Ninad Desai

Lipodystrophy in pediatric HIV

ObjectiveTo assess fat accumulation in children with HIV/AIDS on long term HAART using CDC defined Body mass Index (BMI) criteria and measured Bioelectric Impedance (BI).MethodsProspective study of 48 HIV infected children (ages 6–15 years) on HAART to determine the incidence of lipodystrophy and evaluate methods of determining body fat accumulation. Lipodystrophy was diagnosed using clinical features-truncal obesity with facial/limb wasting. BMI (weight in kg/height in meters2) was plotted on CDC curves to predict the risk of obesity. BI was performed using Omron’s HBF301 body fat analyzer and reported as TBF %/height. Serum cholesterol and triglycerides were measured. Results were compared using ANOVAResultsAverage duration of HAART was 2.4 years. Forty five of 48 patients were on protease inhibitors. Fifteen (31%) developed Lipodystrophy, but CDC BMI curves identify only 7/15 as overweight or at risk for obesity. However, TBF/Ht of 30% (using BI) was 85% sensitive and 88% specific in identifying Lipodystrophy. Hyperlipidemia occurred in 28/48 (58%) overall, in 14/15 (93%) diagnosed with lipodystrophy.ConclusionLipodystrophy is a significant problem in children with HIV/AIDS on HAART. BI is more useful than BMI in identifying patients with abnormal fat accumulation and should be incorporated in their routine assessment in the ambulatory setting.

Pathophysiology of GHRH-growth hormone-IGF1 axis in HIV/AIDS

Aberrations in GHRH—GH –IGF-I axis are common in the complex of HIV, HAART and AIDS. There are 2 distinct mechanisms at play in HIV and AIDS. One is primarly associated with development of lipodystrophy and results in complications such as chronic inflammation, insulin resistance, lipid and metabolic abnormalities. HIV lipodystrophy is found especially in those on highly active anti-retroviral therapy (HAART). The various processes involved in lipodystrophy result in the suppression of pituitary GH production. The mechanism of low GH levels relates to increased somatostatin tone, decreased Ghrelin, increased free fatty acids (FFA) and insulin resistance. On the other hand in AIDS wasting syndrome; elevated GH and low IGF-1 levels are seen suggesting GH resistance. The GHRH analog—Tesamorelin is the only treatment option, which is FDA approved for use in reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. Although long-term clinical trials and experience is needed to further study the benefits and risks of Tesamorelin.

Management of a large organized intraatrial catheter-tip thrombus in a child with acquired immunodeficiency syndrome using escalating tissue plasminogen activator infusions.

Objectives: To describe the dissolution of a large organized intraatrial catheter-tip thrombus using a novel aggressive dose escalation of tissue plasminogen activator infusion. Design: Case report. Setting: A six-bed pediatric intensive care unit (ICU) at a university hospital. Patient: An 8-yr-old with acquired immunodeficiency syndrome with a large organized intraatrial thrombus at the tip of an indwelling central venous catheter placed for total parenteral nutrition 2 months before presentation. Intervention: Escalating dose of tissue plasminogen activator infusion. Measurements: A large intraatrial catheter-tip thrombus (2.5 × 3 cm) was an incidental finding on an echocardiogram done to assess cardiac function. The thrombus occupied almost half the right atrial cavity and hit the tricuspid valve with each heartbeat without obstruction of tricuspid inflow. The catheter had no blood return from either lumen for >1 month. Protein C, protein S, and antithrombin III were normal, and factor V Leiden and prothrombin gene mutations were absent. Blood cultures were negative. Pediatric and cardiovascular surgeons recommended open-heart surgery as the safest option for catheter removal to avoid the risk of superior vena cava occlusion, vascular rupture, or embolization. A second opinion concurred. A trial of thrombolytic therapy with tissue plasminogen activator infusions was started at 0.1 mg/kg/hr for 6 hrs daily. No change in thrombus size was seen on a followup echocardiogram after 4 days. An aggressive dose escalation (0.15, 0.2, 0.25 mg/kg/hr for 6 hrs) was done over the next 5 days in an attempt to avoid open-heart surgery. Risks regarding disseminated intravascular coagulation and bleeding were presented to the parents. Main Results: Followup echocardiogram on day 10 showed complete resolution of the thrombus. No changes in respiratory/hemodynamic status or oxygen saturation were observed. Studies for disseminated intravascular coagulation remained stable, and no clinical bleeding was seen. The catheter was safely removed surgically; pathology examination showed no residual thrombus. Conclusions: Prolonged infusion of tissue plasminogen activator in escalating doses was safe and effective in the management of a large intracardiac catheter-tip thrombus and helped avoid open-heart surgery. In view of the potential hazards of tissue plasminogen activator, close pediatric ICU monitoring is indicated with the use of high-dose tissue plasminogen activator infusions.

