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Signe Sørup,1 Bianka Darvalics,1 Jakob Schöllhammer Knudsen,1 Anne Staub Rasmussen,1 Cathrine Fonnesbech Hjorth,1 Søren Viborg Vestergaard,1 Azza Ahmed Khalil,2 Leo Russo,3 Dina Oksen,4 Emmanuelle Boutmy,4 Patrice Verpillat,4 Mikael Rørth,1,5 Deirdre Cronin-Fenton1 1Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University & Aarhus University Hospital, Aarhus, Denmark; 2Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 3Worldwide Medical and Safety, Pfizer, Collegeville, PA, USA; 4Global Epidemiology, Merck Healthcare KGaA, Darmstadt, Germany; 5Department of Oncology, Rigshospitalet, Copenhagen, DenmarkCorrespondence: Signe Sørup, Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, Aarhus, DK-8200, Denmark, Tel +45 871 68230, Fax +45 87 16 72 15, Email SigneSorup@clin.au.dkPurpose: To develop algorithms to identify number of lines of anti-neoplastic therapy per patient based on the Danish National Patient Registry (DNPR) and identify which algorithm has the highest percentage agreement with a reference standard of documentation in medical records.Patients and Methods: We included 179 patients diagnosed between January 1, 2012, and December 31, 2016, with stage II, III, or IV urothelial cell carcinoma or stage III or IV epithelial ovarian cancer, gastric adenocarcinoma, renal cell carcinoma, or non-small cell lung cancer (NSCLC). We developed two algorithms for number of lines of anti-neoplastic therapy based on dates and treatment codes (eg, “treatment with cisplatin” or “cytostatic treatment”) in the DNPR. First, to denote a change in line of therapy the “Time-based algorithm” used the number of days between consecutive administrations. Second, the “Drug-based algorithm” used information on drug names if available or the number of days between consecutive administrations if no drug names were specified. We calculated the percentage agreement between the algorithms setting the number of allowed days between consecutive administrations from 28 to 50 and the reference standard – information on anti-neoplastic therapy drugs abstracted from medical records and subsequently coded according to lines of anti-neoplastic therapy.Results: For the “Time-based algorithm”, the highest percentage agreement with the reference standard was found when using < 45 days between consecutive administrations (67.6%; 95% CI: 60.1– 73.8%). However, the percentage agreement was higher for the “Drug-based algorithm” using < 45 days between consecutive administrations for registrations where the drug name was unspecified (90.5%; 95% CI: 85.0– 93.7%).Conclusion: The algorithm for number of lines of anti-neoplastic therapy that had the highest percentage agreement with the reference standard (medical records) incorporated both registration of specific drug names and < 45 days between consecutive administrations if the drug name was unspecified in routinely recorded data from DNPR.Keywords: positive predictive value, medical records review, duration of chemotherapy, medical oncologic treatments, Denmark

Signe Sørup,1 Bianka Darvalics,1 Azza Ahmed Khalil,2 Marianne Nordsmark,2 Mette Hæe,2 Frede Donskov,3 Mads Agerbæk,2 Leo Russo,4 Dina Oksen,5 Emmanuelle Boutmy,5 Patrice Verpillat,5 Deirdre Cronin-Fenton1 1Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University & Aarhus University Hospital, Aarhus, Denmark; 2Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 4Worldwide Medical and Safety, Pfizer, Collegeville, PA, USA; 5Global Epidemiology, Merck Healthcare KGaA, Darmstadt, GermanyCorrespondence: Signe SørupDepartment of Clinical Epidemiology, Aarhus University & Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Aarhus N, DenmarkTel +45 871 68398Email SigneSorup@clin.au.dkPurpose: Few studies have described real-world treatment patterns and survival before the widespread use of immune checkpoint inhibitors (ICIs). We aimed to describe anti-cancer treatment including the use of programmed cell death-1 and ligand-1 (PD-1/PD-L1) ICIs and overall survival (OS) in advanced cancer patients as a benchmarking real-world standard before widespread use of ICIs.Patients and Methods: Using nationwide Danish medical registries, we assembled cohorts of Danish patients with advanced non-small cell lung cancer (NSCLC) (n=12,283), urothelial carcinoma (n=2504), epithelial ovarian cancer (n=1466), gastric adenocarcinoma (n=1457), and renal cell carcinoma (RCC) (n=1261) diagnosed between 1/1/2013 and 31/12/2017. We describe anti-cancer treatment and OS using proportions, medians, and Kaplan–Meier methods.Results: Between 9% (ovarian cancer) and 25% (gastric adenocarcinoma) of patients did not receive anti-cancer treatment. The remaining patients received surgery, radiation therapy, and/or medical therapy. Chemotherapy was the most frequent medical therapy in all cohorts except for RCC (tyrosine kinase inhibitors). PD-L1/PD-1 ICIs were used in 7– 8% of the NSCLC and RCC cohorts—mainly as second or higher line treatments. OS was longest in patients starting treatment with surgery (eg 25.6 months [95%-confidence interval (CI)=21.9– 29.4] for NSCLC and 21.4 months [95%-CI=19.8– 23.5] for urothelial carcinoma) and shortest for radiation therapy (eg 3.9 months [95%-CI=3.6– 4.2] for NSCLC and 12.6 months [95%-CI=9.2– 17.5] for urothelial carcinoma). NSCLC patients starting with medical therapy had OS between these limits. Median OS for NSCLC patients starting treatment with PD-L1/PD-1 ICIs was 21.4 months (95%-CI=13.9-not estimable).Conclusion: Most patients with advanced NSCLC, urothelial carcinoma, epithelial ovarian cancer, gastric adenocarcinoma and RCC had poor OS in an era where only a minority received PD-L1/PD-1 ICIs. This information on treatment patterns and survival is important as a benchmarking real-world standard before widespread use of ICIs.Keywords: cancer, treatment, survival, immunotherapy, programmed cell death-1 immune checkpoint inhibitors, programmed cell death-ligand-1 immune checkpoint inhibitors

OBJECTIVE: The risk of operation in cardiac surgery increases logarithmically with advanced age. In older individuals, additional comorbidities compel the clinician to deal with postoperative complications. The mortality and morbidity rates of emergency coronary artery bypass surgery (CABG) in the presence of acute coronary syndrome (ACS), or just after it, are higher than those of elective surgeries. In our study, we compared the outcomes of off-pump coronary bypass (OPCAB) and on-pump coronary bypass surgery (ONCAB) in this high-risk subgroup. PATIENTS AND METHODS: 383 octogenarians who underwent isolated emergency CABG due to ACS were divided into two groups according to the coronary bypass technique. Group 1 (off-pump) median age (IQR) 84 years (min: 80-max: 99, n = 130); Group 2, (on-pump) median age 85 years (min: 80-max: 89, n=253). Preoperative, intraoperative, and postoperative data were collected retrospectively on standard variables. OPCAB and ONCAB outcomes were compared. RESULTS: ONCAB patients had a significantly longer intensive care unit stay, longer hospital stay, more transfused erythrocyte suspension, more low cardiac output syndrome and acidosis, a higher rate of acute renal failure and a higher rate of stroke than OPCAB patients (respectively; p=0.003; p=0.008; p=0.002; p=0.031; p=0.038, p=0.022, respectively). CONCLUSIONS: We showed that emergency OPCAB as a revascularization option in elderly patients with acute coronary syndrome is more advantageous in terms of preventing major postoperative complications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ventricular arrhythmias were the most frequent manifestations in patients with COVID-19. Both the natural course of the disease and the treatment drugs used have effects on ventricular repolarization. The objective of this study was to evaluate the effects of repolarization parameters obtained from surface electrocardiography (ECG) on prognosis. PATIENTS AND METHODS: Participants were 205 consecutive patients hospitalized with COVID-19 diagnosis. The 12-lead surface ECG was obtained from each patient on admission. The ECG results were evaluated against the patients’ clinical characteristics and outcomes by experienced cardiology specialists. RESULTS: The mean age was higher in the non-survivor group compared to the survivor group (57.4 ± 15.7 vs. 65.6 ± 16.6; p = 0.001). The demographical characteristics were similar between the survivor and non-survivor groups. Multivariate analyses demonstrated that age (OR: 1.041; p = 0.009), D-dimer (OR: 1.002; p = 0.031), high-sensitivity troponin I (hs-TnI) (OR: 1.010; p = 0.041), pneumonia on computed tomography (CT) (OR: 4.985; p < 0.001), the peakto- end interval of the T wave (Tp-e) (OR: 3.421; p < 0.001), and Tp-e/QTc ratio (OR: 1.978; p = 0.013) were statistically significant independent predictors in terms of determining mortality. CONCLUSIONS: Prolonged Tp-e interval and increased Tp-e/QTc ratio on admission are decent predictors and linked with mortality. ECG is a practical study to evaluate prognosis and potential arrhythmias, as well as initiating suitable treatment. