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Background Chronic hepatitis C virus (HCV) infection is associated with increased cardiovascular risks. We aimed to investigate the impact of direct acting antiviral (DAA) on HCV-associated cardiovascular events. Methods In this retrospective cohort study, patients with the diagnosis of chronic HCV were retrieved from multi-institutional electronic medical records, where diagnosis of HCV was based on serum HCV antibody and HCV–RNA test. The patients eligible for analysis were then separated into patients with DAA treatment and patient without DAA treatment. Primary outcomes included acute coronary syndrome, heart failure (HF), venous thromboembolism (VTE), stroke, cardiovascular death, major adverse cardiovascular event (MACE), and all-cause mortality. Outcomes developed during follow-up were compared between DAA treatment and non-DAA treatment groups. Results There were 41 565 patients with chronic HCV infection identified. After exclusion criteria applied, 1984 patients in the DAA treatment group and 413 patients in the non-DAA treatment group were compared for outcomes using inverse probability of treatment weighting. Compared to patients in non-DAA treatment group, patients in DAA treatment group were associated with significantly decreased HF (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.44–0.97, P = 0.035), VTE (HR: 0.19, 95% CI: 0.07–0.49, P = 0.001), MACE (HR: 0.73, 95% CI 0.59–0.92, P = 0.007), and all-cause mortality (HR: 0.50, 95% CI: 0.38–0.67, P Conclusions Chronic HCV patients treated with DAA experienced lower rates of cardiovascular events and all-cause mortality than those without treatment. The reduction of VTE was the most significant impact of DAA treatment among the cardiovascular outcomes.

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes—best-corrected visual acuity (BCVA) and central macular thickness (CMT)—were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.

Objectives/hypothesis To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. Study design Retrospective study. Methods Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. Results The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. Conclusions The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. Level of evidence 4 Laryngoscope, 2021.

Environmental carcinogenic exposures are major contributors to global disease burden yet how they promote cancer is unclear. Over 70 years ago, the concept of tumour promoting agents driving latent clones to expand was first proposed. In support of this model, recent evidence suggests that human tissue contains a patchwork of mutant clones, some of which harbour oncogenic mutations, and many environmental carcinogens lack a clear mutational signature. We hypothesised that the environmental carcinogen

IMPORTANCE: The majority of the patients with head and neck cancer (HNC) experience taste dysfunction (TD) during or after radiotherapy (RT). However, prospectively collected data for taste dysfunction have been limited, especially in the era of intensity-modulated RT (IMRT). OBJECTIVE: To evaluate the taste function in patients with HNC receiving IMRT by investigating the association between time course and recovery of TD in both acute and late phases. DESIGN, SETTING, AND PARTICIPANTS: From August 2017 to November 2020, patients treated at the Chang Gung Memorial Hospital with curative or postoperative IMRT for HNC were enrolled in this prospective cohort study. The data analysis was performed from March 2021 to January 2022. EXPOSURES: IMRT with and without concurrent chemotherapy. MAIN OUTCOMES AND MEASURES: Taste function was measured using the whole-mouth solution method for 4 tastes (salt, sweet, sour, and bitter). Subjective evaluations (National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03] and Subjective Total Taste Acuity scale) were used. Patient self-reported quality of life was evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35). RESULTS: A total of 87 patients (78 [90%] men and 9 [10%] women; mean [range] age, 58 [31-80] years) were enrolled. Overall TD rates were 79 of 86 (91.9%), 63 of 83 (75.9%), 27 of 81 (33.3%), 5 of 56 (8.9%), and 2 of 30 (6.7%) during RT, and 1 week, 3 months, 6 months, and 1 year after RT, respectively. Positive correlation occurred between objectively measured taste loss for the 4 taste qualities and subjective perception of taste loss. Only oral cavity mean dose 4000 cGy or greater predicted TD 3 months after RT. The mean oral cavity doses to the predicted 15% (D(15)), 25% (D(25)), and 50% (D(50)) probabilities were 25, 38, and 60 Gy at 3 months and 57, 60, and 64 Gy at 6 months, respectively. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients still experienced TD during and at 3 months after RT. Only a few patients experienced long-term TD. A high oral cavity dose was associated with TD in patients with HNC receiving IMRT. Reducing oral cavity dose may promote early recovery of taste function after IMRT.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/ HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL).To investigate early perioperative QoL after CRS/HIPEC, which has not been discussed in Taiwan.This single institution, observational cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 mo after CRS/HIPEC (S3).Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results.QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

