Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials.

BACKGROUND: A model was built that characterized effects of individual factors on five-year prostate cancer (PCa) risk in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This model was validated in a third San Antonio Biomarkers of Risk (SABOR) screening cohort. METHODS: A prediction model for 1- to 5-year risk of developing PCa and Gleason > 7 PCa (HG PCa) was built on PLCO and SELECT using the Cox proportional hazards model adjusting for patient baseline characteristics. Random forests and neural networks were compared to Cox proportional hazard survival models, using the trial datasets for model building and the SABOR cohort for model evaluation. The most accurate prediction model is included in an online calculator. RESULTS: The respective rates of PCa were 8.9%, 7.2%, and 11.1% in PLCO (n = 31,495), SELECT (n = 35,507), and SABOR (n = 1790) over median follow-up of 11.7, 8.1 and 9.0 years. The Cox model showed higher prostate-specific antigen (PSA), BMI and age, and African American race to be associated with PCa and HGPCa. Five-year risk predictions from the combined SELECT and PLCO model effectively discriminated risk in the SABOR cohort with C-index 0.76 (95% CI [0.72, 0.79]) for PCa, and 0.74 (95% CI [0.65,0.83]) for HGPCa. CONCLUSIONS: A 1- to 5-year PCa risk prediction model developed from PLCO and SELECT was validated with SABOR and implemented online. This model can individualize and inform shared screening decisions.

Lineage of origin in rhabdomyosarcoma informs pharmacological response.

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.

Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma.

BACKGROUND: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments. METHODS: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. RESULTS: Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). CONCLUSIONS: These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

The Effect of Trabeculae Carneae on Left Ventricular Diastolic Compliance: Improvement in Compliance With Trabecular Cutting.

The role of trabeculae carneae in modulating left ventricular (LV) diastolic compliance remains unclear. The objective of this study was to determine the contribution of trabeculae carneae to the LV diastolic compliance. LV pressure-volume compliance curves were measured in six human heart explants from patients with LV hypertrophy at baseline and following trabecular cutting. The effect of trabecular cutting was also analyzed with finite-element model (FEM) simulations. Our results demonstrated that LV compliance improved after trabecular cutting (p < 0.001). Finite-element simulations further demonstrated that stiffer trabeculae reduce LV compliance further, and that the presence of trabeculae reduced the wall stress in the apex. In conclusion, we demonstrate that integrity of the LV and trabeculae is important to maintain LV stiffness and loss in trabeculae leads to more LV compliance.

The Latino Eyelid: Anthropometric Analysis of a Spectrum of Findings.

PURPOSE: Published anthropometric measurements of the Latino eyelid are limited. This study describes features spanning the morphologic range from non-Latino whites to East Asians in the spectrum of the Latino eyelid. METHODS: A cross-sectional study of 68 people (32 Latinos, 18 non-Latino whites, and 18 East Asians, ages 18-39), approved by the Institutional Review Board and HIPAA-compliant, was performed. Saliva samples determined genetic components. Indirect anthropometric measurements were performed with ImageJ software. Eyelid measurements included margin reflex distance, palpebral fissure height, eyelid crease height, orbital height, horizontal fissure length, inner and outer canthal distances, medial and lateral canthal angles, and lateral canthal angle of inclination. Additionally, exophthalmometry and epicanthal folds were recorded. RESULTS: Analysis of 184 markers from HumanExome Chip data revealed distinct clustering patterns. Genetically, the Asian participants were in 1 group, the whites in another group, and the Latinos spanned the spectrum between these 2 groups. In Latinos, the inner canthal distance and lateral canthal angle of inclination were similar to Asians, whereas the eyelid crease spanned the range from Asians to whites. Half of the Latinos had epicanthal folds. CONCLUSIONS: Latinos possess a spectrum of eyelid features spanning the morphologic characteristics from those of non-Latino whites to those of East Asians. These normative data on Latinos from Texas and Mexico aid in the diagnoses of Latino eyelid disorders and are a reference for optimizing oculofacial surgery outcomes.

Serial Percent Free Prostate Specific Antigen in Combination with Prostate Specific Antigen for Population Based Early Detection of Prostate Cancer.

