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  • 1
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    Online Resource
    Low-Dose Aspirin for the Primary Prevention of Cardiovascular Disease in Diabetic Individuals: A Meta-Analysis of Randomized Control Trials and Trial Sequential Analysis
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 5 ( 2019-05-05), p. 609-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 5 ( 2019-05-05), p. 609-
    Abstract: Background: Evidence of low-dose aspirin as the primary prevention strategy for cardiovascular disease (CVD) in diabetes are unclear. This study was designed to evaluate the effect of low-dose aspirin use for the primary prevention of CVD in diabetes. Methods: We collected randomized controlled trials of low-dose aspirin for the primary prevention of CVD in adults with diabetes lasting at least 12 months from Medline, Embase, and the Cochrane Library up to 10 November 2018. Two reviewers extracted data and appraised the reporting quality according to a predetermined protocol (CRD4201811830). This review was conducted using Cochrane standards, trial sequential analysis, and the Grading of Recommendation. The primary outcomes were major adverse cardiovascular events (MACE, including non-fatal myocardial infarction, ischemia stroke, and cardiovascular death) and an incidence of major hemorrhage (major intracranial hemorrhage and major gastrointestinal bleeding). Results: In this primary prevention (number = 29,814 participants) meta-analysis, low-dose aspirin use reduced the risk of MACE by 9% and increased the risk of major hemorrhage by 24%. The benefits were only observed in subjects of age ≥ 60 years while reducing the same risk of MACE. In efficacy, it reduced the risk of stroke but not myocardial infarction. No increase in all-cause mortality or cardiovascular death was observed. Conclusions: We suggested the use of low-dose aspirin as the primary prevention strategy for CVD in diabetes, particularly in an older population. The absolute benefits were largely counterbalanced by the bleeding hazard.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8050609
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 2
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    Preoperative Serum Macrophage Migration Inhibitory Factor Level Correlates with Surgical Difficulty and Outcome in Patients with Autoimmune Thyroiditis
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 18 ( 2021-09-07), p. 4034-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 18 ( 2021-09-07), p. 4034-
    Abstract: Surgical treatment for autoimmune thyroid disease is theoretically risky due to its chronic inflammatory status. This study aimed to investigate the correlation between preoperative serum migration inhibitory factor (MIF) levels and the difficulty of thyroidectomy in patients with autoimmune thyroiditis. Forty-four patients (average age: 54 years) were prospectively recruited: 30 with autoimmune thyroiditis and 14 with nodular goiter. Preoperative serum samples were collected to measure MIF levels. The difficulty of thyroidectomy was evaluated using a 20-point thyroidectomy difficulty scale (TDS) scoring system. The potential correlations between MIF levels and clinicopathological features as well as postoperative complications were analyzed. Preoperative serum thyroid-stimulating hormone (TSH), TSH receptor antibody, thyroid peroxidase antibodies levels, TDS score, and serum MIF levels were significantly higher in the autoimmune thyroiditis group than those in the goiter group. MIF levels were significantly associated with postoperative transient recurrent laryngeal nerve injury and hypoparathyroidism. MIF levels were positively correlated with TDS score, operation time, and blood loss in the autoimmune thyroiditis group. Increased preoperative serum MIF levels are associated with higher TDS scores, operation time, blood loss, and postoperative complications. Preoperative serum MIF level may be a useful predictor of difficult thyroidectomy and help surgeons provide better preoperative management.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10184034
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 3
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    The Current Status and Future Prospects of KAGRA, the Large-Scale Cryogenic Gravitational Wave Telescope Built in the Kamioka Underground
    MDPI AG ; 2022
    In:  Galaxies Vol. 10, No. 3 ( 2022-04-26), p. 63-
    Details
    In: Galaxies, MDPI AG, Vol. 10, No. 3 ( 2022-04-26), p. 63-
    Abstract: KAGRA is a gravitational-wave (GW) detector constructed in Japan with two unique key features: It was constructed underground, and the test-mass mirrors are cooled to cryogenic temperatures. These features are not included in other kilometer-scale detectors but will be adopted in future detectors such as the Einstein Telescope. KAGRA performed its first joint observation run with GEO600 in 2020. In this observation, the sensitivity of KAGRA to GWs was inferior to that of other kilometer-scale detectors such as LIGO and Virgo. However, further upgrades to the detector are ongoing to reach the sensitivity for detecting GWs in the next observation run, which is scheduled for 2022. In this article, the current situation, sensitivity, and future perspectives are reviewed.
