Research Items (149)
The outcomes of acute promyelocytic leukemia (APL) in pregnancy are 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.
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., Whether case volume affects outcomes after chemotherapy among patients with acute myeloid leukemia (
- Nov 2018
The impact of iron chelation therapy (ICT) on overall survival (OS) and progression to acute myeloid leukemia (AML) in patients with iron overload and International Prognostic Scoring System low- or intermediate-risk myelodysplastic syndromes (MDS) is not well understood. We conducted a systematic review and meta-analysis of published studies of ICT in patients with MDS to better elucidate these relationships. We searched PubMed, EMBASE, Cochrane databases, and the World Health Organization Clinical Trial Registry for studies reporting the impact of ICT on OS in patients with low- or intermediate-risk MDS. Studies were examined for demographics, effect measures, and potential bias risk. Fixed and random-effects models were used to calculate adjusted OS and adjusted hazards ratio (aHR) estimates, respectively, among the different studies. Nine observational studies (four prospective and five retrospective) were identified. For patients with MDS, ICT was associated with an overall lower risk of mortality compared with no ICT (aHR 0.42; 95% confidence interval (CI) 0.28–0.62; P < 0.01); however, there was significant heterogeneity across the studies. In studies reporting progression to AML, ICT was not associated with decreased risk of progression (odds ratio 0.68; 95% CI 0.31–1.43; P < 0.030). This systematic review and meta-analysis of nine nonrandomized trials demonstrated significant reduction in risk of mortality in patients with iron overload and low- or intermediate-risk MDS treated with ICT; however, a causal relationship cannot be established. Randomized, controlled trials are needed to more definitively evaluate the relationship between ICT and survival in patients with iron overload and low- or intermediate-risk MDS.
- Sep 2018
Background: Although provider-level volume is frequently associated with outcomes in cancers requiring complex surgeries, whether similar relations exist for cancers treated primarily with systemic therapy is unknown. Methods: Using a population-based cohort analysis of older adults diagnosed with diffuse large B cell lymphoma (DLBCL) during the years 2004-2011, we evaluated the association between oncologist volume and 4 clinical outcomes (receipt of any chemotherapy, receipt of an anthracycline-containing or equivalent regimen, early hospitalization, and overall survival). Our primary explanatory variable was lymphoma treatment volume, defined as the number of patients with newly diagnosed lymphoma for which an oncologist initiated therapy during a 12-month look-back period from each incident DLBCL case. Results: We identified 8247 Medicare beneficiaries who were newly diagnosed with DLBCL. Chemotherapy was administered to 6202 (75.2%) beneficiaries, and 71.4% of cytotoxic regimens contained an anthracycline. Beneficiaries who were treated by higher-volume oncologists had increased odds of receiving chemotherapy (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.24-1.70; P <.001) and of receiving an anthracycline-containing regimen (aOR, 1.26; 95% CI, 1.06-1.50; P = .009). Receiving care from a higher-volume provider was also associated with decreased hospitalization (aOR, 0.80; 95% CI, 0.69-0.95; P = .007) and improved survival (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001). Conclusion: In older adults diagnosed with DLBCL, receiving care from a provider with more experience treating lymphoma patients was associated with receipt of guideline-adherent therapy, reduced hospitalizations, and improved survival. Clinical volume may be an important factor in providing high-quality cancer care in the modern era.
Current guidelines recommend therapeutic phlebotomy for all polycythemia vera (PV) patients and additional cytoreductive therapy (eg, hydroxyurea [HU]) for high-risk PV patients. Little is known about the impact of these therapies in the real-world setting. We conducted a retrospective cohort study of older adults diagnosed with PV from 2007 to 2013 using the linked Surveillance, Epidemiology, and End Results-Medicare database. Multivariable Cox proportional hazards models were used to assess the effect of phlebotomy and HU on overall survival (OS) and the occurrence of thrombotic events. Of 820 PV patients (median age = 77 years), 16.3% received neither phlebotomy nor HU, 23.0% were managed with phlebotomy only, 19.6% with HU only, and 41.1% with both treatments. After a median follow-up of 2.83 years, 37.2% (n = 305) of the patients died. Phlebotomy (yes/no; hazard ratio [HR] = 0.65; 95% confidence interval [CI], 0.51-0.81; P < .01), increasing phlebotomy intensity (HR = 0.71; 95% CI, 0.65-0.79; P < .01), and a higher proportion of days covered (PDC) by HU were all significantly associated with lower mortality. When thrombosis was the outcome of interest, phlebotomy (yes/no; HR = 0.52; 95% CI, 0.42-0.66; P < .01) and increasing phlebotomy intensity (HR = 0.46; 95% CI, 0.29-0.74; P < .01) were significantly associated with a lower risk of thrombotic events, so was a higher HU PDC. In this population-based study of older adults with PV reflecting contemporary clinical practice, phlebotomy and HU were associated with improved OS and decreased risk of thrombosis. However, both treatment modalities were underused in this cohort of older PV patients.
- Aug 2017
Rarely, penetrating atherosclerotic ulcers can rupture into the wall of the aorta, resulting in acute aortic dissection. This article describes a woman with an incidental diagnosis of type A aortic dissection secondary to a penetrating atherosclerotic ulcer of the ascending aorta. Although surgical repair of the aortic root was recommended, the patient refused treatment and left against medical advice.
Aim: This study determined the epidemiology of developing leukemic transformation in patients with myeloproliferative neoplasms (MPN). Methods: We utilized the Surveillance, Epidemiology and End Results 13 database to identify 83 cases of leukemic transformation in MPN (n = 9335). Results: The 5-year cumulative incidence of leukemic transformation was higher in male versus female (2.17 vs 1.09%, p < 0.001), and in myelofibrosis (2.19%; 95% CI: 1.36-3.34%), compared with essential thrombocythemia (0.37%; 95% CI: 0.19-0.65%) and polycythemia vera (0.72%; 95% CI: 0.46-1.07%; p < 0.001). Patients had a median survival of 2 months after leukemic transformation, worse in older patients and without any impact of prior MPN subtypes. Conclusion: Myelofibrosis has a higher risk of leukemic transformation. Overall survival is dismal regardless of MPN subtypes.
Background With improving outcomes of patients with Follicular Lymphoma (FL), it is imperative to focus on survivorship issues including development of Second Primary Malignancies (SPM). We used a large US database to measure the risk of SPM among FL survivors Methods We used the Surveillance Epidemiology and End Results-13 registry to identify FL patients from 1992 to 2011. We calculated risk of SPM, developing ≥6 months after diagnosis, using Standardized Incidence Ratio (SIR) and Absolute Excess risk (AER). We calculated the cumulative incidence of SPM using competing risk method and risk factors for SPM using univariate and multivariate methods. Results Out of a total of 15,517 cases of FL followed for a median of 71 months, 1540 patients (9.9%) developed SPM with SIR of 1.08 and AER of 11.3 per 10,000 person years. Significantly increased risk was noted for Hodgkin Lymphoma (SIR 5.85), acute myeloid leukemia (SIR 4.88) and the following sites: oral cavity and pharynx (SIR 1.43), stomach (SIR 1.43), lung and bronchus (SIR 1.35), melanoma of skin (SIR 1.38), other non-epithelial cancers of the skin (SIR 2.88), urinary bladder (SIR 1.24) and kidney/renal pelvis (SIR 1.43). The cumulative incidence of SPM was 11.06% at 10 years. Multivariate regression showed that age > 65y (SHR 1.57; p<0.001), male gender (SHR 1.43; p<0.001) and receipt of radiation (SHR 1.24; p=0.001) predicted a higher rate of SPM. Conclusion Patients with FL have increased risk of both hematologic and solid malignancies. Risk factors for SPM include advanced age, male and radiation therapy.
7057 Background: The HMA azacitidine improved overall survival (OS) compared to conventional care in patients with HR-MDS in the landmark randomized clinical trial AZA-001 by a median of 9.5 months compared to conventional care regimens. However recent registry data from USA (Zeidan et al, 2016) and Spain (Bernal et al, 2015) did not show substantial population-level gains in OS. We used HMA market entry in the US (2004-06) as a natural experiment to assess the effect of HMA on OS. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare data.Individuals were included if they were 66 years or older in age, had refractory anemia with excess blasts (RAEB, considered to have HR-MDS), and were diagnosed in 2001-11.We performed 2-stage residual inclusion instrumental variable (IV) analysis, using diagnosis year as the IV. Residuals from the first stage model were added to the second stage regression to control for effects of unobserved factors between HMA treatment and OS. We also adjusted for demographic characteristics, comorbidity, disability status and transfusion receipt. Results: Among 2,581 patients with RAEB, the median OS from diagnosis was 9 months, and 35.8% received HMAs. In the first stage model, diagnosis year was a strong predictor of HMA (2001-06 vs. 2011, Odds Ratio = 0.004-0.56, P-value < .01). In IV analysis, patients who received HMAs showed no gain in OS (Hazard Ratio (HR) = 0.93, 95% Confidence Interval (CI) = 0.76-1.14), while there was a strongly protective effect of unobservable characteristics on OS (HR = 0.58, 95% CI = 0.47-0.73). Conclusions: In our US population-based analysis,HMA use was not associated with survival prolongation in older adults with HR-MDS. It is unclear if this is related to suboptimal use of HMAs (alternate schedules, doses, number of cycles), use of decitabine (which did not show survival benefit in randomized studies), or the unselected nature (compared to strict eligibility in clinical trials) of patients receiving HMAs at the community level. Better understanding of these issues is vital for optimal HMA patient selection and administration.
