Publications by authors named "Hiroyuki Suzuki"

635 Publications

[Association between Immunotherapy with Immune Checkpoint Inhibitors(Anti-PD-1 Antibodies)and Intestinal Microbiota].

Gan To Kagaku Ryoho 2021 Sep;48(9):1096-1099

Dept. of Chest Surgery, Fukushima Medical University.

Immune checkpoint inhibitors(ICIs)are playing an increasingly important role in the treatment of cancer. In the field of lung cancer, ICIs are widely administered from primary therapy to maintenance therapy after chemoradiation for non-small cell lung cancer. However, excluding tumor proportion score(TPS)for PD-L1, no other biomarker has been reported to be clinically useful. While many biomarkers are being searched for, analysis of intestinal microbiota is attracting attention as a parameter that may reflect immune status. Research on the relationship between ICIs and gut microbiota has expanded worldwide after 2 reports in Science in 2015. In a study in which the gut microbiota of ICI-treated patients was transplanted into germ-free mice, enhanced antitumor effects were observed in the group that received gut microbiota from the response group, suggesting the possibility of stool transplantation. At the same time, when Akkermansia muciniphila, which is one of the mucin-degrading bacteria, was ingested by mice transplanted with non-responsive gut microbiota, a portion of tumor-infiltrating T cells increased on tumor localization, indicating the effect of changes in gut microbiota. In addition, there is a possibility that the anti-tumor effect may be enhanced by the effect of metabolites on immune cells in the blood rather than the gut microbiota itself, and the analysis of metabolites produced by bacteria is attracting attention. In our department, we have analyzed the intestinal microbiota of 25 non-small cell lung cancer patients treated with anti- PD-1 antibody. Although we have achieved diversity and identification of specific bacterial species, analysis of bacterial metabolites will be important in the future when considering the impact of the intestinal microbiota on immune cells. The gut microbiota is not only a biomarker for the treatment of ICIs, but also has the potential to create an immune state that facilitates the effects of ICI by changing the gut environment and metabolites.
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September 2021

Clinical Importance of Regimens in Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Macrovascular Invasion.

Cancers (Basel) 2021 Sep 3;13(17). Epub 2021 Sep 3.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child-Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively ( < 0.05, < 0.05). The complete response (29%) and objective response rate (76%) of New FP were significantly higher than those of LFP ( < 0.001, < 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC.
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http://dx.doi.org/10.3390/cancers13174450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431395PMC
September 2021

Copper-64-Labeled Antibody Fragments for Immuno-PET/Radioimmunotherapy with Low Renal Radioactivity Levels and Amplified Tumor-Kidney Ratios.

ACS Omega 2021 Aug 12;6(33):21556-21562. Epub 2021 Aug 12.

Laboratory of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8675 Japan.

Copper-64 (Cu)-labeled antibody fragments such as Fab are useful for molecular imaging (immuno-PET) and radioimmunotherapy. However, these fragments cause high and persistent localization of radioactivity in the kidneys after injection. To solve this problem, this study assessed the applicability of a molecular design to Cu, which reduces renal radioactivity levels by liberating a urinary excretory radiometabolite from antibody fragments at the renal brush border membrane (BBM). Since 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) forms a stable complex with Cu, NOTA-conjugated Met-Val-Lys-maleimide (NOTA-MVK-Mal), which is a radio-gallium labeling agent for antibody fragments, was evaluated for applicability to Cu. The MVK linkage was recognized by the BBM enzymes to liberate [Cu]Cu-NOTA-Met although the recognition of the MVK sequence for the [Cu]Cu-NOTA-MVK derivative was reduced compared with that of its [Ga]Ga-counterpart, probably due to the difference in the charge of the metal-NOTA complexes. When injected into mice, [Cu]Cu-NOTA-MVK-Fab resulted in similar renal radioactivity levels to the Ga-labeled counterpart. In addition, [Cu]Cu-NOTA-MVK-Fab resulted in lower renal radioactivity levels than those from Cu-labeled Fab using a conventional method, without a reduction in the tumor radioactivity levels. These findings indicate that our approach to reducing renal radioactivity levels by liberating a radiolabeled compound from antibody fragments at the renal BBM for urinary excretion is applicable to Cu-labeled antibody fragments and useful for immuno-PET and radioimmunotherapy.
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http://dx.doi.org/10.1021/acsomega.1c02516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388099PMC
August 2021

Analysis of onset and clinical characteristics in Japanese patients with infantile hemangioma.

Drug Discov Ther 2021 Aug 26. Epub 2021 Aug 26.

Department of Dermatology, Wakayama Medical University, Wakayama, Japan.

