Risk factors for metabolic syndrome among overweight and obese Hispanic children attending a pediatric clinic in New Braunfels, Texas

Childhood obesity is a persistent problem in the U.S., especially among Hispanics. Health complications like hypertension, type II diabetes, and metabolic syndrome (Met-S) are being seen at younger ages, and current screening procedures may be inadequate. This study sought to describe the risk factors for Met-S present in a sample of 106 overweight and obese Hispanic children, aged 5-14 years, participating in Nutrition and Exercise Start Today (NEST), a randomized weight management intervention trial at a rural health clinic in New Braunfels, Texas; and to determine associations between these factors and other clinical and socio-demographic characteristics linked to obesity. Baseline data was analyzed for the prevalence of large waist circumference (WC), elevated blood pressure (BP), high fasting serum glucose and serum triglycerides (TG), and low serum HDL cholesterol, in relationship with selected sample characteristics. Main findings included high baseline prevalence rates of large WC (77%), reduced HDL (57%), and elevated BP (30%). WC was significantly associated with BMI percentile and the serum liver function test alanine aminotransferase (ALT) by Fisher's exact test (p<0.001 and p=0.032, respectively), while there were significant relationships between HDL and both female gender and ALT. BMI percentile and ALT were associated with all sets of Met-S diagnostic criteria examined. BMI percentile also had a strong association (p=0.005) with total number of Met-S risk factors, while ALT had a weaker association (p=0.093). WC is a low-cost, simple measure whose use may improve clinic surveillance for childhood obesity and complications like Met-S. WC, BP, HDL and ALT may be used as part of targeted screening for obesity complications like Met-S, particularly in situations where resources are limited.^

Survival analysis of circulating tumor cells in triple-negative breast cancer

Background. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% (1.38 million) of the total new cancer cases and 14% (458,400) of the total cancer deaths in 2008. [1] Triple-negative breast cancer (TNBC) is an aggressive phenotype comprising 10–20% of all breast cancers (BCs). [2-4] TNBCs show absence of estrogen, progesterone and HER2/neu receptors on the tumor cells. Because of the absence of these receptors, TNBCs are not candidates for targeted therapies. Circulating tumor cells (CTCs) are observed in blood of breast cancer patients even at early stages (Stage I & II) of the disease. Immunological and molecular analysis can be used to detect the presence of tumor cells in the blood (Circulating tumor cells; CTCs) of many breast cancer patients. These cells may explain relapses in early stage breast cancer patients even after adequate local control. CTC detection may be useful in identifying patients at risk for disease progression, and therapies targeting CTCs may improve outcome in patients harboring them. Methods . In this study we evaluated 80 patients with TNBC who are enrolled in a larger prospective study conducted at M D Anderson Cancer Center in order to determine whether the presence of circulating tumor cells is a significant prognostic factor in relapse free and overall survival . Patients with metastatic disease at the time of presentation were excluded from the study. CTCs were assessed using CellSearch System™ (Veridex, Raritan, NJ). CTCs were defined as nucleated cells lacking the presence of CD45 but expressing cytokeratins 8, 18 or 19. The distribution of patient and tumor characteristics was analyzed using chi square test and Fisher's exact test. Log rank test and Cox regression analysis was applied to establish the association of circulating tumor cells with relapse free and overall survival. Results. The median age of the study participants was 53years. The median duration of follow-up was 40 months. Eighty-eight percent (88%) of patients were newly diagnosed (without a previous history of breast cancer), and (60%) of patients were chemo naïve (had not received chemotherapy at the time of their blood draw for CTC analysis). Tumor characteristics such as stage (P=0.40), tumor size (P=69), sentinel nodal involvement (P=0.87), axillary lymph node involvement (P=0.13), adjuvant therapy (P=0.83), and high histological grade of tumor (P=0.26) did not predict the presence of CTCs. However, CTCs predicted worse relapse free survival (1 or more CTCs log rank P value = 0.04, at 2 or more CTCs P = 0.02 and at 3 or more CTCs P < 0.0001) and overall survival (at 1 or more CTCs log rank P value = 0.08, at 2 or more CTCs P = 0.01 and at 3 or more CTCs P = 0.0001. Conclusions. The number of circulating tumor cells predicted worse relapse free survival and overall survival in TNBC patients.^

