Murad, M. Hassan

AbstractBackgroundComprehensive treatment recommendations for Merkel cell carcinoma are complex. We aimed to systematically review the published data on recurrence and mortality rates associated with various treatment approaches for Merkel cell carcinoma.MethodsSearch of MEDLINE, Embase, Web of Science, and Scopus from inception to August 2015. Studies were included that reported comparative survival and recurrence data for two or more treatment modalities. Two reviewers independently reviewed and abstracted recurrence and mortality rates. Event rates for individual treatment arms in each study were pooled and meta‐analyzed across studies using a random‐effects model.ResultsFifty‐two retrospective studies met inclusion criteria, revealing a total of 1,804 patients with primary Merkel cell carcinoma with data available for analyses. The recurrence rate was higher for surgery alone (55.0%) versus a combination of surgery and radiotherapy (39.0%) (odds ratio, 2.089; 95% CI, 1.374–3.177; P < 0.001). Combination therapy including surgery, radiotherapy, and chemotherapy had a higher mortality rate (44.6%) than did combined surgery and radiotherapy (23.2%) (odds ratio, 2.688; 95% CI, 1.196–6.037; P = 0.02).ConclusionsThe treatment of Merkel cell carcinoma with surgery plus adjuvant radiotherapy may produce lower recurrence rates.

Background and Purpose: We performed a systematic review and meta-analysis comparing rates of recanalization, good neurological outcome, and mortality between patients treated with three modern devices used for endovascular treatment of acute ischemic stroke. Materials and Methods: We performed a comprehensive literature search on studies reporting outcomes of endovascular treatment of acute ischemic stroke. We selected studies including≥30 patients treated with either the Trevo stent-retriever, Penumbra aspiration system or the Solitaire stent-retriever. Outcomes studied included mrs≤2, 90-day mortality, symptomatic and intracranial hemorrhage (sICH), recanalization. Outcomes were pooled across studies using a random-effects meta-analysis. Results: 27 articles with 2666 patients were included (1514 Solitaire, 260 Trevo and 892 Penumbra). Rates of good neurological outcome (mRS≤2) were higher in the Solitaire group (54.0%, 95%CI=49.0-58.0%) than the Penumbra group (39.0%, 95%CI=31.0%-47.0%) (P<0.01). There was a trend towards higher rates of good neurological outcome in the Solitaire compared to the Trevo group (P=0.08). Rates of 90-day mortality were significantly lower in the Solitaire group (16.0%, 95%CI=11.0%-22.0%) than in the Penumbra group (27.0%, 95%CI=24.0%-30.0%) (P<0.01) and the Trevo group (23.0%, 95%CI=13.0-33.0)(P=0.01). Recanalization rates were similar between groups at 80.0% (95%CI=75.0%-84.0% for the Solitaire group, 82.0% (95%CI=75.0%-88.0%) for the Penumbra group (P=0.54) and 76.0% (95%CI=68.0-83.0) for the Trevo group (P=0.13 vs Penumbra and P=0.27 vs. Solitaire). Conclusions: Meta-analysis of incidence rates in noncomparative series reporting on over 2500 patients suggests that the Solitaire device maybe associated with superior neurological outcomes and lower rates of 90-day mortality. Comparative studies are needed to confirm these observations.

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.

Importance: Right bundle branch block (RBBB) is observed in approximately 5-14% of patients with heart failure (HF). Multiple observational studies have reported the association of RBBB with clinical outcomes in patients with HF. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with HF. Data Sources: We have systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts that described all cause or cardiovascular mortality in patients with RBBB and HF. We excluded studies that reported unadjusted outcome, i.e.: unadjusted event rates. Knowledge synthesis: We pooled reported risk ratio and hazard ratio. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: We found 12 relevant observational studies enrolling over 38,000 patients. Risk of bias was assessed using the Newcastle-Ottawa Scale. Included studies had at least a moderate quality. Seven of those evaluated prognosis of patients with RBBB and heart failure. After a mean follow up period of 2.5 years (range: 1-5 years), RBBB was associated with a statistically significant increased risk of all-cause mortality compared to patients with heart failure but no BBB, RR 1.27, 95% CI (1.08-1.50), Figure 1. The other 5 studies evaluated CHF patients receiving cardiac resynchronization therapy (CRT), comparing outcomes of patients with RBBB to those with LBBB. After a mean f/u period of 3 years, patients with RBBB were once again found to have an increased risk of all-cause mortality, RR 1.45, 95% CI 1.12-1.89. Conclusion and Relevance: RBBB in patients with HF is associated with higher all-cause mortality in comparison to patients without inter-ventricular conduction defects, as well as LBBB patients in patients undergoing CRT setting.