Purpose Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL). This study aimed to investigate early perioperative QoL after CRS/HIPEC, which has rarely been discussed in the literature. Methods This single institution, prospective cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 months after CRS/HIPEC (S3). Results Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results. Conclusion QoL and symptom severity improved or returned to baseline in most categories within 3 months after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

BackgroundThe major mechanisms of arteriovenous graft (AVG) failure due to intimal hyperplasia (IH) are smooth muscle cell proliferation and inflammation. Therefore, carvedilol may improve AVG primary patency because of its anti-proliferative and anti-inflammatory activities.MethodsThe data of end-stage renal disease patients receiving regular hemodialysis were collected from the National Health Insurance Research database. The end point was the first percutaneous transluminal angioplasty (PTA) for AVG failure or death during a follow-up period of two years or the end of 2013. The analysis was calculated with Cox proportional hazard model.ResultsThere were 3028 patients treated with carvedilol and 13,704 patients not treated with carvedilol. According to a univariate analysis, the carvedilol group was younger, received more anti-hypertensive medications and platelet aggregation inhibitors, and had higher rates of diabetes mellitus and hyperlipidemia but had lower rates of hypotension and smoking. According to a multivariate analysis, after controlling for covariates, the use of carvedilol for more than 84 days reduced the probability of a first PTA for AVG failure by 9% compared with no use of carvedilol ( p = 0.021), but the use of carvedilol for 1 to 84 days did not.ConclusionThe results of this study indicate that the use of carvedilol for more than 84 days improves the primary patency of AVGs, but the use of carvedilol for less than 84 days does not.

Systemic lupus erythematosus (SLE) might increase deep neck infection (DNI) risk, but evidence supporting this hypothesis is limited. In this retrospective follow-up study, the SLE–DNI association was investigated using data from the Registry for Catastrophic Illness Patients, which is a subset of the Taiwan National Health Insurance Research Database. All patients newly diagnosed as having SLE in 1997–2011 were identified, and every SLE patient was individually matched to four patients without SLE according to sex, age, and socioeconomic status. The study outcome was DNI occurrence. DNI treatment modalities and prognoses in SLE and non-SLE patients, along with the association of steroid dose with DNI risk, were also studied. In total, 17,426 SLE and 69,704 non-SLE patients were enrolled. Cumulative DNI incidence was significantly higher in the SLE cohort than in the non-SLE cohort (p p p = 0.033). The between-group differences in tracheostomy use and hospitalisation duration were nonsignificant. In SLE patients, high steroid doses significantly increased DNI incidence (≥3 vs. p

BACKGROUND: Pacing-induced cardiomyopathy is an undesired outcome in patients with atrioventricular block (AVB), and our animal model showed lipotoxic cardiomyopathy after pacing.OBJECTIVES: The purpose of this study was to explore the mechanisms and clinical outcomes of statins in AVB patients receiving pacing.METHODS: Rat ventricular cardiomyocytes were treated with atorvastatin, liver X receptor (LXR) agonist, and LXR antagonist during pacing. Pigs were divided into 3 groups: right ventricular pacing, pacing with concomitant atorvastatin treatment, and sham control. Clinically, we enrolled 1717 AVB patients who had received a permanent pacemaker from Chang Gung Memorial Hospital Medical database. The primary outcome (cardiovascular death or heart failure [HF] hospitalization) and individual outcome were compared between statin and nonstatin groups after inverse probability of treatment weighting.RESULTS: Lipid accumulation in rat cardiomyocytes by pacing was significantly reduced by treatment with LXR agonist and atorvastatin, whereas LXR antagonist counteracted the atorvastatin effect on lipid expression. Left ventricular ejection fraction (LVEF) was significantly lower in the AVB pig pacing group compared to the group concomitantly treated with atorvastatin. Moreover, lipid accumulation and fibronectin expression were significantly ameliorated by concomitant treatment with atorvastatin. In the clinical study, the statin group had a significantly lower risk of the primary outcome event (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.56-0.84), less HF hospitalization (HR 0.45; 95% CI 0.30-0.67), and higher LVEF than the nonstatin group.CONCLUSION: In experimental models, atorvastatin ameliorated lipid accumulation in cardiomyocytes and fibrosis in left ventricular myocardium induced by pacing. Clinically, treatment with statins was associated with less HF hospitalization and cardiovascular death in AVB patients receiving pacemaker therapy.

