Childhood cancer survivor satisfaction with characteristics of clinical care

This study investigated the characteristics of a clinic that affect how satisfied survivors of childhood cancer are with their medical care. Questionnaire and interview data from the Passport for Care: Texas Implementation project collected between January 2011 to April 2012 were analyzed. Eleven clinics in Texas participated. Questionnaire respondents were childhood cancer survivor patients who had been off therapy for at least 2 years, or their parents. Interview respondents were clinical providers or research staff at the participating clinics. The outcomes evaluated were answers to a single question on satisfaction with care and a composite Percent Satisfaction Score created from seven other questionnaire items that were correlated (Spearman Rho >0.3) with the question on satisfaction. The following characteristics were also evaluated: sex, age, race, education, and type of cancer. The following clinic indicators were evaluated: type of clinic (general vs. dedicated cancer survivor clinics), number of providers, number of survivors, ratio of survivors/providers, distribution of handouts, distribution of treatment summaries, and use of Children's Oncology Group (COG) guidelines. ^ The only demographic characteristic that affected satisfaction was race. A Kruskal-Wallis test showed a statistically significant difference (Chi-square 6.129, 2 d.f., p = 0.0467). To analyze this further, Wilcoxon Rank Sum test of pairings of the three groups were performed. A Bonferroni correction for multiple testing was applied, with p = 0.017 indicating significance at alpha = 0.05. There was no significant difference between the White and Hispanic groups or between the Hispanic and "Other" groups. For the White and "Other" groups there was a significant difference for the satisfaction item (p = 0.0123) but not for the Percent Satisfaction Score (p = 0.0289). These results suggest that race may influence satisfaction and should be evaluated further in future studies. ^ None of the clinic indicators affected the Percent Satisfaction Score. Going to a clinic that distributed patient information handouts (Wilcoxon Rank Sum p = 0.048) and going to a clinic with >=100 survivors (Wilcoxon Rank Sum p = 0.021) were associated with increased satisfaction. The population of childhood cancer survivors is a growing group of individuals with special health needs. In the future survivors will likely seek medical care in a variety of clinical settings, so it is important to investigate features to improve patient satisfaction with clinical care.^

Social and economically influenced factors associated with breast cancer treatment among blacks and whites. A qualitative study

Background: Despite the fact breast cancer mortality has declined in recent years, the mortality gap between African-American and white women continues to grow. A part of these disparities may be due to either inadequately following guideline recommended treatment or treatment delays. Although racial/ethnic disparities in breast cancer treatment and mortality have been extensively documented, the mechanisms by which these disparities occur remain largely unknown. Social and economically influenced factors such as choice of providers, distance of treatment facility, transportation, health insurance, and job related factors may also contribute to racial differences in breast cancer treatment; however, these have not been explored sufficiently in previous research. ^ Aim: The purpose of this study was to evaluate the role of social and economically influenced factors that may contribute to racial disparities in the receipt of guideline recommended treatment using the Health Disparities Model. ^ Methods: In this qualitative comparative case study, data from medical records, structured telephone interviews, and in-depth patient interviews explored the relationship between social and economically influenced factors and breast cancer treatment. Transcripts were analyzed using standard iterative process followed by immersion/crystallization approach. Participants were identified through rapid ascertainment from the New Jersey Cancer Registry and this study included 8 African-American and 8 white women aged 20-85 years old diagnosed with early stage breast cancer between 2003-2007, matched on age, race, and physician recommended treatment. ^ Results: We did not identify differences by race in factors that influenced the receipt of breast cancer treatment among the individual matched pairs. Four prominent themes emerged among women from both groups who experienced similar difficulties influenced by socioeconomic factors. Choice of providers, distance of facility, health insurance, and job related factors all contributed to breast cancer treatment experience among these women. Conclusions: We identified common issues influenced by socioeconomic factors and its relation with the receipt of breast cancer treatment, regardless of race. However, more research is needed to study the additional factors conveying racial differences affecting breast cancer treatment. ^

NOVEL THERAPEUTIC TARGETS IDENTIFIED BY HIGH-THROUGHPUT TECHNOLOGIES FOR TRIPLE-NEGATIVE BREAST CANCER

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

In-utero exposure to chemotherapy: What are the long term effects?

