Dose-response association of benzodiazepine use and development of deep vein thrombosis.

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.

Comparative analysis of diabetes risk in patients with obstructive sleep apnea undergoing different treatment approaches.

The bidirectional relationship between obstructive sleep apnea (OSA) and diabetes mellitus (DM) has been explored in several studies. O'Connor-Reina et al., published a paper entitled: "Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study" to examine a cohort study comparing the effects of surgery and continuous positive airway pressure (CPAP) on the risk of diabetes in patients with OSA. The study findings suggest that both therapies offer protection against diabetes, with upper airway surgery demonstrating better preventive efficacy than CPAP. However, potential biases and confounding variables should be considered, such as race, ethnicity, socioeconomic factors, BMI, glucose levels, HbA1c values, medication use and healthy dietary habits. Besides using International Classification of Diseases codes, the definition of DM as an outcome can also incorporate specific laboratory indicators and the use of diabetes treatment medications. Furthermore, subgroups analysis defined by demographic variables, such as age, sex, and race is recommended. The limitations of the study also include potentially data omissions due to reliance on electronic medical records from specific healthcare institutions. To enhance research comprehensiveness, alternative data sources and collaborations with additional healthcare institutions are suggested for future investigations.

Association of treatment delay and stage with mortality in breast cancer: a nationwide cohort study in Taiwan.

Breast cancer is the fifth leading cause of cancer death globally. In this retrospective study, we investigated the effects of the diagnosis-to-first-treatment interval (DFTI) and other related factors on cancer-specific survival in patients with breast cancer. We included 49,426 patients newly diagnosed as having breast cancer during 2011-2017. The Cox proportional hazards model was used to analyze the hazard ratio (HR) for mortality with various DFTIs; the HRs of the 31-60-, 61-90-, and ≥ 91-day DFTI groups did not differ significantly compared with the reference group (DFTI ≤ 30 days). After stratifying the patients according to initial tumor stage and age, we found that patients aged 55-64 and ≥ 65 years with stage II breast cancer treated ≥ 91 days after diagnosis had a 3.34- and 2.93-fold higher mortality risk (95% confidence intervals [CIs] 1.29-8.69 and 1.06-8.10, respectively). Patients aged ≥ 65 years with stage IV breast cancer treated within 61-90 or ≥ 91 days after diagnosis had a 7.14- and 34.78-fold higher mortality risk (95% CIs 1.28-39.82 and 3.08-393.32, respectively). In conclusion, DFTI is associated with mortality in patients with stage II and IV breast cancer, especially at an older age.

Deep Venous Thrombosis and Risk of Consequent Sepsis Event: A Retrospective Nationwide Population-Based Cohort Study.

Deep vein thrombosis causes several acute and chronic vessel complications and puts patients at risk of subsequent sepsis development. This unique study aimed to estimate the risk of sepsis development in DVT patients compared with non-DVT patients. This population-based cohort study used records of a longitudinal health insurance database containing two million patients defined in Taiwan's National Health Insurance Research Database (NHIRD). Our study included patients aged over 20 years with a new diagnosis of DVT with at least two outpatient department visits or an admission between 2001 and 2014. Patients with a diagnosis of sepsis before the index date were excluded. Propensity score matching (PSM) was used to homogenize the baseline characteristics between the two groups. To define the independent risk of the DVT group, a multivariate Cox proportional hazard model was used to estimate the hazard ratios. After PSM, the DVT group (n = 5753) exhibited a higher risk of sepsis (adjusted hazard ratio, aHR, 1.74; 95% CI, 1.59-1.90) compared with non-DVT group (n = 5753). Patients with an increased risk of sepsis were associated with being elderly aged, male, having diabetes, chronic kidney disease, chronic obstructive pulmonary disease, stroke, malignancy, and use of antibiotics. In conclusion, this population-based cohort study demonstrated an increased risk of sepsis in DVT patients compared with non-DVT patients. Thus, early prevention and adequate treatment of DVT is necessary in clinical practice.

Phenethyl isothiocyanate suppresses EGF-stimulated SAS human oral squamous carcinoma cell invasion by targeting EGF receptor signaling.

Phenethyl isothiocyanate (PEITC) is a natural compound that is involved in chemoprevention as well as inhibition of cell growth and induction of apoptosis in several types of cancer cells. Previous studies have revealed that PEITC suppresses the invasion of AGS gastric and HT-29 colorectal cancer cells. However, the effects of PEITC on the metastasis of SAS oral cancer cells remain to be determined. Our results showed that PEITC treatment inhibited the invasion of EGF-stimulated SAS cells in a concentration-dependent manner, but appeared not to affect the cell viability. The expression and enzymatic activities of matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) were suppressed by PEITC. Concomitantly, we observed an increase in the protein expression of both tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2) in treated cells. Furthermore, PEITC treatments decreased the protein phosphorylation of epidermal growth factor receptor (EGFR) and downstream signaling proteins including PDK1, PI3K (p85), AKT, phosphorylated IKK and IκB to inactivate NF-κB for the suppression of MMP-2 and MMP-9 expression. In addition, PEITC can trigger the MAPK signaling pathway through the increase in phosphorylated p38, JNK and ERK in treated cells. Our data indicate that PEITC is able to inhibit the invasion of EGF-stimulated SAS oral cancer cells by targeting EGFR and its downstream signaling molecules and finally lead to the reduced expression and enzymatic activities of both MMP-2 and MMP-9. These results suggest that PEITC is promising for the therapy of oral cancer metastasis.

Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells.

Kaempferol is a natural flavonoid that possesses anti-proliferative and apoptosis-inducing activities in several cancer cell lines. In the present study, we investigated the anti-metastatic activity of kaempferol and its molecular mechanism(s) of action in human osteosarcoma cells. Kaempferol displayed inhibitory effects on the invasion and adhesion of U-2 osteosarcoma (OS) cells in a concentration-dependent manner by Matrigel Transwell assay and cell adhesion assay. Kaempferol also inhibited the migration of U-2 OS cells in a concentration-dependent manner at different treatment time points by wound-healing assay. Additional experiments showed that kaempferol treatment reduced the enzymatic activities and protein levels of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator (uPA) by gelatin and casein-plasminogen zymography assays and western blot analyses. Kaempferol also downregulated the mRNA levels of MMP-2 and MMP-9 by quantitative PCR analyses. Furthermore, kaempferol was able to reduce the protein phosphorylation of ERK, p38 and JNK by western blotting. By electrophoretic mobility-shift assay (EMSA), we demonstrated that kaempferol decreased the DNA binding activity of AP-1, an action likely to result in the reduced expression of MMP-2, MMP-9 and uPA. Collectively, our data showed that kaempferol attenuated the MAPK signaling pathways including ERK, JNK and p38 and resulted in the decreased DNA binding ability of AP-1, and hence, the downregulation in the expression and enzymatic activities of MMP-2, MMP-9 and uPA, contributing to the inhibition of metastasis of U-2 OS cells. Our results suggest a potential role of kaempferol in the therapy of tumor metastasis of OS.