Identification of genetic risk factors for cerebellar mutism in pediatric brain tumor patients

Following posterior fossa surgery for resection of childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET), cerebellar mutism (CM) may develop. This is a condition of absent or diminished speech in a conscious patient with no evidence of oral apraxia, which can be accompanied by other symptoms of the posterior fossa syndrome complex, which includes ataxia and hypotonia. Little is known about the etiology. Therefore, we conducted a SNP, gene, and pathway-level analysis to assess the role of host genetic variation on the risk of CM in M/PNET subjects following treatment. Cases (n= 20) and controls (n= 53) were recruited from the Childhood Cancer Epidemiology and Prevention Center, in Houston, TX. DNA samples were genotyped using the Illumina Human 1M Quad SNP chip. Ten pathways were identified from logistic regression used to identify the marginal effect of each SNP on CM risk. The minP test was conducted to identify associations between SNPs categorized to genes and CM risk. Pathways were assessed to determine if there was a significant enrichment of genes in the pathway compared to all other pathways. There were 78 genes that reached the threshold of min P ≤0.05 in 948 genes. The Neurotoxicity pathway was the most significant pathway after adjusting for multiple comparisons (q=0.040 and q=0.005, using Fisher's exact test and a test of proportions, respectively). Most genes within the Neurotoxicity pathway that reached a threshold of minP ≤0.05 were known to have an apoptosis function, possibly inducing neuronal apoptosis in the dentatothalamocortical pathway, and may be important in CM etiology in this population. This is the first study to assess the potential role of genetic risk factors on CM. As an exploratory study, these results should be replicated in a larger sample. ^

Factors associated with the retention of HIV-infected children in care in Botswana

Lost to follow up (LTFU) in the care and treatment of HIV/AIDS represents a particularly problematic aspect when evaluating the success of treatment programs. Identifying modifiable factors that lead to LTFU would be important if we are to design effective retention interventions. The purpose of this study was to identify the challenges faced by children seeking care and treatment at a large HIV Clinic in Botswana. In order to identify those factors, we used mixed methods from different sources of information available at the Baylor Clinic. The first method involved a case-control study through which we interviewed a select representation of children 1-18 years who, at some point in time, have attended clinic at Baylor Clinic in Gaborone, Botswana. We document this in detail using the first journal article. We defined LTFU as patients who had not attended clinic for more than 6 months at the onset of the study; the comparison group was recruited from among those who have attended clinic at any point in the 6 months leading to the start of study. Factors were compared between the cases and controls. The second methodology involved conducting in-depth interviews with health providers to elicit their opinions and experiences dealing with patients at the at the Baylor clinic in general and the LTFU patients in particular. We document this methodology and its findings in the second journal article. ^ We found that most patients that are LTFU failed to engage with the clinic. Most of the LTFU made only one visit to the clinic (47.66%) as compared to less than 1% in the control group (P<0.01, 2-tailed Fisher's exact test). Among the interviewed patients, psychosocial factors such as stigma, religious beliefs, child rebellion and disclosure of HIV status concerns were characteristic of the LTFU population, but psychosocial issues were not cited among the comparison group. We also found that these psychosocial aspects of the patients point towards a bigger problem of mental health that needs to be addressed. Socioeconomic factors such as lack of transport, school-related activities and forgetting check-up dates were cited predominantly by the controls than cases. ^ From these findings, there is need to target interventions towards engaging pediatric patients at their initial clinic visit. Such interventions would focus on psychosocial support, as well as involving faith-based organizations in planning joint responses.^

THE IMPACT OF FAMILY HISTORY ON MEDULLARY THYROID CANCER IN MEN2A PATIENTS

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were classified as having local or distant MTC and whether they had progressive MTC. MTC status and age were assessed at diagnosis and most advanced MTC stage. For those without MTC, age was recorded at prophylactic thyroidectomy or last follow-up if the patient did not have a thyroidectomy. For each pedigree, the mean age of members without MTC, with MTC, and the proportion of RET mutation carriers with local or distant and progressive MTC were calculated. We assessed differences in these variables using ANOVA and the Fisher’s exact test. Sufficient data for analysis were available for families with mutated codons 609 (92 patients from 13 families), 618 (41 patients from 7 families), and 634 (152 patients from 13 families). The only significant differences found were the mean age of patients without MTC between families with codon 609 and 618 mutations even after accounting for prophylactic thyroidectomy (p=0.006 and 0.001, respectively), and in the mean age of MTC diagnosis between families with codon 618 and 634 mutations even after accounting for symptomatic presentation (p=0.023 and 0.014, respectively). However, these differences may be explained by generational differences in ascertainment of RET carriers and the availability of genetic testing when the proband initially presented.