There is not a large body of evidence on in-utero exposure to chemotherapy for pregnancy-associated cancers to help determine the long term effects on offspring. This study is a systematic review of long term follow-up to find evidence for adverse outcomes in exposed offspring. In order for studies to be eligible for this systematic review, they had to have a median follow up of at least 24 months with the resulting child. PubMed, Medline, and Scopus were the databases used, and we included all eligible articles, regardless of the date of publication. The search resulted in six articles meeting the eligibility requirements. The review of findings of these studies suggested that there is not enough evidence to make a determination of the risk of chemotherapy for the offspring. Exposed children in the sample of reviewed papers did have some medical conditions, but the rate and type did not differ from the non-exposed population. However, a limitation of this literature review is the very small sample size of publications on this important topic. This finding of few studies on this topic is an important result of this systematic review. More research and long term follow-up studies must be conducted to address this issue.^

Evaluating the Utility of Clinical Criteria for the Identification of Lynch Syndrome among Endometrial Cancer Patients

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting. Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic medical record, and all tumors were tested for expression of the DNA mismatch repair proteins through immunohistochemistry. Tumors exhibiting loss of MSH2, MSH6 and PMS2 were designated as probable Lynch Syndrome (PLS). For tumors exhibiting immunohistochemical loss of MLH1, we used the PCR-based MLH1 methylation assay to delineate PLS tumors from sporadic tumors. Samples lacking methylation of the MLH1 promoter were also designated as PLS. The sensitivity and specificity for SGO criteria for detecting PLS tumors was calculated. We compared clinical and pathologic features of sporadic tumors and PLS tumors. A simplified cost-effectiveness analysis was also performed comparing the direct costs of utilizing SGO criteria vs. universal tumor testing. Results: In our cohort, 43/408 (10.5%) of endometrial carcinomas were designated as PLS. The sensitivity and specificity of SGO criteria to identify PLS cases were 32.7 and 77%, respectively. Multivariate analysis of clinical and pathologic parameters failed to identify statistically significant differences between sporadic and PLS tumors with the exception of tumors arising from the lower uterine segment. These tumors were more likely to occur in PLS tumors. Cost-effectiveness analysis showed clinical criteria and universal testing strategies cost $6,235.27/PLS case identified and $5,970.38/PLS case identified, respectively. Conclusions: SGO 5-10% criteria successfully identify PLS cases among women who are young or have significant family history of LS related tumors. However, a larger proportion of PLS cases occurring at older ages with less significant family history are not detected by this screening strategy. Compared to SGO clinical criteria, universal tumor testing is a cost effective strategy to identify women presenting with endometrial cancer who are at elevated risk for having LS.

Cancer screening behaviors among Asian Americans in Houston, Texas

Background: Cancer is the second-leading cause of death in the United States, and Asian Americans/Pacific Islanders are the only racial/ethnic group for which cancer is the leading cause of death. Regular cancer screenings help to identify precancerous lesions and cancer at an earlier stage, when the cancer is more treatable. Ethnic disparities in participation in cancer screenings are also striking, and evidence indicates that Asian Americans may have lower rates of cancer screening participation than other racial/ethnic groups. The Health of Houston Survey 2010 (HHS 2010) is an address-based survey, administered via telephone, website, and mail, of over 5,000 respondents in Houston and Harris County that provides recent data on the health status and needs of the Houston community. HHS 2010 researchers oversampled for Asians and Vietnamese Americans in order to obtain a sample size large enough to obtain statistical power. This dataset provides a unique opportunity to examine the cancer screening behaviors and predictors of Vietnamese and Chinese Americans living in Houston, Texas.^ Methods: This study was a secondary data analysis of HHS 2010 data. The data were analyzed to compare the breast, cervical, and colorectal cancer screening compliance rates of Vietnamese and Chinese Americans with other racial/ethnic groups in Houston, Texas. Key predictors of participation and barriers to cancer screening were identified.^ Results: The results of this study indicate that in Houston, Vietnamese Americans and Asian Americans as a whole have strikingly lower rates of participation in cancer screenings compared to other ethnic groups. Chinese Americans had the highest rate of noncompliance for mammography of all ethnic groups; Asian Americans and Vietnamese Americans also had high rates of noncompliance. Similarly, Vietnamese and Asian Americans had high rates of noncompliance with colorectal cancer screening recommendations. Importantly, Vietnamese, Chinese, and Asian Americans had by far the worst pap test participation, with noncompliance rates more than double that of all other racial/ethnic groups. In general, the findings indicated several key predictors in cancer screening behaviors, including English language proficiency, years lived in the United States, health insurance, college education, and income; however, the significance and patterns of these variables varied by ethnic group as well as cancer site.^ Conclusions: This secondary analysis highlights the disparities in cancer screening participation among Vietnamese, Chinese, and Asian Americans in Houston, Texas and indicate the need to identify Asian Americans as a high-risk group in need of health promotion attention. Barriers to screening and educational needs appear to be specific to each target ethnic group. Thus, health educators and health professionals in Houston must focus on the specific educational needs of the key ethnic groups that make up the Houston population. Further, more ethnic-specific research is needed to examine the health behaviors and needs of Houston's Asian American subgroups.^