6593 Background: Despite the high complexity of cancer therapies, studies evaluating provider-level volume and outcomes of systemic treatments are lacking. As rituximab was the first approved monoclonal immunotherapy, and has the potential for severe infusion reactions, we hypothesize that low provider volume is associated with early rituximab discontinuation. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results -Medicare data.Individuals 66+ years old with B cell non-Hodgkin lymphoma (NHL) diagnosed during 2004-2011 and 1+ rituximab claims were included. A provider was assigned to each patient-rituximab initiation using Medicare claims. We used a 12-month lookback from each initiation to categorize provider volume (0, 1-2, or 3+ rituximab initiations) in the prior year. Our primary outcome was early discontinuation, defined as receipt of 1-2 rituximab cycles within 180 days of initiation. We used a modified Poisson regression to account for provider level correlation and estimated the relative risk of early discontinuation in patients with 6+ months of follow up after rituximab initiation. A Cox proportional hazards model was used to measure the impact of discontinuation on overall survival. Results: A total of15,110 patients (median age: 75 years) initiated rituximab with 2,684 providers. The majority (70.4%) initiated rituximab in conjunction with chemotherapy and 1,146 (7.6%) experienced early rituximab discontinuation. Provider experience with rituximab during the previous 12 months was associated with early discontinuation in a dose-dependent manner (adjusted relative risk [aRR]: 1.57, [95% confidence interval [CI]:1.35-1.83], p < .001 for 0 vs 3+ initiations; aRR: 1.19 [95% CI:1.03-1.37], p = .02 for 1-2 vs. 3+ initiations). In addition, rituximab discontinuation was associated with a higher risk of death (adjusted hazard ratio: 1.39 [95% CI:1.28-1.52], p < .001). Conclusions: Lower physician volume is associated with increased risk of early discontinuation in older adults initiating rituximab for NHL. Due to the association between early discontinuation and mortality, physician volume may be an important factor in providing high quality NHL care.
Background: tAML, compared to de novo AML, has higher adverse features and a shorter overall survival (OS). The use of chemotherapy and hematopoietic cell transplant (HCT), and OS of tAML outside of clinical trials has not been studied well. Current study was designed to identify the treatment patterns and OS of tAML based on a national database. Methods: A total of 1,611 cases of tAML were identified between 2001-2011 using the National Cancer Database (NCDB). Data on age, race, gender, income, insurance and educational status, Charlson comorbidity index (CCI), receipt of chemotherapy and HCT were abstracted. Log-rank test was used to test equality of survivor function among the variables. Factors that attained statistical significance during bivariate analysis were factored into multivariate analysis using Cox Regression model. Results: Median age at diagnosis was 63 years (range 18-90), with 54% < 65 years, 59% females and 80% Caucasians. 67% underwent chemotherapy (20% single agent, 45% multiple agents and 2% unknown). 19% received HCT. Median OS was 6.7 months (m) with 1-year OS of 33%. Median OS was lower among patients ≥65 versus < 65 years (4.1 vs. 9.5 m; p < 0.001), those with higher comorbidity burden (7.8 m for CCI of 0, 6.0 m for CCI of 1, and 3.8 m for CCI of 2; p < 0.001), and diagnosed before versus during/after 2008 (5.6 vs. 7.7 m, p = 0.05). Median OS was higher among patients who received chemotherapy (8.4 vs. 3.7 m; p < 0.001) and HCT (22.6 vs. 4.9 m, p < 0.001), as compared to those who did not. Cox regression model showed the predictors of OS to be: receipt of HCT (hazard ratio, HR 0.36); use of multiagent chemotherapy (HR 0.80); age≥65 years (HR 1.25), higher comorbidities (HR of 1.21 for CCI of 1, and 1.45 for CCI of 2) and diagnosis on or after 2008 (HR of 0.81). Conclusions: Over half of patients with tAML are younger adults ( < 65 years), however, the receipt of chemotherapy and HCT is relatively low. OS is poor in general but improves with the use of multiagent chemotherapy and HCT. OS is worse in older patients and those with comorbidities. Given a dismal prognosis, older patients may be managed by leukemia team with expertise in geriatric oncology and should be encouraged to participate in clinical trials of novel therapies.
Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared one-month mortality and longer-term overall survival (OS) of 60,738 patients with AML, who received first course treatment between 2003-2011 at academic or non-academic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one-month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at non-academic centers in that they were younger with a median age of 62 versus 70 years (p <0.0001), more often an ethnic minority (p <0.0001), had lower education level (p=0.005), lower co-morbidity score (p <0.0001), a different income (p<0.0001) and insurance profile (p<0.0001), and more often received chemotherapy (p<0.0001) and transplant (p<0.0001). Receipt of care at non-academic centers was associated with worse one-month mortality (29% vs. 16%, p<0.0001) and five-year OS (15% vs. 25%; p<0.0001). After adjusting for prognostic covariates, the one-month mortality (odds ratio, 1.52; 95% confidence interval, CI 1.46-1.59; p <0.0001) and OS were significantly worse in non-academic centers, compared to academic centers. Our large database study suggests that the receipt of initial therapy at academic centers is associated with lower one-month mortality and higher long-term OS. Investigation of the underlying reasons may allow reducing this disparity. This article is protected by copyright. All rights reserved.
The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE ® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48) recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66); 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17- 73); 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days). Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.
- Feb 2017
Background: We evaluated surgical trends for gastric diffuse large B-cell lymphoma (gDLBCL) before and after the approval of rituximab and whether an association of early mortality existed in patients treated after approval of rituximab. Patients and methods: We utilized the Surveillance Epidemiology and End Results (SEER) 18 database to extract data on patients with gDLBCL diagnosed between 1983-2012. Primary site-specific cancer-directed surgery using SEER site-specific surgical codes and annual trends were analyzed. Patients were analyzed before and after 2006, the year rituximab gained U.S. Food and Drug Administration approval. Results: Joinpoint trend analysis showed the sharpest decline in surgical rates between 2000-2010. Adjusted surgical rates computed using poisson regression declined from 54.4% in 1983 to 6.9% in 2012, with an annual percentage change of -8.9% (95% confidence interval=-9.7% to -8.3%; p-value <0.01). No significant mortality increase at 30 and 60 days was found. Conclusion: While rituximab appears to have significantly changed how surgery is utilized for patients with gDLBCL, early mortality was unchanged.
Our objective was to determine the clinical manifestations and outcomes of mycophenolate mofetil (MMF)-induced diarrhea. Major databases were searched to include 44 articles that provided data on 560 episodes of diarrhea induced by MMF or its derivatives. Results depicted the median age of 45 years (range 8-70); 29% were females. The latency between use of MMF and onset of diarrhea was 990 days (range 12- 5760). Watery diarrhea was the presenting symptom in 98%. MMF was discontinued or dose reduced in 56%, switched to enteric coated mycophenolate mofetil sodium in 12%, and continued in 14%. Eighty-five percent of cases who were managed with discontinuation/dose reduction of MMF and 81% of cases who switched from MMF to enteric coated mycophenolate mofetil sodium responded. The median time to response for either change to enteric coated mycophenolate sodium or discontinuation/dose reduction of MMF was 20 days (range 1-120 days). Thus, MMF-induced diarrhea generally presents with watery diarrhea, and a majority of patients respond to discontinuation or dose reduction of MMF within a few weeks. Where continuation of MMF is important, a different drug formulation may be an option.
- Jan 2017
Introduction Concurrent hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) is rare; management is inadequately described in the literature. Methods Retrospective chart review and clinical follow-up. Results Five patients are described. The first patient developed synchronous HCL and CLL and was treated with rituximab for 13 months with HCL in remission and stable CLL. The second patient developed HCL and was treated with cladribine. His disease recurred 7 years later which was retreated with cladribine. Seven years later, he developed asymptomatic CLL. The third patient developed CLL, managed expectantly, then developed HCL 10 months later, and was treated with cladribine. Although his HCL went into remission, there was a slow redevelopment of CLL for which expectant management was done. The fourth patient developed concurrent CLL and HCL, received cladribine, with subsequent development of worsening abdominal lymphadenopathy and was lost to follow-up. The last patient developed concurrent HCL and CLL and was also diagnosed with lung adenocarcinoma; this patient was also lost to follow-up. Conclusion The development of concurrent HCL and CLL may indicate a common origin. Patients with HCL may subsequently develop CLL, thus mimicking a relapse of HCL. Therapy requires individualized approach including watchful waiting in asymptomatic cases. Rituximab may be useful to treat both disorders simultaneously.
Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment.
Background: Studies on the outcome of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) are limited. Methods: We compared the outcome of AYA (19-30 years) patients with AML and PML and pediatric (0-18 years) patients with AML (pAMLs) and APL (pAPLs) utilizing the Surveillance Epidemiology and End Results-18 registry. Early mortality rate (EMR), defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment-related mortality. Survival statistics were computed using the Kaplan-Meier method. Multivariate analysis was done using logistic regression and the Cox proportional hazard regression model. Results: A total of 6343 patients with AML were identified; 44.7% were AYAs. pAMLs had lower EMR (6.2% vs. 9.2%; P < .01) and higher overall survival (OS) (1-year, 70.3% vs. 62.1%; 5-year, 48.2% vs. 36.4%; P < .01). Nine hundred twenty patients with APL were also identified; 59.5% were AYAs. No statistically significant difference was found between AYAs with APL and pAPLs in EMR (11.4% vs. 14.1%; P = .23) and OS (1-year, 83.8% vs. 81.2%; P = .31 and 5-year, 68.2% vs. 73.1%; P = .11]. Comparing all patients with AML and APL, AYAs with APL and pAPLs had higher EMR (11.4% and 14.1% vs. 6.2% and 9.2%; P ≤ .01) but better OS than AYAs with AML and pAMLs (5-year OS, 68.2% and 73.1% vs. 48.2% and 36.4%; P ≤ .01). Conclusion: Our analysis shows AYAs with AML have worse EMR and OS compared with pAMLs. AYAs with APL and pAPLs have similar outcomes. To our knowledge, this is the first study reporting outcomes of AYAs with APL and pAPLs using a large population-based registry and their comparison with same age patients with AML.
Aim: To determine the risk of second primary malignancy (SPM) and survival of patients with essential thrombocythemia (ET). Methods: We identified all patients with ET diagnosed during 2001 to 2011 from the Surveillance, Epidemiology and End Results (SEER) 18 database. Actuarial and relative survival methods were used to calculate the survival statistics. We utilized the SEER 13 database to calculate SPM. We used multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.1.5) to calculate SIR and excess risk of SPM for ET patients. Results: Age standardized five-year cause-specific survival was greater for patients < 50 years vs those ≥ 50 years (99.4% vs 93.5%, P < 0.01). Five-year cause-specific survival was lower for men vs women (70.2% vs 79.7%). A total of 201 patients (2.46%) developed SPM at a median age of 75 years. SPMs occurred at an observed/expected (O/E) ratio of 1.26 (95%CI: 1.09-1.45, P = 0.002) with an absolute excess risk (AER) of 37.44 per 10000 population. A significantly higher risk was noted for leukemia (O/E 3.78; 95%CI: 2.20-6.05, P < 0.001; AER 11.28/10000). Conclusion: ET patients have an excellent cause-specific five-year survival but are at an increased risk of SPM, particularly leukemia, which may contribute to excess deaths.
- Aug 2016
Background: While radical nephroureterectomy is the treatment of choice for localized or regional urothelial carcinoma of the upper urinary tract (UTUC), the role of adjuvant radiotherapy is unclear, with conflicting data from various small studies. Patients and methods: We sought to study the impact of adjuvant radiotherapy on UTUC by utilizing the Survelliance, Epidemiolgy, and End Results (SEER) 9 database from 1998-2011. Results: Of 2,572 identified cases, 113 patients (4.4%) received adjuvant radiotherapy, with a median age of 74 years (range=22-100 years). In univariate analysis, patients treated with adjuvant radiation therapy seemed to have a lower survival time than those without radiation therapy (19 months versus 31 months, p<0.05). However, after adjusting for covariates, including age at diagnosis, gender, race, year of diagnosis, stage, histological grade and surgery, radiation therapy did not seem to influence survival (hazard ratio=0.68; 95% confidence interval=0.68-1.06, p=0.85). Conclusion: This hypothesis-generating, population-based analysis shows that adjuvant radiotherapy may not influence survival among patients with locoregional UTUC.
- Jul 2016
Highlights • Ischemic stroke is an uncommon complication among adults with DKA, that confers a worse prognosis. • Traditional risk factors for stroke including older age, stroke history, hypertension and hyperlipidemia appear to predict the risk of IS in these patients. Demographic and clinical characteristics of patients with diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome patients, with and without cerebral edema
Coronary-cameral fistula (CCF) is an anomalous connection between a coronary artery and a cardiac chamber or major vessel, seen in about 0.8% of the cases undergoing coronary angiography. Most patients are asymptomatic and diagnosis is made incidentally during coronary angiography. We present an image case of CCF which was found incidentally during pre-liver transplantation work up.
- Jun 2016
Lead fractures are uncommon complications of pacemaker implantation. This article describes a patient with an incidental diagnosis of multiple atrial lead fractures many years after pacemaker implantation.
Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare entity with no previous population-based study. Materials and methods: We used the Surveillance, Epidemiology, and End Results 18 database to identify adult patients with SPTCL and peripheral T-cell lymphoma not otherwise specified (PTCL NOS) diagnosed between 1973 and 2011. The actuarial survival of SPTCL was compared with a propensity-matched cohort of PTCL NOS. Multivariate analysis was conducted using weighted Cox proportional hazard regression model. Results: Patients with SPTCL (n = 118), compared with PTCL NOS (n = 3296), were more likely to be younger (median age of 47 vs. 62 years; P < .01), women (67% vs. 40%, P < .01), and diagnosed with stage I/II disease (46% vs. 36%; P = .01). The 5-year actuarial, relative, and cause-specific survival for SPTCL was 40%, 57%, and 64%, respectively. After propensity-matching, the 5-year overall survival (OS) of SPTCL was better than that of PTCL NOS (57% vs. 40%; P < .01). In a multivariate analysis, mortality was significantly lower among SPTCL versus PTCL NOS (hazard ratio, 0.54; 95% confidence interval, 0.39-0.75; P < .01). Among patients with SPTCL, advanced age (P < .01) and diagnosis before the year 2008 (P = .02) were predictors of worse OS. Conclusion: Our study provides characteristics and OS of a large cohort of SPTCL. Compared with PTCL NOS, SPTCL patients were more likely to be younger, female, and diagnosed at an early stage. The OS of SPTCL was better than PTCL NOS.
A 69-year-old female with history of immobilization presented with shortness of breath and generalized weakness and was found to have large saddle pulmonary embolus on CT scan. Further evaluation with a transthoracic echocardiography revealed a moderately enlarged and hypokinetic right ventricle with a pulmonary artery clot of about 1.5 cm seen at the bifurcation while the ultrasound of the legs was negative for deep vein thrombosis.
Background: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors. Methods: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML. Results: Patients with sAML (median age: 47 years; 82% <60 years) were significantly younger than de novo AML cases (66 years; p < 0.01). sAML had worse overall survival (OS) than de novo AML (p < 0.01). OS was better in younger patients and in more recent years. Conclusion: Older patients with sAML have a dismal OS and should be enrolled in trials of novel therapies. Younger patients have improved OS and hence may benefit from curative intent intensive therapy and allogeneic transplant.
- Mar 2016
Objectives: Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome is a rare inflammatory arthritis, characterised by symmetrical distal synovitis, pitting oedema of the hands and feet, absence of rheumatoid factor, and favourable response to glucocorticoids. The aim of our study is to further delineate the clinical and laboratory features, and response to treatment. Methods: We performed a systematic electronic search of Medline, PubMed, EMBASE, ACR and EULAR databases for case reports, case series, and related articles of RS3PE. Statistical analysis was done comparing categorical variables with Chi-square tests and frequencies of means via t-tests. Binary logistic regression analysis was performed to identify predictors of erosions, recurrence, malignancy and rheumatologic disorders. Results: 331 cases of RS3PE were identified from 121 articles. RS3PE was found in older patients (71±10.42 years) predominantly in males (n= 211, 63.36%), was symmetrical (n=297/311, 95.50%) involved the hands (n=294/311, 94.53%) A concurrent rheumatologic condition was reported in 22 cases (6.65%), and malignancy in 54 cases (16.31%). Radiographic joint erosions were found in 5.5%. Most patients responded to medium-dose glucocorticoids (16.12±9.5 mg/day). Patients with concurrent malignancy requiring non-significantly higher doses of prednisone (18.12 vs. 15.76 mg, p 0.304) and higher likelihood of recurrence of disease (OR 4.04, 95% CI 1.10-14.88, p=0.03). Conclusions: The symptoms and unique findings that make up RS3PE appear to represent a steroid-responsive disease that may be a harbinger of an underlying malignancy. More study is needed to understand the molecular origins of RS3PE in order to determine whether it is a separate disease process. Patients with concurrent cancer tend to have more severe presentations and higher rates of recurrence.
