Citations

Abstract Background: Human papillomavirus (HPV) vaccination rates in the United States remain low and lag behind other recommended adolescent vaccines. Studies evaluating the association of geographic and area-level characteristics with HPV vaccination rates provide a valuable resource for public health planning. Method: We used the Rochester Epidemiology Project data linkage system to ascertain HPV vaccination rates between 2010 and 2015 in a 7-county region of southern Minnesota. Geocoded individual patient data were spatially linked to socioeconomic data from the American Community Survey at the census block group level. Bayesian hierarchical logistic regression was used to model incident vaccination rates, adjusting for individual- and area-level sociodemographic characteristics, and geolocation. Geolocation was modeled as an approximated Gaussian field using a Stochastic Partial Differential Equations approach. All models were estimated using Integrated Nested Laplace Approximations. Results: In adjusted models, increasing age and female sex were associated with increased HPV vaccination. Lower socioeconomic status was associated with decreased rates of initiation [adjusted odds ratio (AOR); 95% confidence interval = 0.90 (0.86–0.95)], completion of the second dose [AOR = 0.88 (0.83–0.93)], and completion of the third dose [AOR = 0.85 (0.80–0.92)]. Geographic spatial analysis demonstrated increased odds of vaccination for the eastern region and in the greater Rochester metropolitan area, showing significant spatial variation not explained by individual level characteristics and ACS block group-level data. Conclusions: HPV vaccination rates varied geographically and by individual and geographically indexed sociodemographic characteristics. Impact: Identifying geographic regions with low HPV vaccination rates can help target clinical and community efforts to improve vaccination rates. Cancer Epidemiol Biomarkers Prev; 26(4); 533–40. ©2017 AACR. See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”

BACKGROUND: Critically ill patients frequently receive plasma transfusion under the assumptions that abnormal coagulation test results confer increased risk of bleeding and that plasma transfusion will decrease this risk. However, the effect of prophylactic plasma transfusion remains poorly understood. The objective of this study was to determine the relationship between prophylactic plasma transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to the intensive care unit (ICU) at a single academic institution between January 1, 2009 and December 31, 2013. Inclusion criteria included age ≥18 years and an international normalized ratio measured during ICU admission. Multivariable propensity-matched analyses were used to evaluate associations between prophylactic plasma transfusion and outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of hospital- and ICU-free days and mortality within 30 days of ICU discharge. RESULTS: A total of 27,561 patients were included in the investigation with 2472 (9.0%) receiving plasma therapy and 1105 (44.7%) for which plasma transfusion was prophylactic in nature. In multivariable propensity-matched analyses, patients receiving plasma had higher rates of red blood cell transfusion (odds ratio: 4.3 [95% confidence interval: 3.3–5.7], P < .001) and fewer hospital-free days (estimated % increase: −11.0% [95% confidence interval: −11.4, −10.6%], P < .001). There were no significant differences in ICU-free days or mortality. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of plasma in the critically ill was not associated with improved clinical outcomes. Further investigation examining the utility of plasma transfusion in this population is warranted.

AbstractPleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy‐number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A‐PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%–60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A‐PXA (93%), BRAF V600E (87%), and wild‐type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses −22 (n = 11), −14 (n = 7), −13 (n = 5). Losses and copy‐neutral loss of heterozygosity were significantly more common in A‐PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy‐number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A‐PXA with areas of distinct low‐ and high‐grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy‐number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy‐number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.

Objectives To determine the prognostic potential of a 24‐gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer‐specific mortality (PCSM) after radical prostatectomy (RP). Patients and Methods Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time‐dependent c‐index analysis, Cox proportional hazards regression and Kaplan–Meier survival analysis. Results Higher Sig24 scores were significantly associated with higher pathological Gleason scores in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time‐to‐event information, indicated that patients with high Sig24 scores also had a higher risk of developing metastasis (hazard ratio [HR] 3.78, 95% confidence interval [CI]: 1.96–7.29; P < 0.001) or of PCSM (HR 6.54, 95% CI: 2.16–19.83; P < 0.001). Conclusions The findings of the present study show the applicability of Sig24 for the prognosis of metastasis or PCSM after RP. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.

Abstract Serum levels of miR-194 have been reported to predict prostate cancer recurrence after surgery, but its functional contributions to this disease have not been studied. Herein, it is demonstrated that miR-194 is a driver of prostate cancer metastasis. Prostate tissue levels of miR-194 were associated with disease aggressiveness and poor outcome. Ectopic delivery of miR-194 stimulated migration, invasion, and epithelial–mesenchymal transition in human prostate cancer cell lines, and stable overexpression of miR-194 enhanced metastasis of intravenous and intraprostatic tumor xenografts. Conversely, inhibition of miR-194 activity suppressed the invasive capacity of prostate cancer cell lines in vitro and in vivo. Mechanistic investigations identified the ubiquitin ligase suppressor of cytokine signaling 2 (SOCS2) as a direct, biologically relevant target of miR-194 in prostate cancer. Low levels of SOCS2 correlated strongly with disease recurrence and metastasis in clinical specimens. SOCS2 downregulation recapitulated miR-194–driven metastatic phenotypes, whereas overexpression of a nontargetable SOCS2 reduced miR-194–stimulated invasion. Targeting of SOCS2 by miR-194 resulted in derepression of the oncogenic kinases FLT3 and JAK2, leading to enhanced ERK and STAT3 signaling. Pharmacologic inhibition of ERK and JAK/STAT pathways reversed miR-194–driven phenotypes. The GATA2 transcription factor was identified as an upstream regulator of miR-194, consistent with a strong concordance between GATA2 and miR-194 levels in clinical specimens. Overall, these results offer new insights into the molecular mechanisms of metastatic progression in prostate cancer. Cancer Res; 77(4); 1021–34. ©2016 AACR.

Abstract Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer. Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and &gt;28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09–2.07 and 1.69; 95% CI, 1.07–2.65, respectively; Ptrend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27–2.49 and 1.94; 95% CI, 1.19–3.18, respectively; Ptrend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366–75. ©2016 AACR.