Baseline quality of life as a predictor of exercise intervention adherence among endometrial cancer survivors

Background: The objective of this analysis is to test whether baseline quality of life (QOL) measurements, body mass index (BMI) and prior exercise behavior are significantly associated with (1) telephone counseling adherence, and (2) activity at the final assessment, in a physical activity promoting intervention among endometrial cancer survivors.^ Methods: One hundred endometrial cancer survivors not currently meeting physical activity guidelines completed baseline QOL and anthropometric assessments to measure general physical and mental health [Medical Outcomes Survey (SF-36)], sleep patterns and sleep quality [Pittsburgh Sleep Quality Index (PSQI)], perceived stress [Perceived Stress Scale (PSS)], cancer-specific concerns of long-term survivors [Quality of Life in Adult Cancer Survivors (QLACS)], and psychological distress [Brief Symptom Inventory-18 (BSI-18)]. Survivors were counseled by telephone during the 6-month intervention and their completion rate determined their adherence. The primary variables of interest included age, baseline BMI, baseline activity level, time since diagnosis, education, treatment received, and the SF-36 physical and mental component scores.^ Results: Final activity was most closely linked with baseline activity (p<.001) and less invasive surgery, being leaner and older, and experiencing less pain and more vitality. Telephone counseling was also predicted well by baseline activity, working less and having better overall cancer-related functioning.^ Conclusion: Above and beyond the QOL measures, baseline activity was the strongest predictor of both final activity and telephone counseling adherence. While education, surgery treatment type and bodily pain were important predictors for final exercise and employment status and cancer-related quality of life were important predictors for telephone counseling adherence, considering adaptive exercise interventions that focus heavily on engaging inactive participants may be a way to produce better exercise-related outcomes in the endometrial cancer survivor population.^

External validation study of a clinical prediction rule for ambulation outcomes after traumatic spinal cord injury

The main objective of this study was to determine the external validity of a clinical prediction rule developed by the European Multicenter Study on Human Spinal Cord Injury (EM-SCI) to predict the ambulation outcomes 12 months after traumatic spinal cord injury. Data from the North American Clinical Trials Network (NACTN) data registry with approximately 500 SCI cases were used for this validity study. The predictive accuracy of the EM-SCI prognostic model was evaluated using calibration and discrimination based on 231 NACTN cases. The area under the receiver-operating-characteristics curve (ROC) curve was 0.927 (95% CI 0.894 – 0.959) for the EM-SCI model when applied to NACTN population. This is lower than the AUC of 0.956 (95% CI 0.936 – 0.976) reported for the EM-SCI population, but suggests that the EM-SCI clinical prediction rule distinguished well between those patients in the NACTN population who were able to achieve independent ambulation and those who did not achieve independent ambulation. The calibration curve suggests that higher the prediction score is, the better the probability of walking with the best prediction for AIS D patients. In conclusion, the EM-SCI clinical prediction rule was determined to be generalizable to the adult NACTN SCI population.^

