Citations

Abstract Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4–57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2–5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Cancer Epidemiol Biomarkers Prev; 24(7); 1121–9. ©2015 AACR.

Growing evidence suggests that pretransplant alpha‐fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin‐reactive alpha‐fetoprotein (AFP‐L3), and des‐gamma‐carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow‐up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP‐L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9‐6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4‐5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3‐12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4‐4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0‐24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8‐18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility. Liver Transpl 21:599–606, 2015. © 2015 AASLD.

Background and Purpose— Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Methods— Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. Results— The sample included 148 367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission ( r 2 =0.107). No important additional effect for any other variable was detected when added to this model. Conclusions— This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set.

BACKGROUND: Pediatric traumatic brain injury (TBI) contributes to impairments in functioning in everyday settings. Evidence suggests that online family problem-solving therapy (FPST) may be effective in reducing adolescent behavioral morbidity. This article examines the efficacy of Counselor-Assisted Problem Solving (CAPS), a form of online FPST in improving long-term functional outcomes of adolescents with TBI relative to Internet resources only. METHODS: Children, aged 12 to 17 years, who were hospitalized in the previous 7 months for TBI were enrolled in a multisite, assessor-blinded randomized controlled trial. Consented participants were randomly assigned to CAPS or an Internet resource comparison (IRC) condition. Outcomes were assessed at baseline and at follow-ups 6, 12, and 18 months postbaseline. The Child and Functional Assessment Scale and the Iowa Family Interaction Rating Scale (IFIRS) served as primary outcomes of child and family functioning respectively. RESULTS: For the Child and Functional Assessment Scale total, we found a significant group × time interaction, with less impaired functioning for the CAPS group than for the IRC group at the final follow-up. Parent education moderated the efficacy of CAPS on overall rates of impairment and school/work functioning, with the advantage of CAPS over IRC evident at the final follow-up only for participants with less-educated parents. Neither group differences nor group × time interactions were found for the IFIRS. CONCLUSIONS: Relatively brief, online treatment shortly after injury may result in long-term improvements in child functioning, particularly among families of lower socioeconomic status. Clinical implementation of CAPS during the initial months postinjury should be considered.

AbstractBackgroundRib fracture stabilization has become a more accepted practice although stabilization of the most cephalad ribs presents a unique challenge. We present our experience with use of a 90° drill and screwdriver to bridge these difficult rib fractures.MethodsThis retrospective review included patients who underwent rib fracture stabilization from August 1, 2009, through September 30, 2012. Patients were divided into two groups: those whose procedure used the 90° device and those that did not. Data were compared using standard statistical analysis and reported as percentages and medians [interquartile ranges]. P values <0.05 were considered significant.ResultsWe identified 89 patients: 29 (33 %) had 90° devices used and 60 (67 %) did not. There were no differences between groups in age, sex, Trauma‐Related Injury Severity Score, the presence of flail chest, occurrence of pneumonia, and intensive care unit or hospital length of stay. The Injury Severity Score was higher in the 90° group (22 vs. 16; P = 0.03). The highest rib stabilized was different between the 2 groups (3 [2–5] vs. 5 [2–9]; P = 0.001), with more third rib stabilizations in the 90° group (38 vs. 20 %; P = 0.04) as well as more total number of ribs fixed (5 vs. 4; P = 0.001). There was no difference in operative time between the 2 groups.ConclusionsThe surgical reach for rib fracture stabilization has been extended with use of a 90° drill and screwdriver. High fractures under the scapula where access is technically challenging can be stabilized without prolonging operative times.