PURPOSE: We characterized the diagnostic properties of serial percent free prostate specific antigen in relation to prostate specific antigen in a multiethnic, multiracial cohort of healthy men. MATERIALS AND METHODS: A total of 6,982 percent free prostate specific antigen and prostate specific antigen measurements were obtained from participants in a greater than 12-year Texas screening study comprising 1,625 men who never underwent biopsy, 497 who underwent 1 or more biopsies negative for prostate cancer and 61 diagnosed with prostate cancer. We evaluated the ROC AUC of percent free prostate specific antigen and the proportion of patients with fluctuating values across multiple visits determined according to 2 thresholds (less than 15% vs 25%). The proportion of cancer cases in which percent free prostate specific antigen indicated a positive test before prostate specific antigen greater than 4 ng/ml did and the number of negative biopsies that would have been spared by negative percent free prostate specific antigen test results were calculated. RESULTS: Percent free prostate specific antigen fluctuated around its threshold of less than 25% (less than 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, and with negative and positive biopsies, respectively. At the same thresholds, percent free prostate specific antigen tested positive earlier than prostate specific antigen in 71.4% and 34.2% of cancer cases, respectively. Among men with multiple negative biopsies and PSA greater than 4 ng/ml, percent free PSA would have tested negative in 31.6% and 65.8%, respectively. CONCLUSIONS: Percent free prostate specific antigen should accompany prostate specific antigen testing to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation.

Drug Overdose: Differing Risk Models for Women and Men among Opioid Users with Non-Cancer Pain.

OBJECTIVE: To examine risk factors for drug overdose by sex reflecting differing patterns of opioid and other drug use. DESIGN: National privately insured cohort. SUBJECTS: 206,869 subjects filling ≥2 opioid prescriptions from January 2009 through July 2012. METHODS: Sex-specific prediction models for future drug overdose developed and validated using variables measured within 6 months after starting opioids: demographics, substance use, comorbidities, opioid dose, and psychoactive drugs. Logistic regression and split-sample validation were used. RESULTS: Area under the receiver operating curves (AUCs) for both sex-specific risk models (0.80) were higher (P < 0.001) than for daily opioid dose alone. Risk factors for drug overdose were similar by sex but effects differed. For both sexes, substance use was the strongest predictor but the adjusted odds ratio (AOR) [95% CI] was 5.95 [4.33, 8.06] for women vs. 4.69 [3.24, 6.68] for men. AORs for daily opioid dose rose monotonically in men to 2.42 [1.76, 3.28] for high vs. low dose but were non-monotonic in women with 1.79 [1.35, 2.35] for high dose. AOR for 1-60 days of antidepressants vs. none was significant only in men (1.98 [1.32, 2.9]). AOR for benzodiazepine use was higher in men than women (2.75 vs 2.35, respectively). Zolpidem use was significant only in women. AUCs for sex-specific models were lower for the opposite sex and significantly lower for the men's model in the women's derivation dataset. CONCLUSIONS: These models reveal similar risk factors by sex for drug overdose in opioid users but significant differences in effects that, if validated in other cohorts, may inform differing risk management strategies.

Older Stroke Patients with High Stroke Scores Have Delayed Door-To-Needle Times.

INTRODUCTION: The timely administration of intravenous (IV) tissue plasminogen activator (t-PA) to acute ischemic stroke patients from the period of symptom presentation to treatment, door-to-needle (DTN) time, is an important focus for quality improvement and best clinical practice. METHODS: A retrospective review of our Get With The Guidelines database was performed for a 5-hospital telestroke network for the period between January 2010 and January 2015. All acute ischemic stroke patients who were triaged in the emergency departments connected to the telestroke network and received IV t-PA were included. Optimal DTN time was defined as less than 60 minutes. Logistic regression was performed with clinical variables associated with DTN time. Age and National Institutes of Health Stroke Scale (NIHSS) score were categorized based on clinically significant cutoffs. RESULTS: Six-hundred and fifty-two patients (51% women, 46% White, 45% Hispanic, and 8% Black) were included in this study. The mean age was 70 years (range 29-98). Of the variables analyzed, only arrival mode, initial NIHSS score, and the interaction between age and initial NIHSS score were significant. DTN time more than or equal to 60 minutes was most common in patients aged more than 80 years with NIHSS score higher than 10. CONCLUSIONS: The cause of DTN time delay for older patients with higher NIHSS score is unclear but was not related to presenting blood pressure or arrival mode. Further study of this subgroup is important to reduce overall DTN times.

Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Liver biopsy is the only reliable way of diagnosing and staging NASH but its invasive nature limits its use. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative. We studied its clinical value in a large multiethnic NAFLD population and examined its relationship to clinical/metabolic/histological parameters. METHODS: 424 middle-aged subjects in whom we measured adipose tissue, liver and muscle insulin resistance (IR), liver fat by MRS (n=275) and histology (n=318). RESULTS: Median CK-18 were elevated in patients with vs. without NAFLD by MRS (209 [IQR: 137-329] vs. 122 [IQR: 98-155]U/L) or with vs. without NASH (232 [IQR: 151-387] vs. 170 [IQR: 135-234]U/L, both p<0.001). Plasma CK-18 raised significantly with any increase in steatosis, inflammation and fibrosis, but there was a significant overlap across disease severity. The CK-18 AUROC to predict NAFLD, NASH or fibrosis were 0.77 (95% CI=0.71-0.84), 0.65 (95% CI=0.59-0.71) and 0.68 (95% CI=0.61-0.75), respectively. The overall sensitivity/specificity for NAFLD, NASH and fibrosis were 63% (57-70%)/83% (69-92%), 58% (51-65%)/68% (59-76%) and 54% (44-63%)/85% (75-92%), respectively. CK-18 correlated most strongly with ALT (r=0.57, p<0.0001) and adipose tissue IR (insulin-suppression of FFA: r=-0.43; p<0.001), less with steatosis, lobular inflammation and fibrosis (r=0.28-0.34, all p<0.001), but not with ballooning, BMI, metabolic syndrome or T2DM. CONCLUSIONS: Plasma CK-18 has a high specificity for NAFLD and fibrosis, but its limited sensitivity makes it inadequate as a screening test for staging NASH. Whether combined as a diagnostic panel with other biomarkers or clinical/laboratory tests may prove useful requires further study.

SNOT-22 Quality of Life Scores Improve After Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP). METHODS: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups. RESULTS: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores (P = .244). The CSF rhinorrhea group improved more in runny nose (P < .001), postnasal discharge (P < .001), wake up at night (P = .024), and embarrassed (P = .002). The CRSsNP group improved more in sneezing (P = .027), nasal blockage (P < .001), decreased sense of smell/taste (P = .011), thick nasal discharge (P < .001), facial pain/pressure (P = .008), and the ear/facial domain (P = .010). CONCLUSIONS: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related, chronic, irreversible fibrotic lung disease. IPF is associated with increased senescent cells burden, which may be alleviated with administration of senescent cell targeting drugs termed 'senolytics'. We previously conducted an open-label single-arm pilot study of the senolytic combination of dasatinib and quercetin (D + Q) in patients with IPF but lack of control group limited interpretation and next-stage trial planning. The primary objective of this confirmatory randomized placebo-controlled pilot trial (RCT; NCT02874989) was to report adverse events with D + Q and inform study feasibility for future efficacy trials. METHODS: Twelve participants with IPF aged >50 years were blinded and randomized at a 1:1 ratio to either receive three weeks of D + Q (D: 100 mg/d and Q: 1250 mg/d, three consecutive days per week) or matching placebo. FINDINGS: All participants completed the scheduled drug dosing regimen (108/108 doses) and planned assessments (60/60). While the placebo arm reported fewer overall non-serious AEs (65 vs 22), there were no serious adverse events related to D + Q. Most AEs in the D + Q arm are common in IPF patients or anticipated side effects of D. Sleep disturbances and anxiety were disproportionately represented in the D + Q arm (4/6 vs 0/6). Frailty, pulmonary, or physical function were explored before and after intermittent D + Q; though under-powered to evaluate change, these measures do not appear to differ meaningfully between groups. INTERPRETATION: Intermittently-dosed D + Q in patients with IPF is feasible and generally well-tolerated. Further prospective studies, such as a larger RCT, are needed to confirm the safety and efficacy of D + Q in patients with IPF. FUNDING: This work was supported by National Institutes of Health grants R33AG61456 (JLK, TT), Robert and Arlene Kogod (JLK, TT), the Connor Fund (JLK, TT), Robert J. and Theresa W. Ryan (JLK, TT), and the Noaber Foundation (JLK, TT) San Antonio Claude D. Pepper Older Americans Independence Center's (OAIC)Pilot/Exploratory Studies Core (PESC) Grant (AMN, NM); NIHK01 AG059837 (JNJ), P30 AG021332 (SBK, JNJ); NIHR37 AG013925 (JLK), the Connor Group (JLK), Glenn/AFAR BIG Award (JLK), Robert J. and Theresa W. Ryan (JLK), and the Noaber and Ted Nash Long Life Foundations (JLK).

Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

OBJECTIVES: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP). METHODS: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared. RESULTS: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (P < .001) and was more likely to designate this symptom as most important (P < .001). The CRSsNP group scored significantly higher in nasal blockage (P < .001), thick nasal discharge (P < .001), facial pain/pressure (P < .001), and in the ear/facial (P < .001) and rhinologic (P = .003) domains. Multivariable logistic regression revealed that runny nose (P < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P < .001), thick nasal discharge (P < .001), and facial pain/pressure (P = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P = .676). CONCLUSIONS: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

Children's Afterschool Culinary Education Improves Eating Behaviors.

Objectives: Culinary education may be one way to improve children's eating behaviors. We formatively evaluated the effect of a hands-on afterschool 12-module, registered dietitian-led culinary education program on healthy eating behaviors in a predominately Hispanic/Latino, low-socioeconomic community. Methods: Of 234 children participating in the program, 77% completed both pre- and post-assessment surveys (n = 180; mean age 9.8 years; 63.3% female; 74.3% Hispanic/Latino, 88.4% receiving free/reduced lunch). In addition to program satisfaction, we assessed changes in children's self-reported fruit, vegetable, and whole-grain consumption, knowledge, and culinary skills using binary and continuous mixed effects models. We report false discovery rate adjusted p-values and effect sizes. Results: 95.5% of participants reported liking the program. Improved whole grain consumption had a medium effect size, while effect sizes for whole grain servings and vegetable consumption were small, but significant (all p < 0.05). Culinary skills increased between 15.1 to 43.4 percent points (all p < 0.01), with medium to large effect sizes. Conclusions: The program was well-received by participants. Participants reported improved eating behaviors and culinary skills after program completion. Therefore, this hands-on afterschool culinary education program can help improve healthy eating in a predominantly Hispanic/Latino, low-socioeconomic community.

Hereditary Cancer Gene Variants in Hispanic Men With a Personal or Family History of Prostate Cancer.

BACKGROUND: Mutations in several common hereditary cancer genes are associated with prostate cancer, but there is limited information on the prevalence of these mutations in Hispanic men. MATERIALS AND METHODS: We selected men at high risk for genetic mutations from 1515 Hispanic men enrolled in the San Antonio Biomarkers of Risk for prostate cancer (SABOR) cohort. Inclusion criteria included men with a diagnosis of prostate cancer or a first-degree family history of prostate cancer. We performed germline genetic testing using the Color Genomics platform, sequencing 30 genes associated with hereditary cancer risk. Additionally, we assessed ancestral informative markers to determine the admixture of the ethnically unique cohort. RESULTS: Of the 275 subjects who met selection criteria, 263 patients had sufficient samples for sequencing. We identified 3.8% of patients (10 of 263) with a pathogenic or likely pathogenic mutation in the 30 genes tested, of whom 70% would not have met established criteria for genetic testing. Six of these mutations were in BRCA1/2 or ATM. There was a significant inverse association between the percentage of Native American ancestry and the risk of prostate cancer, OR 0.11 (95% CI 0.02-0.76, P = .025). CONCLUSION: Hispanic men with either a personal or family history of prostate cancer carry mutations in hereditary cancer genes at a significant rate, on par with non-Hispanic counterparts with similar risk factors.

Disproportionate Burden of COVID-19 Infection Among Hispanic Patients During the First COVID-19 Surge in South Texas.