Physician attitudes on the HPV vaccine

The quadrivalent HPV vaccine was developed primarily for the prevention of cervical cancer. The vaccine, originally approved for females, was recently approved by the American Committee for Immunization Practices to be administered to males, allowing federal programs to pay for the vaccination for both males and females. However, uptake for this vaccination has been low. Studies show that physicians have great influence over whether or not parents decide to vaccinate their children. In this study, a survey was mailed out asking physicians about their attitude towards the HPV vaccination and what they believed to be the barriers to the vaccination of their patients. The analysis of the data included descriptive statistics and chi-square analysis in order to compare the differences in responses between male and female patients. The vast majority of physicians supported the vaccination of both females and males. However, the perceived barriers to vaccinating females differed from males, with physicians believing that parents' concern about sexual promiscuity was a greater barrier to vaccination in girls than boys (p=0.007). The other major significant difference in perceived barriers among physicians is the belief that physicians in general are less likely to promote the vaccination in males compared to females (p=0.01). Despite evidence to the contrary, it seems more patient education is needed regarding sexual promiscuity and its association with the HPV vaccine. There may also be a need for increased physician education regarding the use of the HPV vaccine for male patients.^

Intensive care unit utilization among patients with cancer at the end of life

Over the last 2 decades, survival rates in critically ill cancer patients have improved. Despite the increase in survival, the intensive care unit (ICU) continues to be a location where end-of-life care takes place. More than 20% of deaths in the United States occur after admission to an ICU, and as baby boomers reach the seventh and eighth decades of their lives, the volume of patients in the ICU is predicted to rise. The aim of this study was to evaluate intensive care unit utilization among patients with cancer who were at the end of life. End of life was defined using decedent and high-risk cohort study designs. The decedent study evaluated characteristics and ICU utilization during the terminal hospital stay among patients who died at The University of Texas MD Anderson Cancer Center during 2003-2007. The high-risk cohort study evaluated characteristics and ICU utilization during the index hospital stay among patients admitted to MD Anderson during 2003-2007 with a high risk of in-hospital mortality. Factors associated with higher ICU utilization in the decedent study included non-local residence, hematologic and non-metastatic solid tumor malignancies, malignancy diagnosed within 2 months, and elective admission to surgical or pediatric services. Having a palliative care consultation on admission was associated with dying in the hospital without ICU services. In the cohort of patients with high risk of in-hospital mortality, patients who went to the ICU were more likely to be younger, male, with newly diagnosed non-metastatic solid tumor or hematologic malignancy, and admitted from the emergency center to one of the surgical services. A palliative care consultation on admission was associated with a decreased likelihood of having an ICU stay. There were no differences in ethnicity, marital status, comorbidities, or insurance status between patients who did and did not utilize ICU services. Inpatient mortality probability models developed for the general population are inadequate in predicting in-hospital mortality for patients with cancer. The following characteristics that differed between the decedent study and high-risk cohort study can be considered in future research to predict risk of in-hospital mortality for patients with cancer: ethnicity, type and stage of malignancy, time since diagnosis, and having advance directives. Identifying those at risk can precipitate discussions in advance to ensure care remains appropriate and in accordance with the wishes of the patient and family.^

Optimal, minimax, and Bayesian two-stage designs in two-dose phase II clinical trials

Background: For most cytotoxic and biologic anti-cancer agents, the response rate of the drug is commonly assumed to be non-decreasing with an increasing dose. However, an increasing dose does not always result in an appreciable increase in the response rate. This may especially be true at high doses for a biologic agent. Therefore, in a phase II trial the investigators may be interested in testing the anti-tumor activity of a drug at more than one (often two) doses, instead of only at the maximum tolerated dose (MTD). This way, when the lower dose appears equally effective, this dose can be recommended for further confirmatory testing in a phase III trial under potential long-term toxicity and cost considerations. A common approach to designing such a phase II trial has been to use an independent (e.g., Simon's two-stage) design at each dose ignoring the prior knowledge about the ordering of the response probabilities at the different doses. However, failure to account for this ordering constraint in estimating the response probabilities may result in an inefficient design. In this dissertation, we developed extensions of Simon's optimal and minimax two-stage designs, including both frequentist and Bayesian methods, for two doses that assume ordered response rates between doses. ^ Methods: Optimal and minimax two-stage designs are proposed for phase II clinical trials in settings where the true response rates at two dose levels are ordered. We borrow strength between doses using isotonic regression and control the joint and/or marginal error probabilities. Bayesian two-stage designs are also proposed under a stochastic ordering constraint. ^ Results: Compared to Simon's designs, when controlling the power and type I error at the same levels, the proposed frequentist and Bayesian designs reduce the maximum and expected sample sizes. Most of the proposed designs also increase the probability of early termination when the true response rates are poor. ^ Conclusion: Proposed frequentist and Bayesian designs are superior to Simon's designs in terms of operating characteristics (expected sample size and probability of early termination, when the response rates are poor) Thus, the proposed designs lead to more cost-efficient and ethical trials, and may consequently improve and expedite the drug discovery process. The proposed designs may be extended to designs of multiple group trials and drug combination trials.^

