RESUMEN
STUDY OBJECTIVE: To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management. DESIGN: A nested case-control study utilizing data from a longitudinal health insurance database. SETTING: The study is based on a longitudinal health insurance database spanning 2000-2019 in Taiwan. PATIENTS: A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis. INTERVENTION: Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls. MEASUREMENT: Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk. MAIN RESULTS: No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83-1.01), indicating no substantial increase in risk. CONCLUSION: Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential.
Asunto(s)
Analgésicos , Dolor Crónico , Demencia , Gabapentina , Humanos , Gabapentina/efectos adversos , Femenino , Masculino , Estudios de Casos y Controles , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Anciano , Demencia/epidemiología , Demencia/inducido químicamente , Persona de Mediana Edad , Taiwán/epidemiología , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
Peripheral arterial occlusive disease (PAOD) is a clinical manifestation of systemic atherosclerosis and is always associated with cerebrovascular disease and various complications. The aim of our study is to evaluate the relationship between the coronavirus disease 2019 (COVID-19) infection and the subsequent PAOD development. A retrospective cohort study was conducted and individuals with COVID-19 infection were identified from the TriNetX analytics platform. A total of 2 206 065 patients with COVID-19 infection and 2 206 065 patients without COVID-19 infection were recruited after exclusion and matching. The primary outcome was the development of PAOD after the COVID-19 infection. The Cox proportional hazard regression was adopted to yield the hazard ratio (HR) and 95% confidence interval (CI) of PAOD between groups. After the whole follow-up period, the incidence of PAOD was significantly higher in the COVID-19 group at both the 3-month follow-up (HR: 1.27, 95% CI: 1.24-1.30) and the 12-month follow-up (HR: 1.33, 95% CI: 1.31-1.35) The Kaplan-Meier analysis with the log-rank test demonstrated a higher cumulative probability of PAOD in the COVID-19 group compared to the non-COVID-19 group (p < 0.001). In stratified analysis using 65 years as the threshold, both age groups in the COVID-19 group exhibited a higher risk of PAOD. Similarly, in the sex and race stratified analysis, the COVID-19 group performed a higher risk of PAOD in both subgroups. In conclusion, the COVID-19 infections are strongly associated with an increment of PAOD incidence.
Asunto(s)
Arteriopatías Oclusivas , COVID-19 , Enfermedad Arterial Periférica , Humanos , Estudios Retrospectivos , Factores de Riesgo , Incidencia , COVID-19/complicaciones , COVID-19/epidemiologíaRESUMEN
Background: The mortality rate associated with nontraumatic intracranial hemorrhage (NTICrH) remains consistently high under the current care modality. The effectiveness of tranexamic acid (TXA) as a treatment option is still a subject of debate. This study aims to assess the association between TXA administration and both short-term and long-term mortality rates in patients with NTICrH. Methods: We conducted a retrospective cohort study using data from the Taiwan National Health Insurance Research Database (NHIRD) spanning from January 2000 to December 2017. The study population consists of NTICrH patients admitted to the ICU, divided into two groups: patients who were treated with TXA and those who were not. Propensity score matching (PSM) was conducted to balance the baseline characteristics of the two groups. Cox proportional hazard analysis was conducted to estimate the hazard ratio (HR) for the all-cause mortality. Sensitivity analyses were performed using the inverse probability of treatment-weighted hazard ratio (IPTW-HR). To assess the timing of TXA use, we compared the risk of all-cause mortality within 180 days between patients receiving early TXA treatment and those receiving late TXA treatment. Results: There was no significant difference in 180-day all-cause mortality between the groups; the hazard ratio was 1.07 (95% CI: 0.96-1.20) in patients treated with TXA compared to those without TXA treatment. Within 7 days of admission, patients treated with TXA had a lower hazard ratio of 0.81 (95% CI: 0.74-0.90) for all-cause mortality. Conclusions: Lower mortality within the first 7 days was observed in patients with NTICrH who received TXA.