Background: Obesity has been regarded as a risk factor for epiblepharon. This study aims to investigate the age- and sex-specific relationship between epiblepharon and obesity in children.Methods: A retrospective case-control study was conducted using Chang Gung Research Database. Children ≤ 18 years of age with epiblepharon were identified from 1 January 2009 to 31 December 2019. Children were classified into four groups: underweight, normal, overweight and obese groups.Results: A total of 513 patients and 1026 controls (57.7% of males) aged 1 to 18 matched by sex and age were included in the analysis. The median body mass index (BMI) of children with epiblepharon was significantly higher than that of children without epiblepharon (p < 0.001). In the subgroup analysis, among boys aged 4 to 9 years, the BMI in boys with epiblepharon was significantly higher than that in boys without epiblepharon (p < 0.05) and the risk of epiblepahron in overweight and obese boys was significantly higher than in non-overweight boys (OR = 1.74, 95% CI = 1.07-2.82; OR = 3.06, 95% CI = 1.56-6.03). On the other hand, among girls aged 13 to 18 years, the BMI in adolescent girls with epiblepharon was significantly higher than that in the control group (p < 0.05) and overweight and obese girls had statistically higher risk of persistent epiblepharon than non-overweight girls (OR =3.70, 95% CI = 1.38-9.97).Conclusions: The association between obesity and epiblepharon varies in strength according to age in a sex-specific manner.

Objectives: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database. Methods: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database collected over January, 2000, to December, 2013. Results: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P = .021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P = .018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P = .015). Conclusions: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years.

To examine the association of laryngoplasty, voice therapy, and pneumonia rate in patients with unilateral vocal fold paralysis (UVFP).Population-based retrospective cohort study.Data were collected from the LHID2000 (Longitudinal Health Insurance Database 2000), containing the information of 1 million randomly selected patients in Taiwan.In the LHID2000, we identified 439 patients having new diagnoses of UVFP from 1997 to 2013. We grouped the aforementioned patients according to UVFP treatment and probed the occurrence of pneumonia: 305 patients underwent laryngoplasty or voice therapy, and 134 patients did not undergo treatment. Follow-up procedures were executed for the enrollees until death or December 31, 2013, representing the end of the study period. We assessed the association of UVFP treatment and pneumonia by executing Cox proportional hazards regression.The pneumonia cumulative incidence was significantly higher among enrolled patients without treatment than in those receiving treatment (Laryngoplasty was associated with a lower incidence of short- and long-term pneumonia in patients with UVFP. Physicians should encourage patients with UVFP at risk of aspiration to receive prompt evaluation as well as treatment.

Background: We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection. Methods: This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999. Results: During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18–1.24], 1.48 (95% CI, 1.37–1.59), 1.50 (95% CI, 1.34–1.68), and 1.88 (95% CI, 1.61–2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group). Conclusions: The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC. Impact: AA may increase the risk of PLC in HCV-positive populations.

