-
1.
Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial.
Katakami, N, Mita, T, Yoshii, H, Shiraiwa, T, Yasuda, T, Okada, Y, Kurozumi, A, Hatazaki, M, Kaneto, H, Osonoi, T, et al
Cardiovascular diabetology. 2023;(1):143
Abstract
BACKGROUND This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. METHODS This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. RESULTS The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. CONCLUSIONS Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.
-
2.
Serial changes in cardiac sympathetic nervous function after transcatheter aortic valve replacement: A prospective observational study using 123I-meta-iodobenzylguanidine imaging.
Kadoya, Y, Zen, K, Tamaki, N, Nakamura, S, Fujimoto, T, Yashige, M, Takamatsu, K, Ito, N, Yamano, M, Yamano, T, et al
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2022;(5):2652-2663
Abstract
BACKGROUND Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear. METHODS Patients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. 123I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart-mediastinum ratio (H/M) and washout rate. RESULTS Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029). CONCLUSION CSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity.
-
3.
Search for nutritional and inflammatory marker ratios to predict neutropenia in FEC therapy for breast cancer: A retrospective observational study.
Nakamura, T, Matsubara, H
International journal of clinical pharmacology and therapeutics. 2022;(10):422-429
Abstract
OBJECTIVE Nutritional and inflammatory marker ratios are known to predict response to chemotherapy in breast cancer, but whether they predict adverse effects caused by chemotherapy remains unclear. We investigated whether nutritional and inflammatory marker ratios before starting FEC therapy (5-fluorouracil, epirubicin, and cyclophosphamide) predict grade 4 neutropenia as a serious adverse effect. MATERIALS AND METHODS 61 patients with breast cancer who started FEC therapy for the first time as preoperative or postoperative chemotherapy were studied. Relevant nutritional and inflammatory marker ratios were compared between patients who developed grade 4 neutropenia (n = 44) and those who did not (n = 17). RESULTS In univariate analysis, occurrence of neutropenia was related significantly (p < 0.05) to pre-FEC-therapy white blood cell count, platelet count, neutrophil count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score. Analysis using cutoff values obtained from receiver operating characteristic curves showed that LMR, NLR, and PLR predicted grade 4 neutropenia. However, multivariate logistic regression analysis identified no independent factor associated with grade 4 neutropenia. A post-hoc power analysis revealed an inadequate sample size. CONCLUSION Inflammatory marker ratios, especially PLR, may predict grade 4 neutropenia caused by FEC therapy for breast cancer. Although multivariate analysis identified no independent predictive markers in this study due to inadequate sample size, further prospective large-scale research is needed to examine the usefulness of nutritional and inflammatory marker ratios for predicting adverse effects.
-
4.
Survival benefits of gastrectomy compared to conservative observation for older patients with resectable gastric cancer: a propensity score matched analysis.
Ito, S, Ohgaki, K, Kawazoe, T, Wang, H, Nakamura, T, Maehara, S, Adachi, E, Ikeda, Y, Maehara, Y
Langenbeck's archives of surgery. 2022;(6):2281-2292
Abstract
PURPOSE Radical gastrectomy is considered the first choice of curative treatment for older patients with gastric cancer (GC). However, there is limited data on the survival benefits of gastrectomy for older patients with GC. METHODS This was a retrospective observational study where medical records of patients aged ≥ 75 years with clinically resectable primary GC, comprising 115 patients who underwent radical surgery (S group) and 33 patients who received conservative therapy (non-S group) (total cohort) and 44 propensity-matched patients (matched cohort), were reviewed. Survival and independent risk factors, including comorbidities and systemic nutritional and inflammatory statuses, were evaluated. RESULTS In the total cohort, the 5-year overall survival (OS) in the S group was significantly higher than that in the non-S group (53.7% vs 19.7%, P < 0.0001). In the matched cohort, the 3-year OS in the S group was significantly higher than that in the non-S group (59.4% vs 15.9%, P < 0.01). Multivariate analysis of the total cohort showed that no surgery was an independent prognostic factor for poor OS (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.91-7.20, P = 0.0001). In the S group in the total cohort, the multivariate analysis showed that renal disease (HR 2.51, 95% CI 1.23-5.12, P < 0.05) was an independent prognostic factor for poor OS. CONCLUSIONS Gastrectomy for older patients improved the prognosis; however, careful patient selection is essential, especially among those with renal disease.