Infantile hemangioma (IH) is a common benign tumor during infancy, although the detailed mechanism behind it has not been fully elucidated. Based on previous studies, we hypothesized that formation of hemangioma might be triggered by secondary physiological events (perinatal hypoxia or mechanical stress during delivery) in patients carrying germline risk mutations. We aimed to clarify the mechanism by evaluating whether head and neck lesions were more frequent in patients in who IH appeared after birth compared with those in who it was present at birth. Clinical data of 62 lesions in 51 patients with IH were collected. All patients were analyzed for correlation of onset with gender, localization, family histories, gestational age, birth weight, and clinical subtypes. Distribution of lesions on the head and neck was slightly more frequent in the after-birth IH group, compared with those with IH present at birth, but without significant difference (47.6% vs. 40.0%, p = 0.32). On the other hand, the ratio of superficial and deep type IH at birth was significantly altered compared with that in IH after birth (19:0 vs. 26:7, p = 0.039). In addition, IHs appearing after birth tended to more commonly have multiple lesions than those with IH present at birth, with statistically significant difference (25.8% vs. 0%, p = 0.0164). There may therefore be different triggers for IHs at birth and IH after birth. Further studies with greater number of patients are necessary to validate these findings.
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http://dx.doi.org/10.5582/ddt.2021.01066DOI Listing
August 2021

Pathological Complete Response after Immune-Checkpoint Inhibitor Followed by Salvage Surgery for Clinical Stage IV Pulmonary Adenocarcinoma with Continuous Low Neutrophil-to-Lymphocyte Ratio: A Case Report.

Case Rep Oncol 2021 May-Aug;14(2):1124-1133. Epub 2021 Jul 19.

Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.

Immune-checkpoint inhibitors (ICIs) play a crucial role in the treatment of advanced nonsmall cell lung cancer (NSCLC); however, most patients fail this treatment after a limited period. We here report a patient with a pathological complete response after treatment with ICI for stage IV pulmonary adenocarcinoma. A 73-year-old man was referred to our hospital because of hoarseness. A roentgenogram and chest CT scan revealed a huge (78-mm diameter) pulmonary tumor in the right upper lobe and a tumor with cavitation in the left lower lobe. A CT scan also showed enlarged upper mediastinal lymph nodes (LNs). Transbronchial lung biopsy of the tumors showed adenocarcinomas in both. The tumor in the right upper lobe was considered to be the primary with mediastinal LNs metastasis and that in the left lower lobe a pulmonary metastasis. The disease was determined to be cT4N2M1a stage IVA. He was treated with first-line chemotherapy comprising cisplatin, pemetrexed, and bevacizumab for 6 cycles. However, 6 months after initial treatment, the primary and metastatic tumors enlarged, and he was treated with second-line anti-programed death 1 therapy for 7 months with a partial response. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed weak accumulation of FDG in the primary tumor only with no accumulation in the left pulmonary metastasis or mediastinal lymph node (LNs), despite the LNs still being enlarged. He was diagnosed as having ycT1bN0M0 stage IA2 disease and underwent right upper lobectomy. Postoperative pathological findings revealed that cancer tissues had been replaced by scar tissue and that CD4-positive T cells, rather than CD8-positive T cells, were predominant. It was also noted that he had a lower neutrophil-to-lymphocyte ratio (NLR) during immunotherapy than before immunotherapy and after surgery. He was diagnosed to be ypT0N0M0 stage 0 (Ef.3). His postoperative course was uneventful, and he remained well for 12 months after surgery with no further treatment. Neoadjuvant chemotherapy with ICIs for advanced NSCLC may be a promising modality, even for clinical stage IV disease, in the near future. Furthermore, NLR during immunotherapy may be a promising biomarker of ICIs treatment.
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http://dx.doi.org/10.1159/000515509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339520PMC
July 2021

[Ⅲ. Advances of Treatment Strategies for Locally Advanced Non-Small Cell Lung Cancer].

Gan To Kagaku Ryoho 2021 Aug;48(8):1027-1032

Dept. of Chest Surgery, Fukushima Medical University, School of Medicine.

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August 2021

[Thorax/Lung and Mediastinum, Pleura: Cancer].

Authors:
Hiroyuki Suzuki

Gan To Kagaku Ryoho 2021 Aug;48(8):1012-1013

Dept. of Chest Surgery, Fukushima Medical University, School of Medicine.

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August 2021

Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments.

Transl Oncol 2021 Aug 11;14(11):101201. Epub 2021 Aug 11.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

Objective: Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib.

Methods: Antitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015.

Results: In mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p < 0.05); however, there were no significant differences in overall survival and time to progression. Adverse events including alopecia, thrombocytopenia, and pancreatic enzymes elevation in the combination chemotherapy were higher than those of sorafenib. No patient treated with the combination chemotherapy discontinued treatment due to severe adverse events.

Conclusions: Sorafenib plus MC S-1 seems to be effective and tolerable for patients with advanced HCC and could be considered a treatment option for these patients.
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http://dx.doi.org/10.1016/j.tranon.2021.101201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363883PMC
August 2021

Glycoprotein non-metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation.

Cancer Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Breast cancer is the most common cancer among women. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression confers tumorigenic potential, as evidenced by invasive tumor growth in vivo, sphere formation, and cellular migration and invasion to non-tumorigenic mammary epithelial cells. In this study, we focused on the serine (S) residue in the intracellular domain of GPNMB (S530 in human isoform b and S546 in mouse), which is predicted to be a phosphorylation site. To investigate the roles of this serine residue, we made an antibody specific for S530-phosphorylated human GPNMB and a point mutant in which S530 is replaced by an alanine (A) residue, GPNMB(SA). Established GPNMB(SA) overexpressing cells showed a significant reduction in sphere formation in vitro and tumor growth in vivo as a result of decreased stemness-related gene expression compared to that in GPNMB(WT)-expressing cells. In addition, GPNMB(SA) impaired GPNMB-mediated cellular migration. Furthermore, we found that tyrosine kinase receptor signaling triggered by epidermal growth factor or fibroblast growth factor 2 induces the serine phosphorylation of GPNMB through activation of downstream oncoproteins RAS and RAF.
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http://dx.doi.org/10.1111/cas.15090DOI Listing
July 2021

Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults.

