Citations

Abstract Background: Previous reports suggest that relatives of colorectal cancer (CRC)-affected probands carrying the BRAF p.V600E mutation are at an increased risk of CRC and extracolonic cancers (ECC). In this study, we estimated the association between a family history of either CRC or ECC and risk of CRC with a BRAF p.V600E mutation. Methods: Population-based CRC cases (probands, ages 18–59 years at diagnosis), recruited irrespective of family cancer history, were characterized for BRAF p.V600E mutation and mismatch repair (MMR) status. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results: The 690 eligible probands showed a mean age at CRC diagnosis of 46.9 ± 7.8 years, with 313 (47.9%) reporting a family history of CRC and 53 (7.7%) that were BRAF-mutated. Probands with BRAF-mutated, MMR-proficient CRCs were less likely to have a family history of CRC than probands that were BRAF wild-type (OR, 0.46; 95% CI, 0.24–0.91; P = 0.03). For probands with a BRAF-mutated CRC, the mean age at diagnosis was greater for those with a CRC-affected first- or second-degree relative (49.3 ± 6.4 years) compared with those without a family history (43.8 ± 10.2 years; P = 0.04). The older the age at diagnosis of CRC with the BRAF p.V600E mutation, the more likely these probands were to show a family history of CRC (OR, 1.09 per year of age; 95% CI, 1.00–1.18; P = 0.04). Conclusions: Probands with early-onset, BRAF-mutated, and MMR-proficient CRC were less likely to have a family history of CRC than probands that were BRAF-wild-type. Impact: These findings provide useful insights for cancer risk assessment in families and suggest that familial or inherited factors are more important in early-onset, BRAF-wild-type CRC. Cancer Epidemiol Biomarkers Prev; 22(5); 917–26. ©2013 AACR.

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single‐nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders. Hum Brain Mapp 35:1226–1236, 2014 . © 2013 Wiley Periodicals, Inc.

Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.

Objective To describe a standardized methodology for the performance of peripheral nerve blocks ( PNB s) in the treatment of headache disorders. Background PNBs have long been employed in the management of headache disorders, but a wide variety of techniques are utilized in literature reports and clinical practice. Methods The A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures convened meetings during 2010‐2011 featuring formal discussions and agreements about the procedural details for occipital and trigeminal PNBs . A subcommittee then generated a narrative review detailing the methodology. Results PNB indications may include select primary headache disorders, secondary headache disorders, and cranial neuralgias. Special procedural considerations may be necessary in certain patient populations, including pregnancy, the elderly, anesthetic allergy, prior vasovagal attacks, an open skull defect, antiplatelet/anticoagulant use, and cosmetic concerns. PNBs described include greater occipital, lesser occipital, supratrochlear, supraorbital, and auriculotemporal injections. Technical success of the PNB should result in cutaneous anesthesia. Targeted clinical outcomes depend on the indication, and include relief of an acute headache attack, terminating a headache cycle, and transitioning out of a medication‐overuse pattern. Reinjection frequency is variable, depending on the indications and agents used, and the addition of corticosteroids may be most appropriate when treating cluster headache. Conclusions These recommendations from the A merican H eadache S ociety S pecial I nterest S ection for PNBs and other I nterventional P rocedures members for PNB methodology in headache disorder treatment are derived from the available literature and expert consensus. With the exception of cluster headache, there is a paucity of evidence, and further research may result in the revision of these recommendations to improve the outcome and safety of these interventions.

Background Cam-type femoral impingement is caused by structural abnormalities of the hip and is recognized as a cause of degenerative hip arthritis. Identifiable etiologies of this structural abnormality include congenital malformation, pediatric hip disease, and malunion of femoral neck fractures after internal fixation. Purpose The purpose of this study was to determine the prevalence of radiographic impingement in healed Orthopaedic Trauma Association (OTA) type 31B fractures treated with reduction and internal fixation. Methods Seventy OTA 31B hip fractures treated with internal fixation were identified from our institutional trauma database and radiographs were retrospectively reviewed for signs of impingement. Mean follow-up was 53 months after fracture. Alpha angle, Mose templates, and femoral head retroversion were the measurements used to determine impingement. Results The overall prevalence of any sign of radiographic impingement was 75%. Alpha angle was elevated in 32 hips (46%), asphericity was present in 46 femoral heads (65%), and femoral head retroversion was present in 26 hips (37%). The rates were highest in displaced subcapital fractures (OTA 31B-3) with a 63% (13/19) prevalence of elevated alpha angle, 68% (14/19) prevalence of asphericity, and 47% (10/19) prevalence of retroversion. Conclusions Prevalence of radiographic signs of impingement in this population is higher than expected based on population-based controls. Surgeons must be vigilant about reduction and fixation of femoral neck fractures. Malunion should be recognized as early intervention may be beneficial in improving long-term outcomes.

Background Socioeconomic status (SES) is an important determinant of health, but SES measures are frequently unavailable in commonly used datasets. Area-level SES measures are used as proxy measures of individual SES when the individual measures are lacking. Little is known about the agreement between individual-level versus area-level SES measures in mixed urban–rural settings. Methods We identified SES agreement by comparing information from telephone self-reported SES levels and SES calculated from area-level SES measures. We assessed the impact of this agreement on reported associations between SES and rates of childhood obesity, low birth weight <2500 g and smoking within the household in a mixed urban–rural setting. Results 750 households were surveyed with a response rate of 62%: 51% male, 89% Caucasian; mean child age 9.5 years. Individual-level self-reported income was more strongly associated with all three childhood health outcomes compared to area-level SES. We found significant disagreement rates of 22–31%. The weighted Cohen's κ indices ranged from 0.15 to 0.22, suggesting poor agreement between individual-level and area-level measures. Conclusion In a mixed urban–rural setting comprised of both rural and urbanised areas, area-level SES proxy measures significantly disagree with individual SES measures, and have different patterns of association with health outcomes from individual-level SES measures. Area-level SES may be an unsuitable proxy for SES when individual rather than community characteristics are of primary concern.