Background
Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is ...scarce.
Methods
The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated.
Results
Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related.
Conclusions
In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.
Air pollution has been reported to be associated with chronic obstructive pulmonary disease (COPD). Our study aim was to examine the mediating effects of air pollution on climate-associated health ...outcomes of COPD patients. A cross-sectional study of 117 COPD patients was conducted in a hospital in Taiwan. We measured the lung function, 6-min walking distance, oxygen desaturation, white blood cell count, and percent emphysema (low attenuation area, LAA) and linked these to 0–1-, 0–3-, and 0–5-year lags of individual-level exposure to relative humidity (RH), temperature, and air pollution. Linear regression models were conducted to examine associations of temperature, RH, and air pollution with severity of health outcomes. A mediation analysis was conducted to examine the mediating effects of air pollution on the associations of RH and temperature with health outcomes. We observed that a 1 % increase in the RH was associated with increases in forced expiratory volume in 1 s (FEV1), eosinophils, and lymphocytes, and a decrease in the total-lobe LAA. A 1 °C increase in temperature was associated with decreases in oxygen desaturation, and right-, left-, and upper-lobe LAA values. Also, a 1 μg/m3 increase in PM2.5 was associated with a decrease in the FEV1 and an increase in oxygen desaturation. A 1 μg/m3 increases in PM10 and PM2.5 was associated with increases in the total-, right-, left, upper-, and lower-lobe (PM2.5 only) LAA. A one part per billion increase in NO2 was associated with a decrease in the FEV1 and an increase in the upper-lobe LAA. Next, we found that NO2 fully mediated the association between RH and FEV1. We found PM2.5 fully mediated associations of temperature with oxygen saturation and total-, right-, left-, and upper-lobe LAA. In conclusion, climate-mediated air pollution increased the risk of decreasing FEV1 and oxygen saturation and increasing emphysema severity among COPD patients. Climate change-related air pollution is an important public health issue, especially with regards to respiratory disease.
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•Temperature was positively associated with oxygen saturation in COPD.•Temperature was negatively associated with emphysema severity in COPD.•PM2.5 was negatively associated with emphysema severity in COPD patients.•The impacts of temperature on COPD severity are mediated by air pollution.
BACKGROUND:Although the short-term advantages of natural orifice specimen extraction are widely recognized, controversy exists concerning oncologic safety after laparoscopic surgery for colorectal ...cancer.
OBJECTIVE:This study aimed to investigate the impact of natural orifice specimen extraction on local recurrence and long-term survival of patients undergoing colorectal cancer surgery.
DESIGN:This is a propensity score-matched comparative study.
SETTING:This study presents a single-center experience.
PATIENTS:We retrospectively analyzed the records of patients who underwent curative laparoscopic anterior resection for American Joint Committee on Cancer stage I to III sigmoid or upper rectal cancer in 2011 to 2014, based on prospectively collected data.
INTERVENTIONS:Oncologic outcomes were compared between patients undergoing natural orifice or conventional specimen extraction by minilaparotomy. Patients were matched 1:1 according to propensity scores calculated by logistic regression analysis with the following covariatesAmerican Joint Committee on Cancer stage, tumor diameter, age, sex, BMI, and T stage. Cox proportional hazards regression analysis was performed to determine the impact on oncologic outcome.
MAIN OUTCOME MEASURES:The primary outcomes measured were local recurrence and disease-free survival rates at 5 years.
RESULTS:Of 392 eligible patients, 188 were matched (94 undergoing natural orifice specimen extraction and 94 undergoing conventional extraction by minilaparotomy). Median follow-up was 50.3 months. The cumulative local recurrence risk at 5 years was 2.3% and 3.5% (p = 0.632), whereas 5-year disease-free survival for all tumor stages combined was 87.3% and 82.0% (p = 0.383) in laparoscopic anterior resection with natural orifice specimen extraction and conventional extraction groups. T3 and T4 stages were the only variables independently associated with disease-free survival.
LIMITATIONS:This study was limited because it focused on a single center, was a retrospective analysis, contained no long-term anorectal function testing, and had a small sample size.
CONCLUSION:Long-term oncologic outcomes of patients undergoing laparoscopic anterior resection with natural orifice specimen extraction for sigmoid and upper rectal cancer do not differ from those undergoing conventional extraction. Thus, natural orifice specimen extraction could be a viable alternative to reduce abdominal wall insult in laparoscopic colorectal operations for malignancy in selected patients. See Video Abstract at http://links.lww.com/DCR/B241.