    Type of Medium: Online Resource
    ISSN: 2075-4434
    URL: Article
    DOI: 10.3390/galaxies10030063
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2691049-4
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  • 4
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    Malignancy Prediction Capacity and Possible Prediction Model of Circulating Tumor Cells for Suspicious Pulmonary Lesions
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 6 ( 2021-05-21), p. 444-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 6 ( 2021-05-21), p. 444-
    Abstract: More and more undetermined lung lesions are being identified in routine lung cancer screening. The aim of this study was to try to establish a malignancy prediction model according to the tumor presentations. From January 2017 to December 2018, 50 consecutive patients who were identified with suspicious lung lesions were enrolled into this study. Medical records were reviewed and tumor macroscopic and microscopic presentations were collected for analysis. Circulating tumor cells (CTC) were found to differ between benign and malignant lesions (p = 0.03) and also constituted the highest area under the receiver operation curve other than tumor presentations (p = 0.001). Since tumor size showed the highest sensitivity and CTC revealed the best specificity, a malignancy prediction model was proposed. Akaike information criterion (A.I.C.) of the combined malignancy prediction model was 26.73, which was lower than for tumor size or CTCs alone. Logistic regression revealed that the combined malignancy prediction model showed marginal statistical trends (p = 0.0518). In addition, the 95% confidence interval of combined malignancy prediction model showed less wide range than tumor size ≥ 0.7 cm alone. The calculated probability of malignancy in patients with tumor size ≥ 0.7 cm and CTC 〉 3 was 97.9%. By contrast, the probability of malignancy in patients whose tumor size was 〈 0.7 cm, and CTC ≤ 3 was 22.5%. A combined malignancy prediction model involving tumor size followed by the CTC count may provide additional information to assist decision making. For patients who present with tumor size ≥ 0.7 cm and CTC counts 〉 3, aggressive management should be considered, since the calculated probability of malignancy was 97.9%.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11060444
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 5
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    Prognostic Value of Lymph Node-To-Primary Tumor Standardized Uptake Value Ratio in Esophageal Squamous Cell Carcinoma Treated with Definitive Chemoradiotherapy
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 3 ( 2020-03-06), p. 607-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 3 ( 2020-03-06), p. 607-
    Abstract: We aimed to investigate the prognostic value of the relative maximum standardized uptake value (SUV) of metastatic lymph node (LN) compared with that of primary tumor (SUVLN/SUVTumor) based on a pretreatment [18F]-FDG PET/CT scan in patients with clinically node-positive esophageal squamous cell carcinoma (cN+ ESCC) treated with definitive chemoradiotherapy (dCRT). We retrospectively evaluated cN+ ESCC patients who underwent a PET/CT scan before dCRT. Time-dependent receiver operating characteristics analysis was performed to identify the optimal cutoff value for SUVLN/SUVTumor. Prognostic influences of SUVLN/SUVTumor on distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using the Kaplan–Meier method and log-rank test for univariate analysis and Cox’s proportional hazards regression model for multivariate analysis. We identified 112 patients with newly diagnosed cN+ ESCC. After a median follow-up of 32.0 months, 50 (44.6%) patients had distant failure and 84 (75.0%) patients died. Patients with high SUVLN/SUVTumor (≥ 0.39) experienced worse outcomes than low SUVLN/SUVTumor ( 〈 0.39) (two-year DMFS: 26% vs. 70%, p 〈 0.001; two-year OS: 21% vs. 48%, p = 0.001). Multivariate analysis showed that SUVLN/SUVTumor was an independent prognostic factor for both DMFS (adjusted HR 2.24, 95% CI 1.34–3.75, p = 0.002) and OS (adjusted HR 1.61, 95% CI 1.03–2.53, p = 0.037). Pretreatment of SUVLN/SUVTumor is a simple and useful marker for prognosticating DMFS and OS in cN+ ESCC patients treated with dCRT, which may help in tailoring treatment and designing future clinical trials.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12030607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 6
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    Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 12 ( 2021-06-12), p. 2954-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 12 ( 2021-06-12), p. 2954-
    Abstract: Background: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and metastatic rates. Methods: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. Results: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). Conclusions: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13122954
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 7
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    Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study
    MDPI AG ; 2021
    In:  Cancers Vol. 14, No. 1 ( 2021-12-21), p. 15-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 1 ( 2021-12-21), p. 15-
    Abstract: (1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1–4 and 〉 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1–4 mm) were significantly lower than those observed in patients with clear margins ( 〉 4 mm; all p values 〈 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins ( 〉 4 mm) should be considered a key surgical goal to improve outcomes in this patient group.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14010015
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 8