OBJECTIVE To investigate the association between rheumatoid arthritis (RA) and deep neck infection (DNI). STUDY DESIGN Retrospective cohort study. METHODS Patients newly diagnosed with RA between 2000 and 2011 were identified from the National Health Insurance Research Database in Taiwan. Moreover, patients without RA were randomly selected and matched at a 1:4 ratio by age, sex, urbanization level, income, and diabetes mellitus. The patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of DNI. RESULTS In total, 30,207 patients with RA and 120,828 matched patients without RA were enrolled. Patients with RA had a significantly higher cumulative incidence of DNI than those without RA (P

Background: The successful inhibition of the PD-1/PD-L1 axis and CTLA-4 has opened the era of immuno-oncology, however only a few patients with metastatic colorectal cancer (mCRC) and microsatellite instability (MSI, ~5%) derive survival benefits from these treatments. BRAF genomic alterations, mainly V600 point mutations, comprise 10-15% of cases and have a poorer prognostic phenotype. Method: The public domain genomic database (via cBioPortal and AACR Project GENIE) was used as an external control to explore the genomic make-up of BRAF-mutated and BRAF-wild mCRC tumors. The Wilcoxon sum rank test was used for the genome-wide association analysis, and the Kaplan-Meier method was used to estimate survival. Besides, clinical observations on extraordinary responses to regorafenib plus nivolumab therapy in two patients with microsatellite stable (MSS) mCRC with BRAF genomic alterations were reported. Result: The CRC cohort comprised 2,936 patients and the immune checkpoint inhibitor (ICI) treated cohort comprised 1,661 patients, of which 110 (6.6%) were CRC patients. BRAF genomic alterations (CRC versus ICI cohort: 12.4% versus 11.8%, respectively) were significantly associated with POLE and PRKDC gene mutations (p80 month, log rank p80 versus 15 months, log rank p=0.121) Conclusion: BRAF-mutated malignancies represent a sub-population of MSS CRC with higher TMB, which could benefit from a combination of regorafenib and nivolumab therapy. Citation Format: Feng-Che Kuan, Chung-Sheng Shi, Yu-Ying Wu, Meng-Hung Lin. Braf-altered microsatellite-stable metastatic colorectal cancer: A niche for immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5212.

e14589 Background: The treatment of BRAF-mutated melanoma leads the evolution of management in BRAF-mutated human malignancies from targeted agents to immune checkpoint inhibition. The correlation between BRAF genomic alterations and mutation burden is not well-studied as well as its prognostic role and predictive role to immune checkpoint inhibitors. Methods: Three Public genomic database (AACR GENIE v.11 [N = 119,058], MSKCC pan-cancer [10,080], MSKCC ICI [1,608]) were retrieved from cBioPortal ( https://www.cbioportal.org ). Raw data of cancer types, BRAF status, mutation counts (MC), exposure to immune checkpoints inhibitors (ICIs), and survival were analyzed. Violin plots were used to compare the distribution of MC among BRAF-altered and -wild tumors, and the Kaplan-Meier method was used to estimate survival rates. Statistical significance was set at a two-sided P < 0.05. Results: BRAF genomic alterations exist in 7,361 (6.2%, AACR GENIE v.11), 560 (5.6%, MSKCC pan-cancer) and 165 patients (10.3%, MSKCC ICI). There are 4,851 (4.1%), 357 (3.6%), and 312 (19.4%) patients with melanoma in these database, respectively. AACR GENIE v.11 includes the other two MSKCC databases, and 10.7% (N = 1,074) patients in MSKCC pan-cancer databases are also cases in MSKCC ICI. The median MCs were 7/Mb and 4/Mb, with interquartile ranges of 1 to 1,467 and 1 to 821 in the BRAF-altered and -wild tumors in AACR GENIE v.11. In this three databases, the distribution of MC was different between the BRAF-altered and -wild tumors (p < 0.001). In MSKCC pan-cancer cohort, the median overall survival in BRAF-altered and -wild tumors are 22.8 vs. 26.3 months (logrank p = 0.005). In MSKCC ICI cohort, the median overall survival of BRAF-altered and -wild tumors are 47.0 vs. 17.0 months (logrank p < 0.001). Conclusions: BRAF genomic alterations are associated with higher mutation counts, represent a poor prognostic factor and positively predictive to immune checkpoint inhibition among human malignancies.