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress is known to affect left ventricular functions negatively. There is a strong bidirectional connection between diabetes mellitus (DM) and oxidative stress. In parallel, left ventricular dysfunction is observed more frequently, even in patients with DM without other risk factors. In this context, the objective of this study is to comparatively investigate the potential relationship between oxidative stress and subclinical left ventricular dysfunction (SCLVD) assessed by Myocardial Performance Index (MPI) in patients with and without DM., Research Design and Methods: The sample of this observational cross-sectional single-center study consisted of 151 patients who were evaluated for oxidative stress and SCLVD by tissue Doppler echocardiography. Patients' total oxidant status (TOS), total antioxidant status (TAS), and Oxidative Stress Index (OSI) values were calculated. The effects of oxidative stress and DM on MPI were analyzed., Results: There were 81 patients with DM (mean age: 46.17±10.33 years) and 70 healthy individuals (mean age: 45.72±9.04 years). Mean TOS and OSI values of the DM group were higher than healthy individuals (5.72±0.55 vs 5.31±0.50, p = <0.001; and 4.92±1.93 vs 1.79±0.39, p = <0.001; respectively). The mean TAS value of the DM group was significantly lower than the healthy group (1.21±0.40 vs 3.23±0.51, p = <0.001). There was a significant correlation between OSI and MPI mitral in the DM group (R 0.554, p = <0.001) but not in the healthy group (R -0.069, p=0.249)., Conclusions: Both oxidative stress and myocardial dysfunction were found to be more common in patients with DM. The study's findings indicated the negative effect of oxidative stress on myocardial functions. Accordingly, increased oxidative stress caused more significant deterioration in MPI in patients with DM compared with healthy individuals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Coronary slow flow (CSF) is a condition commonly encountered during angiography. Recent studies have shown the adverse effects of CSF on left ventricular diastolic functions. CSF reportedly increases the novel ventricular repolarization parameters. Ranolazine is a preparation with a prominent anti-anginal activity that has positive effects on anti-arrhythmic and diastolic parameters. In this context, this study was carried out to investigate the effects of ranolazine on left ventricular diastolic functions and repolarization in patients with CSF., Material and Methods: Forty-six patients with CSF and 29 control subjects were included in the patient and control groups, respectively. Both groups received ranolazine for one month and were evaluated using 12-lead electrocardiography, conventional echocardiography, and tissue Doppler imaging at the baseline and after one month of ranolazine treatment., Results: Corrected P, QT dispersion, and Tp-e interval values were significantly higher in the patient group than in the control group. There was a significant decrease in isovolumic relaxation time (IVRT) and deceleration time (DT) values after the ranolazine treatment compared to the baseline values in the patient group but not the control group. A significant increase was observed in the mean E and A velocities and the mean E/A ratio after the ranolazine treatment compared to the baseline values in the patient group. Additionally, there was a significant difference between the Tp-e interval and corrected P dispersion values measured after the ranolazine treatment compared to the baseline values in the patient group but not in the control group., Conclusion: This study's findings demonstrated that ranolazine positively affected impaired diastolic functions and repolarization parameters, particularly in patients with CSF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Oksen, Aslan, Ozmen and Yavuz.)

