other preoperative characteristic images or perioperative parameters between groups A and B.

Conclusion: A 320-row dynamic contrast CT scanner can detect meningiomas with a high probability of severe adhesion toward the brain surface and postoperative intraparenchymal hematoma.
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http://dx.doi.org/10.1007/s00701-020-04295-9DOI Listing
September 2020
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