- Jan 2016
Background: Secondary hemophagocytic syndrome (SHPS) is a syndrome that develops as a result of infection, autoimmunity, or underlying malignancy. We studied novel predictors of mortality among adults with SHPS. Patients and methods: SHPS were identified from the Nationwide Inpatient Sample for 2009 to 2011 using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes. Charlson comorbidity index (CCI) was used for comorbidity assessment, excluding malignancy. Patient- and hospital-related factors on mortality were assessed by chi-square test or analysis of variance. P values were 2 sided, and the level of significance was .05. Results: A total of 276 patient hospitalizations with SHPS were identified. Forty-four had an associated malignancy, 38 (86%) of which were hematologic. Median age was 42 years (range, 18-89 years). A total of 66% (n = 182) had a CCI of 0, 13% (n = 27) had a CCI of 1, and 21% (n = 57) had a CCI of 2 or more. On bivariate analysis, inpatient mortality rate was significantly higher in malignancy-associated hemophagocytic syndrome (HPS) (odds ratio [OR], 2.07; P = .04), age ≥ 50 years (OR, 3.46; P < .01), CCI ≥ 2 (OR, 3.04; P < .01), and Medicare patients (OR, 2.32; P < .01). In multivariate analysis, CCI ≥ 2 remained an independent predictor of survival in the overall study cohort (OR, 3.52; 95% confidence interval, 1.51-8.18; P < .01). Conclusion: Malignancy-associated HPS, CCI ≥ 2, age > 50 years, and Medicare patients were associated with a worse in-hospital mortality. In multivariate analysis, greater comorbidity burden appeared to be the single most important predictor of mortality. This suggests that outcomes for adults with HPS are predicated by the extent of organ dysfunction at diagnosis.
Diarrhea is a common complication of allogeneic hematopoietic stem cell transplant (HSCT), with an average incidence of approximately 40%-50%. A wide variety of etiologies can contribute to diarrhea in HSCT patients, including medication-induced mucosal inflammation, infections, graft-vs-host disease and cord colitis syndrome in umbilical cord blood transplant. Clinical manifestations can vary from isolated diarrheal episodes, to other organ involvement including pneumonia or myocarditis, and rarely multiorgan failure. The approach for diagnosis of diarrheal disorders in HSCT patients depends on the most likely cause. Given the risk of life-threatening conditions, the development of clinically significant diarrhea requires prompt evaluation, supportive care and specific therapy, as indicated. Serious metabolic and nutritional disturbances can happen in HSCT patients, and may even lead to mortality. In this review, we aim to provide a practical approach to diagnosis and management of diarrhea in the post-transplant period.
- Jan 2016
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately one-third of all non-Hodgkin lymphomas (NHL) and is the most common aggressive NHL. It can arise de novo or as a transformation of an indolent lymphoma. Although rituximab-based immunochemotherapy has improved overall survival (OS) in DLBCL, high-intermediate or high-risk disease is associated with a 4-year OS of approximately 50-60%. Stem cell transplant (SCT) has been extensively investigated in DLBCL in both upfront and salvage settings. Several trials have failed to show an OS benefit with upfront autologous SCT in DLBCL or other aggressive NHL. Therefore, upfront SCT is not currently indicated in an unselected population of patients with aggressive NHL. Approximately 10-15% of patients with DLBCL are refractory to primary rituximab-based therapy or progress soon afterwards. An additional one-third of patients relapse within 2-3 years after initial therapy. Outcomes are generally poor in these patients with chemotherapy alone. Patients, who have chemosensitive relapse are generally taken to autologous SCT if they are transplant candidates. Several strategies including the use of radioimmunotherapy and rituximab have been investigated to improve the outcomes of autologous SCT; however, there is no conclusive evidence of their benefits. Conversely, radiotherapy may have a role and should be utilized before or after SCT in patients with bulky or residual disease in non-irradiated areas. Patients with DLBCL who fail multiple chemotherapies or autologous SCT have poor outcomes with a median OS of approximately 10 months in the rituximab era; such patients should be considered for allogeneic SCT or novel clinical trials. Outcomes with allogeneic SCT are better in patients with good performance status, young age, chemosensitive disease and those who relapse >12 months after autologous SCT. Reduced intensity conditioning or nonmyeloablative conditioning may reduce non-relapse mortality associated with allogeneic SCT, possibly expanding its utilization to older patients. Haploidentical transplant and cord blood transplant are emerging techniques that allow alternative donor options. Advances in the field of autologous and allogeneic SCT continue to change the landscape of hematologic malignancies such as DLBCL.
Primary small cell carcinomas of the breast (SCCB) are rare tumors with limited data on outcomes and treatment strategies. Using a population based approach, we aimed to study outcomes of SCCB and determine whether the use of radiation therapy is associated with better survival among patients with SCCB. Using the Surveillance, Epidemiology and End Results (SEER) registry, we identified patients with SCCB between1973 and 2010. We examined the stage specific survival of these patients and compared it to the stage specific survival of small cell lung cancer (SCLC) from the SEER database over the same accrual period. We further analyzed the impact of radiation therapy on overall survival for SCCB patients using a univariate and multivariate approach. A total of 199 patients with primary SCCB with staging were identified during the study period. Eighty-four patients (42%) had localized disease, 77 (39%) had regional disease and 38 (19%) had distant disease. For comparison, 81,933 patients with SCLC were identified. Outcomes were superior for patients with SCCB with localized (150 vs. 16 months, p < 0.01) and regional disease (56 vs. 13 months, p < 0.01), but not distant disease (7 vs. 7 months, p = 0.43). Use of radiation therapy was not associated with a significant difference in OS for patients with either localized (202 vs. 147 months, p = 0.48) or regional (52 vs. 75 months, p = 0.650) disease. SCCB has a more favorable prognosis by stage for localized and regional disease than SCLC. Adjuvant radiation is not associated with an improvement in survival for patients with localized or regional SCCB in this dataset.
Objective: Drugs currently in use for the management of heparin-induced thrombocytopenia (HIT) have their limitations. Several new oral anticoagulants (NOACs) such as dabigatran, rivaroxaban and apixaban may offer attractive therapy options for HIT. Although the clinical data are sparse on this topic, we have summarized the available clinical data, discussed pertinent in-vitro studies and provided the rational and advantages of using NOACs in patients with suspected or confirmed HIT. We have also reviewed the safety and efficacy of these NOACs in patients with HIT based on published literature. Methods: We reviewed all suspected or confirmed HIT cases treated with NOACs and indexed in English language in MEDLINE and EMBASE by July 2015. The bibliography of each relevant article was searched for additional reports. In-vitro studies and other pertinent literature were briefly discussed. Results: A total of 36 HIT patients were treated with the following NOACs: rivaroxaban (50%), dabigatran (36%) and apixaban (14%). Sixty-one percent of patients received argatroban bolus before NOACs and 3% received rivaroxaban after a lack of response with three-day course of fondaparinux. Three percent (n=1) received rivaroxaban after the patient responded to intravenous immunoglobulin for 2 days, following a lack of response to fondaparinux and bilvalirudin. In another 3% (n=1), prophylactic dose of rivaroxaban was used for 21 days and then changed to dabigatran because of persistent thrombocytopenia. All cases responded with early signs of clinical improvement and increase in platelet counts. A follow-up after a median 47 days (range 4- 450) reported no bleeding or thrombotic complications. Conclusion: In this review, all patients with HIT treated with NOACs responded without any bleeding or thrombotic complication. Although the argatroban bolus might have contributed to a response in some patients, response to NOAC alone in other patients and in-vitro studies provide a proof of principle that NOACs can be effective in the management of HIT. Additionally, properties such as rapid onset of action, oral administration, ease of use and a lack of need for monitoring make these drugs attractive options for HIT. However, given several limitations of prior reports, further confirmation of the results are desirable.
Objective: Safety and efficacy of therapeutic agents used for heparin-induced thrombocytopenia are not established in pregnancy. Methods: MEDLINE database was searched in November 2014 to identify all patients who received therapy for HIT during pregnancy. Results: A total of 12 patients with the median age of 28 years (range 21-39) were diagnosed with HIT at the median gestational age of 20 weeks (range 5-34). Clinical probability (4T) score for HIT was high (50%) or intermediate (50%) and associated with thrombosis in 50%. Patients were initially managed with lepirudin (33%), argatroban (25%), danaparoid (25%) or fondaparinux (17%) and ultimately bridged to vitamin K antagonist or maintained on lepirudin. All patients had resolution of HIT. Complications included therapeutic abortion prior to valve replacement for valve thrombosis (8%), preterm delivery (18%) and preeclampsia (8%). Except for one instance of hypoplastic lung related to preterm delivery, none of the other newborns had any complications during delivery. Conclusion: Confirmed cases of HIT in pregnant patients appear to be rare. Within the limits of retrospective analysis, the use of argatroban, danaparoid, fondaparinux and lepirudin may be effective in preventing the thrombotic complications of HIT in pregnancy. The effect of HIT or its therapy on obstetrical complications cannot be determined based on this study since many of the obstetrical complications are common in otherwise healthy pregnancies. Although this study did not identify any fetal teratogenicity except hypoplastic lung related to preterm delivery, small number of cases treated with various therapies precludes any definite conclusion.
Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs 11 months), 1 year OS: 35% vs 47% (p=0.05), 2 year OS: 16% vs 31% (p<0.01), and 5 year OS: 7% vs 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.
Epitheliod hemangioendothelioma (EHE) is a rare tumor of vascular origin. The pleural variant has only been reported around 20 times in English literature. It commonly occurs in older men and carries a poor prognosis with average survival lasting from a few weeks to months. Pleural EHE (PEHE) can be a diagnostic challenge due to its rarity as well as similarities to other pleural and vascular tumors. There is currently no standard treatment for EHE. Due to the rarity of this disease, reaching a final diagnosis is challenging. It′s clinical, radiological, and pathological resemblance to malignant mesothelioma can cause a delay in diagnosis. Special stains such as CD31, CD34, and factor VIII related antigen can help differentiate between the two. Ordering appropriate stains in a timely manner can help avoid misdiagnosing PEHE.
With the advent of widespread tumor genetic profiling, an increased number of mutations with unknown significance are being identified. Often, a glut of uninterpretable findings may confuse the clinician and provide little or inappropriate guidance in therapeutic decision-making. This report describes a method of protein modeling by in silico analysis (ie, using computer simulation) that is easily accessible to the practicing clinician without need for further laboratory analysis, which can potentially serve as a guide in therapeutic decisions based on poorly characterized tumor mutations. An example of this model is given wherein poorly characterized KIT, PDGFRB, and ERBB2 mutations were discovered in a patient with treatment-refractory metastatic transitional cell carcinoma of the renal pelvis. The KIT and PDGFRB mutations were predicted to be pathogenic using in silico analysis, whereas the ERBB2 mutation was predicted to be benign. Based on these findings, the patient was treated with pazopanib and achieved a partial response that lasted for 7.5 months. We propose that in silico analysis be explored as a potential means to further characterize genetic abnormalities found by tumor profiling assays, such as next-generation sequencing.
BCR/ABL negative or atypical chronic myeloid leukemia (CML) is a rare hematologic malignancy with an estimated incidence of 1–2% of BCR/ABL positive CML. Clinical features of BCR/ABL negative CML resembles those of BCR/ABL positive CML but does not have BCR/ABL fusion gene; rearrangement of platelet-derived growth factor receptor (PDGFR)-A, PDGFR-B or FGFR1 is also absent [Vardiman et al. 2008]. BCR/ABL negative CML, however, is associated with mutations in CSF3R (up to 40%), SETBP1 (~10%) and JAK2V617F (~5%) [Gotlib et al. 2013]. KRAS or NRAS mutations may also be common in BCR/ABL negative CML (35% in a multicenter study) [Wang et al. 2014]. In addition, a study utilizing whole-exome sequencing has revealed the presence of ETNK1 mutations in 8–13% of patients with BCR/ABL negative CML [Gambacorti-Passerini et al. 2015]. World Health Organization (WHO) criteria for the diagnosis of BCR/ABL negative CML additionally include the presence of leukocytosis ⩾13 × 109/l with circulating neutrophil precursors ⩾10%, monocytes <10% and minimal basophils (usually <2%); bone marrow hypercellularity with granulocytic proliferation and dysplasia; and blood and bone marrow blast count of <20% [Vardiman et al. 2008]. The rarity of the disease has largely precluded conduction of any prospective study to optimize treatment strategy of BCR/ABL negative CML. Similarly, the mutations associated with the disease were hitherto undiscovered, which prevented identification of therapeutic targets and drug development. Consequently, BCR/ABL negative CML has been managed with palliative therapy such as hydroxyurea, low-dose cytarabine and interferon, which results in a median overall survival (OS) of approximately 2 years in small retrospective studies [Onida et al. 2002; Breccia et al. 2006]. A recent multicenter study demonstrated that BCR/ABL negative CML is distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms and has a worse OS (12 versus 22 months) and acute myeloid leukemia-free survival (11 versus 19 months) [Wang et al. 2014]. A population-based study on the outcomes of BCR/ABL negative CML is lacking. In this population-based study, we utilized the Surveillance, Epidemiology and End Results (SEER) database to analyze the characteristics and outcomes of BCR/ABL negative CML. Such information is useful for patient education and may provide background information for clinical trials in the future.
Background: Anal adenocarcinoma (AA) represents 5% to 10% of anal cancer. Little is known about its natural history and prognosis. Using population-based data, we defined the outcomes of AA relative to other anorectal malignancies. Patients and methods: We analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients ≥ 18 years old with AA, squamous cell carcinoma of the anus (SCCA), and rectal adenocarcinoma (RA) diagnosed between 1990 and 2011. Median overall survival (OS), 1-year, 3-year, 5-year, and 10-year OS were computed using actuarial methods. The log rank test was used to estimate the difference between Kaplan-Meier survival curves. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival, including age, year diagnosed, sex, stage, surgery, and radiation. Results: Of 57,369 cases, 0.8% (n = 462) were patients with AA, 87.8% (n = 50,382) were patients with RA, and 11.4% (n = 6525) were patients with SCCA. The median age for AA was 69 years (range, 20-96 years), 66 years (range, 18-103 years) for RA, and 66 years (range, 14-104 years) for SCCA. The median OS was significantly lower for AA (33 months), compared with SCCA (118 months) and RA (68 months) (P < .01). In multivariate analysis, AA had a worse prognosis compared with SCCA (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.59-0.75; P < .01) and RA (HR, 0.68; 95% CI, 0.61-0.77; P < .01), after adjusting for age, sex, race, stage, grade, radiation, and surgery. There was a strong trend for improved survival among patients who received radical surgery (HR, 0.71; 95% CI, 0.51-1.00; P = .05). Conclusion: AA confers a significantly worse prognosis than SCCA and RA.
Objectives: The efficacy and safety of fondaparinux, an emerging therapeutic option for heparin-induced thrombocytopenia (HIT), remain unclear in cardiac surgery patients with HIT. Methods: Using several search criteria, we reviewed all cases of fondaparinux use in patients who developed HIT after any cardiovascular intervention and were indexed in MEDLINE by August 2014. Based on pre-specified criteria, cases were divided into confirmed HIT, probable HIT and possible HIT. The outcome of fondaparinux use in each group was compared using Chi-square test. Results: Of 43 total cases, 22 had confirmed HIT and 21 had possible HIT. Valve replacement or repair (39%) and heart transplant or ventricular assist device placement (21%) were the most common preceding cardiovascular interventions. Creatinine clearance <30 ml was present in 27% and 52% of confirmed and possible HIT respectively. Overall the risk of new thrombosis and bleeding with fondaparinux were 4.6% and 7% respectively, without any differences in the two subgroups. The majority (86%) of cases improved clinically; of the remainder patients, more cases with possible HIT died than those with confirmed HIT (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding. Conclusion: The risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and comparable to outcomes reported in literature with other agents.
Obesity is an independent risk factor for venous thromboembolism (VTE), and the risk rises further in the postarthroplasty period. Although medication doses often require adjustment for the altered pharmacokinetic profile in obese patients, the efficacy and safety of a fixed-dose regimen of new oral anticoagulants (NOACs) in overweight and obese patients remain unclear. Relevant studies were identified through searches of major databases. Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE in postarthroplasty patients were included. Efficacy and safety outcomes with NOACs in overweight (BMI 25-29 kg/m) and obese (BMI ≥ 30 kg/m) patients were assessed. In five trials involving 16 674 patients, NOACs were found similar to LMWH in preventing VTE and VTE-related deaths after arthroplasty in both overweight and obese patients [odds ratio (OR) 0.64, P = 0.19 and OR 0.76, P = 0.43, respectively]. Similarly, the risk of major or clinically relevant bleeding was similar to LMWH in overweight patient with a trend toward lower bleeding in obese patients (OR 0.83, P = 0.54 and OR 0.44, P = 0.07 respectively). Apixaban was found to be more effective than LMWH in obese patients (OR 0.54, P = 0.01) with the lower dose of dabigatran (150 mg) being less effective (OR 1.81, P = 0.02). Our study suggests that a fixed-dose regimen of dabigatran might be ineffective in severe obesity. However, apixaban at the currently recommended dose seems to be superior to LMWH in obese patients with noninferior bleeding risk.
Association between sarcoidosis and antiphospholipid syndrome (APS) is rare with few reported cases. We sought to systematically review the published cases of APS with sarcoidosis to better characterize the demographics, clinical characteristics, treatment, and the outcome of this association. Systematic electronic search for case report, case series, and related articles published until May 2014 was carried out and relevant data were extracted and analyzed. Four cases of APS with sarcoidosis were identifi ed exclusively in females. These cases were seen in the sixth decade of life. Pulmonary embolism and central retinal artery occlusion were the presenting thrombotic events. All the patients were treated with lifelong anticoagulation with warfarin. During the median follow-up period of 5.5 months, additional thrombotic events were not observed. Although rare, sarcoidosis may be associated with APS. Further reporting of the cases will help to better establish this association, elucidate pathogenesis, and defi ne clinical characteristics and outcomes.