Objective: Empagliflozin, an oral anti-diabetic drug that inhibits the sodium-dependent glucose co-transporter 2 (SGLT2), has pleiotropic effects on the myocardium. The aim of the study is to investigate the effect of empagliflozin on atrial electromechanical delay (AEMD) and the left atrial (LA) mechanical functions in patients with type 2 diabetes mellitus (DM)., Method: In total 62 patients (40.3% female, mean age 50.5 ± 8.6 years old) with type 2 DM were enrolled to the study. Participants were used a SGLT2 inhibitor (empagliflozin 10-25 mg/daily) for 6 months. Patients were examined initially and after 6 months with echocardiography. LA volume was recorded, atrial conduction times were measured using tissue Doppler imaging (TDI)., Results: No significant change was observed in LA volumes (maximal, minimal, and presystolic), total emptying and passive emptying volume at the end of 6 months; however, there was a significant decrease in active emptying volume (8.3 ± 2.9 ml/m 2 vs. 7.9 ± 2.9 ml/m 2 , p = 0.04). The posteroanterior lateral, septal, and tricuspid conduction times significantly decreased after the empagliflozin treatment. The decrease in right inter-AEMD was statistically significant (13.25 ± 10.21 ms vs. 10.85 ± 9.14 ms, p = 0.011). The changes in inter-AEMD were found to be correlated with the changes in LA active emptying volume (r = 0.408)., Conclusion: Empagliflozin may enhance the structure and electrical conductions of the atrium and may prevent DM patients from DM-2-related functional disorder and arrhythmia., (© 2022 Wiley Periodicals LLC.)

Real-world data (RWD) reflecting patient treatment in routine clinical practice can be used to develop external control groups for single-arm trials. External controls can provide valuable benchmark results on potential comparator drug effectiveness, particularly in rare indications when randomized controlled trials are either infeasible or unethical. This paper describes lessons learned from a descriptive real-world external control cohort study conducted to provide benchmark data for a single-arm clinical trial in a rare oncology biomarker driven disease. Conducting external control cohort studies to evaluate treatment effectiveness in rare indications likely will present data and analysis challenges as seen in the example study. However, there are mitigating measures that can be applied in the study design, identification of RWD sources, and data analysis. The lessons learned and reported here with a proposal of an external control study framework can provide guidance for future research in this area, and may be applicable as well in other rare indications. Taking these learnings into consideration, the use of real-world external controls to contextualize treatment effectiveness in rare indications is a valuable approach and warrants further application in the future., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: There is no study about the relationship between the complexity of coronary artery disease (SYNTAX SCORE; SS), and coronary artery calcium (CAC) score, accompanied with aortic calcium score (ACS) levels. The objective of this study was to investigate the relationship between the preoperative SS and CAC scores accompanying ACS in isolated CABG patients and their postoperative clinical results., Methods: This study included 130 consecutive CABG patients. The mean age of the patients was 62.3 ± 8.62 years (range: 47-84 years). SS was measured using coronary angiography by an experienced cardiologist. We investigated the ACS accompanied with CAC scores using a multidetector computed tomography (MDCT) in the same session, preoperatively. Measurements of the CAC score and ACS were measured by an experienced radiologist, who was unaware of the study in the same session. In order to investigate aortic wall pathology in patients with positive aortic calcification, we provided aortic tissue samples prior to the proximal anastomosis of bypass grafts using No:11 scalpel., Results: Overall median SS was 39 ± 7.2 (range: 15-41). CAC score was zero in 34 patients (26.1%). For the patients with a CAC score of zero, the median SS was 32 ± 9.4. There was no evidence of aortic calcification or plaque formation in 62 patients (47.6%). In these patients, the median SS was 35.6 ± 11.3. No significant difference was found when both groups were compared and for those patients with a calcific score of zero (P = .85). The median CAC score and ACS were 238 ± 122 AU (range: 0-1238 AU) and 112 ± 40 AU (range: 0-730 AU), respectively (P = .0033). For patients with a CAC score and ACS ≥400 AU, the mean SYNTAX score was ≥ 37. SS was correlated with CAC score (R:0.585; P < .0001). SYNTAX was correlated with ACS (R:0.557; P < .001). In multivariate analysis of SS (OR 1.053, 95% CI: 1.003-1.106, P = .039), gender (OR 0.189, 95% CI: 0.053-0.678, P = 0.011), age (OR 1.454, 95% CI: 1.256-1.632, P = .012), and diabetes mellitus (OR 0.341, 95% CI: 1.006-1.124, P = .014) were independent predictors for CAC score and aortic calcification., Conclusions: CAC score and ACS are strongly correlated with the complexity of coronary arteries in CABG patients. The total CAC score (≥ 400 AU) was independently associated with the degree of SS (>37). To prevent MACCE and mortality in CABG patients, we suggest the measurement of CAC score accompanied with ACS using MDCT as a non-invasive method. Highlight points: • Atherosclerotic plaque formation in aorta and coronary arteries are the main risk factors for stroke and infarction in CABG operations. •SYNTAX score value and aortic atherosclerosis levels are directly correlated. •SYNTAX score may predict the complications due to atherosclerosis during heart surgery.

