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Abstract Metabolic syndrome (MetS) is a global health concern with spatial disparities, especially in disadvantaged neighborhoods. This study aimed to examine the association between area‐level socioeconomic deprivation, the availability of medical resources in disadvantaged areas such as the Cijin district, and the prevalence of MetS in Taiwan. We used two representative secondary cross‐sectional datasets, including physical examinations and lifestyle surveys from 2016 to 2020, sourced from the Taiwan Biobank and the Cijin District Adult Lifestyle and Health Survey. Our findings indicate that residing in the Cijin district, characterized by socioeconomic deprivation and limited medical resources, is associated with significantly higher odds of MetS (aOR = 1.45, 95% CI = 1.28–1.64, p

Abstract Background Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. Methods Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. Results Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvβ3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. Conclusions Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.

IntroductionThe objective of this research was to evaluate the risk of major adverse cardiovascular events (MACEs) associated with the use of various proton pump inhibitors (PPIs) in combination with clopidogrel in patients who underwent percutaneous coronary intervention (PCI).MethodsTo accomplish this, we analyzed data from randomized controlled trials and retrospective cohort studies sourced from key electronic databases. These studies specifically examined the effects of different PPIs, such as lansoprazole, esomeprazole, omeprazole, rabeprazole, and pantoprazole, when used in conjunction with clopidogrel on MACEs. The primary focus was on the differential impact of these PPIs, while the secondary focus was on the comparison of gastrointestinal (GI) bleeding events in groups receiving different PPIs with clopidogrel vs. a placebo group. This study's protocol was officially registered with INPLASY (INPLASY2024-2-0009).ResultsWe conducted a network meta-analysis involving 16 studies with a total of 145,999 patients. Our findings indicated that rabeprazole when combined with clopidogrel, had the lowest increase in MACE risk (effect size, 1.05, 95% CI: 0.66–1.66), while lansoprazole was associated with the highest risk increase (effect size, 1.48, 95% CI: 1.22–1.80). Esomeprazole (effect size, 1.28, 95% CI: 1.09–1.51), omeprazole (effect size, 1.23, 95% CI: 1.07–1.43), and pantoprazole (effect size, 1.38, 95% CI: 1.18–1.60) also significantly increased MACE risk. For the secondary outcome, esomeprazole (effect size, 0.30, 95% CI: 0.09–0.94), omeprazole (effect size, 0.34, 95% CI: 0.14–0.81), and pantoprazole (effect size, 0.33, 95% CI: 0.13–0.84) demonstrated an increased potential for GI bleeding prevention.ConclusionsIn conclusion, the combination of lansoprazole and clopidogrel was found to significantly elevate the risk of MACEs without offering GI protection in post-PCI patients. This study is the first network meta-analysis to identify the most effective regimen for the concurrent use of clopidogrel with individual PPIs.Systematic Review Registrationhttps://inplasy.com/inplasy-2024-2-0009/, identifier (INPLASY2024-2-0009).

Abstract Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well‐known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF‐κB and IL‐6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid‐derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug‐resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.

Background The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on‐treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. Methods and Results A total of 7582 patients with on‐treatment systolic blood pressure 0.05). Conclusions In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

