Ranjan Pathak

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.

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.

Eculizumab in Transplant-Associated Thrombotic Microangiopathy.

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. Methods: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. Results: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. Conclusion: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.

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.

Meta-analysis of 21- versus 22-G aspiration needle during endobronchial ultrasound-guided transbronchial needle aspiration.

Background:Two different needle gauges (21 and 22 G) are currently used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Few studies have compared the diagnostic utility of EBUS-TB107NA using 21 versus 22 G needles. We aimed to systematically analyze all existing literature comparing the diagnostic benefit of these 2 needles. Methods:A systematic search for the identification of all relevant studies comparing 21 and 22 G needles in EBUS-TBNA was performed using the MEDLINE, EMBASE, SCOPUS databases up to September 21, 2014. All the extracted data underwent meta-analysis using Review Manager 5.3 and Comprehensive Meta-analysis 3.3. Study-specific odds ratios (OR) were calculated and combined using random-effects model. Between study heterogeneity was assessed using the I2 statistic. Results:A total of 5 studies involving 1720 patients were identified. The sample adequacy rate was 89.1% in the 21 G group and 90.0% in the 22 G group and this difference was not statistically significant [OR, 0.94; 95% confidence interval (CI), 0.56-1.59; P=0.82]. Similarly, there was no significant difference in the diagnostic yield (73.7% vs. 58.5%; OR, 1.04; 95% CI, 0.80-1.35; P=0.80) or the mean number of needle passes (mean difference −0.31; 95% CI, −1.1 to 0.47; P=0.44). There were no major complications reported in any of these studies. Conclusions:There were no differences in the diagnostic yield, sample adequacy, or the mean number of needle passes between the 21 and 22 G groups during EBUS-TBNA. Similarly, the complication rates were low and similar between the 2 groups.

Incidence trend of esophageal squamous cell carcinoma: an analysis of Surveillance Epidemiology, and End Results (SEER) database

Esophageal cancer is the sixth leading cause of cancer deaths worldwide [1]. In the USA, an estimated 18,170 new cases of esophageal cancer will be detected in the year 2014 [2]. Although prior studies have shown a decline in the incidence of esophageal squamous cell carcinoma (SCC) in the USA and worldwide [3–5], it is unknown if this continues to be true in recent years. We utilized Surveillance, Epidemiology, and End Results (SEER) 18 database to determine the trend in the incidence of esophageal SCC in the USA between 2000 and 2011. SEER is a program of the National Cancer Institute that provides cancer incidence and survival data from population-based cancer registries covering 28 % of the US population. Eligible patients were identified using SEER histology codes 8050-8089. Age-adjusted rates were plotted by time period using a logarithmic scale for the ordinate. Genderand race-specific trends were also calculated. Data analysis was done using SEER*Stat 8.1.5, and trend analysis was done using Jointpoint regression program 4.1. A total of 344,408 cases of esophageal squamous cell carcinoma were identified during the study period. The study population included 57.9 % males, 82.1 % whites, and 12.1 % African-Americans (AA). The age-adjusted incidence rate steadily decreased from 40.2/100,000 in 2000 to 34.0/100,000 in 2011 (annual percentage change [APC] -1.1, p \ 0.05). The decline in incidence was observed in both sexes and all races (Fig. 1); however, the decline was most prominent in AA males (APC -3.2, p \ 0.05) (Fig. 1a). Our study demonstrates a continual decline in the incidence of esophageal SCC between 2000 and 2011. Prior studies by Trivers et al. [5] and Cook et al. [6] have shown a steady reduction in the incidence of esophageal SCC in the USA prior to 2005. This reduction has been attributed largely to a decreased prevalence of smoking [7]. Although the decline in our study was observed in both genders and all races, it was most prominent in AA males. African-Americans, compared to whites, have higher mortality rate from esophageal cancer; hence, a decrease in the incidence of esophageal SCC in AA is encouraging [2]. This is likely the result of a rapid decline in smoking rates in this population, which highlights the importance of efforts toward risk reduction. It is estimated that between the mid-1970s to early 1990s, the drop in smoking rates among AA youths was twice as much as that among whites [8, 9]. This decline has continued in the recent years as well [10]. SEER is a de-identified database; hence, the accuracy of coding cannot be verified. We were not able to compare the prevalence of risk factors for esophageal SCC among different subgroups that may have accounted for the observed racial differences.

Acute promyelocytic leukemia during pregnancy: a systematic analysis of outcome

The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p < 0.01) and fetal (p < 0.01) complications. To our knowledge, this is the largest systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making.

Role of radiation therapy in primary mediastinal large B-cell lymphoma in rituximab era: A US population-based analysis

The use of radiation (RT) in primary mediastinal large B‐cell lymphoma (PMBCL) may predispose young patients to the risk of cardiopulmonary toxicities and secondary malignancies. We used Surveillance, Epidemiology and End Results (SEER) 18 database to compare the overall survival (OS) differences among adult patients treated with and without RT after rituximab approval in the US. Multivariate analyses were performed using Cox proportional hazards regression to compare OS based on the use of RT while adjusting for age, year of diagnosis, race, stage and gender. PMBCL patients (n = 258), who received RT (48%), were similar in terms of age, gender, race, and stage at diagnosis to patients who did not receive RT. The five year OS was similar between patients treated with versus without RT (82.5% vs. 78.6%, P = 0.47). In a multivariate analysis, the use of RT did not influence OS in the rituximab era (HR 0.83; 95% CI 0.43–1.59; P = 0.56). Rituximab may reduce the benefit of RT in select patients such as those who achieve a metabolic complete remission at the end of chemotherapy. Am. J. Hematol. 90:1052–1054, 2015.