Sri Lakshmi Hyndavi Yeruva

E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer

Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestane in patients with HR-positive advanced breast cancer with disease progression after prior non-steroidal aromatase inhibitor (AI). These results prompted the development of E2112, a phase III registration trial which is investigating entinostat/placebo in combination with exemestane in patients with locally advanced or metastatic breast cancer who have experienced disease progression after a non-steroidal AI. E2112 aims to validate the preclinical and clinical findings supporting the role of HDAC inhibitors in overcoming resistance to endocrine therapy in breast cancer, and ultimately improve outcomes for patients with advanced breast cancer.

Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay

Abstract Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

Pernicious Anemia with Autoimmune Hemolytic Anemia: A Case Report and Literature Review.

Pernicious anemia is a common cause of vitamin B12 deficiency. Here, we discuss a case of a young woman who presented with severe anemia along with a history of iron deficiency anemia. After a review of her clinical presentation and laboratory data, we identified an autoimmune hemolytic anemia and a concomitant pernicious anemia. The concurrence of both these hematological diagnoses in a patient is rare.

Adult ADHD Medications and Their Cardiovascular Implications

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological disorder exhibited by difficulty maintaining attention, as well as hyperactivity and impulsive behavior. Central nervous system (CNS) stimulants are the first line of treatment for ADHD. With the increase in number of adults on CNS stimulants, the question that arises is how well do we understand the long-term cardiovascular effects of these drugs. There has been increasing concern that adults with ADHD are at greater risk for developing adverse cardiovascular events such as sudden death, myocardial infarction, and stroke as compared to pediatric population. Cardiovascular response attributed to ADHD medication has mainly been observed in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events like acute myocardial infarction (AMI), arrhythmia, and cardiomyopathy and its long-term sequelae. We present a unique case of AMI in an adult taking Adderall (mixed amphetamine salts) and briefly discuss the literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD.

Amphetamine Abuse Related Acute Myocardial Infarction

Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI), heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED) with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary.

Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer.

Aromatase inhibitors (AIs) are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.

A novel use of early radiation therapy in the treatment of hyperbilirubinemia in a patient with primary hepatic lymphoma and chronic hepatitis C.

Lymphomas arising in the liver are extremely rare. Here, we describe a case of Hepatitis C virus infection with primary hepatic lymphoma (PHL) presenting with hyperbilirubinemia. A 45-year-old African American male presented with abdominal pain, pruritus, and itching for two days. CT of abdomen and pelvis with contrast showed numerous masses in the liver. The liver biopsy was consistent with diffuse large B cell lymphoma (DLBCL). Conventional chemotherapy was avoided initially because of hyperbilirubinemia. Hence, radiation therapy was given initially to reduce his bilirubin levels and tumor size. The patient was able to complete six cycles of rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) chemotherapy and achieved a complete response verified by positron emission tomography-computed tomography (PET-CT). PHL should be considered when there are numerous space occupying liver lesions seen on imaging. Hyperbilirubinemia may be a reason for delay in treatment for some of these patients. Hence, the role of radiation therapy prior to treatment with R-CHOP is an alternative to management for stage IV diffuse large B cell lymphoma.

Early Cardiac Tamponade in a Patient with Postsurgical Hypothyroidism

Pericardial effusion is a common cardiac manifestation of hypothyroidism, but effusion resulting in cardiac tamponade is extremely rare. We present a case of a 56-year-old African American woman with slurred speech and altered mental status that was initially suspected to have stroke. Her chest X-ray revealed cardiomegaly and subsequent echocardiogram showed a large pericardial effusion with echocardiographic evidence of cardiac tamponade. Clinically, patient did not have pulsus paradoxus or hypotension. Further questioning revealed a history of total surgical thyroidectomy and noncompliance with thyroid replacement therapy. Pericardiocentesis was performed promptly and thyroxine replacement therapy was started. Thereafter, her mental status improved significantly. The management of pericardial effusion associated with hypothyroidism varies depending on size of effusion and hemodynamic stability of the patient. The management strategy ranges from conservative management with close monitoring and thyroxine replacement to pericardiocentesis or creation of a pericardial window.

Complete Response to Single-agent Palbociclib in Metastatic Breast Cancer: A Case Report

Introduction Breast cancer is the most common malignancy diagnosed in women, and it is the second leading cause of cancer-related death in the United States. Estrogen receptor-positive (ERþ) and progesterone receptor-positive (PRþ), human epidermal growth factor receptor 2-negative (HER2 ) is the most common subtype of breast cancer. Although most patients in Western societies present with early stage breast cancer and will likely survive their disease, some patients suffer a recurrence, and other present with de novo metastatic disease. Once metastatic, breast cancer is rarely cured, with a 5-year survival rate of only 24%. Endocrine manipulations are an integral part of treatment of patients with advanced ERþ/PRþ breast cancer. Unfortunately, patients with metastatic disease will eventually suffer disease progression despite endocrine therapy either because of primary or secondary resistance. Depending on initial response, most women will be transitioned to chemotherapy following 1 to 3 lines of endocrine therapy. In contrast to endocrine therapy, chemotherapy is associated with many adverse effects, and, once initiated, women are expected to have more frequent office visits and laboratory tests. Therefore, there has been a search to improve the efficacy of endocrine therapy to delay the administration of chemotherapy and to maintain the quality of life of these patients.

Imported Malaria over Fifteen Years in an Inner City Teaching Hospital of Washington DC

As endemic malaria is not commonly seen in the United States, most of the cases diagnosed and reported are associated with travel to and from the endemic places of malaria. As the number of imported cases of malaria has been increasing since 1973, it is important to look into these cases to study the morbidity and mortality associated with this disease in the United States. In this study, we would like to share our experience in diagnosing and treating these patients at our institution. We did a retrospective chart review of 37 cases with a documented history of imported malaria from 1998 to 2012. Among them, 16 patients had complicated malaria during that study period, with a mean length of hospital stay of 3.5 days. Most common place of travel was Africa, and chemoprophylaxis was taken by only 11% of patients. Travel history plays a critical role in suspecting the diagnosis and in initiating prompt treatment.