-
5.
Evaluation of the nutrient foramen as a suitable landmark in spinal surgery.
Ito, K, Nakamura, T, Hanaoka, Y, Ogiwara, N, Horiuchi, T
The spine journal : official journal of the North American Spine Society. 2022;(5):732-737
Abstract
BACKGROUND CONTEXT The posterior cervical approach is a very popular surgical procedure. Because of the slope-shaped laminae, a suitable landmark for laminectomy, laminoplasty, and pedicle screw placement does not exist. PURPOSE We investigated the association between the nutrient foramen and spinal canal, and the safety of bone gutter placement using nutrient foramina for safe and effective spinal surgery. STUDY DESIGN Observational SETTING University Hospital PATIENT SAMPLES Two hundred and sixty-six consecutive patients treated for cervical pathologies in our university hospital between January 2005 and December 2019. OUTCOME MEASURES We identified the location of nutrient foramina and their anatomical association with the spinal canal using preoperative three-dimensional CT scanning. METHODS We studied the distance between each foramen and the spinal canal, and the angle of the nutrient foramen at each vertebral level. RESULTS The nutrient foramina were always located outside the spinal canal, with an average distance of +3.06±1.74 mm. The lower the spinal level, the closer the nutrient foramen to the spinal canal. CONCLUSIONS The nutrient foramen can be considered a reliable landmark when using the posterior cervical approach.
-
6.
Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma progressing after molecular targeted therapy: A multicenter prospective observational study.
Sugimoto, R, Satoh, T, Ueda, A, Senju, T, Tanaka, Y, Yamashita, S, Koyanagi, T, Kurashige, T, Higuchi, N, Nakamura, T, et al
Medicine. 2022;(40):e30871
-
-
Free full text
-
Abstract
To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.
-
7.
Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study.
Kawai, A, Narahara, H, Takahashi, S, Nakamura, T, Kobayashi, H, Megumi, Y, Matsuoka, T, Kobayashi, E
BMC cancer. 2022;(1):528
Abstract
BACKGROUND Soft tissue sarcomas (STSs) are a heterogeneous group of cancers with over 100 described subtypes. While these cancers are infrequent, the prognosis is quite poor, particularly for those with stage IV metastatic disease. Patients for whom curative resection is difficult or those with recurrent metastatic disease are treated with chemotherapy, although the options are very limited. Eribulin is an approved treatment of all STS subtypes in Japan. Efficacy and safety data for the treatment of rare STS subtypes other than liposarcoma and leiomyosarcoma (L-type sarcomas) are limited. This nationwide, multicenter, prospective, post-marketing observational study was conducted to assess the real-world effectiveness and safety of eribulin in Japanese patients with STS. METHODS Patients with all types of STS and who consented to eribulin treatment were eligible to participate. The observation period was 1 year, starting at treatment initiation, and clinical outcomes were followed up for 2 years after initiating treatment. The primary endpoint was overall survival (OS). Additional outcomes included time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. ORR and DCR were evaluated using imaging findings. Effectiveness results were analyzed both for all patients and by STS subtype. RESULTS A total of 256 patients were enrolled; 252 and 254 were included in the effectiveness and safety analysis set, respectively. Most patients (83.1%) received an initial eribulin dose of 1.4 mg/m2 (standard dose). Respective median OS (95% confidence interval [CI]) was 10.8 (8.5-13.1), 13.8 (10.1-22.3) and 6.5 (5.7-11.1) months for all, L-type, and non-L-type subtypes. The respective median TTF (95% CI) was 2.5 (2.1-2.8), 2.8 (2.3-3.7), and 2.2 (1.6-2.6) months. The ORR and DCR were 8.1 and 42.6%, respectively. Adverse drug reactions (ADRs) and serious ADRs were reported for 83.5 and 18.9% of patients, respectively. The main ADRs were associated with myelosuppression. No significant difference was observed in the incidence of ADRs for patients ≥65 versus <65 years old. CONCLUSIONS Eribulin demonstrated effectiveness and a manageable safety profile for patients with STS, although the effectiveness of eribulin was not demonstrated for some non-L-type subtypes. TRIAL REGISTRATION NCT03058406 ( ClinicalTrials.gov ).