Objectives: To describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations (MET exon 14 [METex14] skipping or MET amplification [METamp]) in real-world clinical care., Methods: This non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB-IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period., Results: A total of 117 patients were included (METex14 n = 70; METamp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the METamp cohort than METex14. Patients in the METex14 cohort were older than those in METamp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients (METex14; METamp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combination-therapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the METex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the METamp cohort, ORR was 36% in first-line and 22% in second-line. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the METex14 cohort and 22.0 months (9.8, 31.2) in METamp., Conclusions: Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

High-dose corticosteroids have been associated with increased risk of serious infection in patients with metastatic melanoma treated with immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4. This potential association needs to be examined further among patients with other cancer types and for other immune checkpoint inhibitors. We examined whether receipt of high-dose corticosteroids was associated with increased rates of hospitalization for infection among 981 Danish renal, urothelial, and lung cancer patients followed from first administration of programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors. Our cohort analysis was based on the information from national medical registries. During follow-up, 522 patients (53.2%) initiated treatment with high-dose corticosteroids and 317 patients (32.3%) experienced at least one hospitalization for infection. In analyses adjusted for age, sex, and previous use of chemotherapy/targeted therapy, initiation of high-dose systemic corticosteroids was associated with increased rate of hospitalization for infections (hazard ratio (HR) = 2.96, 95% confidence interval (CI) = 2.41-3.65) even in patients not receiving any chemotherapy/targeted therapy (HR = 3.66, 95% CI = 2.25-5.96). Our findings showed that high-dose corticosteroid initiation is associated with hospitalization for infection in patients treated with PD-1/PD-L1 immune checkpoint inhibitors. Clinicians and patients should be aware of this risk of infection when initiating treatment with high-dose corticosteroids., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Infective endocarditis (IE) is a heterogenous infection that affects the endothelial surface of the intracardiac structures and other implanted intracardiac devices. We aimed to compare demographical characteristics, causative microorganisms, treatment, and prognosis of prosthetic and native valve endocarditis diagnosed in two separate hospitals., Material and Methods: Between 2010 and 2020, patients admitted with the diagnosis of IE were retrospectively included in our multicenter study. Patients' demographic and epidemiological data, clinical characteristics, infected intracardiac structure and sort of valve, culprit microorganisms, laboratory findings, treatment manifestations and in-hospital outcomes with a period of 6 months were obtained from an electronic medical record system., Results: A total of 173 consecutive patients had diagnosed IE, 60.1% (104 patients) of them native valve endocarditis (NVE) and 39.8 % (69 patients) of them prosthetic valve endocarditis (PVE).  Baseline demographic properties were not different except hypertension and atrial fibrillation. Patients with prior hypertension were 25% (26 patients) in NVE; 39.1% (27 patients) in PVE and the difference was statistically significant. Septic shock was significantly higher in the PVE group than the NVE group (7.4% versus 1%; P = .036), and also recurrent endocarditis occurred more frequently in the PVE group than the NVE group (8.8% versus 1%; P = .016)., Conclusion: In our study, although we detected higher mean age, HT, RDW and atrial fibrillation rates compared with NVE, we did not detect a significant difference in mortality and morbidity.

