Madan Raj Aryal

Impact of hospital volume on outcomes of patients undergoing chemotherapy for acute myeloid leukemia: a matched cohort study

To the editor: In recent years, there has been growing evidence that hospital volume affects survival among patients undergoing a variety of surgical procedures and medical treatments.[1][1],[2][2] Whether case volume affects outcomes after chemotherapy among patients with acute myeloid leukemia (

Meta-Analysis on Risk of Bleeding With Apixaban in Patients With Renal Impairment

Apixaban is a novel oral anticoagulant which is approved for the management of atrial fibrillation and venous thromboembolism prophylaxis. There have been concerns regarding bleeding risks with apixaban in patients with renal impairment. We performed a systematic review and meta-analysis to evaluate the risk of bleeding with apixaban in these patients. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2014). Phase III randomized controlled trials that compared apixaban with conventional agents (vitamin K antagonist and/or warfarin, low molecular weight heparin, aspirin, and placebo) were included. We defined mild renal impairment as creatinine clearance of 50 to 80 ml/min and moderate to severe renal impairment as creatinine clearance <50 ml/min. Study-specific risk ratios were calculated, and between-study heterogeneity was assessed using the I(2) statistics. In 6 trials involving 40,145 patients, the risk of bleeding with apixaban in patients with mild renal impairment was significantly less (risk ratio 0.80, 95% confidence interval 0.66 to 0.96, I(2) = 13%) compared with conventional anticoagulants. In patients with moderate to severe renal impairment, the risk of bleeding with was found to be similar (risk ratio 1.01, 95% confidence interval 0.49 to 2.10, I(2) = 72%). In conclusion, compared with the conventional agents, bleeding risk with apixaban in patients with mild and moderate to severe renal insufficiency is lower and similar, respectively.

Dual Versus Single Antiplatelet Therapy in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis

BACKGROUND Although dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve replacement (TAVR), this approach is not evidence based. We therefore sought to systematically review the current evidence for this practice in terms of 30-day outcome looking at stroke, MI, bleeding, and death. METHODS Relevant studies were identified through electronic literature search. Studies involving single antiplatelet therapy (SAPT) and DAPT in patients undergoing TAVR were included. Study specific risk ratios were calculated and combined using random-effects model meta-analysis. RESULTS Analysis of data from 410 patients, stroke occurred in seven (3.16%) of SAPT and six (3.17%) of DAPT RR=1.03 (95% CI, 0.36-2.96, P=0.96). In analysis of 530 patients, MI occurred in three (1.07%) of SAPT and one (0.40%) of DAPT RR=1.97 (95% CI, 0.29-13.29, P=0.49), significant bleeding (major, life threatening and bleeding requiring transfusion) occurred in 20 (7.11%) of SAPT and 43 (17.27%) of DAPT RR=0.41 (95% CI, 0.25-0.69, P=0.0006). Number needed to harm for major or life threatening bleeding was 10. Death occurred in 15 (6.78%) of SAPT and 15 (7.94%) of DAPT (RR 0.91; 95% CI 0.46-1.79, P=0.78). CONCLUSION Our meta-analysis suggests that at 30 days following TAVR there is no difference between post-procedural SAPT versus DAPT for the risk of stroke or MI and DAPT may have a higher bleeding risk. Adequately powered RCTs are warranted to clarify the optimal antiplatelet treatment strategy following TAVR.

Fondaparinux-associated heparin-induced thrombocytopenia

Large licensing trials did not find any association between the use of fondaparinux and the development of heparin‐induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux‐associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux‐associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management.

Amplatzer PFO occluder device may prevent recurrent stroke in patients with patent foramen ovale and cryptogenic stroke: a meta-analysis of randomised trials.

OBJECTIVE To review efficacy of percutaneous closure of patent foramen ovale compared with medical therapy in prevention of recurrent strokes in patients with cryptogenic stroke. METHODS AND RESULTS Electronic databases; PUBMED, EMBASE, Cochrane registry and web of knowledge were searched for relevant studies. In three randomised clinical trials involving 2303 participants, risk of the recurrent strokes (pooled HR 0.62, 95% CI=0.36-1.07, P=0.09, I(2) =10%) did not show benefit with device closure when compared with medical therapy group on meta-analysis of all three trials. However, on sensitivity analysis in trials using Amplatzer PFO occluder device, the closure of PFO was associated with significantly lower recurrent strokes (pooled HR=0.44, 95% CI=0.21-0.94, P=0.03, I(2)=0%) compared with medical therapy. CONCLUSION The closure of PFO with Amplatzer PFO occluder device was associated with significant reduction in recurrent strokes in patients with cryptogenic stroke and patent foramen ovale. The better outcome in prevention of secondary stroke in patients with cryptogenic stroke and PFO may be associated with type of closure device used.

Rituximab-induced serum sickness: A systematic review

OBJECTIVES To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. METHODS A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0. RESULTS In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögrens syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d. CONCLUSION It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.

Left Atrial Appendage Aneurysm: A Systematic Review of 82 Cases

Aneurysm of the left atrial appendage is rare. We sought to systematically review the published literature on left atrial appendage aneurysm (LAAA) to address its demographic features, clinical characteristics, treatment, complications, and outcomes.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials.

Right atrial appendage aneurysm: a systematic review.

Right atrial appendage aneurysm (RAAA) is rare with fewer than 20 cases reported in the literature. We sought to systematically review the published cases of RAAA in terms of demographics, clinical characteristics, treatment, complications, and outcome.

Papillary fibroelastoma of the aortic valve: An unusual cause of angina

Papillary fibroelastoma of the aortic valve is an uncommon benign tumor of the heart that can present with embolic events. We report a case of 54-year-old lady with exertional chest pain and prior history of ST segment elevation myocardial infarction who was subsequently found to have a fibroelastoma of the aortic valve. The absence of angiographically significant coronary artery disease and resolution of anginal symptoms post-surgery in our patient points to the possibility of fibroelastoma causing these anginal symptoms. Although uncommon, fibroelastoma are being recognized more frequently with the help of transesophageal echocardiography. Hence, in the absence of significant coronary artery disease, we emphasize the importance of consideration of papillary fibroelastoma of the aortic valve as a cause of angina. We also discuss the key aspects of the fibroelastoma including presentation, diagnostic modalities and treatment options.