Scanned Ion Beam Therapy for Thoracic Tumors

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some patients with Hodgkin lymphoma, carbon-ion therapy would reduce the predicted risk of second cancer incidence in the breast compared with proton therapy. The purpose of this work was to determine whether 4D-optimized carbon-ion therapy would significantly reduce the predicted risk of radiation induced second cancers in the breast for female Hodgkin lymphoma patients while preserving tumor control compared with proton therapy. To achieve our goals, we first investigated whether 4D-optimized carbon beam tracking could reduce dose to volumes outside a moving target compared with 3D-optimized carbon beam tracking while preserving target dose coverage. To understand the reliability of scanned carbon beam tracking, we studied the robustness of dose distributions in thoracic targets to uncertainties in patient motion. Finally, we investigated whether using carbon-ion therapy instead of proton therapy would significantly reduce the predicted risk of second cancer in the breast for a sample of Hodgkin lymphoma patients. We found that 4D-optimized ion beam tracking therapy can reduce the maximum dose to critical structures near a moving target by as much as 53%, compared to 3D-optimized ion beam tracking therapy. We validated these findings experimentally using a scanned carbon ion synchrotron and a motion phantom. We found scanned carbon beam tracking to be sensitive to a number of motion uncertainties, most notably phase delays in tracking, systematic spatial errors, and interfractional motion changes. Our findings indicate that a lower risk of second cancer in the breast might be expected for some Hodgkin lymphoma patients using carbon-ion therapy instead of proton therapy. For our reference scenario, we found the ratio of risk to be 0.77 ± 0.35 for radiogenic breast cancer after carbon-ion therapy versus proton therapy. Our findings were dependent on the RBE values for tumor induction and the radiosensitivity of breast tissue, as well as the physical dose distribution.

Azithromycin efficacy in treatment of Chlamydia trachomatis

Adolescents 15 – 19 years of age have the highest prevalence of Chlamydia trachomatis out of any age group, reaching 28.3% among detained youth [1]. The 2010 Center for Disease Control guidelines recommend one dose of azithromycin for the treatment of uncomplicated chlamydia infections based on 97% cure rate with azithromycin. Recent studies found an 8% or higher failure rate of azithromycin treatment in adolescents [2-5]. We conducted a prospective study beginning May, 2012 in the Harris County Juvenile Justice Center (HCJJC) medical department. Study subjects were detainees with positive urine NAAT tests for chlamydia on intake. We provided treatment with Azithromycin, completed questionnaires assessing risk factors and performed a test of cure for chlamydia three weeks after successful treatment. Those with treatment failure (positive TOC) received doxycycline for seven days. The preliminary results summarized herein are based on data collected from May 2012 to January 2013. Of the 97 youth enrolled in the study to date, 4 (4.1%) experienced treatment failure after administration of Azithromycin. Of these four patients, all were male, African-American and asymptomatic at the time of initial diagnosis and treatment. Of note, 37 (38%) patients in the cohort complained of abdominal pain with administration of Azithromycin. Results to date suggest that the efficacy of Azithromycin in our study is higher than the recent reported studies indicating a possible upper bound of Azithromycin. These results are preliminary and recruitment will continue until a sample size of 127 youth is reached.^