Introduction: The morbidity and mortality of the COVID-19 pandemic have disproportionately burdened Hispanic populations in the United States. While health equity research is typically conducted in populations where Hispanics are the minority, this project analyzes COVID-19 racioethnic transmission trends over the first 6 months of the pandemic within a large majority-minority city in South Texas. Methods: Patients diagnosed with COVID-19 across inpatient, emergency department, and outpatient settings of a large county health system were included in a clinical registry. For 4644 COVID-19-positive patients between March 16 and August 31, 2020, demographic and clinical data were abstracted from the registry. Race/ethnicity trends over time were compared for patients with and without COVID-19 diagnoses. Logistic regressions identified predictors of inpatient diagnosis by age, race/ethnicity, and testing delay. Results: The proportion of patients with COVID-19 identifying as Hispanic increased rapidly during the pandemic's first months: from 55.6% in March to 85.7% in June. A significantly greater proportion of patients identified as Hispanic within the COVID-19 cohort compared to other diagnoses cohort. Testing delay was 11.6% longer for Hispanic patients, with each day of testing delay associated with 7% increased odds of inpatient COVID-19 diagnosis. Conclusion: These findings highlight the disproportionate impact of COVID-19 on Hispanic populations even within a majority-minority community. In the United States, Hispanic persons are more likely to work frontline jobs, live in multigenerational homes in poverty, and be uninsured. The burden of COVID-19 cases within Bexar County's largest hospital system reflects this systemic inequity. Identifying racioethnic health disparities supports efforts toward mitigating structural factors that predispose minority groups to illness and death.

Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association.

Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.

Developing a model to predict accrual to cancer clinical trials: Data from an NCI designated cancer center.

INTRODUCTION: As cancer center funds are allocated toward several resources, clinical trial offices and the clinical trial infrastructure is constantly scrutinized. It has been shown that 20% of clinical trials fail to achieve their accrual goal and in an institutional level several trials are open with poor accrual. We sought to identify factors that are associated with clinical trial accrual and develop a model to predict clinical trial accrual. METHODS AND MATERIAL: We identified all clinical trials from 1999 to 2015 at UT Health Cancer Center San Antonio. We included observational as well as interventional clinical trials. We collected several variables such as type of study, type of malignancy, trial phase, PI of study. RESULTS: In total we included 297 clinical trials. We identified several factors to be associated with clinical trial accrual (Sponsor type, trial phase, disease category, type of trial, disease state and whether the trial involved a new investigational agent). We developed a predictive model with an AUC of 0.65 that showed that observational, interventional, industry-sponsored trials and trials authored by the local PI were more likely to achieve their accrual goal. CONCLUSION: We were able to identify several factors that were significantly associated with clinical trial accrual. Based on these factors we developed a prediction model for clinical trial accrual. We believe that use of this model can help improve our cancer centers clinical trial portfolio and help in fund allocation.

Processing transdermal alcohol concentration (TAC) data to detect low-level drinking.

BACKGROUND: Several studies have objectively quantified drinking through the use of Alcohol Monitoring System's (AMS) transdermal alcohol concentration (TAC) device known as SCRAM CAM. Criteria that AMS uses to detect drinking are known to be conservative and only reliably detect heavy drinking equivalent to 5 or more standard drinks. Our group has developed Research Rules used to process TAC data in a manner that will detect low-level and moderate drinking even though it is below the AMS criteria for detection. METHODS: Sixteen male and 14 female paid research volunteers wore TAC monitors for 28 days in their natural environments and responded daily to text message prompts to self-report the previous day's drinking. Current analyses describe the Research Rules that we developed and how use of those rules impacts the detection of self-reported drinking treated as the standard in sensitivity/specificity analysis. RESULTS: We observed 606 occurrences of positive TAC events over a total of 867 days and processed the TAC data to retain 345 as possible drinking events, even though AMS criteria confirmed drinking for only 163 of these events. The kinds of TAC events removed or retained by our rules are illustrated as cases of low and moderate drinking days that were detected by our rules but not by the conservative AMS criteria. AMS-confirmed TAC events have a high specificity (99.8%) to detect primarily heavy drinking, but have a poor sensitivity to detect lower-level drinking and a poor specificity as an indicator of alcohol abstinence. In contrast, our Research Rules detected 100% of TAC events detected by AMS but also detected 31% of the lower-level drinking events not detected by AMS, with 91% specificity. CONCLUSIONS: Reliance upon the AMS criteria for alcohol detection affords a high specificity for detection of heavy drinking but is a poor indicator of abstinence rates. In contrast, use of our Research Rules provides more sensitive means to quantify either any drinking or low-moderate levels of drinking while still maintaining good specificity.