Case Report: Endoscopic Features of Intestinal Smooth Muscle Tumor in a Child with AIDS

Intestinal leiomyosarcomas are exceedingly rare in immunologically intact children, except during infancy. While leiomyosarcomas account for less than 2% of all soft tissue tumors in childhood, they are the second most frequent malignancy in children with the acquired immunodeficiency syndrome (AIDS). In this cohort they are often located in unusual sites for primary soft tissue tumors. This report describes a young girl with advanced AIDS, referred for evaluation of abdominal pain, hematochezia, and wasting syndrome. Colonoscopy revealed two 1- to 2-cm submucosal nodules with central umbilication. Repeat colonoscopy 18 months later revealed no changes in these lesions. Biopsy revealed a submucosal spindle-cell lesion, with necrosis and cellular atypia. Initially it was characterized as a partially excised low-grade leiomyosarcoma. However, the final consensus diagnosis was smooth muscle tumor of uncertain malignant potential. Because of her advanced AIDS, there was no attempt at surgical resection or chemotherapy. Thirty-six months after initial referral, she remains alive without radiographic or clinical evidence of local extension or metastases. Additional data are required to determine the long-term outcome of these indolent submucosal tumors in the digestive tracts of children with AIDS.

A Fast Hemoglobin Variant on Newborn Screening is Associated with α - Thalassemia Trait

Alpha thalassemia trait (a-thal-1) is a common cause of microcytosis in black and Asian populations. A small amount of hemoglobin Barts (2-8%) is transiently present in affected infants at birth and detectable in many newborn screening laboratories; it is a fast-moving hemoglobin on electrophoresis. In order to determine whether a report of a “fast hemoglobin variant” on newborn hemoglobinopathy screening is associated with a diagnosis of alpha thalassemia trait, hemoglobin concentration, red blood cell indices, and peripheral blood smear examination were performed on 18 infants referred for hematologic evaluation of a “fast hemoglobin variant” on newborn screening. All 18 infants with this diagnosis referred for consultation were black; ages ranged from 24 to 86 days (median 40 days). Six of 18 infants (33%) were mildly anemic for age and all 18 were microcytic. The prevalence of a “fast variant” among infants born at our institution is 2.5%. In that conditions other than oc-thal-I that cause microcytosis in early infancy are very uncommon, we conclude that all 18 of our infants with a fast hemoglobin on newborn screening likely have a-thal-1. The newborn screening result is thus a commonly and readily available laboratory report that specifically supports a diagnosis of oc-thal-1, a diagnosis with significant clinical and genetic implications that is usually made only by exclusion.

Endocrinopathies in HIV, AIDS and HAART

The United Nations AIDS Report in 2012 states that there are 34 million people living in the world with HIV/AIDS at the end of 2011; of these 69 % live in sub-Saharan Africa [1]. The Caribbean islands, Eastern Europe and Central Asia are the next three most affected regions of the world. The rate of new infections HIV has decreased to 2.5 million per year. In 2011 the number of people dying from AIDS had fallen down to 1.7 million from 2.3 million in 2005. The number of children who got infected with HIV was approximately 330,000 which have significantly fallen in the last 10 years. New perinatal HIV cases have substantially decreased due to HIV education, screening for HIV in pregnancy, peripartum, intrapartum care for HIV infected mother, formula feeding, postpartum care of the infant and new HAART medications. HIV infection has progressed from an acute disease to a chronic illness with developments in antiretroviral therapies (HAART) along with better prophylaxis and treatment of opportunistic infections are the main contributors to the above advances [2]. In centers such as ours in Brooklyn, a significant cohort of long term survivors of perinatal HIV as well as a concentration large numbers of adults with HIV/AIDS help highlight the evolving clinical picture of this chronic disease and the impact of long term exposure to antiretroviral medications. There is an increase in morbidity and mortality due to secondary issues such as endocrine dys-regulation, although hormonal misbalance is not commonly seen. HIV and AIDS do involve almost all of the hormonal systems and axis (Fig. 1 and Table 1). There are multiple factors that contribute to this hypothalamic pituitary hormonal axis dys-regulation. Direct invasion of the various organs in the axis can be either by opportunistic infections or infiltrative diseases. Viral proteins or cytokines released during viral infection and the chronic inflammatory state that follows, also contribute to these alterations. The actions of these cytokines released by the immune response can both activate or inhibit the hormonal systems. Further, HAART and other medications used to treat HIV infection can contribute to the hypothalamic pituitary hormonal axis dysfunctions. The hypothalamic pituitary adrenal (HPA) axis is the most common of the endocrine axis to be affected by HIV infection [3, 4]. The presentation results in a spectrum of adrenal gland malfunction from overt adrenal insufficiency, impaired adrenal reserves to increased cortisol levels due to a glucocorticoid resistant state. The degree of the thyroid hormone disorders also vary in presentation from nonthyroidal illness or sick euthyroid syndrome to subclinical hypothyroidism, overt hypothyroidism, isolated low T4 levels and hyperthyroidism at the other end of the spectrum. Thyroid hormone dysfunction in HIV is also associated with altered metabolism, poor oral intake and increased prevalence of weight loss and wasting syndrome. HIV infected pediatric and adult populations have a greater incidence in reduction of BMD as compared to the controls [5–12]. Osteoporosis has been reported to be present in up to 15 % of HIV positive patients and a 67 % reduction in BMD. Viral proteins interfere with osteoblastic activity either by direct interaction or by the inflammatory process that they induce. Anti-viral management such as HAART, protease inhibitors, and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) also are involved in disrupting proper bone metabolism (Fig. 1). The interaction of pharmacologic management and inflammatory process A. Bhangoo Pediatric Endocrinology, Miller Children’s Hospital, Long Beach, CA, USA