Front Behav Neurosci 2021 22;15:641608. Epub 2021 Jun 22.

Research Team for Human Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Objective: To assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults.

Design: Two-year prospective, observational study.

Setting And Participants: The study included 405 adults aged 65-84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan.

Methods: Participants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores.

Results: Among individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02-0.62; = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13-0.60; < 0.001).

Conclusion And Implications: Higher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults.
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http://dx.doi.org/10.3389/fnbeh.2021.641608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258380PMC
June 2021

Oral health status and its association with nutritional support in malnourished patients hospitalised in acute care.

Gerodontology 2021 Jul 7. Epub 2021 Jul 7.

Department of Gerodontology and Oral Rehabilitation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Objectives: This cross-sectional study aimed to examine the oral health of malnourished acute-care hospital inpatients, who were the subjects of a nutritional support team (NST). We also aimed to elucidate the systemic and nutritional factors associated with the oral health of those patients.

Background: Interventions by NST are essential for inpatient nutrition management and require the active participation of dental professionals. However, information is limited regarding the state of oral health among acute-stage malnourished inpatients.

Materials And Methods: We enrolled 255 hospitalised patients (101 women, mean age: 69.7 ± 14.4 years) who were referred to an NST for nutrition management between April 2016 and July 2019. The main outcome was the Oral Health Assessment Tool (OHAT) scores. Moreover, we assessed participants' demographic characteristics, nutritional status, number of natural and functional teeth, posterior occlusal support, denture use, Dysphagia Severity Scale, whether oral health management was needed, and the methods of nutrition intake.

Results: Several participants presented with a deteriorated oral health. Consequently, oral health management was often regarded necessary in these patients. Approximately half were fed by parenteral or tube feeding. Multiple regression analysis revealed the OHAT score has a positive association with age (P = .008), and a negative association with body mass index (P = .009) and the method of nutrition intake (P = .028).

Conclusion: Malnourished inpatients at an acute care hospital who were subject to an NST had a deteriorated oral health status. Additionally, poor oral health was associated with poor nutritional status and nutrition intake methods.
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http://dx.doi.org/10.1111/ger.12582DOI Listing
July 2021

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice.

Cancers (Basel) 2021 Jun 3;13(11). Epub 2021 Jun 3.

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC.

Materials And Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs).

Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs.

Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.
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http://dx.doi.org/10.3390/cancers13112786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199943PMC
June 2021

A patient with ALK-positive lung adenocarcinoma who survived alectinib-refractory postoperative recurrence for 4 years by switching to ceritinib.

Thorac Cancer 2021 08 23;12(15):2225-2228. Epub 2021 Jun 23.

Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements are found in ~ 5% of patients with non-small cell lung cancer (NSCLC). Several tyrosine kinase inhibitors (TKIs) have been developed for treatment of so-called ALK-positive NSCLC. In cases of tumor progression during treatment with second-generation ALK-TKIs, such as alectinib, brigatinib, or ceritinib, National Comprehensive Cancer Network guidelines propose a switch to lorlatinib, a third-generation ALK-TKI, or to cytotoxic chemotherapy. However, they do not mention switching to other second-generation ALK-TKIs. Here, we present a rare case of a 53-year-old Japanese woman, who had never smoked, with ALK-positive lung adenocarcinoma who survived alectinib-resistant postoperative recurrence for 4 years by switching to ceritinib. She underwent curative resection for lung adenocarcinoma, but the cancer recurred at the bronchial stump and mediastinal lymph nodes. After platinum-doublet chemotherapy, the patient still had a single growing liver metastasis, but the tumor was found to harbor EML4-ALK rearrangement. Therefore, the patient started to take ALK-TKIs. Alectinib was the second ALK-TKI used to treat this patient. Alectinib shrank the liver metastasis, which was surgically resected. The tumor relapsed again during continued treatment with alectinib, which was switched to ceritinib. Ceritinib was effective for the relapsed tumor and treatment continued well for 4 years. This case report suggests that, in case of tumor progression during treatment with a second-generation ALK-TKI, switching to another second-generation ALK-TKI may be one of the treatment options. Further analyses are warranted to find robust markers to determine which ALK-TKI is best for each patient.
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http://dx.doi.org/10.1111/1759-7714.14058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327688PMC
August 2021

CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma.

Sci Rep 2021 Jun 15;11(1):12554. Epub 2021 Jun 15.