ObjectivesPatients with uremia are prone to infection; however, end-stage renal disease (ESRD) as a risk factor for acute epiglottitis warrants study. We investigated the risk of severe epiglottitis requiring hospitalisation in patients with ESRD.SettingWe conducted a retrospective matched cohort study by using the claims data of Taiwan’s National Health Insurance Research Database.ParticipantsWe identified an ESRD cohort with 87 908 patients newly diagnosed in 2000–2013 and underwent dialysis. The non-ESRD cohort comprised patients who had not received a diagnosis of ESRD, and they were matches to the ESRD cohort (1:1) by sex, age, residence urbanisation level, monthly income, and diabetes and hypertension status.Primary and secondary outcome measuresThe cumulative incidence of epiglottitis at the end of 2013 was analysed with Kaplan-Meier methods and log-rank tests. The HR of epiglottitis was calculated using the Cox proportional hazards model after adjustment for confounding factors.ResultsThe overall epiglottitis incidence rate was 94% greater in the ESRD cohort than in the non-ESRD cohort (10.3 vs 5.3 cases per 100 000 person-years, p=0.002), with an adjusted HR of 1.89 (95% CI: 1.23 to 2.91, p=0.004). In the log-rank analysis, compared with the non-ESRD group, the epiglottitis cumulative incidence was significantly higher in the ESRD group (p=0.003). Epiglottitis did not exhibit an association with higher rates of airway interventions, intensive care unit admissions or longer hospitalisation in patients with ESRD than in controls.ConclusionsThis nationwide matched cohort study indicated that ESRD patients should be monitored for the risk of severe epiglottitis requiring hospitalisation.

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus

This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200–5080 cGy/21–28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN − 3(cT − pT) + 12]2/9.61. The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (

Background This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). Methods This retrospective cohort study included patients with stages III–IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan–Meier method and Cox regression models. Results In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). Conclusions In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.

Background: Little evidence is available about the risk of sudden sensorineural hearing loss (SSNHL) in patients with thyroid diseases. We assessed whether a diagnosis of thyroid disease, particularly hyperthyroidism or hypothyroidism, is associated with SSNHL risk in an Asian population. Material and Methods: This case-control study was conducted with population-based data from Taiwan&rsquo, s National Health Insurance Research Database from January 2000 to December 2013. The case group comprised 3331 adult patients with newly diagnosed SSNHL, and four controls without SSNHL for each case matched by sex, age, monthly income, and urbanization level of residence. Underlying Thyroid diseases were retrospectively evaluated in the case and control groups. Multivariate logistic regression analyses were used to explore relations between thyroid diseases and SSNHL. Results: Of the 3331 cases, 5.7% had preexisting thyroid diseases, whereas only 4.0% of the 13,324 controls had the same condition. After adjustment for sex, age, monthly income, urbanization level of residence, history of hypertension, diabetes mellitus, chronic otitis media, and hyperlipidemia, associations were identified between a history of either hypothyroidism (adjusted odds ratio [AOR], 1.54, 95% CI, 1.02&ndash, 2.32, p&thinsp, =&thinsp, 0.042) or hyperthyroidism (AOR, 1.41, 95% CI, 1.07&ndash, 1.85, 0.015) and an elevated risk of SSNHL. In subgroup analysis, the correlation between hypothyroidism and increased SSNHL risk remained significant only for patients aged over 50 years (AOR, 1.61, 95% CI, 1.01&ndash, 2.57, 0.045), and that between hyperthyroidism and SSNHL was significant only for female patients (AOR, 1.48, 95% CI, 1.09&ndash, 2.01, 0.012). Treatment for hypothyroidism and hyperthyroidism did not alter the association in subgroup analyses. Conclusion: Preexisting hypothyroidism and hyperthyroidism appear associated with SSNHL susceptibility in Taiwan. Physicians should be wary of this elevated risk of SSNHL among patients with previously diagnosed thyroid dysfunction, especially women and patients aged more than 50 years.