BackgroundMeropenem belongs to the carbapenem class, which is categorized as beta-lactam antibiotics. These antibiotics are administered in intermittent bolus doses at specific time intervals. However, the continuous infusion approach ensures sustained drug exposure, maintaining the drug concentration above the minimum inhibitory concentration (MIC) throughout the entire treatment period. This study aimed to find out the association between continuous infusions of meropenem and mortality rates.Materials and methodsWe conducted a search of the PubMed/Medline, EMBASE, Cochrane Central, and ClinicalTrials.gov databases up to 14 August 2023. The six randomized controlled trials (RCTs) were identified and included in our analysis. The random-effects model was implemented using Comprehensive Meta-Analysis software to examine the outcomes.ResultsOur study included a total of 1,529 adult patients from six randomized controlled trials. The primary outcome indicated that continuous infusion of meropenem did not lead to reduction in the mortality rate (odds ratio = 0.844, 95% CI: 0.671–1.061, P =0.147). Secondary outcomes revealed no significant differences in ICU length of stay (LOS), ICU mortality, clinical cure, or adverse events between continuous infusion and traditional intermittent bolus strategies of meropenem. Notably, we observed significant improvements in bacterial eradication (odds ratio 19 = 2.207, 95% CI: 1.467–3.320, P < 0.001) with continuous infusion of meropenem. Our study also suggested that performing continuous infusion may lead to better bacterial eradication effects in resistant pathogens (coefficient: 2.5175, P = 0.0138*).ConclusionContinuous infusion of meropenem did not result in the reduction of mortality rates but showed potential in improving bacterial eradication. Furthermore, this strategy may be particularly beneficial for achieving better bacterial eradication, especially in cases involving resistant pathogens.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Background: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. Methods: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. Results: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%–40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P

Abstract The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti‐hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992–1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow‐up of 25 612.5 person‐years (Average event‐free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47‐2.80]; 1.92 (1.47‐2.51); and 1.79 (1.41‐2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61‐3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80‐3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long‐term risk for cardiovascular events. Cross‐classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension.

Background/Aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses.Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed.Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568).Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Abstract Background Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. Methods We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. Results For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. Conclusions An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer-associated death worldwide with a dismal overall 5-year survival rate of less than 20%. The standard first-line therapy for advanced ESCC is concomitant chemo-radiation therapy (CCRT); however, patients usually develop resistance, resulting in unfavorable outcomes. Therefore, it is urgent to identify the mechanisms underlying CCRT resistance and develop effective treatment strategies. Methods Patients’ endoscopic biopsy tumor tissues obtained before CCRT treatment were used to perform RNA-seq and GSEA analysis. Immunohistochemical (IHC) staining, chromatin immunoprecipitation (ChIP), and promoter reporter analyses were conducted to investigate the relationship between SOX17 and NRF2. Xenograft mouse models were used to study the role of SOX17/NRF2 axis in tumor growth and the efficacy of carboxymethyl cellulose-coated zero-valent-iron (ZVI@CMC). Results In this study, a notable gene expression signature associated with NRF2 activation was observed in the poor CCRT responders. Further, IHC staining of endoscopic biopsy of 164 ESCC patients revealed an inverse correlation between NRF2 and SOX17, a tumor-suppressive transcription factor with low expression in ESCC due to promoter hypermethylation. Using ChIP and promoter reporter analyses, we demonstrated that SOX17 was a novel upstream transcriptional suppressor of NRF2. In particular, SOX17low/NRF2high nuclear level significantly correlated with poor CCRT response and poor survival, indicating that the dysregulation of SOX17/NRF2 axis played a pivotal role in CCRT resistance and tumor progression. Notably, the in-house developed nanoparticle ZVI@CMC functioned as an inhibitor of DNA methyltransferases to restore expression of SOX17 that downregulated NRF2, thereby overcoming the resistance in ESCC. Additionally, the combination of ZVI@CMC with radiation treatment significantly augmented anticancer efficacy to inhibit tumor growth in CCRT resistant cancer. Conclusion This study identifies a novel SOX17low/NRF2high signature in ESCC patients with poor prognosis, recognizes SOX17 as a transcriptional repressor of NRF2, and provides a promising strategy targeting SOX17/NRF2 axis to overcome resistance.

