Damianos G. Kokkinidis

Emerging treatments for ulcerative colitis: a systematic review

Abstract Objectives: Various investigational medicinal products have been developed for ulcerative colitis (UC). Our aim was to systematically evaluate novel pharmacological therapeutic agents for the treatment of UC. Material and methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the medical literature was conducted in the MEDLINE database for original research papers published between 01 January 2010 and 31 October 2014. Results: Twenty one studies, including 11,524 adults were analyzed. Thirteen different novel therapeutic drug options were identified. Vedolizumab and golimumab were superior to placebo as induction and maintenance therapy. Tofacitinib showed dose related efficacy for induction therapy. Etrolizumab showed higher clinical remission rates compared to placebo. Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may become a mesalamine alternative for mild to moderate UC. PF00547,659 was well tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept, rituximab and visilizumab did not lead to improved outcomes compared to placebo. Higher concentration of BMS 936557 was associated with improved efficacy compared to placebo. Basiliximab did not enhance corticosteroid efficacy. Conclusions: Patients with UC might achieve clinical response or remission by utilizing some of these agents with a favorable side effect profile. Further studies are needed to evaluate their short- and long-term efficacy and safety.

Second‐generation drug‐eluting stents versus drug‐coated balloons for the treatment of coronary in‐stent restenosis: A systematic review and meta‐analysis

The benefit of drug‐eluting stents (DES) versus drug‐coated balloons (DCB) in coronary artery in‐stent restenosis (ISR) for the prevention of target lesion revascularization (TLR), stent thrombosis, and mortality remains uncertain. Our aim was to synthesize the available evidence from randomized clinical trials (RCTs) and observational studies that directly compare second‐generation drug‐eluting stents (SG‐DES) and DCB for the treatment of coronary ISR.

Revascularization of radiation-induced carotid artery stenosis with carotid endarterectomy vs. carotid artery stenting: A systematic review and meta-analysis

OBJECTIVE The incidence of carotid artery stenosis after head and neck radiation is anticipated to rise due to the increasing survival of patients with head and neck malignancies. It remains unclear whether carotid artery stenting (CAS) or endarterectomy (CEA) is the best treatment strategy for radiation-induced carotid artery stenosis. MATERIALS & METHODS This study was performed according to the PRISMA and MOOSE guidelines. Eligible studies were identified through a comprehensive search of PubMed, Scopus and Cochrane Central until July 20, 2017. A meta-analysis of random effects model was conducted. The I-square statistic was used to assess for heterogeneity. RESULTS Five studies and 143 patients were included. Periprocedural stroke, myocardial infarction (MI) and death rates were similar between the two revascularization approaches. However, the risk for cranial nerve (CN) injury was higher in the CEA group (OR: 7.09; 95% CI: 1.17-42.88; I2 = 0%). CEA was associated with lower mortality rates after a mean follow-up of 50 months (OR: 0.29; 95% CI: 0.09-0.97; I2 = 0%). No difference was identified in long-term restenosis rates between CEA and CAS. CONCLUSIONS Patients with radiation-induced carotid artery stenosis can safely undergo both CAS and CEA with similar risks of periprocedural stroke, MI and death. However, patients treated with CEA have a higher risk for periprocedural CN injuries and a lower risk for long-term mortality.

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long‐Term Childhood Cancer Survivors

BACKGROUND Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk. SUBJECTS, MATERIALS, AND METHODS This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at diagnosis ≤19 years, survival ≥5 years) were followed up over a median time period of 12.3 (5-40.9) years. Independent predictors of cardiovascular mortality (CVM) were combined into a risk score, which was developed in a derivation set (n = 22,374), and validated in separate patient registries (n = 6,437). RESULTS In the derivation registries, older age at diagnosis (≥10 years vs. reference group of 1-5 years), male sex, non-white race, a history of lymphoma, and a history of radiation were independently associated with an increased risk of CVM among long-term CCS (p < .05). A risk score derived from this model (Childhood and Adolescence Cancer Survivor CardioVascular score [CHACS-CV], range: 0-8) showed good discrimination for CVM (Harrells C-index [95% confidence interval (CI)]: 0.73 [0.68-0.78], p < .001) and identified a high-risk group (CHACS-CV ≥6), with cumulative CVM incidence over 30 years of 6.0% (95% CI: 4.3%-8.1%) versus 2.6% (95% CI: 1.8%-3.7%), and 0.7% (95% CI: 0.5%-1.0%) in the mid- (CHACS-CV = 4-5) and low-risk groups (CHACS-CV ≤3), respectively (plog-rank < .001). In the validation set, the respective cumulative incidence rates were 4.7%, 3.1%, and 0.8% (plog-rank < .001). CONCLUSION We propose a simple risk score that can be applied in everyday clinical practice to identify long-term CCS at increased cardiovascular risk, who may benefit from early cardiovascular screening, and risk-reduction strategies. IMPLICATIONS FOR PRACTICE Childhood cancer survivors (CCS) are known to be at increased cardiovascular risk. Currently available prognostic tools focus on treatment-related adverse events and late development of congestive heart failure, but there is no prognostic model to date to estimate the risk of cardiovascular mortality among long-term CCS. A simple clinical tool is proposed for cardiovascular risk stratification of long-term CCS based on easily obtainable information from their medical history. This scoring system may be used as a first-line screening tool to assist health care providers in identifying those who may benefit from closer follow-up and enable timely deployment of preventive strategies.