Supplemental material, sj-pdf-1-vas-10.1177_1708538120923886 for Effect of carvedilol on arteriovenous graft primary patency by Yuan-Hsi Tseng, Chia-Yen Liu, Chuan-Pin Lee, Meng-Hung Lin and Yao-Hsu Yang in Vascular

It was suspected that aristolochic acid-induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV-infected patients. We conducted a retrospective, population-based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV-infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow-up period of 11,643,790 person-years and the overall incidence rate was 291.8 HCCs per 100,000 person-years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11-1.16), 1.21 (95% CI, 1.13-1.29), 1.37 (95% CI, 1.24-1.50) and 1.61 (95% CI, 1.40-1.84) for estimated aristolochic acid of 1-250, 251-500, 501-1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose-response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.

Objective To investigate pneumonia risk among patients with unilateral vocal fold paralysis (UVFP). Study Design Retrospective population-based cohort study. Setting This study used data from the National Health Insurance Research Database of Taiwan, a nationwide population-based database. Subjects and Methods A total of 419 patients newly diagnosed with UVFP between January 1, 1997, and December 31, 2013, were identified from the Longitudinal Health Insurance Database 2000, a nationally representative database of 1 million randomly selected patients. Moreover, 1676 patients without UVFP were matched to patients with UVFP at a 1:4 ratio based on age, sex, socioeconomic status, urbanization level, and site-specific cancers. Patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of pneumonia. Results The cumulative incidence of pneumonia was significantly higher for patients with UVFP than those without UFVP ( P < .001). The adjusted Cox proportional hazard model showed that UVFP was significantly associated with a higher incidence of pneumonia (hazard ratio, 1.97; 95% CI, 1.35-2.86; P < .001). Subgroup analyses demonstrated that UVFP was an independent risk factor of pneumonia for 4 subgroups: young (18-50 years), older (≥51 years), male, and cancer. Conclusion This is the first nationwide population-based cohort study to investigate the association between UVFP and pneumonia. The findings indicate that UVFP is an independent risk factor of pneumonia. Given the study results, physicians should be aware of the potential for pneumonia occurrence following UVFP.

This study produces Ni–SiC composite coatings by electrodeposition with A356 aluminum alloy as the substrate. The concentration of SiC particles in the plating bath and the current density are varied to produce composite coatings with particle concentrations from 2.5 to 12.3 vol%, and hardness from 439 to 538 HV. Dry friction and lubrication friction experiments use a ball-on-disk to determine the frictional behavior of the Ni–SiC composite coatings. The coefficient of friction and wear resistance of a Ni–SiC composite coating is determined for different load and lubrication environments. The results show that in a dry friction environment, a composite coating with a SiC particle content of 8.0–10.0 vol% and a hardness of 500–540HV has a lower coefficient of friction and abrasion rate due to the high hardness and elastic modulus ratio (H/E). In a lubricating environment, load resistance is 150 N if the coating contains 8.0–10.0 vol% particles. When the load is increased to 200 N, a large number of SiC particles are removed due to friction so the Ni-12.3 vol%SiC many oil storage pores are created in the composite coating. This hydraulic lubrication produces a coating with better wear performance.

Objective To investigate the risk of vertigo in patients with sleep apnea. Study Design Retrospective cohort study. Methods This study used data from the National Health Insurance Research Database of Taiwan, a population-based database. A total of 5,025 patients who were newly diagnosed with sleep apnea between January 1, 1997, and December 31, 2012, were identified from the Longitudinal Health Insurance Database 2000, a nationally representative database of 1 million randomly selected patients. Moreover, 20,100 patients without sleep apnea were matched at a 1:4 ratio by age, sex, socioeconomic status, and urbanization level. Patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of vertigo. Results Patients with sleep apnea had a significantly higher cumulative incidence of vertigo than those without sleep apnea (P < 0.001). The adjusted Cox proportional hazard model showed that sleep apnea was significantly associated with a higher incidence of vertigo (hazard ratio, 1.71; 95% confidence interval [CI], 1.48–1.97; P < 0.001). Sensitivity and subgroup analyses were performed to adjust for confounders, including head trauma, diabetes mellitus, hypertension, stroke, and obesity. Sleep apnea was demonstrated to be an independent risk factor for vertigo. Conclusion This is the first nationwide population-based cohort study to investigate the association between sleep apnea and vertigo. The findings strongly support that sleep apnea is an independent risk factor for vertigo. Based on the study results, physicians should be aware of potential vertigo occurrence following sleep apnea. Level of Evidence 4. Laryngoscope, 2017