Objective Thromboembolic events such as acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary artery embolism and renal artery embolism are a rare condition but a major cause of morbidity and mortality. In this study we discussed low-dose thrombolytic therapy, in patients with thromboembolic events in the intensive care unit.Methods The study was performed on 12 consecutive patients [8 female; 50.3±16.0 (35-95) years] with acute thromboembolism including acute coronary syndrome related prosthetic heart valve thrombosis, acute pulmonary embolism and acute renal embolism who were treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. We evaluated mainly in-hospital safety and also effectiveness.Total treatment episodes was 1.66±0.88 (1-4) times.Results All thromboembolic events have been successfully treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. The success criteria were clinically improvement and radiologically lysis. None of the patients had ischemic stroke, intracranial hemorrhage, embolism (peripheral and recurrence of coronary artery embolism), bleeding requiring transfusion. The most frequent in-hospital complication was a gum bleeding without need for transfusion (two patients).Conclusions In our case series low-dose (25 mg) and slow infusion (6 hours) of t-PA have been performed successfully for thromboembolic events including acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary embolism and renal embolism in patients with in the intensive care unit. Safety is promising and if efficacy will be proved; this method may be a valuable alternative to standard fibrinolytic regimen.

Background: There is a dearth of updated epidemiological data on the prevalence and annual incidence of coronary artery disease (CAD) and lower extremity artery disease (LEAD) in Western countries., Aims: To describe the incidence and prevalence of CAD and LEAD, associated medication patterns and long-term outcomes in France., Methods: This was a retrospective cohort study using French claims data from a representative sample of the French general population. Any hospitalization or long-term disease status for CAD or LEAD between January 2010 and December 2016 was collected to identify incident cases., Results: Of the 763,338patients screened in the study period, 8559 incident cases of CAD and 4399 of LEAD were identified, with an overall mean follow-up of 2.9±2.0years. The incidence of CAD, LEAD and CAD or LEAD remained stable over the years, and in 2016 were at 33.5 per 10,000person-years, 15.1per 10,000person-years and 42.5 per 10,000person-years, respectively. The prevalence of CAD increased from 3.1% in 2010 to 4.2% in 2016, and LEAD from 1.6% to 2.4%. Most patients received guideline-recommended medication with antithrombotic drugs and lipid-lowering drugs following the index event. However, most of the medications initiated were subsequently discontinued during follow-up. Incident CAD or LEAD was associated with considerable morbidity-particularly an incidence of all-cause hospitalization of 7976.9 per 10,000person-years-and all-cause mortality, with an incidence of 542.8 per 10,000person-years., Conclusion: In recent years, the prevalence of CAD or LEAD has increased progressively, resulting in considerable morbidity and mortality., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC)., Methods: Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010-2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer., Results: We used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94-0.96), urothelial carcinoma = 0.78 (95% CI: 0.70-0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83-0.88), MCC = 0.77 (95% CI 0.68-0.89), and NSCLC = 0.91 (95% CI 0.90 - 0.92)., Conclusion: Predictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Many clinical challenges have been encountered in electrophysiology laboratories (EP) while implanting intracardiac defibrillators for lethal arrhythmias, using pacemakers for bradyarrhythmias, placing pacemakers with multiple leads in patients with heart failure and cardiac ablation procedures. In this environment, anesthesiology plays a very critical role to ensure patients comfort, as well as maintains operator's convenience and facilitate management of undesired situations. EP laboratories are mostly used for diagnosis of certain heart diseases. Meanwhile, with the exponential increase in interventional procedures in our decade, electrophysiologists' need to cooperate with the anesthesiologists more frequently. The literature is still unclear about the effects of anesthetic agents on cardiac conduction pathways, but as we know with our previous data, the most agents we are using currently have more or less effect on the cardiac conduction systems. In this review, we aimed to describe the safe anesthesia methods in cardiac diagnostic procedures and have a closer look up the anesthetic outcomes of these procedures. This article comprehensively reviews the anesthesia practice encountered in electrophysiology laboratories.