Objective: Multiple large population based observational studies have evaluated the association of various ECG changes with long term adverse outcomes demonstrating conflicting results regarding the significance of right bundle branch block (RBBB). Therefore, we conducted a systematic review and meta-analysis to determine the prognostic significance of RBBB in healthy population. Methods: This systematic review follows an a priori established protocol and is reported following the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We systematically searched EMBASE, Web of Science and Scopus through January 2014. We also consulted with content experts to recommend studies for screening. Reviewers working independently and in duplicate screened all eligible abstracts, selecting randomized trials and prospective cohort studies that described all cause mortality or cardiovascular death in patients with RBBB. We excluded studies that reported unadjusted outcome or unadjusted event rates. For statistical analysis, hazard ratios were considered to approximate risk ratios. The main outcomes of the study are all-cause mortality and cardiovascular mortality. Results: Based on the eligibility, four large cohorts, with total patient count > 100,000 were included in the meta-analysis. Risk of bias was assessed using the Newcastle-Ottawa scale and included studies were deemed to be of high quality. As demonstrated in Figure 1, RBBB was not associated increase in all-cause mortality (RR 1.05; 95% CI 0.89-1.25) or cardiovascular mortality (RR 1.09; 95% CI 0.70-1.69). Conclusion: In asymptomatic healthy patients, RBBB is not associated with poor outcome.

Introduction: Conflicting results exist regarding the impact of gender on survival after Sudden Cardiac Arrest (SCA). Hypothesis: Assess association between female gender and survival after SCA Methods: An electronic search of Embase, Ovid MEDLINE In-Process & Non-Indexed Citations and EBM Reviews - Cochrane Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic Reviews and Google was conducted (January 1948 to January 2014) for studies of any study design and language, examining the gender effect on survival at hospital discharge after a SCA. Two independent reviewers selected studies and extracted data. The inter-rater agreements kappa were measured at the first and second selection steps. Moreover, the pooled OR and 95% CI, concerning women vs. men survival at hospital discharge after an OHCA were calculated with a random effect model. Subgroups analyses were performed, according to the cardiac origin of OHCAs and according to the study quality. Study quality criteria were based on the New Castle Ottawa Scale. Results: After a detailed screening of 556 citations, 12 studies were identified involving 404 621 patients. The inter-rater agreements kappa was high for the 2 study selection steps (0.91 and 1). In most studies, women were older and had less favorable baseline characteristics including a lower prevalence of witnessed-OHCA, OHCA in a public location, bystander cardio-pulmonary resuscitation and shockable rhythms compared to men. However and after adjustment for these differences, women were more likely to survive at hospital discharge (N=12; OR: 1.11 [1.02-1.21]; p=0.013). This result remains in studies analyzing OHCA of presumed cardiac origin (N=7; OR: 1.17 [1.03-1.34]; p=0.017) and in studies of high quality (N=7; OR: 1.11 [1.02-1.21]; p=0.017). Conclusion: Despite less favorable baseline characteristics, women are more likely to survive at hospital discharge after an OHCA. Further studies are needed to explain this paradox.

Background The association between the 9p21-3 locus and coronary heart disease (CHD) is well known. We performed a systematic review of the literature to assess whether this locus was associated with severity of coronary atherosclerosis. Data Sources Multiple relevant electronic databases were searched through September 2012 for English language studies with comparative design. Data extraction We tested the association of the 9p21-3 locus: 1) measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CHD Prognostic Index (Dc.PI)]. 2) angiographic outcomes [change in minimum lumen diameter ([[Unable to Display Character: &#8710;]]MLD) and number of new lesions at follow-up] and 3) key clinical outcomes (all-cause mortality, recurrent myocardial infarction and need for coronary revascularization). Genotypes were classified either as homozygous low risk (Lo) or homozygous high risk (Hi). Data Synthesis Relative risks (RR) were pooled using the random effects model. Seventeen distinct data sets that included 15,826 participants were analyzed. Ten studies (n=9807) reported number of diseased vessels at baseline. Hi genotype was associated with a 33.7% increased risk of triple vessel disease (95% CI 1.08-1.65; p=0.01). The Hi genotype was associated 0.27 higher baseline Gensini Score (95% CI 0.04-0.48; p=0.01) in 3787 individuals. The locus was not associated with Dc.PI [RR=0.21 (95% CI -0.14-0.55; p=0.25)]. The high risk genotype did not predict [[Unable to Display Character: &#8710;]]MLD or number of new lesions at follow-up. There was no difference between Hi and Lo genotypes in terms of all-cause mortality [RR=1.13 (95%CI 0.90-1.41;p=0.28)], recurrent myocardial infarction (95%CI 0.92-1.40; p=0.24) or frequency of coronary revascularization [RR=1.101 95% CI (0.78-1.57); p=0.56]. Conclusion An association between 9p21-3 and greater baseline severity of coronary atherosclerosis was seen in this meta-analysis. However no association was seen between 9p21-3 and adverse angiographic and clinical outcomes which may be due to diminishing genetic risk following dietary modification and statin therapy.

OBJECTIVES: To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION: Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION: Data were collected on all-cause mortality, hospital length of stay, heart failure–related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS: Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46–0.67; p < 0.05; I2 = 12%) and heart failure–related readmissions (relative risk, 0.50; 95% CI, 0.33–0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, –3.28 d; 95% CI, –4.14 to –2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92–662.81; p < 0.05; I2 = 76%), weight loss (mean difference, –1.76 kg; 95% CI, –2.52 to –1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98–8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47–70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, –0.46 mg/dL; 95% CI, –0.51 to –0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS: Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.