This paper presents the first successful application of α-zirconium phosphate/polyurethane (ZrP/PU) nanocomposites for corrosion protection. ZrP nanoplatelets were synthesized using a reflux method and modified with a polyetheramine surfactant (Jeffamine M1000) to form organic ZrP nanoplatelets. ZrP/PU nanocomposite films were based on PU and ZrP with different ZrP contents from 0.5–5 wt%. To probe the internal morphology of ZrP/PU nanocomposites, their cross-sections were examined by scanning and transmission electron microscopy. The results reveal that ZrP dispersed very well in PU films and that no substantial agglomeration occurred. Well-dispersed ZrP nanoplatelets in a PU matrix could effectively enhance the moisture barrier properties of ZrP/PU films. The water vapor transmission rate was significantly reduced to 84 g m−2 per day for ZrP/PU films compared to 194 g m−2 per day for pure PU films. Using a series of electrochemical measurements of corrosion potential (Ecorr), polarization resistance (Rp), corrosion current (Icorr), and electrochemical impedance spectroscopy, ZrP/PU coatings on cold-rolled steel electrodes were also found to exhibit enhanced corrosion protection properties compared to pure PU coatings.

// Feng-Che Kuan 1, 2 , Shih-Hong Li 3 , Chih-Liang Wang 3, 4 , Meng-Hung Lin 5 , Ying-Huang Tsai 6, 7 , Cheng-Ta Yang 3, 7 1 Department of Hematology and Oncology, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 2 Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan 33302, Taiwan 3 Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan 4 Department of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan 5 Cencer of Excellence for Chang Gung Research Datalink, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 6 Division of Respiratory and Critical Care Medicine, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 7 Department of Respiratory Therapy, Chang-Gung University, Taoyuan 33302, Taiwan Correspondence to: Cheng-Ta Yang, email: yang1946@cgmh.org.tw Keywords: gefitinib, erlotinib, afatinib, Leu858Arg, Thr790Met Received: August 15, 2016 Accepted: November 14, 2016 Published: December 07, 2016 ABSTRACT Background: Gefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival. Materials and Methods: We conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals. Findings: Of the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib ( n = 304, 67.6%), erlotinib ( n = 63, 14.3%), or afatinib ( n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5–16.5), 11.2 months in the erlotinib arm (IQR: 4.9–16.7), and 10.3 months in the afatinib arm (IQR: 7.0–14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group. Interpretation: Afatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.

Background: Deep neck infection (DNI) can progress to become a life-threatening complication. Liver cirrhosis, which is related to poor immune conditions, is a likely risk factor for DNI. This study investigated the risk and mortality of DNI in patients with decompensated liver cirrhosis (DLC). Methods: We performed a nationwide cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan. We included a total of 33,175 patients with DLC between 2000 and 2013, from the Catastrophic Illness Patient Database, a subsection of the NHIRD, along with 33,175 patients without cirrhosis who were matched in a 1:1 proportion for age, sex, and socioeconomic status. The occurrence of DNI was the primary study outcome. The risk, treatment, and mortalities of DNI were evaluated in the study and comparison cohorts. Results: DLC Patients had a significantly higher incidence of DNI than noncirrhotic patients (p &lt, 0.001). The adjusted Cox proportional hazard regression showed that DLC was associated with a significantly higher risk of DNI (adjusted hazard ratio, 4.11, 95% confidence interval, 3.16&ndash, 5.35, p &lt, 0.001). The mortality rate in cirrhotic patients with DNI was not significantly higher than that in noncirrhotic patients with DNI (11.6% vs. 9.8%, p = 0.651). Conclusions: This study is the first to investigate the correlation between DLC and DNI. The study findings strongly indicate that DLC is an independent risk factor for DNI. Cirrhotic patients with DNI do not have a significantly poorer survival rate than noncirrhotic patients with DNI. Therefore, physicians should be alert to potential DNI occurrence in DLC patients. Besides this, intensive care and appropriate surgical drainage can yield similar survival outcomes in DLC-DNI and noncirrhosis-DNI patients.