Abstract Aim The incidence and characteristics of iatrogenic comminution (IC) are unknown, and the influence of IC on fracture union is unclear. This study was aimed to investigate the (1) incidence and characteristics of IC and (2) the outcomes of IC following antegrade interlocking nailing of simple femoral shaft fractures. Methods We retrospectively collected data on patients who experienced simple femoral shaft fractures and underwent antegrade interlocking nailing between February 2009 and December 2016. The incidence and characteristics of IC were examined. According to the presence of IC, patients were divided into two groups: an IC group and a non-IC (NIC) group. Demographic information and nonunion rates were compared between the two groups. Potential risk factors for IC (age, gender, body mass index (BMI), nail fit ratio, reduction technique, and greater trochanter nail entry) were analyzed using univariate and multivariate logistic regression. The aforementioned variables, along with IC occurrence, were also assessed as potential risk factors for nonunion at 12 and 24 months after operation using multivariate logistic regression. Results Of the 211 total patients, IC occurred in 20.9% (n = 44) of patients. Most ICs were found at the level of the isthmus, and involved the medial cortex. Compared with the NIC group, higher nonunion rates were observed in the IC group at 12 months (31.8% vs. 12.5%, p = 0.002) and 24 months (18% vs. 6.5%, p = 0.017) after surgery. Age older than 35 years old was related with the occurrence of IC in univariate analysis. Multivariate analysis found no risk factor associated with IC. Open reduction technique, IC occurrence and higher BMI were identified as the risk factors of nonunion at 12 months and 24 months after surgery in multivariate analysis. Conclusion IC is a non-rare complication in antegrade interlocking nailing of simple femoral shaft fractures and was associated with higher nonunion rate. Age older than 35 years old showed a trend toward increasing risk of iatrogenic fracture comminution. In multivariate analysis, open reduction technique, IC occurrence and higher BMI significantly correlated with fracture nonunion. Level of evidence Level IV.

Abstract Background The current guideline recommends patients who meet high probability criteria for choledocholithiasis to receive endoscopic retrograde cholangiopancreatography (ERCP). However, adverse events can occur during ERCP. Our goal is to determine whether endoscopic ultrasound (EUS) before ERCP can avoid unnecessary ERCP complications, especially in patients with a negative CT scan. Methods A total of 604 patients with high probability of choledocholithiasis were screened and 104 patients were prospectively enrolled. Patients with malignant biliary obstruction, altered GI anatomy, and choledocholithiasis on CT scan were excluded. Among them, 44 patients received EUS first, and ERCP if choledocholithiasis present (EUS-first group). The other 60 patients received ERCP directly (ERCP-first group). The baseline characteristics, presence of choledocholithiasis, and complications were compared between groups. All patients were followed for 3 months to determine the difference in recurrent biliary event rate. Cost-effectiveness was compared between the two strategies. Results There was no marked difference in age, sex, laboratory data, presenting with pancreatitis, and risk factors for choledocholithiasis. Overall, 51 patients (49.0%) had choledocholithiasis, which did not justify the risk of direct ERCP. In the EUS-first group, 27 (61.4%) ERCP procedures were prevented. The overall complication rate was significantly lower in the EUS-first group compared to the ERCP-fist group (6.8% vs. 21.7%, P = 0.04). The number-needed-to-treat to avoid one unnecessary adverse event was 6.71. After a 3-month follow-up, the cumulative recurrence biliary event rates were similar (13.6% vs. 15.0%, P = 0.803). EUS-first strategy was more cost-effective than the ERCP-first strategy (mean cost 2322.89$ vs. 3175.63$, P = 0.002). Conclusions In high-probability choledocholithiasis patients with a negative CT, the EUS-first strategy is cost-effective, which can prevent unnecessary ERCP procedures and their complications.