Higher baseline dietary fat and fatty acid intake is associated with increased risk of incident prostate cancer in the SABOR study.

BACKGROUND: To study the association of nutrient intake measured by baseline food frequency questionnaire and risk of subsequent prostate cancer (PCa) in the SABOR (San Antonio Biomarkers of Risk) cohort study. METHODS: After IRB approval, more than 1903 men enrolled in a prospective cohort from 2000 to 2010 as part of the SABOR clinical validation site for the National Cancer Institute Early Detection Research Network. Food and nutrient intakes were calculated using a Food Frequency Questionnaire. Cox proportional hazards modeling and covariate-balanced propensity scores were used to assess the associations between all nutrients and PCa. RESULTS: A total of 229 men were diagnosed with PCa by prostate biopsy. Among all nutrients, increased risk of PCa was associated with intake of dietary fat scaled by the total caloric intake, particularly saturated fatty acid (SFA) [HR 1.19; 95% CI, 1.07-1.32), P value < 0.001, False discovery rate (FDR) 0.047] and trans fatty acid (TFA) [HR per quintile 1.21; (95% CI) (1.08-1.35), P < 0.001, FDR 0.039]. There was an increased risk of PCa with increasing intake of monounsaturated fatty acid (MUFA) (HR per quintile 1.14; 95% CI 1.03-1.27, P = 0.01, FDR 0.15) and cholesterol [HR per quintile 1.13; 95% confidence interval (95% CI) (1.02-1.26), P-value 0.02, FDR 0.19]. CONCLUSION: After examining a large, population-based cohort for PCa diagnosis, we identified dietary total fat and certain fatty acids as associated with increased risk of PCa. We found no factors that were protective from PCa. Dietary modification of fatty acid intake may reduce risk of PCa.

Incorporation of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG into Prostate Cancer Prevention Trial Risk Calculator.

BACKGROUND: The Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) is a commonly used risk tool for predicting the outcome on biopsy based on the established risk factors. OBJECTIVE: To determine whether incorporation of the novel urinary markers prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) into the PCPTRC improves its discrimination, accuracy, and clinical net benefit. DESIGN, SETTING, AND PARTICIPANTS: Since PCA3 and T2:ERG were not measured as part of the PCPTRC, a Bayesian modeling approach was used to combine data where the markers were measured in a Michigan cohort with the PCPTRC as prior probabilities to form an updated PCPTRC. This update was compared to the existing PCPTRC on an independent Early Detection Research Network cohort in terms of discrimination, calibration, and decision curve analysis. RESULTS AND LIMITATIONS: Among the 1225 Michigan biopsies, 57.7%, 24.0%, and 18.3% were negative, with low- and high-grade (Gleason grade≥7) prostate cancer, respectively. Evaluated on the Early Detection Research Network validation set comprising 854 biopsies, areas under the curve (95% confidence interval) for predicting high-grade cancer in the 854 biopsies comprising the validation set were 70.0% (66.0-74.0%), 76.4% (72.8-80.0%), and 77.1% (73.6-80.6%) for the PCPTRC alone, with PCA3 added, and PCA3 and T2:ERG added, respectively. Net benefit was improved for the updated PCPTRC, while calibration was not. Limitations are that the updated PCPTRC is based on two different cohorts, the PCPT and Michigan, and that 20% of the validation set came from the Michigan center. More validation is required; hence, the updated risk tool is posted online. CONCLUSIONS: Incorporation of PCA3 into the PCPTRC improved validation on an independent cohort, whereas T2:ERG offered negligible utility in addition to PCA3. PATIENT SUMMARY: After passing external validation, prostate cancer antigen 3 has been added to the online Prostate Cancer Prevention Trial Risk Calculator for use by patients in deciding whether to proceed to biopsy. TMPRSS2:ERG did not improve prediction on the external validation set, but is included for further validation.