Sumit Dahal

Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura

Objectives: Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. Methods: Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. Results: A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159 mmHg (range 123–190 mmHg). All had prominent renal dysfunction (mean creatinine of 5.2 mg/dl, range 1.7–13 mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60 × 103/µl, range 12–131 × 103/µl). Reported cases (n = 9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18–96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. Conclusion: Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.

Secondary acute myeloid leukemia in survivors of Hodgkin lymphoma

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.

Systemic therapy in stage IV pancreatic cancer: A population-based analysis using the National Cancer Data Base

Background: Pancreatic cancer accounts for approximately 7% of all cancer deaths. More than half of all pancreatic cancers are stage IV at diagnosis, where systemic chemotherapy is used with the goal of life prolongation as well as palliation. The patient characteristics and health system factors that drive the use of systemic therapy are unknown. Method: This is a retrospective study of stage IV pancreatic cancer patients (n = 140,210) diagnosed between 2000 and 2011 in the NCDB. NCDB contains approximately 70% of new cancer diagnosis from more than 1500 accredited cancer programs in the United States and Puerto Rico. Chi-squared test was used to determine any differences in characteristics of patients who did or did not receive systemic therapy. Results: Our study demonstrated that only 49.1% of stage IV pancreatic cancer patients received systemic therapy. The use of systemic therapy is significantly lower in female, African American/Hispanic, patients older than 40 years, those without insurance or with Medicare and Medicaid, higher Charlson Comorbidity Score, poor economic and educational status and in nonacademic centers. Conclusions: This is the largest study to evaluate the determinants of systemic therapy use in stage IV pancreatic cancer. The use of systemic therapy was significantly lower in patients older than 40 years, lower educational status, nonprivate insurance and with higher Charlson Comorbidity Scores. In addition, the use of systemic therapy was lower with female sex, African Americans/Hispanic, and lower socio-economic status. Understanding the barriers in the use of systemic therapy as well as appropriate utilization of systemic therapy can both optimize cancer care.

Chemotherapy use in stage III colon cancer: a National Cancer Database analysis.

Background: Although adjuvant chemotherapy in stage III colon cancer improves overall survival, prior studies have shown that it is underused. We analyzed different factors that may influence its use. Methods: This is a retrospective study of stage III colon cancer patients (n = 207,718) diagnosed between 2000 and 2011 in the National Cancer Data Base (NCDB). The NCDB contains ~70% of new cancer diagnosis from >1500 American College of Surgeons accredited cancer programs in the United States and Puerto Rico. The chi-squared test was used to determine any difference in characteristics of patients who did or did not receive chemotherapy. Results: A total of 35% of all stage III colon cancer patients, and 38% of stage III cases undergoing surgery, did not receive adjuvant chemotherapy. The use of chemotherapy had increased in recent years (64% in 2007–2011 versus 59% in 2000–2002; p < 0.0001). Its use was lower in whites (61%), females (60%), patients ⩾60 years (55%), patients with one or more comorbidities (55%), nonacademic centers (62%), those with medicare insurance (52%), lower education (61%) and income levels (59%, all p < 0.0001). The nonwhite and uninsured were more likely to be <60 years old. Conclusion: More than one-third did not receive adjuvant chemotherapy, although its use has increased in more recent years. Age was one of the most important determinants of chemotherapy use, which may explain higher rates in nonwhite and uninsured. In addition to patient characteristics, race, gender and socioeconomic factors influence chemotherapy use. These findings have important implications for healthcare reform.

Fondaparinux for Management of Heparin-induced Thrombocytopenia after Cardiovascular Intervention: A Systematic Review.

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, similar percentage of cases with possible HIT and confirmed HIT died (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding. CONCLUSION Within the limitations of this study, the risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and largely comparable to outcomes reported in literature with other agents.

Hyperacute liver injury following intravenous fluconazole: A rare case of dose-independent hepatotoxicity

Fluconazole is a triazole antifungal medication used in the treatment of various fungal infections. It is available in both oral and parenteral formulations. Liver damage has been reported with fluconazole use, but most commonly it is benign elevated liver transaminases. Acute liver failure (ALF) in fluconazole use is rare, with cases being reported sporadically in literature and large cohorts describing incidence rates of acute liver injury ranging from 0.0 to 31.6/10,000 patients. We present a case of a 45-year-old African-American male with no history of liver disease who presented with superficial candidiasis and superimposed bacterial cellulitis. He was subsequently started on intravenous fluconazole and clindamycin. Shortly after he developed ALF and a drug-induced liver injury (DILI) was suspected. Fluconazole was stopped, and the clinical picture improved shortly afterward, leading to a diagnosis of fluconazole-induced ALF. Patient underwent laboratory and clinical evaluation to exclude competing etiologies of liver injury as well as a standardized assessment for causality and disease severity such as Roussel Uclaf Causality Assessment Method/Council for International Organizations of Medical Sciences score, which concluded a “Highly Probable” DILI, and a Naranjo score identifying adverse drug reaction (ADR) which concluded a “Definite ADR.” Due to the severity of ALF and the routine use of fluconazole in clinical practice, clinicians should be aware that fluconazole can be a causative agent of ALF, even in low-risk populations.

Demographic and other characteristics of nodal non-Hodgkin's lymphoma managed in academic versus non-academic centers.

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 <

Myocardial Infarction as an Early Presentation in Thrombotic Thrombocytopenic Purpura: A Rare Case Series

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.

Hypereosinophilic Syndrome Complicated by Eosinophilic Myocarditis With Dramatic Response to Steroid

Renal and neurological involvements are frequently seen in thrombotic thrombocytopenic purpura (TTP). Cardiac involvement, however, has been rarely reported. In this article, we present 2 cases of myocardial infarction in patients with TTP. In the first case, a young man presented with non–ST-segment elevation myocardial infarction that resolved promptly with plasmapheresis. The second patient developed ST-segment elevation myocardial infarction early in the course of the disease and died before plasmapheresis could be initiated. Hence, a high degree of suspicion with prompt diagnosis and treatment is needed to prevent mortality associated with cardiac involvement in TTP.

Drug-Induced Liver Injury: An Institutional Case Series and Review of Literature:

Introduction. Eosinophilic myocarditis is an infiltrative disease that affects the myocardium leading to various presentations. It can be precipitated by medications, helminthiasis, or hypereosinophilic syndrome. Case. We present the case of a young, male patient who presented with palpitations and dyspnea and was found to have heart failure with reduced ejection fracture of 12%. His past medical history was significant for recent lung problem treated with steroids. Based on his history and laboratory findings, he was started on intravenous steroids for treatment of eosinophilic myocarditis. Within 3 days, his ejection fracture improved to 35%. Conclusion. Given the nonspecific clinical presentations, mimicking other diseases, high index of suspicion is warranted to diagnose eosinophilic myocarditis. This is crucial as early detection and treatment with steroids can lead to a dramatic response.