CAROTID ARTERY ENDARTERECTOMY VERSUS CAROTID ARTERY STENTING FOR RESTENOSIS AFTER CAROTID ARTERY ENDARTERECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Carotid artery restenosis may occur after ipsilateral carotid endarterectomy (CEA). It remains unclear whether carotid artery stenting (CAS) or a repeat CEA (redoCEA) is the best treatment strategy for carotid artery restenosis. This study was performed according to the PRISMA and MOOSE guidelines

Effect of Open- vs Closed-Cell Stent Design on Periprocedural Outcomes and Restenosis After Carotid Artery Stenting: A Systematic Review and Comprehensive Meta-analysis

Purpose:To compare periprocedural complications and in-stent restenosis rates associated with open- vs closed-cell stent designs used in carotid artery stenting (CAS). Methods: A systematic search was conducted to identify all randomized and observational studies published in English up to October 31, 2017, that compared open- vs closed-cell stent designs in CAS. Identified studies were included if they reported the following outcomes: stroke, transient ischemic attack (TIA), myocardial infarction (MI), hemodynamic depression, new ischemic lesions detected on imaging, and death within 30 days, as well as the incidence of in-stent restenosis. A random-effects model meta-analysis was employed. Model results are reported as the odds ratio (OR) and 95% confidence interval (CI). The I2 statistic was used to assess heterogeneity. Results: Thirty-three studies (2 randomized trials) comprising 20, 291 patients (mean age 71.3±3.0 years; 74.6% men) were included. Patients in the open-cell stent group had a statistically significant lower risk of restenosis ⩾40% (OR 0.42, 95% CI 0.19 to 0.92; I2=0%) and ⩾70% (OR 0.23, 95% CI 0.10 to 0.52; I2=0%) at a mean follow-up of 24 months. No statistically significant differences were identified for periprocedural stroke, TIA, new ischemic lesions, MI, hemodynamic depression, or death within 30 days after CAS. Sensitivity analysis of the 2 randomized controlled trials only did not point to any significant differences either. Conclusion: Use of open-cell stent design in CAS is associated with a decreased risk for restenosis when compared to the closed-cell stent, without significant differences in periprocedural outcomes.

The predictive value of baseline pulmonary hypertension in early and long term cardiac and all-cause mortality after transcatheter aortic valve implantation for patients with severe aortic valve stenosis: A systematic review and meta-analysis

BACKGROUND Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH). OBJECTIVE To determine the association of PH with early and late cardiac and all-cause mortality after TAVI. METHODS We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed. RESULTS In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality). CONCLUSION This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.

Percutaneous closure of patent foramen ovale vs. medical treatment for patients with history of cryptogenic stroke: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Patients with history of cryptogenic stroke are more likely to have a patent foramen ovale (PFO) and should be managed with antithrombotic agents, while the alternative option is percutaneous closure of PFOs. Our aim was to perform a meta-analysis of randomized controlled trials (RCTs) comparing percutaneous closure vs. medical treatment for patients with PFO and prior cryptogenic stroke. METHODS Medline, Scopus and Cochrane databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. New ischemic stroke was defined as the primary endpoint. A sensitivity analysis was performed for Amplatzer device. Subgroup analyses were performed for different patient and PFO characteristics for the composite endpoints as defined by the included RCTs. RESULTS In total of 3440 patients were included in this meta-analysis. Closure devices were superior to medical therapy for prevention of recurrent ischemic strokes (HR = 0.29; CI: 0.02-0.56), but were associated with increased risk of new onset of atrial fibrillation (AF) and atrial flutter (RR = 4.67; CI: 2.22-9.81). However, in the sensitivity analysis for Amplatzer device, there was no difference between the two groups in new onset of atrial arrhythmias. Closure devices were superior across all different subgroups when compared to medical treatment with the exception of patients with a small shunt. CONCLUSION This meta-analysis shows that closure devices for patients with PFO and history of cryptogenic stroke can significantly decrease the risk of a new ischemic stroke. The use of Amplatzer device was not associated with increased risk of newly diagnosed atrial arrhythmias.

Proximal embolic protection versus distal filter protection versus combined protection in carotid artery stenting: A systematic review and meta-analysis

OBJECTIVE Proximal embolic protection devices (P-EPD) and distal filters (DF) are used to prevent distal cerebral embolizations during carotid artery stenting (CAS). We compared their comparative effectiveness in regards to prevention of intraprocedural and periprocedural adverse events, including ischemic lesions (ipsilateral and contralateral), stroke, transient ischemic attacks (TIA) and death. We also compared the combination of the two neuroprotection strategies vs. a single strategy in regards to ischemic lesions and stroke. MATERIALS & METHODS This study was performed according to the PRISMA and MOOSE guidelines and eligible studies were identified through search of PubMed, Scopus and Cochrane Central. A meta-analysis was conducted with the use of a random effects model. The I-square statistic was used to assess for heterogeneity. RESULTS Twenty-nine studies involving 16,307 patients were included. There was a significant reduction in ischemic lesions with the use of P-EPD among observational studies (RR: 0.66 [0.45-0.97]). There were no statistically significant differences for the other outcomes between the two treatment groups. CONCLUSIONS There is a number of studies reporting outcomes on the comparison between P-EPD and DF for CAS. P-EDP can reduce distal embolization phenomena resulting into ischemic lesions when compared to DF based on the results from real-world studies. P-EPD was not superior however, in regards to periprocedural stroke, TIA and death. Further studies are anticipated to provide a clear answer to this debate.