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. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
Studies describing seasonal variations in acute gouty arthritis note seasonal variation, but disagree on timing, with most showing a peak in spring months while others show peaks later in the year. Various theories on the effect of weather and immune system changes on the chronobiology of monosodium urate crystals' equilibrium and precipitation have been proposed. We aimed to shed light on this question by examining the seasonal variation in the incidence of acute gouty arthritis in the USA using a large inpatient database. We used the Nationwide Inpatient Sample (NIS) database to identify patients aged ≥18 years with primarydiagnosis of acute gouty arthritis (International Classification of Diseases, 9th Revision, Clinical Modificationcode 274.01) from 2009-2011 during hospitalization. We used the Edwards recognition and estimation ofcyclic trend method to study the seasonal variation of the incidence of acute gout and z-test to compare theseasonal incidences. A total of 28,172 hospitalizations with primary diagnosis of acute gouty arthritis were reported in the USA from 2009-2011. The peak incidence of acute gout was seen in November (peak/low ratio 1.34, 95 % CI 1.29-1.38, p < 0.05). The highest number of hospitalizations was observed in autumn months while the lowest incidence was observed in spring (28.12 vs. 23.13 %, p < 0.001). The peak incidence of acute gout seems to be in the fall with its peak in the month of November. This seasonality may shed light into the pathophysiology of acute attacks and better management of patients with gout who are at risk of acute attacks.
Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. 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. 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. © The Author(s) 2015.
Early mortality (EM) is all too frequent during induction chemotherapy for acute myeloid leukemia. Older patients shoulder an undue amount of this burden as a result of the inherent biology of their disease and increased comorbidities. EM rates in academic centers have seen a sharp decline over the past 20 years; however, data from population-based registries show that EM rates for the general population have significantly lagged behind. In this review, we analyze the data available on EM in academic centers and the general population, explore recent improvements in supportive care and the use of predictive models, and finally investigate the relationship between case volume and complications during chemotherapy.
Brugada Syndrome (BS) is an inherited ion channelopathy characterized by an electrocardiographic (ECG) pattern of a coved type ST segment elevation in right precordial leads with or without right bundle branch block. A 23-year old male presented with right lower quadrant abdominal pain. Further evaluation revealed a diagnosis of acute appendicitis. The patient developed a febrile episode on second post-operative day of laparoscopic appendectomy. ECG revealed features consistent with BS. Prompt control of temperature in the patient resolved the ST-segment elevation and prevented potentially life-threatening arrhythmias. Febrile episodes in susceptible patients may unmask a concealed BS. Prompt control of temperature is advocated to reduce the risk of life-threatening arrythmias.
Acute megakaryocytic leukemia (AMegL) is a biologically heterogenous subtype of acute myeloid leukemia (AML) that arises from megakaryocytes. Improvements in the accuracy of diagnosing AMegL as well as interest in the molecular analysis of leukemias have led to an increased amount of data available on this rare AML subtype. In this review, we will analyze the diverse molecular features unique to AMegL and how they have influenced the development of novel treatment strategies, including polyploidization. The review will also consider the data available on clinical outcomes in AMegL and how it is a poor individual prognostic factor for AML. Finally, the role of allogeneic hematopoietic stem cell transplant in AMegL will be explored. Copyright © 2015. Published by Elsevier Ltd.
Background: Cancer therapy and outcomes are known to be affected by various demographic features and hospital types. We aimed to identify the characteristics of non-Hodgkin's lymphoma (NHL) patients associated with receipt of care at academic centers. Method: This is a retrospective study of all patients diagnosed with nodal NHL between 2000 and 2011 in the National Cancer Database (NCDB), who received the diagnosis, and all or part of their initial therapy in the reporting hospital (n = 243,436). Characteristics of patients receiving care in academic versus nonacademic centers were compared using the Chi-square test. Results: Approximately 27% received care in academic centers. Patients receiving care in nonacademic centers, compared with academic centers, were more likely to be ⩾60 years (69% versus 58%, p < .0001), White (89% versus 80%, p < .0001) and have lower educational attainment (>12% without high school diploma: 72% versus 69%, p < .0001) and economic status (household income <$49,000: 66% versus 61%, p < 0.0001). Patients receiving care in nonacademic centers were less likely to travel ⩾25 miles (21% versus 26%, p < 0.0001). White patients, compared with non-Whites, were more likely to be ⩾60 years (70% versus <50%, p < 0.0001), which probably explains less care in academic centers. Conclusions: Patients ⩾60 years and those with poorer educational attainment and economic status were less likely to receive care in academic centers. Care in academic centers required a longer commute. Elderly patients frequently have inferior outcomes and may benefit from clinical trials with novel agents and expertise at academic centers.
Although the median survival in polycythemia vera (PV) is 14 years, mortality is higher than age and sex-matched population. We included 3941 PV patients diagnosed between 2000-2010 from Surveillance, Epidemiology and End Results (SEER) 13 registry to determine five-year survival and to calculate the incidence of second primary malignancies (SPM). The actuarial 5 year survival in the overall cohort was 79.5%. The cumulative incidence of SPM was 13.1% at 10 years. SPMs occurred at a standardized incidence ratio (SIR) of 1.29 (95% CI 1.16-1.43; p <0.001) with an absolute excess risk (AER) of 42.49 per 10,000 population. A significantly higher risk was noted for acute myeloid leukemia (SIR 12.24; 95% CI 8.17-17.8; p value <0.001) and chronic myeloid leukemia (SIR 10.66; 95% CI 3.75-19.6; p value <0.001). Patients with PV are at a high risk of SPM and leukemic transformation, which may compromise long-term survival.
To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. 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. 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 Sjögren's 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.
Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.
Prior studies demonstrated that secondary acute promyelocytic leukemia (sAPL) and de novo APL may but not consistently have similar overall survival (OS). We used the Surveillance, Epidemiology, and End Results (SEER) 13 database to compare their OS. Patients with sAPL (n=90), compared to de novo APL (n=1600), were more likely to be older, White and diagnosed after year 2005. Mortality rate at 1 month (28.9% vs. 23.0%, p=0.20) and five-year OS (42% vs. 50%, p=0.24) was similar between sAPL and de novo APL. In a multivariate analysis, sAPL was associated with similar OS as de novo APL (hazard ratio, HR 1.11; 95% confidence interval, CI 0.78-1.58; p=0.546). This population-based study demonstrated no difference in OS or early mortality rate between sAPL and de novo APL. sAPL can be managed very similarly to de novo APL and does not need to be excluded from clinical trials of APL.
We present a case of 56-year-old male with small cell carcinoma of the lung with metastatic tumor nodule of the umbilicus. To our knowledge, this is only the second reported case of small cell lung cancer associated with Sister Mary Joseph's nodule.
Late onset seroma is a rare post-operative complication occurring after various surgeries including thymectomy. Most cases are asymptomatic; however, seromas occurring in the mediastinal cavity may cause compression symptoms including airway compression or cardiac tamponade. We present a 62-year-old male with a history of thymectomy for myasthenia gravis who presented with cardiac tamponade several years ago. Further evaluation revealed a late onset seroma anteriorly compressing the cardiac chambers resulting in tamponade physiology.
Dear Editor, Concerns have been raised regarding the difficulties of communicating uncertainty without increasing fear and paranoia by citing the recent events related to the Ebola virus disease. In today's age, the Internet and social media have become important sources of information for the general public. Concerns have been raised about undue public panic and hysteria being spread through the Internet and social media. Using Google Trends (Google Inc., Mountain View, CA, USA), we examined the temporal trend of search volume for the term “Ebola” from September 1, 2014 to November 6, 2014. We observed four distinct peaks in the search volumes surrounding the news of four cases of Ebola diagnosis in the US [Figure 1]. Analysis of the location of the search query revealed that four of the top five cities being monitored for Ebola were from the US. With the rise of the Internet and social media as the go-to sources of information, it is important for public health agencies to have greater Internet and social media presence, so as to properly disseminate the information (or the lack of it) and prevent undue fear and paranoia. Figure 1 Graph showing four distinct peaks in the search volumes surrounding the news of four cases of Ebola diagnosis in the US
Cigarette smoking is a major risk factor in the progression of atherosclerosis and has been shown to cause endothelial dysfunction, inflammation, and modification of lipid profile. However, its role in the pathogenesis of vulnerable coronary plaque remains unknown. We investigated the relationship between cigarette smoking and the development of vulnerable coronary artery plaque using virtual histology intravascular ultrasound (VH-IVUS). Data from consecutive patients who underwent VH-IVUS assessment of native coronary artery stenosis during clinically indicated cardiac catheterization at our institution over a 2-year period were analyzed. Baseline demographic and study characteristics were collected on all patients. Coronary plaque compositions of the culprit lesion were compared on bivariate and multivariate analysis. We analyzed data on 160 patients with a mean age of 60 ± 11 years. Sixty-nine percent of these patients were admitted for acute coronary syndrome, 31% were smokers, and the mean plaque burden was 66%. On average, 58% of these plaques were fibrous, 19% were fibro-fatty, 18.3% had a necrotic core, and 5.4% were composed of dense calcium. Cigarette smokers had a higher burden of necrotic core (20.7% vs 17.2%; P=.04). On multivariate analysis, cigarette smoking was independently associated with a 4.54% increase in the burden of necrotic core (P=.01). Older age (>80 years) was also a predictor of higher necrotic core burden (P=.02). In conclusion, cigarette smoking is associated with a higher burden of necrotic core in coronary atherosclerotic plaques. This may represent one of the mechanisms for increased cardiovascular events.