ObjectiveWhether dysrhythmia is a risk factor of sudden sensorineural hearing loss (SSNHL) remains unclear. In this study, we aimed to investigate the risk of developing SSNHL among patients with dysrhythmia in different age and gender groups by using population-based data in Taiwan.MethodsWe conducted a matched cohort study by analyzing data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. 41,842 newly diagnosed dysrhythmia patients and 83,684 comparison subjects without dysrhythmia were selected from claims. The incidence of sudden sensorineural hearing loss at the end of 2013 was determined in both groups. Univariate and multivariate logistic regression analyses were used to investigate the risk of SSNHL among patients with dysrhythmia.ResultsThe incidence of SSNHL was 1.30-fold higher in the dysrhythmia group compared with the control group (53.2 versus 40.9 per 100,000 person-years), and using Cox proportional hazard regressions, the adjusted hazard ratio (HR) was 1.40 (95% confidence interval [CI], 1.15-1.70). Gender-stratified analysis revealed a significantly higher risk of SSNHL in patients with dysrhythmia than in those without dysrhythmia for both men and women (HR = 1.34, 95% CI = 1.02-1.76, P = 0.039, HR = 1.35, 95% CI = 1.02-1.78, P = 0.035, respectively). Age-stratified analysis revealed remarkable associations between dysrhythmia and SSNHL among those aged less than 40 years and more than 65 years (HR = 2.18, 95% CI = 1.03-4.64, P = 0.043 and HR = 1.54, 95% CI = 1.14-2.09, P = 0.006, respectively).ConclusionsOur findings support dysrhythmia as an independent risk factor for SSNHL. Based on the study results, clinicians managing patients with dysrhythmia should be aware of the increased risk of developing SSNHL, especially among patients aged 65 years, and counsel patients to seek medical advice immediately if they experience any acute change in their hearing ability.

This paper presents the design and implementation of a memristor-based oscillator, investigating potential analog applications for memristors. Inspired from relaxation oscillator operation, the circuit flows a constant current through a memristor in two directions alternately, increasing or decreasing the memristance and the resulting voltage. A following comparator compares the voltage against two thresholds. Switches are then used to control the current direction according to the comparators' output and close the feedback loop for oscillation. Designed and implemented with Winbond 90-nm CMOS and HfO 2 -ReRAM technology, measurement results show an operating frequency range of 300 – 1150 kHz, power consumptions of 700 to 830 μW, and κ of

Sudden sensorineural hearing loss (SSNHL) has significant impact on quality of life. It may result from viral infection, but the relationship between hepatitis B virus (HBV) infection and SSNHL remains uncertain. To investigate the risk of developing SSNHL in patients with HBV, we conducted a nationwide, population-based, retrospective cohort study from the Taiwan National Health Insurance Research Database. A total of 33,234 patients diagnosed with HBV infection and 132,936 control subjects without viral hepatitis were selected from claims made from 2000 to 2008. Each patient was followed for at least 5 years to identify new-onset SSNHL. Among the 166,170 patients, 279 patients (303,793 person-years) from the HBV cohort and 845 patients (1,225,622 person-years) from the control cohort were diagnosed with SSNHL. The incidence of SSNHL was 1.33-fold higher in the HBV group than in the control group (0.92 vs. 0.69 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.315 (95% confidence interval [CI] = 1.148 to 1.506) calculated using a Cox proportional hazard regression model. We also observed that HBV patients in the 50 to 64 years of age subgroup showed the highest incidence of SSNHL and the highest adjusted hazard ratio (HR = 2.367; 95% CI = 1.958 to 2.861). Patients with HBV infection had a higher risk of acquiring SSNHL than patients without viral hepatitis. For the early detection and timely treatment of SSNHL, clinicians should be aware of the increased risk of SSNHL in HBV patients and arrange auditory examinations for those complaining about acute hearing change.