Department of Basic Pathology, Graduate School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Malignant mesothelioma is a cancer with a poor survival rate. It is difficult to diagnose mesotheliomas because they show a variety of histological patterns similar to those of various other cancers. However, since currently used positive markers for mesotheliomas may show false positives or false negatives, a novel mesothelial positive marker is required. In the present study, we screened 25 claudins and found that claudin-15 is expressed in the mesothelial cells. We made new rat anti-human claudin-15 (CLDN15) monoclonal antibodies that selectively recognize CLDN15, and investigated whether CLDN15 is a good positive marker for malignant pleural mesotheliomas (MPMs) using MPM tissue samples by immunohistochemistry and semi-quantification of the expression level using an immunoreactive score (IRS) method. Of 42 MPM samples, 83% were positive for CLDN15. The positive ratio was equal to or greater than other positive markers for MPMs including calretinin (81%), WT-1 (50%), and D2-40 (81%). In 50 lung adenocarcinoma sections, four cases were positive for CLDN15 and the specificity (92%) was comparable with other markers (90-100%). Notably, CLDN15 was rarely detected in 24 non-mesothelial tumors in the tissue microarray (12/327 cases). In conclusion, CLDN15 can be used in the clinical setting as a positive marker for MPM diagnosis.
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http://dx.doi.org/10.1038/s41598-021-91464-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206149PMC
June 2021

Randomized Controlled Trial of the Picture Book Reading Program on Cognitive Function in Middle-Aged People.

Front Psychiatry 2021 19;12:624487. Epub 2021 May 19.

Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

To delay cognitive decline, it is important to engage actively in preventive activities from middle age (50-64 years of age). We have developed a cognitive intervention program using picture book reading, and demonstrated that it is effective for improving memory in older adults. However, the effect of the intervention on memory and other cognitive functions in middle-aged people has not been examined. The current study investigated the effects of the picture book reading program on cognitive function in middle-aged people. This single-blind (examiners were blinded) randomized controlled trial was conducted in Tokyo, Japan. A total of 65 participants were randomly assigned to the intervention group (IG) ( = 32), in which members attended 12 picture book reading classes held once a week, or the active control group (CG) ( = 33), in which members received lectures on health maintenance. Cognitive tests were conducted before and after the intervention. The primary outcome was memory, and the secondary outcomes were verbal function and executive function. The results showed that there was no significant difference between the IG and the CG in change scores (post minus pre) for memory. On the other hand, there was a significant difference in change scores of the category fluency, which is a measure of verbal function, suggesting improvements in IG compared to CG. There were also no significant differences in executive function. The results indicated that our previous finding of an improvement in memory function in older adults was not found in middle-aged people. However, the findings suggest that the picture book reading program may affect lexical access ability in verbal function among middle-aged people. Because maintaining verbal function is important for daily communication, these findings suggest that this program may be a useful countermeasure for cognitive decline in middle-aged people. University Hospital Medical Information Network Clinical Trial Registry, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048012, Identifier: UMIN 000042071.
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http://dx.doi.org/10.3389/fpsyt.2021.624487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170038PMC
May 2021

Intimal thickening and disruption of the media occur in the arterial walls of coronary arteries not associated with coronary arterial aneurysms in patients with Kawasaki disease.

BMC Cardiovasc Disord 2021 06 5;21(1):278. Epub 2021 Jun 5.

Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan.

Background: Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries that are not associated with CAA.

Methods: We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings during the most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R; arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT.

Results: Fifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality during the most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thicknesses in groups R and N were 475 and 355 µm, respectively (p = 0.007). The incidences of media disruption were 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group.

Conclusions: Intimal thickening and disruption of the media occur in coronary arteries with acute phase CAAs that later regress in the convalescent phase, as well as in arteries with normal CAG findings in the acute and convalescent phases.
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http://dx.doi.org/10.1186/s12872-021-02090-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180057PMC
June 2021

AST-120 Treatment Alters the Gut Microbiota Composition and Suppresses Hepatic Triglyceride Levels in Obese Mice.

Endocr Res 2021 Jun 1:1-8. Epub 2021 Jun 1.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. The existence of a relationship between the microbiota and the pathology of hepatic steatosis is also becoming increasingly clear. AST-120, an oral spherical carbon adsorbent, has been shown to be useful for delaying dialysis initiation and improving uremic symptoms in patients with chronic kidney disease. However, little is known about the effect of AST-120 on fatty liver. AST-120 (5% w/w) was administrated to 6-week-old male mice for 8 weeks. The body weight, blood glucose and food consumption were examined. Hepatic triglyceride (TG) levels, lipid droplets and epididymal fat cell size were measured. The gut microbiota compositions were investigated in feces and cecum. Significant decreases of the hepatic weight and hepatic TG levels were observed in the AST-120-treated mice. Furthermore, AST-120 treatment was also associated with a decrease of Bacteroidetes, increase of Firmicutes, and a reduced ratio of Bacteroidetes to Firmicutes (B/F ratio) in the feces in the mice. The B/F ratio in the feces was correlated with the liver weight and area of the liver occupied by lipid droplets in the mice. These data suggest that AST-120 treatment alters the composition of the fecal microbiota and suppresses hepatic TG levels in the mice.
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http://dx.doi.org/10.1080/07435800.2021.1927074DOI Listing
June 2021

Randomized phase II study of daily and alternate-day administration of S-1 for adjuvant chemotherapy in completely-resected stage I non-small cell lung cancer: results of the Setouchi Lung Cancer Group Study 1301.

