Delayed Diagnosis of Cardiac Amyloidosis Secondary to Multiple Myeloma.

Cardiac amyloidosis is a rare condition with only 2,500 new cases reported yearly in the United States of America (USA). The prognosis of cardiac amyloidosis is particularly grim. The median survival is 6 months from onset of congestive heart failure (CHF) symptoms. CHF is a common presentation as the second leading cause of hospitalization in the senile population in the USA. We report a case of an 83-year-old man who presented with the classic symptoms of CHF including bilateral lower extremity edema, shortness of breath, and weight gain. Upon further workup, an echocardiogram revealed strain patterns suggestive of cardiac amyloidosis and bone marrow biopsy confirmed the diagnosis of multiple myeloma. Unfortunately, despite starting treatment with steroids and chemotherapy, the patient succumbed to his condition in a matter of weeks. We report this case to highlight that cardiac amyloidosis secondary to multiple myeloma can present in the form of new onset, quickly deteriorating CHF long before any classic multiple myeloma symptoms manifest.

Acute kidney injury secondary to thrombotic microangiopathy associated with idiopathic hypereosinophilic syndrome: a case report and review of the literature.

BACKGROUND: Renal involvement in idiopathic hypereosinophilic syndrome is uncommon. The mechanism of kidney damage can be explained as occurring via two distinct pathways: (1) thromboembolic ischemic changes secondary to endocardial disruption mediated by eosinophilic cytotoxicity to the myocardium and (2) direct eosinophilic cytotoxic effect to the kidney. CASE PRESENTATION: We present a case of a 63-year-old Caucasian man who presented to our hospital with 2 weeks of progressively generalized weakness. He was diagnosed with idiopathic hypereosinophilic syndrome with multiorgan involvement and acute kidney injury with biopsy-proven thrombotic microangiopathy. Full remission was achieved after 8 weeks of corticosteroid therapy. CONCLUSION: Further studies are needed to investigate if age and absence of frank thrombocytopenia can serve as a prognostic feature of idiopathic hypereosinophilic syndrome, as seen in this case.

Characterization of purine-rich element binding protein B as a novel biomarker in acute myelogenous leukemia prognostication.

Acute myelogenous leukemia (AML) is an aggressive hematologic cancer characterized by infiltration of proliferative, clonal, abnormally differentiated cells of myeloid lineage in the bone marrow and blood. Malignant cells in AML often exhibit chromosomal and other genetic or epigenetic abnormalities that are useful in prognostic risk assessment. In this study, the relative expression and novel single-stranded DNA (ssDNA) binding function of purine-rich element binding proteins A and B (Purα and Purß) were systematically evaluated in established leukemia cell lines and in lineage committed myeloid cells isolated from patients diagnosed with a hematologic malignancy. Western blotting revealed that Purα and Purß are markedly elevated in CD33+ /CD66b+ cells from AML patients compared to healthy subjects and to patients with other types of myeloid cell disorders. Results of in silico database analysis of PURA and PURB mRNA expression during hematopoiesis in conjunction with the quantitative immunoassay of the ssDNA-binding activities of Purα and Purß in transformed leukocyte cell lines pointed to Purß as the more distinguishing biomarker of myeloid cell differentiation status. Purß ssDNA-binding activity was significantly increased in myeloid cells from AML patients but not from individuals with other myeloid-related diseases. The highest levels of Purß activity were detected in myeloid cells from primary AML patients and from AML patients displaying other risk factors forecasting a poor prognosis. Collectively, these findings suggest that the enhanced ssDNA-binding activity of Purß in transformed myeloid cells may serve as a unique and measurable phenotypic trait for improving prognostic risk stratification in AML.

Epigenetic landscape of acute myelogenous leukemia--moving toward personalized medicine.

Acute myeloid leukemia (AML) is an aggressive hematologic cancer that is characterized by accumulation of immature myeloid cells in the blood and bone marrow. The malignant cells in AML have reduced capacity to mature fully, and often exhibit chromosomal abnormalities, defects in cell signaling, and abnormal cell cycle control. Genetic and epigenetic changes are implicated in the onset and progression of AML. While progress has been made in using genetic and epigenetic changes as prognostic features of AML, these findings have not yet been effectively translated into novel treatment strategies. Disappointingly, rates of recurrence in AML remain high and overall survival is poor. Research strategies should focus on developing a comprehensive landscape of genetic and epigenetic changes in individual patients with AML to expand the clinicians' therapeutic armamentarium and to individualize and optimize treatment.

Recent advances and novel agents for FLT3 mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) is a devastating hematologic malignancy that affects both older adults as well as children. Treatments available for AML largely depend on cytotoxic agents and often the only curative option is an allogeneic bone marrow transplant, an option limited to young persons and associated with high morbidity and mortality. There is an urgent need for the identification of new myeloid targets and an understanding of the key genetic mutations involved in disease progression and prognosis. One such mutation is the internal tandem duplication (ITD) in the FMS-like tyrosine kinase receptor-3 (FLT3) gene which confers an inferior outcome that is attributed to a higher relapse rate. In this review, we evaluate the FLT3-ITD mutation and discuss the recent data regarding emerging approaches using FLT3 inhibitors for the treatment of AML.

