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Serum chemokine CC-motif ligand 17 is a predictive marker of severe COVID-19 in haemodialysis patients: A retrospective observational study.
Beppu, H, Fukuda, T, Otsubo, N, Kawanishi, T, Ogawa, T, Abe, Y, Endo, M, Hanawa, T, Sugita, C, Kikkawa, Y, et al
Nephrology (Carlton, Vic.). 2023;(4):240-248
Abstract
BACKGROUND Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.
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The Role of a Composite Fitness Score in the Association Between Low-Density Cholesterol and All-Cause Mortality in Older Adults: An Individual Patient Data Meta-Analysis.
van der Ploeg, MA, Poortvliet, RKE, Bogaerts, JMK, van der Klei, VMGTH, Kerse, N, Rolleston, A, Teh, R, Robinson, L, Jagger, C, Arai, Y, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2023;(9):1708-1716
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Abstract
BACKGROUND In the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score. METHODS A 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score. RESULTS Composite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80-0.94]; p < .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75-0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83-1.15]; p = .78), the test for subgroups differences was not significant. CONCLUSIONS In this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores.
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Systematic identification of ALK substrates by integrated phosphoproteome and interactome analysis.
Adachi, J, Kakudo, A, Takada, Y, Isoyama, J, Ikemoto, N, Abe, Y, Narumi, R, Muraoka, S, Gunji, D, Hara, Y, et al
Life science alliance. 2022;(8)
Abstract
The sensitivity of phosphorylation site identification by mass spectrometry has improved markedly. However, the lack of kinase-substrate relationship (KSR) data hinders the improvement of the range and accuracy of kinase activity prediction. In this study, we aimed to develop a method for acquiring systematic KSR data on anaplastic lymphoma kinase (ALK) using mass spectrometry and to apply this method to the prediction of kinase activity. Thirty-seven ALK substrate candidates, including 34 phosphorylation sites not annotated in the PhosphoSitePlus database, were identified by integrated analysis of the phosphoproteome and crosslinking interactome of HEK 293 cells with doxycycline-induced ALK overexpression. Furthermore, KSRs of ALK were validated by an in vitro kinase assay. Finally, using phosphoproteomic data from ALK mutant cell lines and patient-derived cells treated with ALK inhibitors, we found that the prediction of ALK activity was improved when the KSRs identified in this study were used instead of the public KSR dataset. Our approach is applicable to other kinases, and future identification of KSRs will facilitate more accurate estimations of kinase activity and elucidation of phosphorylation signals.
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Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration: A case report and literature review.
Kojima, H, Kitago, M, Iwasaki, E, Masugi, Y, Matsusaka, Y, Yagi, H, Abe, Y, Hasegawa, Y, Hori, S, Tanaka, M, et al
World journal of gastroenterology. 2021;(3):294-304
Abstract
BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lympha-denectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS- FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.
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The effects of amino acid/protein supplementation in patients undergoing hemodialysis: A systematic review and meta-analysis of randomized controlled trials.
Matsuzawa, R, Yamamoto, S, Suzuki, Y, Abe, Y, Harada, M, Shimoda, T, Imamura, K, Yamabe, S, Ito, H, Yoshikoshi, S, et al
Clinical nutrition ESPEN. 2021;:114-121
Abstract
BACKGROUND & AIMS We evaluated the efficacy of the intervention consisting of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis. METHODS This systematic review and meta-analysis identified potential studies through a systematic search of 4 electronic databases and references from eligible studies from database inception to August 2020. We included only randomized controlled trials reporting the efficacy of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis. RESULTS Of 6529 unique citation records, 4 studies including 243 participants were selected for inclusion in the meta-analysis. Although there were no significant differences in muscle mass and muscle strength between the intervention and control groups, amino acid/protein supplementation was shown to significantly improve physical function (shuttle walk, MD 32.7, 95% CI 21.7 to 43.7, P < 0.001; gait speed, MD 0.07, 95% CI 0.01 to 0.13, P = 0.02; timed up and go, MD -0.42, 95% CI -0.68 to -0.15, P = 0.002) in patients on hemodialysis. CONCLUSIONS We confirmed the positive effect of amino acid/protein supplementation on physical function in people undergoing hemodialysis. However, there is still insufficient evidence, and more rigorously designed randomized controlled trials with high quality are needed.
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Epidemiology of the association between serum 25-hydroxyvitamin D levels and musculoskeletal conditions among elderly individuals: a literature review.
Arima, K, Mizukami, S, Nishimura, T, Tomita, Y, Nakashima, H, Abe, Y, Aoyagi, K
Journal of physiological anthropology. 2020;(1):38
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Abstract
BACKGROUND Vitamin D deficiency is associated with osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. Elderly individuals are more likely to present with poor musculoskeletal conditions. Recently, several epidemiological studies have assessed the correlation between serum 25-hydroxyvitamin D (25(OH)D) levels and musculoskeletal conditions in elderly individuals. MAIN TEXT Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Numerous studies have shown a positive association between serum 25(OH)D levels and bone mineral density. Only a few studies have reported an association between serum 25(OH)D levels and quantitative ultrasound (QUS) parameters. Low serum 25(OH)D level may be a risk factor for hip fracture. However, data on the association between vitamin D deficiency and the incidence of non-hip fracture are contrasting. Falls are a major cause of mortality and morbidity in older adults. Several prospective population-based cohort studies have shown that low 25(OH)D levels are associated with an increased risk of falls. Reduced muscle strength and physical performance are risk factors for adverse events, including disability, institutionalization, and mortality. The role of vitamin D in musculoskeletal functionality (muscle weakness and physical performance) among elderly individuals is still controversial. Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability among older adults. Data on the association between serum 25(OH)D levels and OA are contrasting. CONCLUSION Some studies have shown that vitamin D deficiency may be a risk factor for poor musculoskeletal conditions, such as osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. However, other studies did not find an association between serum 25(OH)D levels and musculoskeletal conditions.