RESUMEN
HO-3867, a synthetic curcumin analog, has displayed various tumor-suppressive characteristics and improved bioabsorption over its parent compound. However, its influences on the development of hepatocellular carcinoma (HCC) are poorly defined. To address this, we tested the anticarcinogenic impact of HO-3867 and investigated the underlying mechanisms in fighting liver cancer. Our result demonstrated that HO-3867 reduced the viability of HCC cells, accompanied by promotion of cell cycle arrest at the sub-G1 stage and apoptotic responses. Furthermore, a distinctive profile of apoptosis associated proteins, encompassing elevated heme oxygenase-1 (HO-1) level and caspase activation, was detected in HO-3867-stimulated HCC cells. In addition, such HO-3867-mediated elevation in caspase activation was dampened by pharmacological suppression of p38 activities. Taken together, our findings unveiled that HO-3867 triggered cell cycle arrest and apoptotic events in liver cancer, involving a p38-mediated activation of caspase cascades. These data highlighted a usefulness of curcumin or its analogs on the management of hepatocarcinogenesis.
Asunto(s)
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Curcumina/farmacología , Apoptosis , Hemo-Oxigenasa 1 , Caspasas , Caspasa 3/metabolismo , Línea Celular Tumoral , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Benzodiazepines have sedative effects that cause reduced activity in users and may increase the risk of deep vein thrombosis. However, few studies have examined this potential risk of benzodiazepine use. This study examined the association between benzodiazepine use and the risk of deep vein thrombosis (DVT) in adults in Taiwan using a longitudinal health insurance database. The study population included 12,546 individuals with DVT and 50,184 matched controls. Results showed that benzodiazepine use was associated with an increased risk of DVT occurrence (adjusted odds ratio [aOR]: 1.66; 95 % CI, 1.54-1.79; P <0.001), with a dose-response relationship. Patients with a higher defined daily dose had a higher risk of DVT, with ORs of 1.65-, 2.09-, and 2.16-fold higher for those with an average benzodiazepine dose of <0.5, 0.5-0.9, or ≥1 (DDD/day), respectively, compared to nonbenzodiazepine users. Stratification by age, sex, and follow-up duration yielded similar results. This study highlights the need to evaluate the association and benefits of benzodiazepine prescription to decrease the risk of DVT development.
Asunto(s)
Benzodiazepinas , Trombosis de la Vena , Adulto , Humanos , Benzodiazepinas/efectos adversos , Factores de Riesgo , Hipnóticos y Sedantes/efectos adversos , Trombosis de la Vena/inducido químicamente , Trombosis de la Vena/epidemiología , Trombosis de la Vena/complicaciones , Taiwán/epidemiologíaRESUMEN
Background and Objectives: Local anesthetics administered via epidural catheters have evolved from intermittent top-ups to simultaneous administration of continuous epidural infusion (CEI) and patient-controlled epidural analgesia (PCEA) using the same device. The latest programmed intermittent epidural bolus (PIEB) model is believed to create a wider and more even distribution of analgesia inside the epidural space. The switch from CEI + PCEA to PIEB + PCEA in our department began in 2018; however, we received conflicting feedback regarding workload from the quality assurance team. This study aimed to investigate the benefits and drawbacks of this conversion, including the differences in acute pain service (APS) staff workload, maternal satisfaction, side effects, and complications before and after the changeover. Materials and Methods: Items from the APS records included total delivery time, average local anesthetic dosage, and the formerly mentioned items. The incidence of side effects, the association between the duration of delivery and total dosage, and hourly medication usage in the time subgroups of the CEI and PIEB groups were compared. The staff workload incurred from rescue bolus injection, catheter adjustment, and dosage adjustment was also analyzed. Results: The final analysis included 214 and 272 cases of CEI + PCEA and PIEB + PCEA for labor analgesia, respectively. The total amount of medication and average hourly dosage were significantly lower in the PIEB + PCEA group. The incidences of dosage change, manual bolus, extra visits per patient, and lidocaine use for rescue bolus were greater in the PIEB + PCEA group, indicating an increased staff workload. However, the two groups did not differ in CS rates, labor time, maternal satisfaction, and side effects. Conclusions: This study revealed that while PIEB + PCEA maintained the advantage of decreasing total drug doses, it inadvertently increased the staff burden. Increased workload might be a consideration in clinical settings when choosing between different methods of PCEA.