RESULTADOS ONCOLÓGICOS A LARGO PLAZO DE RESECCIONES ANTERIORES LAPAROSCÓPICAS PARA CÁNCER A TRAVÉS DE ORIFICIO NATURAL FRENTE A EXTRACCIÓN CONVENCIONAL DEL ESPÉCIMENUN ESTUDIO DE CASOS Y CONTROLESSi bien las ventajas a corto plazo de la extracción de especímenes por orificio natural son ampliamente reconocidas, existe controversia con respecto a la seguridad oncológica después de la cirugía laparoscópica para el cáncer colorrectal.Investigar el impacto de la extracción de especímenes por orificio natural en la recurrencia local y la supervivencia a largo plazo de pacientes sometidos a cirugía de cáncer colorrectal.Estudio comparativo con emparejamiento por puntuación de propensión.Experiencia en un centro único.Analizamos retrospectivamente los registros de pacientes que se sometieron a resección anterior laparoscópica curativa para cáncer sigmoideo o rectal superior AJCC en estadio I–III en 2011–2014, con base en datos recolectados prospectivamente.Los resultados oncológicos se compararon entre pacientes sometidos a extracción por orificio natural o convencional mediante minilaparotomía de especímenes. Los pacientes fueron emparejados 1:1 de acuerdo con los puntajes de propensión calculados por análisis de regresión logística con las siguientes covariablesestadio AJCC, diámetro del tumor, edad, sexo, índice de masa corporal y estadio T. Se realizó un análisis de regresión de riesgos proporcionales de Cox para determinar el impacto en el resultado oncológico.Recurrencia local y tasas de supervivencia libre de enfermedad a los 5 años.De 392 pacientes elegibles, 188 fueron emparejados (94 sometidos a extracción de espécimen por orificio natural y 94 a extracción convencional por minilaparotomía). La mediana de seguimiento fue de 50.3 meses. El riesgo cumulativo de recurrencia local a 5 años fue de 2.3% y 3.5% (p = 0.632), mientras que la supervivencia libre de enfermedad a 5 años para todas las etapas tumorales combinadas fue de 87.3% y 82.0% (p = 0.383) en los grupos de resección anterior laparoscópica con extracción de espécimen por orificio natural y extracción convencional, respectivamente. Las etapas T3 y T4 fueron las únicas variables asociadas independientemente con la supervivencia libre de enfermedad.Centro único, análisis retrospectivo, ausencia de pruebas de función anorrectal a largo plazo y tamaño de muestra pequeño.Los resultados oncológicos a largo plazo de los pacientes sometidos a resección anterior laparoscópica con extracción de espécimen por orificio natural para cáncer sigmoideo y rectal superior no difieren de los de aquellos sometidos a extracción convencional. Por lo tanto, la extracción de especímenes por orificio natural podría ser una alternativa viable para reducir el insulto a la pared abdominal en operaciones colorrectales laparoscópicas por malignidad en pacientes selectos. Consulte Video Resumen en http://links.lww.com/DCR/B241.
The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in ...the literatures.
The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses.
Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses.
nRT was associated with improved OS in our study population.
Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to ...treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy.
CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used.
Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio aSHR=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients.
Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.
Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, ...resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters.
We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by
C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366.
Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 47% men and 299 53% women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10
) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 77% of 273 participants) than after EAML14 therapy (134 48% of 277; p<0·0001).
We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy.
The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation.
For the Chinese translation of the abstract see Supplementary Materials section.
Abstract
In this study, the National Health Insurance Research Database of Taiwan was used to examine the recurrence and death risk for stage 0 colorectal cancer patients. We examined stage 0 ...colorectal cancer patients to identify factors causing recurrence and death.
This is a retrospective study, and stage 0 colorectal cancer patients that are registered in the Taiwan Cancer Registry of the Health Promotion Administration in 2007 to 2012 were included. The database was linked to the National Health Insurance Research Database, and subjects were followed up until the end of 2016. The mean follow-up period was 69 months. Bivariate analysis methods (log-rank test) and Cox proportional hazards model were used to evaluate the risk of recurrence and death and demographic characteristics, economic factors, environmental factors, health factors, treatment and hospitals, and absence/presence of postoperative tests were used to examine related risk factors.