Aim: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy., Patients & Methods: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients., Results: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months., Conclusion: The low ORR and brief DOR underscore the need for novel therapies.

Background and Aims: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer; few treatments exist for patients with advanced disease. Once tumors metastasize to distant sites, patients generally receive chemotherapy, but response duration and progression-free survival (PFS) are typically short. Few studies have assessed the efficacy of second-line chemotherapy for metastatic MCC. Here, we studied outcomes in patients who received ≥ 2 lines of chemotherapy for metastatic MCC., Materials and Methods: Patients in an MCC-specific registry diagnosed with stage IV MCC between November 1, 2004, and September 15, 2015, and treated with second-line or later chemotherapy were analyzed retrospectively. Patient records, including baseline characteristics, immunocompetent status, and responses to prior chemotherapy, were evaluated. Patients meeting eligibility criteria were followed through December 31, 2015., Results: Of 29 patients with metastatic MCC and immunocompetent status who had received ≥ 2 lines of chemotherapy, 3 achieved a partial response, for an objective response rate (ORR) of 10.3% (95% CI, 2.2-27.4). In the overall population including patients with immunocompetent and immunocompromised status ( n = 34), the ORR was 8.8% (95% CI, 1.9-23.7). The median duration of response was 1.9 months (range, 1.3-2.1 months; 95% CI, 1.3-2.1). In the immunocompetent population, median PFS and overall survival were 3.0 months (95% CI, 2.5-6.0) and 5.3 months (95% CI, 4.3-6.0), respectively., Conclusions: The low response rates and limited durability confirm previous reports of the ineffectiveness of second-line or later chemotherapy in patients with metastatic MCC and provide a benchmark for assessing clinical benefit of new treatments., Competing Interests: CONFLICTS OF INTEREST JCB reports grants and personal fees from Merck Serono, during the conduct of the study; personal fees from EMD Serono, Merck Serono, Pfizer, MSD, Takeda, Lytex, CureVac, Roche, and Novartis, and grants and personal fees from BMS, outside the submitted work. SU reports personal fees from BMS and MSD, and grants and personal fees from Medac, outside the submitted work. TE reports grants and personal fees from MSD and BMS, outside the submitted work. CP reports personal fees from Novartis, BMS, Roche, Amgen, and MSD, outside the submitted work. PM reports personal fees from Pierre Fabre, GSK, MSD, Roche, BMS, and Novartis, outside the submitted work. DS reports grants and personal fees from Novartis and BMS, personal fees from Amgen, GSK, Sysmex, and Boehringer Ingelheim, outside the submitted work. LM is an employee of EMD Serono, Inc, Billerica, MA, USA (a business unit of Merck KGaA, Darmstadt, Germany). CH, DO, and MB are employees of Merck KGaA, Darmstadt, Germany. All other authors have nothing to disclose.

Background: Acute aortic syndromes, being mostly underdiagnosed due to unspecific symptoms, are associated with high morbidity and mortality. Diagnosis carried out by transesophageal echocardiography, computed tomography and magnetic resonance imaging. However, there are lots of biochemical assays being investigated, but none of them used reliably to identify acute aortic syndromes. Biomarkers could accelerate the diagnostic time with cost effective way and could get place in definitive diagnostic algorithm of acute aortic syndrome. This review aims to identify contribution and value of biomarkers in acute aortic syndromes., Methods: We searched the contribution and value of biomarkers such as D - Dimer, Smooth muscle myosin heavy chain (sm - MHC), Calponin, and Soluble elastin fragments (sELAF) in acute aortic syndromes at the literature., Results: Twenty two actual papers were included in this review for searching the contribution and value of biomarkers in the acute aortic syndromes., Conclusion: Biomarkers accelerate the diagnosis and direct patients to imaging modalities with a risk classification. Plenty of biomarkers have been investigated so far but none of them were used in clinical routine. Currently none of the biomarkers can reliably identify acute aortic syndromes. Each of them has some limitation in term of sensitivity or specificity. Although, there is no single biomarker that can be safely used but a combination of the assays may increase the sensitivities and specificities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)