Old age (≤65 years), relapsed or refractory disease, and the presence of FMS-like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation are poor prognostic factors in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib have been shown to have a potential role in treating relapsed or refractory AML with FLT3 mutations. In the present report, the use of sorafenib in combination with cytarabine and idarubicin resulted in disease control for 7 months in an older patient with relapsed FLT3-positive AML. This case report and the existing literature indicate that sorafenib has disease activity against relapsed AML with the FLT3-ITD mutation in older patients. Larger multicenter studies should be conducted to confirm these findings, which have the potential to improve outcomes in this high-risk AML subgroup. Copyright © 2015 by the National Comprehensive Cancer Network.
Birth weight of a child is an important indicator of its vulnerability for childhood illness and chances of survival. A large number of infant deaths can be averted by appropriate management of low birth weight babies and prevention of factors associated with low birth weight. The prevalence of low birth weight babies in Nepal is estimated to be about 12-32%.Our study aimed at identifying major determinants of low birth weight among term babies in Nepal. A hospital-based retrospective case control study was conducted in maternity ward of Tribhuvan University Teaching Hospital from February to July 2011. A total of 155 LBW babies and 310 controls were included in the study. Mothers admitted to maternity ward during the study period were interviewed, medical records were assessed and anthropometric measurements were done. Risk factors, broadly classified into proximal and distal factors, were assessed for any association with birth of low-birth weight babies. Regression analysis revealed that a history of premature delivery (adjusted odds ratio; aOR5.24, CI 1.05-26.28), hard physical work during pregnancy (aOR1.48, CI 0.97-2.26), younger age of mother (aOR1.98, CI 1.15-3.41), mothers with haemoglobin level less than 11gm/dl (aOR0.51, CI0.24-1.07) and lack of consumption of nutritious food during pregnancy (aOR1.99, CI 1.28-3.10) were significantly associated with the birth of LBW babies. These factors should be addressed with appropriate measures so as to decrease the prevalence of low birth weight among term babies in Nepal.
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. 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 I statistic. 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. 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.
Transcatheter heart valve (THV) embolization is a rare but serious complication of transcatheter aortic valve implantation. Studies, including case reports, case series, and original reports published between 2002 and 2013, with regard to THV embolization were identified with a systemic electronic search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A total of 19 publications describing 71 patients were identified. Most patients (64%) were men, with a mean age of 80 ± 6 years and a mean logistic European System for Cardiac Operative Risk Evaluation score of 22.4 ± 9.3%. Balloon-expandable valves were used in 72% of the patients. The reported transcatheter aortic valve replacement access site was transfemoral in 80% of patients. Most cases (90%) occurred <1 hour after implantation, whereas 10% had late embolization (range 4 hours to 43 days). The most common site of embolization was the ascending aorta (38%), followed by the left ventricle (31%), descending aorta (23%), and aortic arch (8%). Open-heart surgery was required in 28% for valve retrieval and replacement. The 30-day stroke and mortality rates were 11% and 17%, respectively. Ventricular embolization and urgent conversion to open-heart surgery were significantly associated with death during hospitalization (p = 0.017 and p = 0.029, respectively). Likely causes of embolization were identified in 59 patients, with positioning error as the most commonly reported (47%), followed by pacing error (13%). In conclusion, THV embolization occurred early after transcatheter aortic valve implantation. The ascending aorta was the most common site of embolization. Higher 30-day stroke and mortality rates were associated with THV embolization compared with most published series of transcatheter aortic valve implantation outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.
Several studies have reported excellent long-term overall survival (OS) of patients with hairy cell leukemia (HCL) without racial disparity. Studies in other cancers have demonstrated worse mortality among African American (AA) individuals. We used the Surveillance, Epidemiology, and End Results 18 database to identify HCL patients diagnosed between 1978 and 2011. Kaplan-Meier curves were plotted to estimate OS. Univariate analysis using the life table method and multivariate Cox regression model were used to determine the independent effect of race on OS. The study population included 78% men and had a median age of 56 years. Race included 93% white, 3.5% Asian/Pacific Islander, and 3.5% AA. The 10-year OS was significantly less for AA as compared with white and Asian/Pacific Islander individuals (54% vs. 72% vs. 75%; P < .001). A Kaplan-Meier survival curve showed a significantly worse OS for AA versus other races (P < .001). In a multivariate analysis, AA race remained an independent predictor for a worse OS (hazard ratio 1.77; 95% confidence interval, 1.30-2.40; P < .001) after adjusting for age, sex, year of diagnosis, and marital status. In this population-based study, only half of AA patients but more than two-thirds of HCL patients from other racial groups were alive at 10 years. Such drastic racial differences in OS of HCL patients at the population level mandates further evaluation of the contributory biological, socioeconomic, health system, and other factors. Understanding and overcoming such racial disparities might close the racial differences in OS of this potentially curable disease. Copyright © 2015 Elsevier Inc. All rights reserved.
Patients with a history of heparin-induced thrombocytopenia (HIT), who require subsequent anticoagulation, have limited options. Rechallenge with unfractionated heparin (UFH) has been reported but may be associated with a risk of recurrence of HIT. The objective of this study was to determine the safety of heparin reexposure in patients with a history of HIT. Using several search terms, all cases of heparin reexposure in patients with HIT indexed in MEDLINE (English language only) by June 2014 were reviewed. The bibliography of each relevant article was searched for additional reports. In cases of multiple reexposures, each reexposure was identified as a separate instance of reexposure during analysis. A total of 136 patients with a history of HIT had 141 instances of heparin reexposure. Cardiac (76%) and vascular surgeries (11%) were the most common indications. Antiplatelet factor 4/heparin antibodies were positive in 63% of evaluable cases before reexposure. Preexposure plasma exchange (11%) and postexposure nonheparin anticoagulants (63%) were frequently utilized. Complications with heparin reexposure included recurrence of HIT (2.1%, 95% confidence interval 0.73%-6.07%) and bleeding (2.1%). Intraoperative heparin reexposure in patients with a history of HIT has a small risk of developing HIT recurrence. The use of preexposure plasma exchange in patients with positive antiplatelet factor 4/heparin antibody and postexposure nonheparin anticoagulants arguably may have reduced the risk of recurrence of HIT. © The Author(s) 2015.
Diabetes mellitus (DM) is a pro-thrombotic state with enhanced thrombin generation and platelet reactivity. For most patients undergoing percutaneous coronary intervention (PCI), bivalirudin demonstrates efficacy comparable with that of heparin and glycoprotein IIb/IIIa inhibitors (GPIs). Yet, because of their pro-thrombotic condition, we hypothesized that patients with DM may benefit from more aggressive dual antithrombin and antiplatelet therapy. The aim of this paper was to provide a systematic review comparing outcomes of PCI with bivalirudin versus heparin plus GPI in patients with DM using meta-analytical techniques. Eligible studies needed to have reported a subgroup analysis of outcomes among diabetic patients. Six trials comprising 5924 diabetic patients were eligible. At 30 days, bivalirudin was associated with a reduction in net adverse cardiac events [relative risk (RR) 0.81, 95 % confidence interval (CI) 0.70-0.93, p = 0.002] and major bleeds (RR 0.68, 95 % CI 0.49-0.95; p = 0.02), with no difference in composite ischemia (RR 0.92, 95 % CI 0.74-1.14; p = 0.43) or mortality (RR 0.71, 95 % CI 0.45-1.13; p = 0.15). At 1 year, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.73, 95 % CI 0.54-1.00, p = 0.05) despite similar composite ischemia (RR 1.02, 95 % CI 0.56-1.21, p = 0.811). In conclusion, thrombin inhibition with bivalirudin alone was associated with reduced 30-day major bleeding and 1-year all-cause mortality compared with heparin plus GPI in diabetic patients undergoing PCI.
Waldenstrom’s macroglobulinemia (WM) is an uncommon indolent B cell non-Hodgkin lymphoma (NHL) characterized by the presence of bone marrow infiltration of lymphoplasmacytic cells and immunoglobulin M monoclonal gammopathy . Previous small-scale studies have suggested an increased incidence of second primary malignancies (SPMs) including diffuse large B cell lymphoma and other hematological malignancies in patients with WM [1, 2]. We aimed to utilize the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to analyze the risk of SPMs in adult patients with WM.We identified all patients with WM diagnosed during January 1992 to December 2010 from the SEER 13 database using International Classification of Diseases for Oncology, third edition (ICD-O-3) code 9761/3 . We excluded cases diagnosed at autopsy and those who did not have a follow-up. Using the Warren and Gates criteria as modified by NCI , SPM was defined as a metachronous malignancy d ...