BMC Cancer 2021 May 6;21(1):506. Epub 2021 May 6.

Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.

Background: The aim of this multicenter, randomized phase II study was to analyze the feasibility and safety of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological stage I (tumor diameter > 2 cm) non-small cell lung cancer (NSCLC).

Methods: Patients were randomly assigned to receive adjuvant chemotherapy for 1 year comprising either alternate-day oral administration of S-1 (80 mg/m/day) for 4 days a week (Group A) or a 2-week oral administration of S-1 (80 mg/m/day) followed by 1 week of rest (Group B). The primary endpoint was feasibility, which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results: Ninety-three patients were enrolled of whom 90 patients received S-1 treatment. Median follow-up was 66.9 months. The treatment completion rate based on an RDI of 70% or more for 6 months was 84.4% (95%CI; 70.5-93.5%) in group A and 64.4% (95%CI; 48.8-78.1%) in group B. There were no grade 4 adverse events in either group. Moderate or severe adverse events (grade 2 or grade 3) were significantly more frequent in group B (67%) compared with group A (29%, P = 0.001). The 5-year relapse-free survival rate was 87.0 and 80.9% for group A and B, respectively (P = 0.451). The 5-year overall survival rate for all patients (n = 93) was 100 and 89.4% for group A and B, respectively (P = 0.136).

Conclusion: Alternate-day oral administration of S-1 for 1 year as adjuvant chemotherapy was demonstrated to be feasible with low toxicity in completely resected stage I (tumor diameter > 2 cm) NSCLC.

Trial Registration: Trial registration number: UMIN000011994 . Date of registration: 10/8/2013.
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http://dx.doi.org/10.1186/s12885-021-08232-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101150PMC
May 2021

Acute kidney injury successfully treated with autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation: A first-in-human report.

Stem Cells Transl Med 2021 Sep 6;10(9):1253-1257. Epub 2021 May 6.

Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura, Japan.

A 36-year-old man with severe acute kidney injury (AKI) was admitted to Shonan Kamakura General Hospital in Japan. He was diagnosed with refractory hypertension based on a severely elevated blood pressure of 224/116 mmHg and retinal, cardiac, and brain damage revealed by electrocardiogram, fundoscopy, and magnetic resonance imaging, respectively. Although hemodialysis was withdrawn following strict blood pressure control by an angiotensin receptor blocker, severe kidney insufficiency persisted. Therefore, we performed an autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation. Collected CD34-positive cells were directly infused to both renal arteries. The patient's general condition was unremarkable after intervention, and the serum creatinine level gradually improved to 2.96 mg/dL 23 weeks after cell therapy. Although transient fever and thrombocytosis were observed after intervention, no major adverse events were observed. This patient is the first case in a phase I/II clinical trial of autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation for severe AKI with a CD34-positive cell dose-escalating protocol (trial number jRCTb030190231).
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http://dx.doi.org/10.1002/sctm.20-0561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380438PMC
September 2021

Structural Equation Modeling of Tongue Function and Tongue Hygiene in Acute Stroke Patients.

Int J Environ Res Public Health 2021 04 26;18(9). Epub 2021 Apr 26.

Gerodontology and Oral Rehabilitation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.

In acute stroke patients, it is important to maintain tongue hygiene and tongue function for prognosis management. However, the direct relationship between these factors is unclear, since these are often assessed by multiple observables. In this study, we used structural equation modeling (SEM) analysis, a tool to analyze the relationship between concepts that cannot be measured directly, to analyze the relationship between tongue hygiene and tongue function. The subjects were 73 patients with acute stroke admitted to a university hospital who underwent dental intervention. Age, sex, nutritional intake method, clinical severity classification of dysphagia, number of current teeth, number of functional teeth, oral health, tongue movement, tongue coating, number of microorganisms on the tongue surface, tongue surface moisture level, and tongue pressure were measured at the first visit. SEM analysis showed that the relationship between tongue function and tongue hygiene was 0.05 between tongue function and swallowing function was 0.90, and that between tongue hygiene and swallowing function was 0.09. We found no statistical relationship between tongue function and tongue hygiene in acute stroke patients. However, it was reconfirmed that tongue function is strongly related to feeding and swallowing functions.
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http://dx.doi.org/10.3390/ijerph18094567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123496PMC
April 2021

Evaluation of the usefulness of cystic duct three-dimensional computed tomography with non-contrast for before laparoscopic cholecystectomy and endoscopic transpapillary gallbladder drainage in comparison to magnetic resonance cholangiopancreatography.

J Med Imaging Radiat Sci 2021 06 24;52(2):248-256. Epub 2021 Apr 24.

Department of Radiology, Fuji City General Hospital, 50 Takashima-cho, Fuji City, Shizuoka 417-8567, Japan. Electronic address:

Introduction: The purpose of this study is to evaluate whether anatomical variations of the cystic duct and accessory bile duct can be grasped by cystic duct three-dimensional (3D)-computed tomography (CT) using non-contrast CT and to examine the possibility of omitting magnetic resonance cholangiopancreatography (MRCP).