Colorectal cancer screening: Participation and determinants in West Texas

Early detection by screening is the key to colorectal cancer control. However, colorectal cancer screening and its determinants in rural areas have not been adequately studied. This goal of this study was to investigate the screening participation and determinants of colonoscopy, sigmoidoscopy, and/or fecal occult blood test (FOBT) in subjects of Project Frontier from the rural counties of Cochran, Bailey and Parmer, Texas. Subjects ( n=820 with 435 Hispanics, 355 Non-Hispanic Whites, 26 African Americans, and 4 unknown ethnicity; 255 males, 565 females, aged from 40 to 92 years) were from Project FRONTIER. Stepwise logistic regression analysis was performed. Explanatory variables included ethnicity (Hispanic, Non-Hispanic white and African American), gender, health insurance, smoking status, household income, education (years), physical activity, overweight, other health screenings, personal physicians, family history (first-degree relatives) of cancers, and preferred language (English vs. Spanish) for interview/testing. The screening percentage for ever having had a colonoscopy/sigmoidoscopy (51.8%) in this cohort aged 50 years or older is well below the percentage of the nation (65.2%) and Texas (64.6%) while the percentage for FOBT (29.2%) is higher than in the nation (17.2%) and Texas (14.9%). However, Hispanics had significantly lower participation than non-Hispanic whites for colonoscopy/sigmoidoscopy (37.0% vs. 66.0%) and FOBT (16.5% vs. 41.7%), respectively. Stepwise logistic regression showed that predictors for colonoscopy, sigmoidoscopy or FOBT included Hispanic race (p = 0.0045), age (p < 0.0001), other screening procedure (p < 0.0001), insurance status (p < 0.0001) and physician status (p = 0.0053). Screening percentage for colonoscopy/sigmoidoscopy in this rural cohort is well below the national and Texas level mainly due to the lower participation of Hispanics vs. Non-Hispanic whites. Health insurance, having had a personal physician, having had screenings for other cancers, race, and older age are among the main predictors.^

Evaluation of memory B cells among perinatally HIV infected children from Houston Texas

Background: HIV associated B cell exhaustion is a notable characteristic of HIV viremic adults. However, it is not known if such alterations are present in perinatal HIV infected children, whose viral dynamics differs from those seen in adults. In the present study we perform an analysis of B cells subsets and measure antigen-specific memory B cells (MBC) in a pediatric HIV infected cohort. ^ Methods: Peripheral mononuclear cells (PBMC) of perinatal HIV infected individuals are characterized into naïve (CD21hi/CD27−), classic (CD27+), tissue like (CD21lo/CD27 −) and activated MBC (CD27+CD21− ) by FACS. A memory ELISPOT assay is used to detect antibody secreting cells. We measure total IgG and antibodies specific for influenza, HBV, mumps, measles, rubella and VZV. Memory was expressed as spot forming cells (SPC) /million of PBMC. Wilcoxon rank-sum was used to compare unpaired groups and linear regression analysis was used to determine predictors of B cell dysfunction ^ Results: 41 HIV perinatal infected children are included (51.2% females and 65.9% Black). Age at study is median (range) 8.78 years (4.39-11.57). At the time of testing they have a CD4% of 30.9 (23.2-39.4), a viral load (VL) of 1.95 log10 copies/ml (1.68-3.29) and a cumulative VL of 3.4 log10 copy × days (2.7-4.0). Ninety two percent of the children are on cARV for > 6 months. Overall, HIV+ children compared with controls have a significant lower number of IgG and antigen specific SFC. In addition, they have a lower proportion of classical MBC 12.9 (8.09-19.85) vs 29.4 (18.7-39.05); 0.01, but a significant higher proportion of tissue like memory MBC 6.01 (2.79-12.7) vs 0.99 (0.87-1.38); 0.003, compared with controls. Patients are parsed on VL (<400 and ≥ 400 copies/ml) with the objective to evaluate the effect of VL on B cell status. Patients with a VL ≥ 400 copies/ml have a significantly lower IgG, HBV, measles, rubella and VZV SPC compared with those with a VL < 400 copies/ml. There are no significant differences in B cell subpopulations between the groups. A moderate negative correlation was observed between the time of cARV initiation and the frequency of IgG memory B cells, suggesting that early initiation of cARV appears to lead to a better functionality of the IgG memory B cells (P=0.05). A statistically significant positive correlation was observed between the total number of IgG memory cells and the number of antigen-specific memory B cells/SPCs. Suggesting that the progressive recovery of the IgG memory B cell pull goes along with a progressive increase in the number of antigen-specific SPCs. ^ Conclusion: A pediatric cohort in overall good status with respect to HIV infection and on ART has defects in B cell function and numbers (reduced total and antigen specific MBC and increased tissue like and reduced classical MBC).^