RESUMEN
This study aimed to investigate the potential association between glaucoma and peripheral arterial occlusive disease. The study recruited patients, including 101,309 with glaucoma and 1,860,528 without a glaucoma diagnosis, from a population of 2 million patients in the Longitudinal Health Insurance Database. Propensity score matching was performed between the two groups, matching for age, sex, and comorbidities. In total, 95,575 patients with glaucoma and 95,575 patients without glaucoma were analyzed for their risk of developing peripheral arterial occlusive disease. The analysis of the data revealed that the glaucoma group had a higher incidence density (ID = 4.13) of peripheral arterial occlusive disease than the non-glaucoma group (ID = 3.42). The relative risk for the glaucoma group was 1.21 (95% C.I. = 1.15-1.28). Cox proportional hazard model analysis indicated that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease (HR = 1.18; 95% C.I. = 1.12-1.25). The subgroup analysis of the risk of PAOD showed that the glaucoma group had a higher risk of developing peripheral arterial occlusive disease in the age group of 20 to 39 (p for interaction = 0.002). In conclusion, patients with glaucoma were associated with a higher risk of subsequent peripheral arterial occlusive disease compared with those without a diagnosis of glaucoma.
RESUMEN
Introduction: Psoriasis (PSO) is a chronic skin condition that affects a variety of disorders, especially the cardiovascular system. This study investigated the association between PSO and peripheral arterial disease (PAOD). Methods: A retrospective cohort study design was carried out between 2000 and 2018. The exposure subject was a newly diagnosed PSO. The diagnosis of PSO was never elaborated as a comparison subject. Balanced heterogeneity of the two groups was used by propensity score matching. The cumulative incidence of PAOD between the two groups was performed using Kaplan-Meier analysis. The Cox proportional hazard model was used to measure the risk of PAOD risk hazard ratio. Results: After matching the 1: 1 propensity score, 15,696 subjects with PSO and the same number of subjects without the diagnosis of PSO were recruited. The PSO subject had a higher risk of PAOD than the non-PSO subject (adjusted HR = 1.25; 95% CI = 1.03-1.50). In the 40-64-year-old subgroup, the subject of PSO exhibited an increased risk of PAOD than the subject without PSO. Conclusion: Psoriasis is associated with an increased risk of peripheral arterial disease and curative care is necessary to reduce the risk of PAOD..
RESUMEN
Background and objectives: The objective of this study is to elucidate peripheral occlusion artery disease (PAOD) as a risk factor for cellulitis. Materials and Methods: This is a retrospective population-based cohort study. The database is the Longitudinal Health Insurance Database, which covers two million beneficiaries from the entire population of the 2010 registry for beneficiaries in Taiwan. The PAOD group is composed of patients who were newly diagnosed with PAOD from 2001 to 2014. The non-PAOD group is composed of patients who were never diagnosed with PAOD from 2001 to 2015. All patients were followed until the onset of cellulitis, death, or until the end of 2015. Results: Finally, 29,830 patients who were newly diagnosed with PAOD were included in the PAOD group, and 29,830 patients who were never diagnosed with PAOD were included in the non-PAOD group. The incidence densities (ID) of cellulitis were 26.05 (95% CI = 25.31-26.80) patients per 1000 person-years in the PAOD group and 49.10 (95% CI = 48.04-50.19) in the non-PAOD group. The PAOD group had an increased risk of cellulitis (adjusted HR = 1.94, 95% CI = 1.87-2.01) compared to the non-PAOD group. Conclusions: Patients with PAOD were associated with a higher risk of subsequent cellulitis compared to patients without PAOD.