Abstract Background Using endoscopy as the reference, this study evaluated the accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in measuring distance from the incisors to the PET detectable esophageal cancer. If there is high concordance between endoscopic and PET measurements, our results may provide a basis to use FDG PET/CT in cooperation with endoscopic measurement to localize those PET/CT and CT undetectable esophageal tumors for radiotherapy planning. Materials Esophageal cancer patients with pretreatment endoscopy and FDG PET/CT detectable esophageal tumors were recruited retrospectively. The distances from the incisors to the proximal esophageal tumor margins were determined by endoscopy and by the sagittal images of FDG PET/CT. The endoscopic measurement was used as the comparative reference. A nuclear medicine doctor and a radiation oncologist each performed the FDG PET/CT measurement twice for every patient. We analyzed the differences in these measurements, and assessed agreement and reproducibility of the results by the intraclass correlation coefficient (ICC). Results Thirty-four patients, with 35 esophageal tumors, were included. By endoscopy and FDG PET/CT, the mean distances from the incisors to the proximal esophageal tumor margin were 27.3 ± 6.4 cm (range 17.1–40.0 cm) and 26.8 ± 6.3 cm (range 15.7–41.3 cm), respectively. The mean absolute differences between the endoscopic and four FDG PET/CT measurements ranged from 1.129 to 1.289 cm (SD: 0.98–1.19). The measurement agreement between FDG PET/CT and endoscopy by ICC was between 0.962 and 0.971. The intra- and interobserver reproducibilities of the two readers were excellent (intraobserver ICC: 0.985, 0.996; interobserver ICC: 0.976–0.984). Conclusions FDG PET/CT was in high agreement with endoscopy in measuring the distance from the incisors to the proximal esophageal tumor margin. For FDG PET/CT and CT undetectable esophageal cancer, incorporation of the endoscopic measurement with PET/CT might be a way for making radiotherapy plan.

Objective This study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with the glomerular filtration rate (eGFR) on admission for patients with intracerebral hemorrhage. Methods From the Taiwan Stroke Registry data from April 2006 to December 2016, we identified and stratified patients with intracerebral hemorrhage into five subgroups by the eGFR level on admission: ≥90, 60–89, 30–59, 15–29, and Results Both the 1-month and 1-year mortality rates progressively increased with the decrease in eGFR levels. The 1-month mortality rate in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was approximately 5.5-fold greater than that in patients with eGFR ≥ 90 mL/min/1.73 m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 [95% confidence interval (CI) = 2.71–7.78]. Similarly, the 1-year mortality in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was 7.5 times that in patients with eGFR ≥ 90 mL/min/1.73 m2 (2.34 versus 0.31 per 1000 person-days), with an adjusted HR of 4.54 (95% CI 2.95–6.98). Conclusion Impairment of renal function is an independent risk factor for mortality in patients with intracerebral hemorrhage in a gradual way. The eGFR level is a prognostic indicator for patients with intracerebral hemorrhage.

Background: Osteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan. Methods: We identified 13,520 women with OA aged 20–99 newly diagnosed in 2000–2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort. Results: The incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09–1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37–2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24–4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin. Conclusion: Women with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Abstract Background The impact of sagittal spinopelvic alignment on spondylolysis is well established in Caucasian populations. However, prior studies suggest that people from different ethnological backgrounds showed divergence, and a few studies that focused on Asian populations reported conflicting results. The aim of this study is to use the EOS imaging system to evaluate the spinopelvic parameters of spondylolysis patients, and their relationship with spondylolisthesis, disc degeneration, and age in a Taiwanese population. Methods Radiographic sagittal spinopelvic parameters for 45 spondylolysis patients and 32 healthy people were evaluated, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and lumbar lordosis (LL). The spinopelvic parameters were compared between spondylolytic and control groups. These parameters were further compared between spondylolytic subjects with and without spondylolisthesis, with and without high-grade disc degeneration, and young (

Background/Aims Endoscopic ultrasonography (EUS)-guided tissue acquisition requires a long learning curve. We aimed to compare the skill maturation curves between fine needle aspiration (FNA) and biopsy (FNB) for tissue acquisition. Methods The initial 60 procedures performed by the trainee endosonographer (30 FNA vs. 30 FNB) were consecutively enrolled. The difference in procedure performance was compared between the two groups. Learning curves were assessed. Twenty additional cases were subsequently enrolled to assess the consistency of performance in the FNB group. Results The FNB group acquired larger tissue samples (2.35 vs. 0.70 mm2; p

