Citations

Abstract Children who are exposed to secondhand smoke (SHS) are faced with an increased risk of nicotine dependence later in life. We have previously shown that children exposed to SHS have an increased risk of lung cancer as adults. Furthermore, genetic variation plays a role in the susceptibility of individuals to lung cancer. The gene DRD1 mediates dopamine signaling following nicotine exposure, thus we reasoned that DRD1 may be related to lung cancer via modulation of the nicotine reward pathway. Our previous studies identified 4 SNPs (rs4809294, rs2292975, rs4861327, rs686) that were predicted to modulate a microRNA binding site and we assessed the association of these SNPs with lung cancer risk. Our current study investigated whether these SNPs were associated with nicotine dependence and whether this had a subsequent effect on lung cancer risk. We used the National Cancer Institute-Maryland lung cancer case-control study. Cases and controls were recruited from the greater Baltimore metropolitan area. We used ordinal logistic regression to examine the association between SNPs and nicotine dependence. Logistic regression adjusted for age, gender and smoking was used to assess the association between SNPs and lung cancer risk. No significant associations were found between genotypes in the 4 SNPs and nicotine dependence levels (n=1,450). Individuals with the heterozygous allele (AG) exposed to SHS during childhood had increased odds of lung cancer compared to those with the homozygous wild type allele (AA) for rs686 (OR=1.52, CI= 1.12, 2.07). Individuals with the homozygous variant allele (GG) exposed to childhood SHS had increased odds of lung cancer compared to individuals with the homozygous wild type allele (AA) (OR=2.11, CI= 1.45, 3.10). Individuals with the heterozygous allele (GA) and the highest levels of nicotine dependence who were also exposed to childhood SHS, had higher odds of lung cancer than those with the homozygous recessive allele (AA) (OR=3.50, CI=1.37, 8.96). Consistent with earlier findings, heterozygotes (AG) had increased odds of lung cancer but this was not statistically significant (OR=1.90, CI= 0.82, 4.40). To further explore this association, we examined the effect of race on this relationship. Caucasians with the heterozygous allele (AG), the highest levels of nicotine dependence and childhood SHS, had increased odds of lung cancer compared to those with the homozygous recessive allele (AA) for rs686 (OR=1.47, CI=1.06, 2.05). Caucasians with the homozygous allele (GG) who were exposed to childhood SHS, had higher odds of lung cancer compared to individuals with the homozygous recessive allele (AA) for rs686 (OR=1.84, CI=1.15, 2.98). No association was found among African Americans. Although none of the SNPs examined were found to be associated with nicotine dependence, it appears that variations in rs686 may modify an individual's susceptibility to lung cancer due to SHS exposure. Citation Format: Victoria A. Zigmont, Brid M. Ryan, Jin Jen, Ana I. Robles, Cain McClary, Kara Calhoun, Elise D. Bowman, Kirsi Vähäkangas, K. Leigh Greathouse, Wang Yi, Angela S. Wenzlaff, Bo Deng, Ping Yang, Ann G. Schwartz, Curtis C. Harris, Susan Olivo Marston. Childhood exposure to secondhand smoke, nicotine dependence, and DRD1 are associated with lung cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2156. doi:10.1158/1538-7445.AM2014-2156

Accurate quantification of subtle wrist motion changes resulting from ligament injuries is crucial for diagnosis and prescription of the most effective interventions for preventing progression to osteoarthritis. Current imaging techniques are unable to detect injuries reliably and are static in nature, thereby capturing bone position information rather than motion which is indicative of ligament injury. A recently developed technique, 4D (three dimensions + time) computed tomography (CT) enables three-dimensional volume sequences to be obtained during wrist motion. The next step in successful clinical implementation of the tool is quantification and validation of imaging biomarkers obtained from the four-dimensional computed tomography (4DCT) image sequences. Measures of bone motion and joint proximities are obtained by: segmenting bone volumes in each frame of the dynamic sequence, registering their positions relative to a known static posture, and generating surface polygonal meshes from which minimum distance (proximity) measures can be quantified. Method accuracy was assessed during in vitro simulated wrist movement by comparing a fiducial bead-based determination of bone orientation to a bone-based approach. The reported errors for the 4DCT technique were: 0.00–0.68 deg in rotation; 0.02–0.30 mm in translation. Results are on the order of the reported accuracy of other image-based kinematic techniques.

Intraosseous hemangiomas arising from the nasal turbinate are exceedingly rare, with few reported cases in the literature. We describe a 61-year-old man found to have a nasal cavity mass on sinus computed tomograph (CT) and magnetic resonance imaging (MRI). Although an atypical site of occurrence, distinctive internal honeycomb bony trabeculations demonstrated on CT allowed the correct diagnosis of an intraosseous hemangioma to be prospectively proposed by the interpreting radiologist which had direct clinical and surgical impacts.

Objective There is a paucity of data on the impact of complete revascularisation (CR) following percutaneous coronary intervention (PCI) among patients with diabetes with multivessel coronary disease. In this study, we assess the impact of CR, using a relatively simple anatomical definition, on long-term outcomes (median follow-up 7.9 years) in patients with diabetes, and compare with patients without diabetes. Methods 5350 patients with multivessel disease (coronary stenoses ≥70% in ≥2 major epicardial arteries) who underwent PCI between January 1997 and June 2011 were included. Patients were divided into 4 groups according to diabetes and CR status (absence of residual coronary stenosis in major, predominantly proximal, epicardial segments according to Coronary Artery Surgery Study (CASS) classification). Results Patients with diabetes and patients with incomplete revascularisation (IR) had more adverse clinical and angiographic characteristics. IR was frequent in patients with diabetes, and was marginally more common than in patients without diabetes (47% vs 44%, p<0.001). Patients with diabetes and patients without diabetes had higher mortality rates after IR than after CR (HR 1.56 (95% CI (1.39 to 1.85), p<0.001 for patients with diabetes and 1.70 (95% CI (1.50 to 1.92), p<0.001) in patients without diabetes). However, the absolute risk was higher for patients with diabetes (5-year mortality: IR 35.8%, CR 21.2%) than in patients without diabetes (5-year mortality: IR 22.2%, CR 14.1%). In a multivariable model, IR and diabetes mellitus were independent predictors of total mortality. This effect was present in the bare metal stent and drug-eluting stent eras and in patients with stable disease and acute coronary syndromes. Conclusions CR is associated with lower long-term mortality in patients with diabetes and patients without diabetes. However the difference was significantly greater in patients with diabetes compared with patients without diabetes.

A central principle of justice is that similar cases should be decided in similar ways. In pediatrics, however, there are cases in which 2 infants have similar diagnoses and prognoses, but their parents request different treatments. In this Ethics Rounds, we present such a situation that occurred in a single NICU. Three physician-ethicists analyze the issues.

Key PointsThe NF-κB subunits p52 and RelB increase IRF4 promoter activity and expression in PTCL cells. A positive feedback loop involving CD30, NF-κB, and IRF4 drives PTCL cell proliferation and can be blocked by NF-κB inhibitors.

AbstractIn this review, we summarize the recent literature and use case examples to reach diagnostic criteria for the diagnosis of immunoglobulin G4 (IgG4)‐related diseases that may be of relevance to the practicing dermatologist.