Methods: Of patients who underwent non-contrast abdominal CT between May and October 2019, those who underwent MRCP within 1 month before and afterwards were targeted. Seven assessors visually evaluated the cystic duct 3D-CT images on a 5-point scale. Average scores of ≥3 and <3 points were assigned as the good and poor groups, respectively. Regions of interest (ROIs) were placed inside the cystic duct and four places around it, and the CT values in those ROIs were measured. The CT value difference was calculated by subtracting the surrounding CT values from the CT value in the cystic duct and converting the result to an absolute value. The CT value difference was classified into good and poor groups, and statistical analysis was performed. Seven assessors evaluated anatomical variations of the cystic duct and the presence of the accessory bile duct. The results were compared with the MRCP interpretation results to calculate sensitivity, specificity, positive predictive value, and negative predictive value.

Results: The average visual evaluation score was 3.8. The good and poor groups were comprised by 53 (85.5%) and 9 (14.5%) patients, respectively. The CT difference value averages were 54.7 and 15.9 for the good and poor groups, respectively, and the value was significantly higher in the good group (p = 0.001). The comparison results with MRCP were sensitivity=83.3%, specificity=78.0%, positive predictive value=47.6%, and negative predictive value=95.1%.

Conclusion: Cystic duct 3D-CT using non-contrast CT is a useful technique for understanding anatomical variations of the cystic duct and accessory bile duct. Our method may reduce the number of MRCP sessions performed.
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http://dx.doi.org/10.1016/j.jmir.2021.03.037DOI Listing
June 2021

Hearing loss and increased gait variability among older adults.

Gait Posture 2021 06 8;87:54-58. Epub 2021 Apr 8.

Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.

Background: The influence of age-related hearing loss on slow gait has been suggested; however, whether it is associated with increased gait variability, an important predictor of fall risk, remains unclear.

Research Question: Is poor auditory acuity associated with increased gait variability, and does this gait change relate to accidental falls among older adults with hearing loss?

Methods: We studied 107 older adults (mean age, 76.5 years; 80.5 % women). Auditory acuity was measured using a pure tone average (PTA) of hearing thresholds for 0.5-4 kHz tones in the better-hearing ear. Hearing loss was defined as a PTA of >25 dB. Gait speed and spatiotemporal variability (i.e., stride length and time variabilities) were assessed using a 5-m electronic walkway. We also assessed the occurrence of multiple falls within the previous year.

Results: Fifty-two participants (48.6 %) experienced hearing loss. Multiple regression analysis adjusted for potential covariates showed that poor PTA was associated with slower gait speed and stride length variability, but not stride time variability. Among older adults with hearing loss, fall occurrence was associated with an increased stride length variability and not a slow gait or increased stride time variability.

Significance: The association between hearing loss and increased gait variability observed in the present study suggests that age-related hearing loss can jeopardize gait control during daily activities. This leads to increased gait variability and increased risk of accidental falls. Our results provide additional information on how age-related hearing loss increases the risk of falls.
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http://dx.doi.org/10.1016/j.gaitpost.2021.04.007DOI Listing
June 2021

Evaluation of SAMP8 Mice as a Model for Sleep-Wake and Rhythm Disturbances Associated with Alzheimer's Disease: Impact of Treatment with the Dual Orexin (Hypocretin) Receptor Antagonist Lemborexant.

J Alzheimers Dis 2021 ;81(3):1151-1167

Eisai Inc., Woodcliff Lake, NJ, USA.

Background: Many patients with Alzheimer's disease (AD) display circadian rhythm and sleep-wake disturbances. However, few mouse AD models exhibit these disturbances. Lemborexant, a dual orexin receptor antagonist, is under development for treating circadian rhythm disorders in dementia.

Objective: Evaluation of senescence-accelerated mouse prone-8 (SAMP8) mice as a model for sleep-wake and rhythm disturbances in AD and the effect of lemborexant by assessing sleep-wake/diurnal rhythm behavior.

Methods: SAMP8 and control senescence-accelerated mouse resistant-1 (SAMR1) mice received vehicle or lemborexant at light onset; plasma lemborexant and diurnal cerebrospinal fluid (CSF) orexin concentrations were assessed. Sleep-wake behavior and running wheel activity were evaluated.

Results: Plasma lemborexant concentrations were similar between strains. The peak/nadir timing of CSF orexin concentrations were approximately opposite between strains. During lights-on, SAMP8 mice showed less non-rapid eye movement (non-REM) and REM sleep than SAMR1 mice. Lemborexant treatment normalized wakefulness/non-REM sleep in SAMP8 mice. During lights-off, lemborexant-treated SAMR1 mice showed increased non-REM sleep; lemborexant-treated SAMP8 mice displayed increased wakefulness. SAMP8 mice showed differences in electroencephalogram architecture versus SAMR1 mice. SAMP8 mice exhibited more running wheel activity during lights-on. Lemborexant treatment reduced activity during lights-on and increased activity in the latter half of lights-off, demonstrating a corrective effect on overall diurnal rhythm. Lemborexant delayed the acrophase of activity in both strains by approximately 1 hour.

Conclusion: SAMP8 mice display several aspects of sleep-wake and rhythm disturbances in AD, notably mistimed activity. These findings provide some preclinical rationale for evaluating lemborexant in patients with AD who experience sleep-wake and rhythm disturbances.
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http://dx.doi.org/10.3233/JAD-201054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293654PMC
January 2021

Construction of patient-derived tumor models to evaluate anticancer agents and cancer immunotherapy.