The role of thrombin in vascular physiology and pathophysiology continues to impact our understanding of many cellular processes and systems including the function of platelets, endothelial cells, smooth muscle cells, leukocytes and the regulation of the coagulation cascade. Recent acute coronary syndrome clinical trial results that have compared the use of parenteral or oral anticoagulants versus or in combination with anti-platelet agents have forced a reexamination of the importance of thrombin activity in influencing patient outcomes, particularly in the area of secondary prevention. The debate of the need to include oral anticoagulation as a concomitant or replacement therapy to an antiplatelet regimen as a means to improve patient outcomes requires further examination and larger prospective clinical trials. Copyright © 2015. Published by Elsevier Ltd.
The Southwest Oncology Group (SWOG) described the expected early mortality rate (EMR) for patients with non-M3 AML by age enrolled in clinical trials, but it is unclear how generalizable this data is. We sought to compare SWOG's reported EMR to that of the general population by utilizing the case listing session of SEER 18 matched to the accrual periods of the SWOG studies. 26,272 patients were identified within SEER compared to 968 in the SWOG cohort with mortality data. The EMR was 26.7% (7022 events) in the SEER cohort versus 12.2% (116) in the SWOG cohort. The EMR was higher in the SEER cohort in every studied age group and definition of EMR. Stepwise logistic regression analysis identified increasing age, black race (OR 1.15, CI 1.03-1.29, p<0.01), and monocytic differentiation (OR 1.55, CI 1.27-1.89, p<0.01) as predictors of higher EMR. This study demonstrates that EMR in patients with non-M3 AML is higher in the general patient population than reported in SWOG clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.
Blood Cancer Journal is a peer-reviewed, open access online journal publishing pre-clinical and clinical work in the field of hematology with ramifications into translational biology research down to new therapies
Purpose Febrile neutropenia is a potentially life threatening complication of breast cancer chemotherapy associated with a significant amount of morbidity, mortality, and health care resource utilization. Recent data on the national estimates of mortality rate, length of stay, and health care costs among the subpopulation of febrile neutropenia admissions with breast cancer are lacking. Methods We used the Nationwide Inpatient Sample database to identify patients with breast cancer hospitalized for febrile neutropenia from 2009 to 2011. We derived data on inhospital mortality rate, length of stay, and mean health care costs and compared it with previous studies. Results The average inhospital mortality rate during 2009–2011 was 2.6 % (n = 685). Advanced age (≥65 years) was found to be significantly associated with a higher odds of mortality (4.4 vs 1.7 %, OR 2.7, 95 % CI 2.3–3.1, p
Background: Primary angiosarcoma of the breast (PAOB) is rare and institutional series have provided conflicting data on the effect of grade on prognosis. Patients and methods: Using a case listing session of Surveillance, Epidemiology, and End Results (SEER) 18 (1973-2010) we examined outcomes for patients with PAOB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007, and GraphPad Prism 6. Comparisons were made using the Fisher exact test and log rank test (Mantel-Cox); P values were 2-sided. Results: Two hundred twenty-six women with PAOB were identified; median age was 49 (range, 15-107) years and 82% (185) were white. Seventy-two percent (162) had localized disease, 15% (34) regional disease, 7% (16) distant disease, and 6% (14) had unknown staging. Fourteen percent (32) had Grade 1, 24% (55) Grade 2, 30% (68) Grade 3 disease, and grade was unknown in 32% (72) of patients. Median overall survival (OS) for patients with localized, regional, and distant disease was 172, 24, and 16 months, respectively (P < .001). Median OS for patients with localized Grade 1 and 2 disease was not reached versus 36 months for Grade 3 disease (P < .001); 3-year OS was 89% (78) versus 47% (32). There was a strong trend for patients with Grade 3 disease to undergo mastectomy (44%, n = 30 vs. 23%, n = 20; P = .070) and 24% (55) of all patients received radiation. Radiation did not improve survival for localized Grade 1 and 2 disease (P = .676), or Grade 3 disease (P = .589); surgery and grade subgroups were too small for meaningful comparisons regarding radiation. Conclusion: Histologic grade is a significant predictor of survival for patients with localized PAOB. Regardless of grade, adjuvant radiation did not confer a survival benefit for patients with localized disease.
Objective Optimal duration of dual antiplatelet therapy (DAPT), defined as use of both aspirin and a P2Y12 receptor inhibitor, after implantation of drug eluting stents (DES) is still subject of ongoing debate. We systematically review efficacy and safety of 6 months versus 12 months DAPT after implantation of DES. Methods PubMed, Scopus, Cochrane, and databases were searched for studies published until 30th November 2013. The studies were limited to randomized clinical trials. Independent observers abstracted the data on outcomes, characteristics, and qualities of studies included. Random effect model was employed for meta-analysis. Heterogeneity of studies included was analyzed using I-2 statistics. ResultsIn four randomized clinical trials published involving 8,163 patients with DES, 4,081 patients were randomized to shorter and 4,082 patients to longer duration DAPT. The P2Y12 receptor inhibitor used in all four studies was clopidogrel. Longer duration of DAPT did not reduce risk of all cause mortality (pooled OR 0.89, 95% CI 0.67-1.17, P=0.4, I-2=0%), myocardial infarction (pooled OR 1.16, 95% CI 0.85-1.57, P=0.35, I-2=0%) cardiac death (pooled OR 0.88, 95% CI 0.61-1.25, P=0.47, I-2=0%), stent thrombosis (pooled OR 1.29, 95% CI 0.76-2.21, P=0.35, I-2=0%) or cerebrovascular accidents (pooled OR 0.73, 95% CI 0.41-1.27, P=0.26, I-2=0%). Longer duration of DAPT was associated with increased risk of TIMI major bleeding (pooled OR 0.51, 95% CI 0.29-0.89, P=0.02, I-2=0%). Conclusion There was no difference in efficacy outcomes between 6 months of DAPT and 12 months of DAPT in patients with coronary artery disease and DES implantation. Moreover, longer duration of DAPT is associated with increased risk of bleeding complications. (c) 2014 Wiley Periodicals, Inc.
- Jan 2015
Pericardium is a common site for neoplastic involvement that occursdue to direct local invasion by malignancy or metastatic spread via thelymphatics or bloodstream. Malignant involvement of the pericardium oroccasionally treatment of malignancy can cause pericardial effusion.Pericardial effusion can be asymptomatic or cause chest discomfort,dyspnea, tachycardia, hypotension and cardiogenic shock, with increasingamount of fluid. Electrocardiogram, chest x-ray, echocardiography andcardiac catheterization can all aid in diagnosis of pericardial effusion butpericardial fluid and biopsy with histologic and cytologic analysis isrequired for diagnosis on underlying malignancy.Prognosis for patients with malignant pericardial effusion isprimarily dictated by the underlying disease. Since outcome is usuallypoor, goal of treatment is palliation of symptoms and prevention ofrecurrence of effusion. Pericardiocentesis is useful for prevention andtreatment of cardiac tamponade but inadequate in itself because of a highrate of recurrence even when followed by extended tube drainage.Pericardial sclerosis has good success rate but high rate of complicationssuch as arrhythmias and pericardial constriction. This makes it lesspreferred option than pericardial drainage, however, it may be useful forthose, who are unfit for any surgical intervention. Cisplatin andtetracycline are most widely used sclerosing agents. Confirmed malignantpericardial effusion can be treated with relatively high doses ofintrapericardial chemotherapy with minimal systemic side effects but thedisease is restricted to only pericardium on a rare occasion. Indisseminated malignancy, intrapericardial chemotherapy can improvesymptoms of a hemodynamically significant effusion but other moreeffective and inexpensive treatment modalities may also be available.Surgical treatment appears to result in better clinical outcome butselection of healthier patients may be confounding the results. Pericardialfenestration is the most commonly performed surgical procedure thatemploys subxiphoid, video-assisted thoracic surgery (VATS) and minithoracotomyapproaches. This has an overall success rate of 93%,recurrence rate of 6% and perioperative complication rate of 4%.Subxiphoid approach can be performed under local anesthesia and doesnot require single-lung ventilation procedure unlike during VATS.Pericardiectomy is performed using VATS and is the second mostcommonly performed surgical procedure with almost 100% success ratebut with a perioperative complication rate of up to 10%. Pericardioperitonealshunt as a treatment of malignant pericardial effusion has beenreported as a safe and effective treatment but the small study populationmandates further confirmatory studies. Percutaneous balloonpericardiotomy has good outcome, can be performed under localanesthesia and allows early discharge. It is useful in poor surgicalcandidates but has higher complications (up to 32%), which include a riskof pleural effusion, fever and pneumothorax. Outcomes tend to be betterin the high-volume centers.In conclusion, there is a paucity of high-quality studies and a lack oftherapeutic options with significant impact on survival of patients withmalignant pericardial effusion. Safe, cost effective and durable palliativetreatment as well as treatment strategies that can prolong survivalmeaningfully are needed