Our study showed that the 5-year recurrence rate and 5-year mortality rate for stage 0 colorectal cancer are 1.68% and 0.6%, respectively. For stage 0 colorectal cancer, age (61–74 years) is the only factor affecting recurrence in patients (hazard ratio (HR) = 2.44; 95% CI: 1.41–4.22), while age >75 years (HR = 4.35; 95% CI: 1.14–16.68) and Charlson Comorbidity Index >4 points (HR = 7.20, 95% CI: 2.60–19.94) can increase the risk of death. In contrast, patients who underwent one (HR = 0.27, 95% CI: 0.10–0.71) and two or more colonoscopies (HR = 0.26, 95% CI: 0.10–0.70) within 2 years after surgery can reduce the risk of death from stage 0 colorectal cancer. In addition, the risk of recurrence is higher in patients who underwent colonoscopic polypectomy (HR = 2.07, 95% CI: 0.98–4.33) and patients with rectal cancer (HR = 2.74, 95% CI: 0.96–7.83), but these differences are not statistically significant (
P
> .05).
From this study, we can see that age and comorbidity index increase the risk of recurrence and death for stage 0 colorectal cancer, while postoperative colonoscopy can decrease the risk of death.
Early clinical exposure (ECE) is viewed as a way to provide contexts of basic science and highlight its relevance to medical practice. However, very few studies have specifically looked into how the ...ECE experience contributes to students' academic performance. The purpose of this study was to investigate whether ECE experiences (external cause) or students' learning attitudes (internal cause) more closely correlated with medical students' academic performance.
Subjects who participated in the study comprised 109 s-year students at Taipei Medical University. Fifty of the 109 study participants were enrolled in an elective ECE program. The dependent variable in this study was the test score of a systems-based basic sciences (SBBS) course. Independent variables of the study included students' attitudes and test anxiety towards the SBBS course, engagement/length of time spent in ECE, and the ECE learning environment. Data of students' engagement in ECE, levels of their motivational beliefs and test anxiety, differences in the ECE learning environment, and the SBBS final test scores of these 109 respondents were collected for hierarchical multiple regression (HMR) analyses.
Results of the HMR analyses revealed that students' test anxiety towards basic science and also the learning environment of the ECE had significant positive predictive power on their SBBS test scores.
This study discovers that medical students' academic performance in basic science correlates not only with their anxiety to testing, but even more so with the clinical environment they are exposed to. Hence we suggest including further investigations about different learning environments on ECE experiences in future studies.
Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a ...nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure. (Clin Mol Hepatol 2024;30:64-79)
Epidemiological evidence has shown that air pollution is associated with chronic obstructive pulmonary disease (COPD). The objective of this study was to investigate the effects of air pollution on ...patients with COPD and pneumonia. A case-control study of patients who had undergone thoracentesis for pleural effusion drainage in a hospital was recruited for this study. COPD and non-COPD patients with pneumonia respectively served as the case and control groups. Increases in particulate matter of <2.5 μm in aerodynamic diameter (PM2.5) and NO2 increased the risk of pneumonia in COPD patients (adjusted odd ratio (OR) = 4.136, 95% confidence interval (CI) = 1.740–9.832 for PM2.5; adjusted OR = 1.841, 95% CI = 1.117–3.036 for NO2). COPD patients with pneumonia had higher levels of CD14 in pleural effusion than did non-COPD with pneumonia (p < 0.05). An increase in CD14 of the pleural effusion increased the risk of pneumonia in COPD patients (adjusted OR = 1.126, 95% CI = 1.009–1.256). We further observed that an increase in Cu and a decrease in Zn in the pleural effusion increased the risk of pneumonia in COPD patients (adjusted OR = 1.005, 95% CI = 1.000–1.010 for Cu; adjusted OR = 0.988, 95% CI = 0.978–0.997 for Zn). In conclusion, our results suggest that COPD patients had a high risk of pneumonia occurring due to air pollution exposure.
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•Associations between air pollution and pneumonia in COPD patients were determined.•Air pollution increased the risk of pneumonia in COPD patients.•Overexpression of immune responses in COPD with pneumonia.•Alteration in metal increased the risk of COPD with pneumonia.
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