Identification of diabetic retinopathy genes through a genome-wide association study among Mexican-Americans from Starr County, Texas

To identify genetic susceptibility loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas completed detailed physical and ophthalmologic examinations including fundus photography for diabetic retinopathy grading. 103 individuals with moderate-to-severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy were defined as cases for this study. DNA samples extracted from study subjects were genotyped using the Affymetrix GeneChip® Human Mapping 100K Set, which includes 116,204 single nucleotide polymorphisms (SNPs) across the whole genome. Single-marker allelic tests and 2- to 8-SNP sliding-window Haplotype Trend Regression implemented in HelixTreeTM were first performed with these direct genotypes to identify genes/regions contributing to the risk of severe diabetic retinopathy. An additional 1,885,781 HapMap Phase II SNPs were imputed from the direct genotypes to expand the genomic coverage for a more detailed exploration of genetic susceptibility to diabetic retinopathy. The average estimated allelic dosage and imputed genotypes with the highest posterior probabilities were subsequently analyzed for associations using logistic regression and Fisher's Exact allelic tests, respectively. To move beyond these SNP-based approaches, 104,572 directly genotyped and 333,375 well-imputed SNPs were used to construct genetic distance matrices based on 262 retinopathy candidate genes and their 112 related biological pathways. Multivariate distance matrix regression was then used to test hypotheses with genes and pathways as the units of inference in the context of susceptibility to diabetic retinopathy. This study provides a framework for genome-wide association analyses, and implicated several genes involved in the regulation of oxidative stress, inflammatory processes, histidine metabolism, and pancreatic cancer pathways associated with severe diabetic retinopathy. Many of these loci have not previously been implicated in either diabetic retinopathy or diabetes. In summary, CDC73, IL12RB2, and SULF1 had the best evidence as candidates to influence diabetic retinopathy, possibly through novel biological mechanisms related to VEGF-mediated signaling pathway or inflammatory processes. While this study uncovered some genes for diabetic retinopathy, a comprehensive picture of the genetic architecture of diabetic retinopathy has not yet been achieved. Once fully understood, the genetics and biology of diabetic retinopathy will contribute to better strategies for diagnosis, treatment and prevention of this disease.^

For health's sake: Cervical and breast cancer screening

African-Americans make up twelve percent of the United States population, yet they experience morbidity and mortality at a rate that, in some cases, is disproportionate to their numbers. There are numerous health areas, including cancer, in which disparities exist. There are also numerous reasons which have been suggested to explain the high rates of cancer morbidity and mortality experienced by African-Americans. Among the reasons given to explain these differences are lack of knowledge and lack of access to medical care (1). This study sought to increase the knowledge, attitudes, and behavioral intentions of African-American women attending a Baptist church in Houston with regard to cervical cancer, breast cancer, Pap smear, and mammography. It was hypothesized that a church-based cancer education program would produce the desired change in knowledge, attitudes, and behavioral intentions.^ The quasi-experimental design of the study was untreated control group with pretest and posttest and untreated control group with posttest only. Female members of Mount Ararat Baptist Church took part in an eight-week, cancer education program based on social cognitive theory. Baseline data were collected before the start of the program at Mount Ararat and at Solid Rock Baptist Church, control group one. At the end of the program, the follow-up survey was administered at the program church, control church one, and in a third church, Damascus Missionary Baptist Church, which served as the posttest only group. The data were analyzed by Fisher's exact and paired t-test to determine if the program supported the project's hypotheses.^ Results of data analyses supported the major study hypotheses, the exception being behavioral intention to have Pap smear performed. Although the program appeared to have generally influenced changes in the desired direction, the results are limited due to the quasi-experimental design and small sample size. Longer term studies with larger sample sizes are needed to more fully develop and evaluate programs which impact the health of African-Americans. ^