Factor V Leiden (FV Leiden) and Strokes in Children with Sickle Cell Anemia(HbSS). 648

Stroke is a frequent complication in patients with sickle cell anemia. Recently, an increased prevalence of resistance to activated protein C (APCR) has been reported in patients with idiopathic thrombosis. The defect responsible for APCR is a point mutation in the factor V gene IFV Leiden which changes Arg at position 506 to Gln. The estimated frequency of FV Leiden varies from 2 to 5% in the white population with similar or lower frequency in the African American population. This study was undertaken to determine whether FV Leiden is a risk factor for strokes in children with HbSS. The FV Leiden mutation eliminates a restriction enzyme digestion site, yielding characteristic RFLP patterns for heterozygotes and homozygotes. Genomic DNA gDNA) was extracted from peripheral blood mononuclear cells. Polymerase chain reaction (PCR) was used to amplify a 206 bp fragment of the gDNA containing the mutated site, followed by Minl-1 digestion of the amplified product. The digests were run on 4% Nusieve agarose gels and visualized with ethidium bromide. The expected patterns were 3 bands of sizes 123, 47 and 36 bps in patients with the normal FV gene; 4 bands of sizes 159, 123, 47, 36 bps in heterozygotes with Leiden mutation and 2 bands of 159 and 47 bs in homozygotes with the Leiden mutation. Eighteen patients (ages 4 -21 years, median 9.5 years) with Hbss and stroke on chronic transfusion therapy were studied. All patients were African American. Factor V Leiden was not detected in any of the patients studied, suggesting that it probably does not contribute to development of stroke in HbSS. There is no information to disclose.

National Survey of Pediatric Care Providers: Assessing Time and Impact of Coding and Documentation in Physician Practice

Background. Documentation and billing/coding are essential to medical practice. Physicians spend significant time documenting to meet coding and medicolegal requirements, potentially reducing time for patient care and learning. We sought to assess time spent charting in pediatric practice and provider understanding and comfort level regarding billing/coding. Methods. An anonymous web-based survey was emailed to members of American Academy of Pediatrics Section of Pediatric Trainees practicing in the United States. Results. A total of 601 trainees responded to the survey. Thirty-seven percent of trainees spent more than half of patient encounter time documenting in outpatient settings while 62% (P < .01) in inpatient settings. There was a positive correlation between trainees’ apprehension about documentation and reporting increased stress due to documentation (r = 0.32, P < 0.001). Sixty-two percent respondents had no prior training of billing/coding, and >70% feel necessity of including billing/coding in the medical curriculum (P < 0.0001). Conclusions. Our study highlights increasing burden of documentation in practice. Majority of pediatric trainees feel the need to including billing/coding skills as a part of medical curriculum.

Effect of HIV/AIDS and Highly Active Antiretroviral Therapy (HAART) on the Serologic Response to Varicella-Zoster Infection

Effect of HIV/AIDS and Highly Active Antiretroviral Therapy (HAART) on the Serologic Response to Varicella-Zoster Infection

A One-Year Prospective Developmental Assessment of HIV-Positive Infants and Children on Triple Antiretroviral Therapies

A One-Year Prospective Developmental Assessment of HIV-Positive Infants and Children on Triple Antiretroviral Therapies