Abiotrophia Endocarditis in Children with No Underlying Heart Disease: A Rare but a Virulent Organism

Infective endocarditis is extremely rare in children with structurally normal hearts. The most common etiological agents are staphylococcal and streptococcal species. Nutritionally variant streptococci also classified as Abiotrophia species are a group of fastidious organisms that account for only 5% to 6% of all cases of culture‐negative infective endocarditis. Only seven cases of Abiotrophia infective endocarditis have been previously reported in children with no underlying structural heart disease. We report two cases of Abiotrophia infective endocarditis in children without any predisposing factors. Both patients presented with nonspecific symptoms leading to delay in diagnosis. While bacteriological clearance was achieved in both cases, both had a complicated course including development of brain mycotic aneurysms, splenic infarction, renal failure, and irreversible damage to the mitral valve. Both patients required surgical removal of the native mitral valve and replacement. We also present review of seven cases with similar diagnosis published previously in literature and highlight important differences. Our cases highlight special challenges in management of Abiotrophia endocarditis in pediatric patients. As the organism may not be isolated in routine culture media, may present with atypical clinical symptoms and may have a complicated course even without antibiotic failure, a high index of suspicion should be maintained in children with subacute symptoms even with no underlying structural cardiac disease.     

Over-nutrition and metabolic cardiomyopathy

Cardiovascular disease, which accounts for the highest morbidity and mortality in the United States, has several major risk factors, including aging and diabetes. Overweight and obesity, especially abdominal obesity, have been increasingly implicated as independent risk factors in the development of cardiovascular disease. Metabolic and/or diabetic cardiomyopathy has been especially associated with excess body weight caused by chronic over-nutrition and high-fat feeding. In the initial stages, obesity is now understood to cause significant dysregulation of cardiac fatty acid and glucose metabolism. These abnormalities are due, in part, to increased oxidative stress, which in turn can cause deleterious effects on intracellular signaling pathways that control cellular growth and proliferation. This increase in oxidative stress is coupled with reduced anti-oxidant species and dysregulation of metabolic signaling pathways. The cardiomyopathy seen with obesity is associated with increased interstitial fibrosis and diastolic dysfunction. Over time, evolving abnormalities include hypertrophy and systolic dysfunction, eventually leading to heart failure.     

Factors associated with encephalopathy in patients with Salmonella enterica serotype Typhi bacteremia presenting to a diarrheal hospital in Dhaka, Bangladesh

To characterize clinical correlates of typhoid fever-associated encephalopathy, we performed a retrospective chart review of patients with Salmonella enterica serotype Typhi bacteremia who were hospitalized at the International Centre for Diarrhoeal Disease Research, Bangladesh, from February of 2009 to June of 2011. Of 207 patients bacteremic with Salmonella Typhi who were ≥ 5 years of age, we identified 43 (21%) patients with encephalopathy. Univariate analysis revealed that patients with encephalopathy more often presented at ages of 10-24 years and had severe dehydration, low oxygen saturation, high respiratory rate, low leukocyte count, low platelet count, and Widal flagellar H agglutinin (TH) titer ≥ 1:640 compared with typhoid patients without encephalopathy. Multivariate analysis using logistic regression showed that age, dehydration, leukocyte count, and Widal TH titer were independently associated with encephalopathy. Our findings suggest that age, severity of disease, and immune responses are associated with encephalopathy during Salmonella Typhi bacteremia, perhaps reflecting the impact of prominent inflammatory responses.     

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.     

Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT

CY in combination with BU is a widely used conditioning regimen for haematopoietic SCT (HSCT). The aim of this study was to evaluate the pharmacokinetics (PK) of CY and its major metabolite 4-hydroxyCY (HCY) in patients with thalassemia undergoing HSCT. A total of 55 patients received BU (16 mg/kg) followed by CY (160-200 mg/kg) both over 4 days before HSCT. A population PK model was developed to describe the disposition of CY and HCY and the inter-individual (IIV) and inter-occasion variability (IOV). The model was also used to determine the effects covariates including: demographics, Lucarelli classification and polymorphisms in enzymes involved in the metabolism or biotransformation of CY had on CY and HCY disposition. Overall, 17-114% IIV and 12-103% IOV in CY and HCY PK parameters were observed. Body weight and age were the main covariates, which explained the largest portion of the IIV. In addition, CYP2C9*2 explained a significant portion of the IIV in the clearance (P<0.002) and thus the area under the concentration curve (P<0.05) of CY. This covariate model may be used to design and plan targeted dose therapy in this group of pediatric patients, if clinical outcome association with CY PK are proved and target range established.     

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.     

Ewing's sarcoma of the lesser sac masquerading as a pancreatic tumor

Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an uncommon, aggressive, and malignant tumor with a poor patient outcome. Its occurrence in the lesser sac is a rare event and to the best of our knowledge, has not been previously described. The present case was clinically and radiologically misdiagnosed as a pancreatic tumor/gastrointestinal stromal tumor. Histopathology revealed a tumor with "small round cells" that were positive for CD99, confirming the diagnosis of ES/PNET. This report highlights the importance of considering Ewing's sarcoma in the differential diagnosis of intraabdominal, extraintestinal masses.