Use of conjugated estrogens in life-threatening gastrointestinal bleeding in hemodialysis patients--a review.

Hormonal agents (estrogen and progesterone) are being studied for their use in bleeding. This observance was initially explored in a patient with hereditary hemorrhagic telangiectasia (HHT) with epistaxis had variation in bleeding depending on her menstrual cycles.(1) Thus, hormonal therapy was initially used in patients with HHT to control episodes of epistaxis.(2) The literature on hormonal therapy in patients with life-threatening bleeding from gastrointestinal (GI) lesions is very limited. There are a few clinical trials in patients with chronic bleeds. However, no definite guidelines exist on their use in life-threatening GI bleeding in patients with uremia. Here, we describe a case with a life-threatening GI bleeding requiring multiple endoscopies and intensive care unit stay that responded to conjugated estrogens. We have done extensive research on English medical literature on PubMed and Google Scholar on the use of hormonal therapy for GI bleeding in patients with renal failure, and here we present the data as a review.

Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis.

BACKGROUND: Liposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials. METHODS: We conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated. RESULTS: We identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2220 patients, of which1112 patients were treated with liposomal formulations and 1108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF(OR 0.34, 95% CI, 0.24-0.47), alopecia (OR 0.0.25, 95% CI, 0.0.10-0.62), neutropenia (OR 0.62, 95% CI, 0.45- 0.85),(OR 0.89, 95% CI, 0.71-1.125), and thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25). The incidence of PPE was similar in both arms (OR 1.08, 95% CI, 0.11- 10.30). CONCLUSIONS: Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea and vomiting compared with the conventional anthracyclines. The better therapeutic index of liposomal anthracyclines without compromising the efficacy makes it a favorable choice over conventional anthracyclines in elderly patients, patients with risk factors for cardiac disease and patients with prior use of anthracyclines.

Current management and prognostic features for gastrointestinal stromal tumor (GIST).

Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST) account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.

Recent advances and novel agents for gastrointestinal stromal tumor (GIST).

The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic "driver" pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.

Cardiac and pericardial tumors.

Primary cardiac tumors of the heart present often as a clinical dilemma and need to be considered in the differential diagnosis of other cardiovascular diseases. They are infrequent and often asymptomatic. Occasionally, the tumors may be life threatening. Secondary involvement of the heart by extracardiac tumors is much more common. Benign tumors constitute 80% of primary cardiac neoplasms, with myxomas as the most common type. This review describes the pathology, clinical presentation, and treatment of both benign and malignant tumors of both the heart and the pericardium.

Hepatocellular carcinoma in non-cirrhotic liver without evidence of iron overload in a patient with primary hemochromatosis. Review.

BACKGROUND: We report a case of a 70-year-old male with hepatocellular carcinoma (HCC) with a history of hemochromatosis but with no evidence of cirrhosis or iron overload and with a history of exposure to atomic bomb radiation. It is very rare to see hepatocellular carcinoma in the absence of evidence of liver injury. METHODS: We did an extensive review of current English medical literature through Pubmed from 1980 to 2009 and found 14 case reports of patient with hepatocellular cancer in absence of cirrhosis. The details of these cases were reanalyzed as reported and documented for review. RESULTS: There are 14 previous case reports of HCC developing in hemochromatosis in absence of cirrhosis but ten of them had evidence of iron overload in the non-tumorous livers. Our case is the fifth case of Hepatocellular cancer in hemochromatosis in absence of cirrhosis and iron overload. CONCLUSION: Hepatocellular carcinoma is a very rare in absence of cirrhosis but patient with other risk factors like hemochromatosis, viral infections, radiation, and toxin exposure should be monitored closely for any sign and symptoms suggestive of malignancy.

Malignant glomus tumor of kidney: the first reported case and review of literature.

Glomus tumors are mesenchymal neoplasms and are rarely seen in visceral organs like the kidney. Our patient presented with a metastatic, malignant, and highly aggressive glomus tumor in the kidney. In our extensive literature review, we did not come across even a single case of malignant glomus tumor arising in the kidney. We report the clinical presentation, radiologic, and pathological features of our case. Immunohistochemical findings that distinguish our case from other reported cases of glomus tumors arising from the kidney have been discussed. We have also reviewed the criteria for malignancy and other reported malignant glomus tumors.

Psoriasis induced by losartan therapy: a case report and review of the literature.

Psoriasis is a papulosquamous disease of multifactorial etiology. A combination of genetic and environmental agents is implicated in its pathogenesis. A variety of triggers, including infection, stress, and medications, have been recognized as precipitants of this disease. Nonsteroidal anti-inflammatory drugs, beta-blockers, lithium, synthetic antimalarials, and gold are the most common drugs implicated in precipitating psoriasis. We report a patient with psoriasis induced by initiation of losartan therapy, which resolved with discontinuation of the drug. The Naranjo adverse drug reaction probability scale score indicated that the association between losartan use and psoriasis was probable.