Arterio-esophageal fistula (AEF) is a rare life-threatening cause of upper gastrointestinal bleeding. Realizing the risk factors and clinical presentations of AEF will enable us to provide timely diagnosis, efficient treatment, and better outcome. We present a 43-year-old Taiwanese man who had histories of destructive lung, innominate artery-trachea fistula, and received bilobectomy. He was admitted to our hospital with fresh blood drainage from nasogastric tube. He was diagnosed as right fifth intercostal artery esophageal fistula by computed tomography angiography and transcatheter arterial embolization was performed. The bleeding stopped and the patient was discharged uneventfully. The risk factors of AEF include esophageal foreign body, vascular surgery, thoracic arterial malformations, and concurrent chemoradiotherapy in T4-esophageal cancer. Computed tomography angiography may be the most sensitive diagnostic test. Transcatheter arterial embolization or endovascular stent grafting may be considered as the first-line treatment of AEF in the future.

Abstract Background The prognostic significance of cardiac radiation dose in esophageal cancer after definitive concurrent chemoradiotherapy (CCRT) remains largely unknown. We aimed to investigate the association between cardiac dose-volume parameters and overall survival (OS) in esophageal squamous cell carcinoma (ESCC) after definitive CCRT. Methods One hundred and twenty-one ESCC patients undergoing definitive CCRT with intensity modulated radiotherapy technique between 2008 and 2018 were reviewed. Cardiac dose-volume parameters were calculated. Survival of patients and cumulative incidence of adverse events were estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The prognostic significance of cardiac dose-volume parameters was determined with multivariate Cox proportional hazards regression analysis. Results Median follow-up was 16.2 months (range, 4.3–109.3). Median OS was 18.4 months. Heart V5, V10, and V20 were independent prognostic factors of OS. Median OS was longer for patients with heart V5 ≤ 94.3% (24.7 vs. 16.3 months, p = 0.0025), heart V10 ≤ 86.4% (24.8 vs. 16.9 months, p = 0.0041), and heart V20 ≤ 76.9% (20.0 vs. 17.2 months, p = 0.047). Lower cumulative incidence of symptomatic cardiac adverse events was observed among patients with heart V5 ≤ 94.3% (p = 0.017), heart V10 ≤ 86.4% (p = 0.02), and heart V20 ≤ 76.9% (p = 0.0057). Patients without symptomatic cardiac adverse events had a higher 3-year OS rate (33.8% vs. 0%, p = 0.03). Conclusions Cardiac radiation dose inversely correlated with survival in ESCC after definitive CCRT. Radiation dose to the heart should be minimized.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Abstract Background The literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT. Methods A total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis. Results The median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer. Conclusions Dose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.

Abstract Background Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) involvement is a rare disease with poor prognosis. This study aimed to evaluate the outcome of HCC patients receiving radiotherapy (RT) to IVC tumor thrombus. Methods A total of 42 consecutive HCC patients treated with RT to IVC tumor thrombus between September 2007 and October 2018 were enrolled. Overall survival (OS), the response of IVC thrombus, prognostic factors and failure pattern were assessed. Results The median follow-up time was 4.4 months. The median RT equivalent dose in 2-Gy fractions was 48.75 Gy (range, 3.25–67.10). The objective response rate of IVC thrombus was 47.6% (95% confidence interval [CI], 33.3–64.3%). The OS rate at 1 year was 30.0%, with a median OS of 6.6 months (95% CI, 3.7–9.5) from the start of RT. On multivariate analysis, Child-Pugh class, lymph node metastasis, lung metastasis and objective response of IVC thrombus were independent predictors for OS. Lung was the most common site of first progression in 14 (33.3%) patients. For 32 patients without lung metastasis before RT, use of systemic treatment concurrent with and/or after RT was associated with a significantly longer lung metastasis-free survival (5.9 vs. 1.5 months, p = 0.0033). Conclusions RT is effective for IVC tumor thrombus of HCC with acceptable adverse effects. RT might be a treatment option incorporated into combination therapy for HCC involving IVC.