Asunto(s)
Arteriopatías Oclusivas , Enfermedad Arterial Periférica , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Celulitis (Flemón)/etiología , Celulitis (Flemón)/complicaciones , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Factores de Riesgo , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/epidemiologíaRESUMEN
ABSTRACT: Hepatocellular carcinoma (HCC) is a fatal cancer worldwide, and surgical resection remains the standard treatment. Postoperative opioid prescription has been believed to affect cancer recurrence through complex biological pathways. We conducted a retrospective cohort study using the Longitudinal Health Insurance Database of Taiwan to evaluate the relationship between postoperative opioid use and long-term surgical outcomes of patients with HCC. This study had a retrospective cohort design. In total, 812 patients older than 20 years who underwent hepatectomy because of HCC were included. The exposure group comprised patients who used opioids during hospitalization postoperatively. The comparison group included those who never used opioids during hospitalization postoperatively. A Cox proportional hazards model was used to evaluate the overall survival or recurrence-free survival rate between the opioid group and the nonopioid group. A total of 530 patients received opioids postoperatively and 282 patients did not. The hazard ratios of overall survival and recurrence-free survival were 1.10 (95% confidence interval [CI], 0.85-1.41) and 1.15 (95% CI, 0.91-1.46), respectively. Total postoperative opioids were converted into oral morphine milligram equivalents and then divided into 3 equal subgroups: low dose, <40 mg; medium dose, 40 to 144 mg; and high dose, ≥145 mg. The hazard ratios of overall survival were 0.88 (95% CI, 0.63-1.24) for the low-dose group, 1.27 (95% CI, 0.92-1.74) for the medium-dose group, and 1.14 (95% CI, 0.83-1.58) for the high-dose group. Postoperative opioids do not affect overall and recurrence-free survival in patients undergoing hepatectomy or liver transplantation because of HCC. Cancer recurrence should not be a clinical concern regarding postoperative opioid prescription.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Analgésicos Opioides/efectos adversos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/inducido químicamente , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
Although cesarean section (CS) has become a common method of child delivery in recent decades, the choice between general anesthesia (GA) and neuraxial anesthesia (NA) for CS must be carefully considered. Depending on the type of anesthesia used in CS, a major outcome observed is the occurrence of postpartum depression (PPD). This study investigated the association between PPD risk and the anesthesia method used in CS by using data from three linked nationwide databases in Taiwan, namely, the National Health Insurance Research Database, the National Birth Reporting Database, and the National Death Index Database. After propensity score matching by baseline depressive disorders, maternal demographics, status at delivery, infant's health, maternal diseases during pregnancy, and age of partner, we included women who had natural births (n = 15,706), cesarean sections with GA (n = 15,706), and cesarean sections with NA (n = 15,706). A conditional logistic regression was used to estimate the odds ratios and 95% confidence intervals (CIs) of PPDs, including depression, sleep disorder, and medication with hypnotics or antidepressants, under anesthesia during CS. The prevalence rates of combined PPDs were 26.66%, 43.87%, and 36.30% in natural births, CS with GA, and CS with NA, respectively. In particular, the proportions of postpartum use of hypnotic drugs or antidepressants were 21.70%, 39.77%, and 31.84%, which were significantly different. The aORs (95% CIs) were 2.15 (2.05-2.25) for the included depressive disorders, 1.10 (1.00-1.21) for depression, 1.03 (0.96-1.11) for sleep disorder, and 2.38 (2.27-2.50) for medication with hypnotics or antidepressants in CS with GA compared with natural births. Women who underwent CS with GA had a significantly higher risk of depressive disorders and a higher need for antidepressants for sleep problems than those who underwent CS with NA. The risks of PPD were significantly associated with the anesthesia method, especially GA. Our results can assist physicians in carefully considering the appropriate anesthesia method for CS delivery, particularly with regard to postpartum drug abuse and drug safety.
RESUMEN
Thiazide diuretics have long been widely used as antihypertensive agents. In addition to reducing blood pressure, thiazides also control calcium homeostasis and increase bone density. We hypothesized that the use of thiazides in patients with hypertension would reduce overall fracture risk. We used the Taiwan National Health Insurance Research Database to find patients with a hypertension diagnosis who accepted antihypertensive treatment from 2000 to 2017. The patients were further classified into thiazide users and nonthiazide users. Multivariable Cox regression analysis and Kaplan-Meier survival analysis were performed to estimate the adjusted hazard ratios (aHRs) and cumulative probability of fractures. After 1:1 propensity score matching by sex, age, urbanization level of place of residence, income, comorbidities, and medications, there were 18,483 paired thiazide users and non-users, respectively. The incidence densities of fractures (per 1000 person-months) were 1.82 (95% CI: 1.76-1.89) and 1.99 (95% CI: 1.92-2.06) in the thiazide and nonthiazide groups, respectively. The results indicated a lower hazard ratio for fractures in thiazide users (aHR = 0.93, 95% CI: 0.88-0.98). Kaplan-Meier survival analysis revealed a significantly lower cumulative incidence of fractures in the thiazide group (log-rank test; p = 0.0012). In conclusion, our results reveal that thiazide use can reduce fracture risk. When antihypertensive agents are being considered, thiazide may be a better choice if the patient is at heightened risk of fracture.
