OBJECTIVES: This cohort study investigated the correlation between Parkinson’s disease (PD) risk and chronic obstructive pulmonary disease (COPD) risk under particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) exposure. METHODS: Data from the National Health Research Institutes of Taiwan were used in this study. The Environmental Protection Administration of Taiwan established an air quality monitoring network for monitoring Taiwan’s general air quality. COPD was indicated by at least 3 outpatient records and 1 hospitalization for COPD. After the implementation of age, sex, and endpoint matching at a 1:4 ratio, 137 patients and 548 patients were included in the case group and control group, respectively. Based on the 2005 World Health Organization (WHO) standards, monthly air particle concentration data were classified into the following 4 groups in analyses of exposure–response relationships: normal level, and 1.0, 1.5, and 2.0 times the WHO level ([concentration ≥2]×25 μg/m3×number of exposure months). RESULTS: A multivariate logistic regression revealed that the 1.0 and 1.5 WHO level groups did not significantly differ from the normal level group, but the 2.0 WHO level did (odds ratio, 4.091; 95% confidence interval, 1.180 to 14.188; p=0.038). CONCLUSIONS Elevated PM2.5 concentrations were significantly correlated with an increased risk of PD among patients with COPD. Furthermore, exposure to high PM2.5 levels can further increase the risk of PD.

Objective To summarize the experience of utilization of video-assisted endoscopy in 91 patients operated on at Chang Gung Memorial Hospital, Taipei, China.Methods From October 1995, through August 1996, 91 patients (44 male and 47 female) received video-assisted cardiac surgery (VACS). Their ages ranged from 1 year to 79.5 years (25.7±21.7). Indications for surgery were atrial septal defect (59 patients), ventricular septal defect (15), coronary artery disease (4), severe mitral regurgitation (4), severe tricuspid regurgitation (3), thrombosis of mitral mechanical prosthesis (3), left atrial tumor (2), and left ventricular thrombus with dilated cardiomyopathy (1). The VACS was performed through right or left anterior minithoracotomy and guided by video-assisted endoscopic techniques by means of projected images on the video monitor under extracorporeal circulation. The aorta was not cross-clamped and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest (rectal temperature 22.6±4.0℃). Conventional instruments were used.Results All lesions were corrected successfully. The bypass time was 27 to 335 minutes (72.8±52.7). The operative time was 1.3 to 8.5 hours (3.0±1.7). There were no operative deaths and 3 late deaths. Follow-up was complete in all survivors (6 to 16 months, mean 8.7). Most of them were found to be in NYHA functional Ⅰ or Ⅱ.Conclusion Our preliminary experiences demonstrate that VACS is simple and effective in surgical correction of selected cardiac lesions. Short-term results show good outcomes.

Subclavian artery (SCA) perforation is a rare complication while performing SCA intervention. In our present report, a 73-year-old female, with stenosis of the left SCA and situs inversus, presented with exercise-induced left arm weakness. The SCA stenosis was treated with direct stenting with a balloon-expansible Express LD 10×25 mm stent. However, it caused iatrogenic SCA perforation and hemothorax. The perforation was sealed by endovascular repair with operator-modified Endurant II graft stent, which complicated with occlusion of left common carotid artery. And, the carotid artery was rescued by another stent. The graft stent, which was originally designed for abdominal aortic aneurysm, can be modified to suitable length and take as a rescue stent of large vessel with iatrogenic perforation. Due to strong radial force of graft stent, preservation of large side branches should been watched out.
Aged ; Aortic Aneurysm, Abdominal ; Arm ; Carotid Arteries ; Carotid Artery, Common ; Constriction, Pathologic ; Female ; Hemothorax ; Humans ; Situs Inversus ; Stents* ; Subclavian Artery* ; Subclavian Steal Syndrome ; Transplants*

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

BACKGROUND/AIMS: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD. METHODS: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed. RESULTS: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively). CONCLUSIONS: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.
Colectomy ; Colitis, Ulcerative* ; Cooperative Behavior ; Diagnosis ; Emergencies ; Follow-Up Studies ; Hemorrhage ; Humans ; Inflammatory Bowel Diseases* ; Mortality ; Prognosis ; Retrospective Studies* ; Sepsis ; Taiwan* ; Ulcer*

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.