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The risks and characteristics of the delayed bleeding after endoscopic submucosal dissection for early gastric carcinoma in cases with anticoagulants.
Saito, H, Igarashi, K, Hirasawa, D, Okuzono, T, Suzuki, K, Abe, Y, Nawata, Y, Tanaka, Y, Tanaka, I, Unno, S, et al
Scandinavian journal of gastroenterology. 2020;(10):1253-1260
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric carcinoma. Vitamin K antagonists and direct oral anticoagulants (DOAC) were reported to increase the risk of delayed bleeding after ESD. However, the evaluation of ESD cases taking anticoagulants is scarce. We analyzed the risk and characteristics of delayed bleeding after gastric ESD in patients on anticoagulants. METHODS We performed a retrospective observational study at a single center. Consecutive patients who underwent ESD for early gastric carcinoma and took anticoagulants, including warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban, between January 2012 and December 2018, were analyzed. We also calculated delayed bleeding rates for those without anticoagulants. RESULTS Of 1855 eligible patients who underwent gastric ESDs, 143 took anticoagulants. Delayed bleeding occurred in 30 (21.0%) cases taking anticoagulants, with 15 (19.5%) cases in the DOAC group [rivaroxaban, seven cases (21.2%); dabigatran, four cases (20.0%); apixaban, four cases (23.5%); and edoxaban, zero cases (0%)] and 15 cases (22.7%) in the warfarin group. Furthermore, 43/344 (12.5%) patients taking antiplatelets and 76/1368 (5.6%) patients without antithrombic drugs experienced delayed bleeding. Multivariable logistic analysis revealed post-heart valve replacement (OR, 6.56; 95% CI, 1.75-24.7; p < .05) as a risk for delayed bleeding in warfarin-taking patients, while no statistically significant factor was found in DOAC-taking patients. CONCLUSIONS Anticoagulants were associated with a high incidence of severe delayed bleeding. Careful attention should be paid to patients on anticoagulants after gastric ESD, especially those on warfarin after heart valve replacement.
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Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function.
Abe, Y, Tanaka, N
Cells. 2020;(9)
Abstract
The glioma-associated oncogene (GLI) family consists of GLI1, GLI2, and GLI3 in mammals. This family has important roles in development and homeostasis. To achieve these roles, the GLI family has widespread outputs. GLI activity is therefore strictly regulated at multiple levels, including via post-translational modifications for context-dependent GLI target gene expression. The protein arginine methyl transferase (PRMT) family is also associated with embryogenesis, homeostasis, and cancer mainly via epigenetic modifications. In the PRMT family, PRMT1, PRMT5, and PRMT7 reportedly regulate GLI1 and GLI2 activity. PRMT1 methylates GLI1 to upregulate its activity and target gene expression. Cytoplasmic PRMT5 methylates GLI1 and promotes GLI1 protein stabilization. Conversely, nucleic PRMT5 interacts with MENIN to suppress growth arrest-specific protein 1 expression, which assists Hedgehog ligand binding to Patched, indirectly resulting in downregulated GLI1 activity. PRMT7-mediated GLI2 methylation upregulates its activity through the dissociation of GLI2 and Suppressor of Fused. Together, PRMT1, PRMT5, and PRMT7 regulate GLI activity at multiple revels. Furthermore, the GLI and PRMT families have strong links with various cancers through cancer stem cell maintenance. Therefore, PRMT-mediated regulation of GLI activity would have important roles in cancer stem cell maintenance.
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Severe congenital RYR1-associated myopathy complicated with atrial tachycardia and sinus node dysfunction: a case report.
Hayakawa, I, Abe, Y, Ono, H, Kubota, M
Italian journal of pediatrics. 2019;(1):165
Abstract
BACKGROUND Cardiac arrhythmias are sometimes encountered in patients with hereditary myopathies and muscular dystrophies. Description of arrhythmias in myopathies and muscular dystrophies is very important, because arrhythmias have a strong impact on the outcomes for these patients and are potentially treatable. CASE PRESENTATION A girl with severe congenital RYR1-related myopathy exhibited atrial tachycardia and sinus node dysfunction during infancy. She was born after uncomplicated caesarian delivery. She showed no breathing, complete ophthalmoplegia, complete bulbar paralysis, complete facial muscle paralysis, and extreme floppiness. At 5 months old, she developed persistent tachycardia around 200-210 beats per minutes. Holter monitoring revealed ectopic atrial tachycardia during tachyarrhythmia and occasional sinus pauses with junctional escape beats. Propranolol effectively alleviated tachyarrhythmia but was discontinued due to increased frequency and duration of the sinus pauses that led to bradyarrhythmia. There was no evidence of structural heart diseases or heart failure. The arrhythmia gradually resolved spontaneously and at 11 months old, she showed complete sinus rhythm. CONCLUSIONS Although supraventricular arrhythmia is sometimes encountered in congenital myopathies, this is the first report of cardiac arrhythmia requiring drug intervention in RYR1-associated myopathy.
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Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: study protocol for a multicentre, single-blind, randomised controlled clinical trial.
Takeuchi, M, Obara, H, Kawakubo, H, Shinoda, M, Okabayashi, K, Mayanagi, S, Irino, T, Fukuda, K, Nakamura, R, Wada, N, et al
BMJ open. 2019;(5):e028269
Abstract
INTRODUCTION The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries. METHODS AND ANALYSIS We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method. ETHICS AND DISSEMINATION The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER UMIN 000031560; Pre-results.