A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately

地震災害が地域に及ぼす経済的影響 : 直接被害額推定法の提案

The type and intensity of the effects of an earthquake disaster is influenced by the social and economic development patterns prevailing in the region. Thus, it becomes of particular relevance to evaluate the damage caused by such disasters from social and economic perspectives，that is，as part of the development process. Namely，it is important to collect and to analyze the amount of direct and indirect of socioeconomic damages caused by earthquakes for the enhancement of the seismic safety environment in the course of regional development. This study，first of all，develops an experimental equation for estimation of the total amount of direct damage caused by an earthquake in Japan. The evaluation of direct economic loss by the experimental equation is carried out through the use of statistical data “MINRYOKU” which is a database of an accumulated social and economical information in each prefectures and/or cities.1964年新潟地震が発生し、新潟市内では液状化による被害が多発した。この「液状化」現象は世界的に有名になり、地盤工学の分野で発生メカニズムの解明・対策などの技術が飛躍的に進歩した。しかし、新潟市で1,048億円(1994年換算で約1.6兆円)、新潟県で1,300意円(1994年換算で約2.0兆円)の直接被害額が発生し、この直接被害総額は1964年新潟市税収入の約40年分に相当する規模であった。しかし、このような経済的視点からの被害の考察や地震防災の必要性を指摘した事実は見当たらない。同様に、1995年阪神・淡路大震災による被害は、高架橋の横転や大規模な地震火災など、物的被害がセンセーショナルに報道された。しかし、兵庫県における直接被害総額約10兆円の被害規模や、この被害額が震災後も被災地域の社会経済活動に大きく圧し掛かっている事実を詳細に調査・研究しているとは言い難い。今まで、の地域防災計画は、地震発生直後の救急・消火、被災者への対応など救急・応急対応を主眼として構成されていた。もちろん、こうのような緊急・応急対策は重要な対策であるが、他方、地震発生後から始まる地域の復旧・復興、再建、特に、経済活動の早期立ち直りに関する具体な対策が不十分で、あったと推察される。地震後の地域再建過程で問題となるのは、地域経済を如何に速やかに再建させるかである。そのための事前の準備として、経済的被害(直接・間接被害を含む)に関する予測やそれに対する地域経済への影響予測が必要になってくる。しかし、既往の地震災害事例調査を概観すると、そのほとんどが、地震学的観点からの分析・考察、一方、工学分野では物的・人的被害発生の原因究明と対策に限定されていたと言える。物的・人的被害の軽減は地震防災に与えられた究極の課題であるが、同様に、経済的視点からの災害規模の把握・考察さらに経済的対応・対策も必要であると言える。本研究は既往の地震災害を経済的損失面から整理するとともに、直接被害額推定の開発を試みたものである。本論では、1964年以後の被害地震(7地震:表1、2参照)による直接被害額の情報収集・整理を行い、さらに地域固有の「社会経済力」の評価を民力総合指数を用いて行い、両者を対応させることで経験的な直接被害総額推定式(本論の7式)を開発した。この推定式には震度補正項と被害の直接的起因となる地震動、液状化、津波補正の3項目が考慮されている。しかし、社会経済力評価に用いた民力総合指数はストックとフローを合算した指標を用いており、元来、直接被害額とは資本ストックの被災量(額)であるから、この総合指数の中からストックに関連する指標のみを抽出し適切に評価することが重要である。今後の課題として、社会経済力評価の改善とさらに間接被害額も直接被害額と同じかあるいはそれを上回る規模になるとの報告や予測が出ており、それらを今後の研究課題とするものである

Partial suppression of M1 microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosis

BACKGROUND: Accumulating evidence has shown that the inflammatory process participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential of anti-inflammatory agents. Janus kinase 2 (JAK2), one of the key molecules in inflammation, transduces signals downstream of various inflammatory cytokines, and some Janus kinase inhibitors have already been clinically applied to the treatment of inflammatory diseases. However, the efficacy of JAK2 inhibitors in treatment of ALS remains to be demonstrated. In this study, we examined the role of JAK2 in ALS by administering a selective JAK2 inhibitor, R723, to an animal model of ALS (mSOD1(G93A) mice). FINDINGS: Orally administered R723 had sufficient access to spinal cord tissue of mSOD1(G93A) mice and significantly reduced the number of Ly6c positive blood monocytes, as well as the expression levels of IFN-γ and nitric oxide synthase 2, inducible (iNOS) in the spinal cord tissue. R723 treatment did not alter the expression levels of Il-1β, Il-6, TNF, and NADPH oxidase 2 (NOX2), and suppressed the expression of Retnla, which is one of the markers of neuroprotective M2 microglia. As a result, R723 did not alter disease progression or survival of mSOD1(G93A) mice. CONCLUSIONS: JAK2 inhibitor was not effective against ALS symptoms in mSOD1(G93A) mice, irrespective of suppression in several inflammatory molecules. Simultaneous suppression of anti-inflammatory microglia with a failure to inhibit critical other inflammatory molecules might explain this result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-014-0179-2) contains supplementary material, which is available to authorized users

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit

Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V)

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.ArticleACTA NEUROPATHOLOGICA COMMUNICATIONS.4:107(2016)journal articl

Expression of centromere protein F (CENP-F) associated with higher FDG uptake on PET/CT, detected by cDNA microarray, predicts high-risk patients with primary breast cancer

<p>Abstract</p> <p>Background</p> <p>Higher standardized uptake value (SUV) detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) correlates with proliferation of primary breast cancer. The purpose of this study is to identify specific molecules upregulated in primary breast cancers with a high SUV and to examine their clinical significance.</p> <p>Methods</p> <p>We compared mRNA expression profiles between 14 tumors with low SUVs and 24 tumors with high SUVs by cDNA microarray. We identified centromere protein F (CENP-F) and CDC6 were upregulated in tumors with high SUVs. RT-PCR and immunohistochemical analyses were performed to validate these data. Clinical implication of CENP-F and CDC6 was examined for 253 archival breast cancers by the tissue microarray.</p> <p>Results</p> <p>The relative ratios of CENP-F and CDC6 expression levels to β-actin were confirmed to be significantly higher in high SUV tumors than in low SUV tumors (<it>p </it>= 0.027 and 0.025, respectively) by RT-PCR. In immunohistochemical analysis of 47 node-negative tumors, the CENP-F expression was significantly higher in the high SUV tumors (74%) than the low SUV tumors (45%) (<it>p </it>= 0.04), but membranous and cytoplasmic CDC6 expressions did not significantly differ between both groups (<it>p </it>= 0.9 each). By the tissue microarray, CENP-F (HR = 2.94) as well as tumor size (HR = 4.49), nodal positivity (HR = 4.1), and Ki67 (HR = 2.05) showed independent impact on the patients' prognosis.</p> <p>Conclusion</p> <p>High CENP-F expression, correlated with high SUV, was the prognostic indicators of primary breast cancer. Tumoral SUV levels may serve as a pretherapeutic indicator of aggressiveness of breast cancer.</p

Ethnic comparison in takotsubo syndrome : novel insights from the International Takotsubo Registry

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.Open Access funding provided by Universität Zürich. CT has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. has been supported by EU HORIZON 2020 (SILICOFCM ID777204). J.R.G has received a grant “Filling the gap” from the University of Zurich. The InterTAK Registry is supported by The Biss Davies Charitable Trust.info:eu-repo/semantics/publishedVersio