RESUMEN
Peripheral artery occlusive disease (PAOD) and deep vein thrombosis (DVT) can cause a variety of acute and chronic vascular complications and put patients at risk of subsequent sepsis. This study aimed to determine whether DVT compared with PAOD patients would increase the risk of sepsis. This study recruited 43,535 patients newly diagnosed as having PAOD and 6932 patients who were newly diagnosed as having DVT from a population of 2 million patients from the Longitudinal Health Insurance Database. Propensity score matching (PSM) between the PAOD and DVT groups was performed for age, sex, comorbidities, and prior antibiotic administration. A total of 4383 patients with PAOD and 4383 patients with DVT were analyzed for risk of sepsis. The incidence density of sepsis per 1000 person years for patients with PAOD was 25.75 (95% CI = 23.90 to 27.74) and 35.61 (95% CI = 33.29 to 38.09) for patients with DVT. After age, sex, associated comorbidities, and antibiotic administration were adjusted for, the risk of sepsis for the DVT group was 1.46-fold (95% CI = 1.32-1.62) higher than that for the PAOD group. In conclusion, patients with DVT were associated with a higher risk of subsequent sepsis than patients with PAOD. Aging was another risk factor.
Asunto(s)
Enfermedad Arterial Periférica , Sepsis , Trombosis de la Vena , Antibacterianos , Estudios de Cohortes , Humanos , Incidencia , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Sepsis/complicaciones , Sepsis/epidemiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/epidemiologíaRESUMEN
Tranexamic acid (TXA) is an antifibrinolytic pharmacological agent, but its use in gastrointestinal bleeding remains contentious. Moreover, studies on the timing of TXA administration are limited. We examined whether early TXA administration reduced the risk of mortality in patients with gastrointestinal bleeding in a Taiwanese population. We used the National Health Insurance Research Database to identify patients diagnosed with gastrointestinal bleeding with early and late TXA treatment. We defined early treatment as initial TXA treatment in an emergency department and late treatment as initial TXA treatment after hospitalization. Mortality within 52 weeks was the primary outcome. A multivariable analysis using a multiple Cox regression model was applied for data analysis. Propensity score matching (PSM) was performed to reduce the potential for bias caused by measured confounding variables. Of the 52,949 selected patients with gastrointestinal bleeding, 5127 were assigned to either an early or late TXA treatment group after PSM. The incidence of mortality was significantly decreased during the first and fourth weeks (adjusted HR (aHR): 0.65, 95% CI: 0.56−0.75). A Kaplan−Meier curve revealed a significant decrease in cumulative incidence of mortality in the early TXA treatment group (log-rank test: p < 0.0001). Multiple Cox regression analysis revealed significantly lower mortality in the early TXA treatment group compared with the late treatment group (aHR: 0.64, 95% CI: 0.57−0.73). Thromboembolic events were not significantly associated with early or late TXA treatment (aHR: 1.03, 95% CI: 0.94−1.12). A Kaplan−Meier curve also revealed no significant difference in either venous or arterial events (log-rank test: p = 0.3654 and 0.0975, respectively). In conclusion, early TXA treatment was associated with a reduced risk of mortality in patients with gastrointestinal bleeding compared with late treatment, without an increase in thromboembolic events. The risk of rebleeding and need for urgent endoscopic intervention require further randomized clinical trials.