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    Migraine as a Risk Factor for Peripheral Artery Occlusive Disease: A Population-Based Cohort Study
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 22 ( 2020-11-18), p. 8549-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 22 ( 2020-11-18), p. 8549-
    Abstract: We aim to evaluate the development of peripheral occlusive artery disease (PAOD) in patients with migraine by using the National Health Insurance Research Database in Taiwan. A retrospective cohort study was conducted and individuals with diagnostic codes of migraine were enrolled in the study group after excluding those diagnosed with PAOD before the index date. Each subject with migraine was propensity-score matched to another non-migraine patient and the latter served as the control group. A total of 37,288 patients were finally enrolled in the groups. The primary outcome was set as the development of PAOD between the two groups while multiple possible risk factors, including demographic data and comorbidities, were analyzed via the Cox proportional hazards regression. There were 885 and 530 PAOD events in the study and control groups, and the study group had a significantly higher adjusted hazard ratio (1.65, 95% confidential interval: 1.48–1.84, p 〈 0.001), and the cumulative incidence also revealed a correlation between migraine and PAOD. Other potential risk factors related to the existence of PAOD include age, hypertension, chronic kidney disease, diabetes mellitus, coronary artery disease, stroke, and asthma. For individuals without certain systemic diseases including hypertension, chronic liver disease, chronic kidney disease, coronary artery disease, stroke, asthma, or heart failure, the hazard ratio of subsequent PAOD was significantly higher in the migraine patients than that in the non-migraine individuals (all p 〈 0.001). In conclusion, the presence of migraine is a significant risk factor for the development of subsequent PAOD.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17228549
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 9
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    ERCC1 Overexpression Increases Radioresistance in Colorectal Cancer Cells
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 19 ( 2022-09-30), p. 4798-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 19 ( 2022-09-30), p. 4798-
    Abstract: Preoperative concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced rectal cancer patients, but 20–30% do not benefit from the desired therapeutic effects. Previous reports indicate that high levels of ERCC1 reduce the effectiveness of cisplatin-based CCRT; however, it remains unclear as to whether ERCC1 overexpression increases radiation resistance. To clarify the correlation between ERCC1 levels and radiation (RT) resistance, we established two cell lines (HCT116-Tet-on and COLO205-Tet-on), induced them to overexpress ERCC1, detected cell survival following exposure to radiation, established HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models, and detected tumor volume following exposure to radiation. We found that ERCC1 overexpression increased radiation resistance. After regulating ERCC1 levels and radiation exposure to verify the correlation, we noted that increased radiation resistance was dependent on ERCC1 upregulation in both cell lines. For further verification, we exposed HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models to radiation and observed that ERCC1 overexpression increased colorectal cancer tumor radioresistance in both. Combined, our results suggest that ERCC1 overexpression may serve as a suitable CCRT prognostic marker for colorectal cancer patients.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14194798
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 10
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    The Integration of a Three-Dimensional Spheroid Cell Culture Operation in a Circulating Tumor Cell (CTC) Isolation and Purification Process: A Preliminary Study of the Clinical Significance and Prognostic Role of the CTCs Isolated from the Blood Samples of Head and Neck Cancer Patients
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 6 ( 2019-06-06), p. 783-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 6 ( 2019-06-06), p. 783-
    Abstract: Conventional positive and negative selection-based circulating tumor cell (CTC) isolation methods might generally ignore metastasis-relevant CTCs that underwent epithelial-to- mesenchymal transition and suffer from a low CTC purity problem, respectively. To address these issues, we previously proposed a 2-step CTC isolation method integrating a negative selection CTC isolation and subsequent spheroid cell culture. In addition to its ability to isolate CTCs, more importantly, the spheroid cell culture used could serve as a cell culture model mimicking the process of new tumor tissue formation during cancer metastasis. Therefore, it is promising not only to selectively isolate metastasis-relevant CTCs but also to test the potential of cancer metastasis and thus the prognosis of disease. To explore these issues, experiments were performed. The key findings of this study demonstrated that the method was able to harvest both epithelial (E)- and mesenchymal (M)-type CTCs without selection bias. Moreover, both the M-type CTC count and the information obtained from the multidrug resistance-associated protein 2 (MRP2) and MRP5 gene expression analysis of the CTCs isolated via the 2-step CTC isolation method might be able to serve as prognostic factors for progression-free survival in head and neck squamous cell carcinoma.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11060783
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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