Objective: Stroke in young adults is uncommon, and the etiologies and risk factors of stroke in young adults differ from those in older populations. Smoker's paradox is an unexpected favorable outcome, and age difference is used to explain the association between smoking and the favorable functional outcome. This study aimed to investigate the existence of this phenomenon in young stroke patients.Methods: We analyzed a total of 9,087 young stroke cases registered in the nationwide stroke registry system of Taiwan between 2006 and 2016. Smoking criteria included having a current history of smoking more than one cigarette per day for more than 6 months. After matching for sex and age, a Cox model was used to compare mortality and function outcomes between smokers and non-smokers.Results: Compared with the non-smoker group, smoking was associated with older age, higher comorbidities, and higher alcohol consumption. Patients who report smoking with National Institutes of Health Stroke Scale scores of 11–15 had a worse functional outcome (adjusted odds ratio, 0.81; 95% confidence interval, 0.76 – 0.87).Conclusion: Smokers had a higher risk of unfavorable functional outcomes at 3 months after stroke, and therefore, we continue to strongly advocate the importance of smoking cessation.

BackgroundThe literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique.MethodsA total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis.ResultsMedian follow-up was 14.9 months (IQR, 7.0-28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3-10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383-10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053-6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058).ConclusionsT4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

Summary: Sweat-based wearable devices have attracted increasing attention by providing abundant physiological information and continuous measurement through noninvasive healthcare monitoring. Sweat pressure generated via sweat glands to the skin surface associated with osmotic effects may help to elucidate such parameters as physiological conditions and psychological factors. This study introduces a wearable device for measuring secretion sweat pressure through noninvasive, continuous monitoring. Secretion pressure is detected by a microfluidic chip that shows the resistance variance from a paired electrode pattern and transfers digital signals to a smartphone for real-time display. A human study demonstrates this measurement with different exercise activities, showing the pressure ranges from 1.3 to 2.5 kPa. This device is user-friendly and applicable to exercise training and personal health care. The convenience and easy-to-wear characteristics of this device may establish a foundation for future research investigating sweat physiology and personal health care.

Abstract Background Prognosis of esophageal squamous cell carcinoma (ESCC) patients is poor and the concurrent chemoradiation therapy (CCRT) provided to ESCC patients often failed due to resistance. Therefore, development of biomarkers for predicting CCRT response is immensely important. In this study, we evaluated the predicting value of SRY (sex determining region Y)-box 17 (SOX17) protein during CCRT and its dysregulation of transcriptional targets in CCRT resistance in ESCC. Methods Pyrosequencing methylation, RT-qPCR and immunohistochemistry assays were performed to examine the DNA methylation, mRNA expression and protein expression levels of SOX17 in endoscopic biopsy from a total of 70 ESCC patients received CCRT. Cell proliferation, clonogenic survival and xenograft growth were used to confirm the sensitization of ESCC cell line KYSE510 in response to cisplatin, radiation or CCRT treatment by SOX17 overexpression in vitro and in vivo. Luciferase activity, RT-qPCR and ChIP-qPCR assays were conducted to examine transcription regulation of SOX17 in KYSE510 parental, KYSE510 radio-resistant cells and their derived xenografts. Results High DNA methylation coincided with low mRNA and protein expression levels of SOX17 in pre-treatment endoscopic biopsy from ESCC patients with poor CCRT response. SOX17 protein expression exhibited a good prediction performance in discriminating poor CCRT responders from good responder. Overexpression of SOX17 sensitized KYSE510 radio-resistant cells to cisplatin, radiation or CCRT treatment in cell and xenograft models. Importantly, SOX17 transcriptionally down-regulated DNA repair and damage response-related genes including BRCA1, BRCA2, RAD51, KU80 DNAPK, p21, SIRT1, NFAT5 and REV3L in KYSE510 radio-resistant cells to achieve the sensitization effect to anti-cancer treatment. Low expression of BRCA1, DNAPK, p21, RAD51 and SIRT1 was confirmed in SOX17 sensitized xenograft tissues derived from radio-resistant ESCC cells. Conclusions Our study reveals a novel mechanism by which SOX17 transcriptionally inactivates DNA repair and damage response-related genes to sensitize ESCC cell or xenograft to CCRT treatment. In addition, we establish a proof-of-concept CCRT prediction biomarker using SOX17 immunohistochemical staining in pre-treatment endoscopic biopsies to identify ESCC patients who are at high risk of CCRT failure and need intensive care.

