Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells

BACKGROUND: Osteosarcoma is a bone tumor that often affects children and young adults. Although a combination of surgery and chemotherapy has improved the survival rate in the past decades, local recurrence and metastases still develop in 40% of patients. A definite therapy is yet to be determined for osteosarcoma. Anti- tumor compound and a metabolite of estrogen, 2-methoxyestradiol (2-ME) induces cell death in osteosarcoma cells. In this report, we have investigated whether interferon (IFN) pathway is involved in 2-ME-induced anti-tumor effects in osteosarcoma cells. METHODS: 2-ME effects on IFN mRNA levels were determined by Real time PCR analysis. Transient transfections followed by reporter assays were used for investigating 2-ME effects on IFN-pathway. Western blot analyses were used to measure protein and phosphorylation levels of IFN-regulated eukaryotic initiation factor-2 alpha (eIF-2α). RESULTS: 2-ME regulates IFN and IFN-mediated effects in osteosarcoma cells. 2 -ME induces IFN gene activity and expression in osteosarcoma cells. 2-ME treatment induced IFN-stimulated response element (ISRE) sequence-dependent transcription and gamma-activated sequence (GAS)-dependent transcription in several osteosarcoma cells. Whereas, 2-ME did not affect IFN gene and IFN pathways in normal primary human osteoblasts (HOB). 2-ME treatment increased the phosphorylation of eIF-2α in osteosarcoma cells. Furthermore, analysis of osteosarcoma tissues shows that the levels of phosphorylated form of eIF-2α are decreased in tumor compared to normal controls. CONCLUSIONS: 2-ME treatment triggers the induction and activity of IFN and IFN pathway genes in 2-ME-sensitive osteosarcoma tumor cells but not in 2-ME-resistant normal osteoblasts. In addition, IFN-signaling is inhibited in osteosarcoma patients. Thus, IFN pathways play a role in osteosarcoma and in 2-ME-mediated anti-proliferative effects, and therefore targeted induction of IFN signaling could lead to effective treatment strategies in the control of osteosarcoma

Prediction of Successful Pharmacological Cardioversion in Acute Symptomatic Atrial Fibrillation: The Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) Score

Background: Modern personalised medicine requires patient-tailored decisions. This is particularly important when considering pharmacological cardioversion for the acute treatment of haemodynamically stable atrial fibrillation and atrial flutter in a shared decision-making process. We aimed to develop and validate a predictive model to estimate the individual probability of successful pharmacological cardioversion using different intravenous antiarrhythmic agents. Methods: We analysed data from a prospective atrial fibrillation registry comprising 3053 cases of first-detected or recurrent haemodynamically stable, non-permanent, symptomatic atrial fibrillation presenting to an Austrian academic emergency department between January 2012 and December 2017. Using multivariable analysis, a prediction score was developed and externally validated. The clinical utility of the score was assessed using decision curve analysis. Results: A total of 1528 cases were included in the development cohort (median age 69 years, IQR 58–76; 43.9% female), and 1525 cases were included in the validation cohort (median age 68 years, IQR (58–75); 39.5% female). Finally, 421 cases were available for score development and 330 cases for score validation The weighted score included atrial flutter (8 points), duration of symptoms associated with AF (2 = 0.955 and R2 = 0.954) and discrimination in both sets (c-indices: 0.68 and 0.66) and net clinical benefit. Conclusions: A predictive model was developed to estimate the success of intravenous pharmacological cardioversion using different antiarrhythmic agents in a cohort of patients with haemodynamically stable, non-permanent, symptomatic atrial fibrillation. External temporal validation confirmed good calibration, discrimination, and clinical usefulness. The SIC-AF score may help patients and physicians jointly decide on the appropriate treatment strategy for acute symptomatic atrial fibrillation. Registration: NCT03272620

Prediction of Successful Pharmacological Cardioversion in Acute Symptomatic Atrial Fibrillation: The Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) Score

Background: Modern personalised medicine requires patient-tailored decisions. This is particularly important when considering pharmacological cardioversion for the acute treatment of haemodynamically stable atrial fibrillation and atrial flutter in a shared decision-making process. We aimed to develop and validate a predictive model to estimate the individual probability of successful pharmacological cardioversion using different intravenous antiarrhythmic agents. Methods: We analysed data from a prospective atrial fibrillation registry comprising 3053 cases of first-detected or recurrent haemodynamically stable, non-permanent, symptomatic atrial fibrillation presenting to an Austrian academic emergency department between January 2012 and December 2017. Using multivariable analysis, a prediction score was developed and externally validated. The clinical utility of the score was assessed using decision curve analysis. Results: A total of 1528 cases were included in the development cohort (median age 69 years, IQR 58–76; 43.9% female), and 1525 cases were included in the validation cohort (median age 68 years, IQR (58–75); 39.5% female). Finally, 421 cases were available for score development and 330 cases for score validation The weighted score included atrial flutter (8 points), duration of symptoms associated with AF (<24 h; 8 points), absence of previous electrical cardioversion (10 points), and the specific intravenous antiarrhythmic drug (amiodarone 10 points, vernakalant 11 points, ibutilide 13 points). The final score, the “Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) score,” showed good calibration (R2 = 0.955 and R2 = 0.954) and discrimination in both sets (c-indices: 0.68 and 0.66) and net clinical benefit. Conclusions: A predictive model was developed to estimate the success of intravenous pharmacological cardioversion using different antiarrhythmic agents in a cohort of patients with haemodynamically stable, non-permanent, symptomatic atrial fibrillation. External temporal validation confirmed good calibration, discrimination, and clinical usefulness. The SIC-AF score may help patients and physicians jointly decide on the appropriate treatment strategy for acute symptomatic atrial fibrillation. Registration: NCT03272620

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S)

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S)

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARSCoV- 2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S)

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARSCoV- 2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level