-
8.
Geriatric nutritional risk index as a predictor of arrhythmia recurrence after catheter ablation of atrial fibrillation.
Kaneko, M, Nagata, Y, Nakamura, T, Mitsui, K, Nitta, G, Nagase, M, Okata, S, Watanabe, K, Miyazaki, R, Nagamine, S, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(6):1798-1808
Abstract
BACKGROUND AND AIMS The nutritional risk of patients who undergo atrial fibrillation (AF) ablation varies. Its impact on the recurrence after ablation is unclear. We sought to evaluate the relationship between the nutritional risk and arrhythmia recurrence in patients who undergo AF ablation. METHODS AND RESULTS We enrolled 538 patients (median 67 years, 69.9% male) who underwent their first AF ablation. Their nutritional risk was evaluated using the pre-procedural geriatric nutritional risk index (GNRI), and the patients were classified into two groups: No-nutritional risk (GNRI ≧ 98) and Nutritional risk (GNRI < 98). The primary endpoint was a recurrence of an arrhythmia, and its relationship to the nutritional risk was evaluated. We used propensity-score matching to adjust for differences between patients with a GNRI-based nutritional risk and those without a nutritional risk. A nutritional risk was found in 10.6% of the patients, whereas the remaining 89.4% had no-nutritional risk. During a mean follow-up of 422 days, 91 patients experienced arrhythmia recurrences. The patients with a nutritional risk had a significantly higher arrhythmia recurrence rate both in the entire study cohort (Log-rank p = 0.001) and propensity-matched cohort (Log-rank p = 0.006). In a Cox proportional hazard analysis, the nutritional risk independently predicted arrhythmia recurrences in the entire study cohort (hazard ratio [HR]: 3.91, 95% confidence interval [CI]: 1.84-8.35, p < 0.001) and propensity-matched cohort (HR: 6.49, 95% CI: 1.42-29.8, p = 0.016). CONCLUSION A pre-procedural malnutrition risk was significantly associated with increased arrhythmia recurrences in patients who underwent AF ablation.
-
9.
Greater coronary lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound in patients with elevated xanthine oxidoreductase: a mechanistic insight.
Saito, Y, Mori, N, Murase, T, Nakamura, T, Akari, S, Saito, K, Matsuoka, T, Tateishi, K, Kadohira, T, Kitahara, H, et al
Heart and vessels. 2021;(5):597-604
Abstract
Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.
-
10.
Dietary Inflammatory Index Positively Associated With High-Sensitivity C-Reactive Protein Level in Japanese From NIPPON DATA2010.
Yang, Y, Hozawa, A, Kogure, M, Narita, A, Hirata, T, Nakamura, T, Tsuchiya, N, Nakaya, N, Ninomiya, T, Okuda, N, et al
Journal of epidemiology. 2020;(2):98-107
Abstract
BACKGROUND It has been reported that chronic inflammation may play an important role in the pathogenesis of several serious diseases and could be modulated by diet. Recently, the Dietary Inflammatory Index (DII®) was developed to assess the inflammatory potential of the overall diet. The DII has been reported as relevant to various diseases but has not been validated in Japanese. Thus, in the present study, we analyzed the relationship between DII scores and high-sensitivity C-reactive protein (hs-CRP) levels in a Japanese population. METHODS Data of the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010 (NIPPON DATA2010), which contained 2,898 participants aged 20 years or older from the National Health and Nutrition Survey of Japan (NHNS2010), were analyzed. Nutrient intakes derived from 1-day semi-weighing dietary records were used to calculate DII scores. Energy was adjusted using the residual method. Levels of hs-CRP were evaluated using nephelometric immunoassay. Multiple linear regression analyses were performed. RESULTS After adjusting for age, sex, smoking status, BMI, and physical activity, a significant association was observed between DII scores and log(CRP+1) (standard regression coefficient = 0.05, P < 0.01). Although it was not statistically significant, the positive association was consistently observed in almost all age-sex subgroups and the non-smoker subgroup. CONCLUSIONS The current study confirmed that DII score was positively associated with hs-CRP in Japanese.