Abstract Background H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P

Abstract Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

Background/Purpose: The prevalence of Gastroesophageal reflux disease (GERD) is increasing worldwide, including Asia. Although several consensus reports have been published, little is known regarding the adherence of the physicians on the consensus of GERD. We aimed to survey the agreements and adherence of physicians to the Taiwan GERD consensus before and after the continual medical education (CME) courses. Methods: Two-hundred and twenty-seven physicians, including 81 fellows of gastroenterology, 135 qualified gastroenterologists, and 11 non-gastroenterologist attending physicians were invited to the CME course. Their agreements and adherence to the statements before and after the CME course were assessed by the pre-defined questionnaire with the aid of electronic keypads. The adherence rate before and after the CME course were compared by the McNemar test to indicate the changes in their willingness to follow the statements in clinical practice. Results: The rates of agreement of the 227 participating physicians were uniformly greater than 80% for all of the 22 statements. However, the adherence rates were lower than 80% in 16 statements before the CME intervention. The adherence rates were significantly (p

Objective: Post-hoc economic evaluation of a bio-psycho-social intervention in post-war Kosovo from a societal perspective. Design: Cost-effectiveness analysis, cost-utility analysis, and partial cost-benefit analysis using data from a randomized controlled trial. Patients: Thirty-four torture/war victims with comorbid conditions enrolled in 2012–2013. Methods: Participants were randomly assigned to an “intervention” and a “waiting-list” group. Changes in mental, emotional and physical health and functional impairment were assessed before and after treatment, along with increase in labour income as a proxy for productivity gain. The cost of an extra unit of effectiveness and an additional quality-adjusted life year were calculated. Results: The total cost per participant was €1,322 including, or €1,019 excluding, research costs. Wide variations in costs of changes in mental, emotional and physical effectiveness were demonstrated. Multidisciplinary intervention resulted in functional improvement at a cost of €10,508 per quality-adjusted life year gained. With a mean monthly income increase to €133 (18%) after intervention, the intervention cost per participant would be equal to the total increase in monthly income after 4–5 years, assuming the increased level is maintained. Conclusion: Socio-economic benefit associated with quality-adjusted life year gain is shown, although the cost of an additional quality-adjusted life year is above the World Health Organization cost-effectiveness threshold.

Abstract Background Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. Methods A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. Results The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p

Irreducible dislocation of the elbow is an uncommon event. We present the case of a posterolateral elbow dislocation after a fall injury in a 67-year-old woman. A closed reduction performed in the emergency department was unsuccessful since the limited passive range of motion resulted in difficulty to perform longitudinal traction and flexion. Computed tomography images showed that the posterolateral aspect of the capitellum was impacted by the tip of the coronoid process, thus appearing similar to the Hill–Sachs lesion in the humeral head. Subsequent open reduction of the elbow revealed the dislocation to be irreducible since the tip of the coronoid process had wedged into a triangular Hill–Sachs-like lesion in the capitellum. The joint was reduced by providing distal traction on the forearm, and main fragments were disengaged using digital pressure. At the 3-month follow-up, the patient reported no dislocations, and had an acceptable range of motion. Thus, we propose that to avoid iatrogenic injury to the joint or other nearby structures, irreducible dislocations should not be subjected to repeated manipulation.