Oncol Lett 2021 May 22;21(5):406. Epub 2021 Mar 22.

Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan.

An assay system using patient-derived tumor models represents a promising preclinical cancer model that replicates the disease better than traditional cell culture models. Patient-derived tumor organoid (PDO) and patient-derived tumor xenograft (PDX) models have been previously established from different types of human tumors to recapitulate accurately and efficiently their tissue architecture and function. However, these models have low throughput and are challenging to construct. Thus, the present study aimed to establish a simple high-throughput assay system using PDO and PDX models. Furthermore, the current study aimed to evaluate different classes of anticancer drugs, including chemotherapeutic, molecular targeted and antibody drugs, using PDO and PDX models. First, an high-throughput assay system was constructed using PDO and PDX established from solid and hematopoietic tumors cultured in 384-well plates to evaluate anticancer agents. In addition, an evaluation system of the immune response was developed using PDO and PDX. Novel cancer immunotherapeutic agents with marked efficacy have been used against various types of tumor. Thus, there is an urgent need for functional potency assays that can simulate the complex interaction of immune cells with tumor cells and can rapidly test the efficacy of different immunotherapies or antibody drugs. An evaluation system for the antibody-dependent cellular cytotoxic activity of anti-epidermal growth factor receptor antibody and the cytotoxic activity of activated lymphocytes, such as cytotoxic T lymphocytes and natural killer cells, was constructed. Moreover, immune response assay systems with bispecific T-cell engagers were developed using effector cells. The present results demonstrated that assay systems using PDO and PDX may be suitable for evaluating anticancer agents and immunotherapy potency with high reproducibility and simplicity.
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http://dx.doi.org/10.3892/ol.2021.12667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020396PMC
May 2021

Therapeutic Outcomes and Prognostic Factors of Unresectable Intrahepatic Cholangiocarcinoma: A Data Mining Analysis.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume 830-0011, Japan.

Prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is unsatisfactory. Tumor, host, and treatment factors including hepatic arterial infusion chemotherapy (HAIC) are intricately involved in the progression of ICC. We aimed to identify profiles associated with disease control rate (DCR) and the prognosis of patients with unresectable ICC by decision tree analysis. We analyzed 31 consecutive patients with unresectable ICC (median age, 71 years; the male ratio was 58.1%). Stage IVB occupied 51.6% of patients, and 38.7% and 58.1% of patients were treated with gemcitabine plus cisplatin combination therapy and HAIC, respectively. Profiles associated with prognosis as well as DCR were investigated by decision tree analysis. The median survival time (MST) of the patients was 11.6 months, and the DCR was 70.9%. Multivariate correlation analysis showed that albumin levels and WBC levels were significantly correlated with survival time (albumin, ρ = 0.3572, = 0.0485; WBC, ρ = -0.4008, = 0.0280). In decision tree analysis, WBC level was selected as the initial split variable, and subjects with WBC levels of 6800/μL or less (45.1%) showed a long survival time (MST 476 days). We also demonstrated that the profile associated with the highest DCR was "less than 4.46 mg/dL of CRP levels and treatment with HAIC". We demonstrated a new prognostic profile for ICC patients, which consisted of WBC and CRP levels. Moreover, we demonstrated that HAIC was associated with better disease control in ICC patients with low CPR levels. Thus, these new profiles may be useful for the management of ICC patients.
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http://dx.doi.org/10.3390/jcm10050987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957874PMC
March 2021

Diffuse Cystic Metastases in the Lung after Nivolumab Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report.

Case Rep Oncol 2021 Jan-Apr;14(1):34-38. Epub 2021 Feb 18.

Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.

Although diffuse cysts in the lung can be found in many diseases, they are uncommon in metastatic lung adenocarcinoma. They are even more unusual after the administration of immune checkpoint inhibitors. A case of lung adenocarcinoma that developed diffuse cysts in the lungs during treatment with nivolumab is reported. The patient was a 60-year-old woman with postoperative recurrent lung adenocarcinoma in mediastinal lymph nodes and pleural dissemination. After first-line treatment with cisplatin, pemetrexed, and bevacizumab, computed tomography (CT) showed disease progression. Treatment was then switched to nivolumab. After 5 courses of nivolumab, CT showed multiple ground-glass nodules in her lungs. After 4 more courses of nivolumab, the ground-glass nodules increased in size, and cystic air spaces appeared in their centers. The patient did not have any symptoms. Laboratory tests showed no evidence of infection or nivolumab-induced pneumonitis. Sialyl Lewis X-i antigen increased, and positron emission tomography showed abnormal uptake of F-fluorodeoxyglucose in these lesions. Considering this evidence, the cystic lesions were diagnosed as multiple lung metastases. Various differential diagnoses should be considered when diffuse cystic lesions are found in the lungs after the administration of immune checkpoint inhibitors.
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http://dx.doi.org/10.1159/000513426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983537PMC
February 2021

Z-score is a possible predictor of the risk of coronary artery lesion development in patients with Kawasaki disease in Japan.