RESUMEN
Background Fluoroquinolones are first-line antibiotics recommended for the treatment of complicated urinary tract infections (UTIs), with frequent reports of adverse effects of aortic aneurysm (AA) and aortic dissection (AD). We examined whether fluoroquinolones can increase the risk of AA and AD in patients with UTIs in the Taiwanese population. Methods and Results We used the National Health Insurance Research Database to identify patients diagnosed with UTIs under single antibiotic treatment of fluoroquinolones and first-, second-, or third-generation cephalosporins. An AA and AD diagnosis within a year constituted the study event. Multivariable analysis with a multiple Cox regression model was applied for comparing the hazard risk of AA and AD between fluoroquinolones and first- or second-generation cephalosporins. Propensity score matching was performed to reduce the potential for bias caused by measured confounding variables. Among 1 249 944 selected patients with UTIs, 28 568 patients were assigned to each antibiotic group after propensity score matching. The incidence of AA and AD was not significantly different between the fluoroquinolones and first- or second-generation cephalosporins (adjusted HR [aHR], 0.86 [95% CI, 0.59-1.27]). However, the mortality increased in the fluoroquinolones group (aHR, 1.10 [95% CI, 1.04-1.16]). Conclusions Compared with first- or second-generation cephalosporins, fluoroquinolones were not associated with increased risk of AA and AD in patients with UTI. However, a significant risk of mortality was still found in patients treated with fluoroquinolones. The priority is to control infections with adequate antibiotics rather than exclude fluoroquinolones considering the risk of AA and AD for patients with UTI.
Asunto(s)
Aneurisma de la Aorta , Disección Aórtica , Infecciones Urinarias , Disección Aórtica/inducido químicamente , Disección Aórtica/diagnóstico , Disección Aórtica/epidemiología , Antibacterianos/efectos adversos , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/epidemiología , Cefalosporinas , Estudios de Cohortes , Fluoroquinolonas/efectos adversos , Humanos , Factores de Riesgo , Infecciones Urinarias/inducido químicamente , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiologíaRESUMEN
Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide's underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.
Asunto(s)
Movimiento Celular , Proteínas de la Matriz Extracelular/metabolismo , Sistema de Señalización de MAP Quinasas , Niclosamida/farmacología , Osteosarcoma/enzimología , Osteosarcoma/patología , Factor de Crecimiento Transformador beta/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Invasividad NeoplásicaRESUMEN
Antivascular endothelial growth factor (anti-VEGF) therapy has been a standard treatment for patients with metastatic colorectal cancer. However, the risk of thromboembolic events and cardiovascular events associated with this therapy remains controversial. We assessed whether anti-VEGF therapy increases the risk of thromboembolic events or major adverse cardiovascular events (MACEs) in patients with colorectal cancer based on real-world evidence. This retrospective cohort study was designed using linked 2009-2016 nationwide databases, including the Taiwan Cancer Registry, the National Health Insurance Research Database, and Taiwan's National Death Index. In total, 189,708 patients newly diagnosed as having advanced colorectal cancer from 2009 to 2016 were identified and categorized into the anti-VEGF and comparator groups through age, sex, clinical stage, and diagnosis date (within 180 days) matching. Propensity score matching was further performed to balance the baseline characteristics between the two groups. The Kaplan-Meier method was used to create the cumulative incidence curves of thromboembolic events and MACEs, and log-rank tests were used to compare the differences in Kaplan-Meier curves. Competing hazard ratios (HRs) for thromboembolic events and MACEs were estimated using the Fine-Gray method when considering the competing event of death. Statistical analysis was performed using two-tailed tests with a significance level of 0.05. In total, 4635 patients were included in both the anti-VEGF group and comparator group. The risk of thromboembolic events and MACEs did not differ significantly between the two groups. After propensity score matching, the adjusted HR for MACEs or thromboembolic events was 1.040, which for MACEs was 0.989, and that for thromboembolic events was 1.028. The competing HR for MACEs or thromboembolic events was 0.921, which for MACEs, was 0.862, and that for thromboembolic events was 0.908. In conclusion, patients with advanced colorectal cancer who received anti-VEGF therapy did not exhibit significantly higher risks of thromboembolic events and MACEs than those without anti-VEGF therapy. Our study provides real-world evidence regarding the safety of anti-VEGF therapy in Asian patients with advanced colorectal cancer.