BackgroundThis study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome.MethodsWe retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival.ResultsPatients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3).ConclusionLarge primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted.

Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells’ stemness properties in vitro and in vivo . Results: The authors’ data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo . Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient’s clinical outcomes in the future.

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real‐world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006–2016) on aspirin or clopidogrel for secondary stroke prevention were identified in the Taiwan Stroke Registry. Stroke recurrence and mortality rates in patients receiving aspirin (N=34 679) were compared with those receiving clopidogrel (N=7611) during a 12‐month follow‐up period. Propensity score matching and conditional Cox proportional hazards regression model were applied to control confounding factors with 6443 patients in each group. After propensity score matching, stroke recurrence rates were comparable between groups, with 223 patients in the aspirin (3.46%) and 244 in the clopidogrel group (3.79%) (hazard ratio=1.13, 95% confidence interval=0.89–1.43, P=0.311). However, the mortality rate was significantly higher in the clopidogrel group (362 patients, 5.62%) than in the aspirin group (302 patients, 4.69%) (hazard ratio=1.30, 95% confidence interval=1.07–1.58, P=0.008). Results were consistent before and after propensity score matching. Conclusions Clopidogrel was as effective as aspirin for prevention of recurrent stroke in real‐world practice. However, the mortality rate was significantly higher in the clopidogrel than in the aspirin group.

Airline companies join airline alliances to cope with the high level of competition in the airline industry. However, pressure within an alliance is substantial. This study used competitor mapping and awareness-motivation-capability competitive dynamics to analyze airline alliances. The results revealed that alliances compete to recruit airline companies, and the power differences in the alliances are considerable; only a few of the airline companies within the alliance possess power. In addition, we interviewed 2 senior managers to confirm the results of the analysis. A detailed content analysis was performed to test each hypothesis. The findings revealed that companies with low market commonality and high resource similarity can cooperate through resource allocation. We also discovered that the main competitive action was derived from disallowing local airline companies to join an alliance. Leading companies in the alliance generally negotiated for the entire alliance indirectly. This research suggests that companies cooperate not only to control cost but also to increase service quality.

Background: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs), but the risk factors for postoperative stricture have not been elucidated. The objective of this study was to identify and validate a predictor for post-RFA stenosis. Methods: We consecutively enrolled patients with flat-type ‘large’ (length no less than 3 cm extending no less than half the circumference of the esophagus), early ESCNs, treated with balloon-based RFA (12 J/cm 2 –clean–12 J/cm 2 regimen). The tumor and technical factors for postoperative stricture were investigated and we validated the results externally with a society-based multicenter cohort using the same ablation regimen. Results: A total of 51 patients were enrolled (30 in the development set and 21 in the validation set). The complete remission rate at 12 months was 93%, and the rates of perforation and postoperative stenosis were 0% and 17%, respectively. Patients with post-RFA stenosis had a significantly larger longitudinal tumor size (mean 115 versus 61 mm, p = 0.003). There were no significant differences in age, body mass index, tumor circumferential extension, pretreatment histological grade, treatment efficacy or size of balloon catheter between the groups with or without stenosis. The optimal cut-off value was set as 9 cm to predict post-RFA stenosis by receiver operating characteristic curve [area under curve (AUC) = 0.881], which was then confirmed to be a reliable predictor by multivariate analysis (odds ratio, 12.7, 95% confidence interval, 1.18–136.28, p = 0.03) and have a good predictive performance in the validation set (AUC = 0.876). Conclusions: The most frequent adverse event of RFA was esophageal stenosis, for which the longitudinal tumor size was a significant predictive factor. Early intervention or prevention for stricture should be applied for those with long segment (⩾9 cm) ESCNs.

BACKGROUND/AIMS: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. METHODS: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. RESULTS: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p

Background. Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. Aims. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. Methods. The 126 gastric ulcer patients (H. pylori infected n=46; NSAID related n=30; combined with two factors n=50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Results. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P