Eur J Pediatr 2021 Sep 24;180(9):2797-2805. Epub 2021 Mar 24.

Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan.

Risk factors for coronary artery lesion (CAL) development in patients with Kawasaki disease (KD) include male sex, age < 12 months, intravenous immunoglobulin (IVIG) resistance, and delayed diagnosis.. We aimed to explore the relationship between CAL development and Z-score. We enrolled 281 patients with KD who were treated with our protocol. Echocardiography was performed in three phases: pre-treatment (P1), post-treatment (P2), and 4 weeks after onset (P3). The highest Z-score of the right, left main, left anterior descending, and left circumflex coronary arteries was expressed as Zmax at each phase. P3-Zmax ≥ 2.5 represented CAL development. Clinical parameters, such as laboratory data and Z-scores, were retrospectively compared between patients with and without CAL development. Sixty-seven patients (23.8%) showed a P1-Zmax ≥ 2.0, and CAL development occurred in 21 patients (7.5%). Independent risk factors associated with CAL development were P1-Zmax, a ΔZmax (P2-Zmax - P1-Zmax) ≥ 1, male sex, < 12 months of age, and resistant to the first intravenous immunoglobulin (IVIG) administration (adjusted odds ratio [95% confidence interval]: 198 [1.01-3.92], 4.04 [1.11-14.7], 6.62 [1.33-33.04], 4.71 [1.51-14.68], 5.26 [1.62-17.13], respectively). Using receiver operating characteristic curve analysis, a P1-Zmax ≥ 1.43 detected CAL development with an area under the curve of 0.64 (sensitivity = 81.0%; specificity = 48.1%).Conclusion: Our results suggest that P1-Zmax and a ΔZmax (P2-Zmax - P1-Zmax) ≥ 1 may predict CAL development. What is Known: • KD is an acute vasculitis predominantly affecting the coronary artery of young children. • Although P1 Z-max ≥ 2.0 has been a predictor of CAL development, it has not yet been shown in Japan. What is New: • P1-Zmax and a ΔZmax ≥ 1 are presumably associated with CAL development. • In the ROC curve analysis, P1-Zmax ≥ 1.43 detected CAL development, a sensitivity (81%) and a specificity (48%). We need to consider intensified initial therapy for patients with these risk factors.
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http://dx.doi.org/10.1007/s00431-021-04006-1DOI Listing
September 2021

43-Year-Old Female With Fever and Bullous Skin Lesion.

Clin Infect Dis 2020 12;71(10):2763-2764

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.

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http://dx.doi.org/10.1093/cid/ciaa206DOI Listing
December 2020

Motor Imagery Deficits in High-Functioning Older Adults and Its Impact on Fear of Falling and Falls.

J Gerontol A Biol Sci Med Sci 2021 Aug;76(9):e228-e234

Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Japan.

Background: Older adults at risk of falling or who have fear of falling (FoF) present a discrepancy between "imagined" and "performed" actions. Using the gait-related motor imagery paradigm, we investigated whether prediction accuracy in motor execution is associated with the onset of FoF and with prospective falls among older adults with FoF.

Methods: A cohort of 184 community-dwelling older adults was tested for imaginary and executed Timed Up and Go (TUG) tests at a fast pace at baseline. They were first asked to imagine performing TUG and estimate the time taken to complete it (iTUG) and then to perform the actual trial (aTUG); the difference between the 2 times was calculated. Prospective falls were monitored between baseline and 2-year follow-up of FoF assessment.

Results: At follow-up, 27 of 85 participants without FoF at baseline (31.8%) had developed FoF. Twenty-seven of 99 participants (27.2%) with FoF at baseline experienced falls. A significantly shorter iTUG duration, when compared with aTUG, was observed in those who developed FoF or experienced multiple prospective falls, indicating overestimation of their TUG performance. The adjusted logistic regression model showed that a greater ΔTUG (ie, tendency to overestimate) at baseline was associated with an increased risk of new-onset FoF among those without FoF at baseline and multiple prospective falls among those with FoF at baseline.

Conclusions: Deficits in motor imagery (ie, overestimation of physical capabilities), reflecting impairment in motor planning, could provide an additional explanation of the high risk of FoF and recurrent falls among people with FoF.
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http://dx.doi.org/10.1093/gerona/glab073DOI Listing
August 2021

IMA genome - F14 : Draft genome sequences of Penicillium roqueforti, Fusarium sororula, Chrysoporthe puriensis, and Chalaropsis populi.

IMA Fungus 2021 Mar 5;12(1). Epub 2021 Mar 5.

Department of Biochemistry, Genetics and Microbiology, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, Private bag X20, Pretoria, 0028, South Africa.

Draft genomes of Penicillium roqueforti, Fusarium sororula, Chalaropsis populi, and Chrysoporthe puriensis are presented. Penicillium roqueforti is a model fungus for genetics, physiological and metabolic studies, as well as for biotechnological applications. Fusarium sororula and Chrysoporthe puriensis are important tree pathogens, and Chalaropsis populi is a soil-borne root-pathogen. The genome sequences presented here thus contribute towards a better understanding of both the pathogenicity and biotechnological potential of these species.
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http://dx.doi.org/10.1186/s43008-021-00055-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934431PMC
March 2021
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