Citations

ObjectiveTo identify new genetic associations with juvenile and adult dermatomyositis (DM).MethodsWe performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.ResultsCompared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.ConclusionOur findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.

BACKGROUND AND OBJECTIVE: Previous studies suggest that former late preterm infants are at increased risk for learning and behavioral problems compared with term infants. These studies have primarily used referred clinical samples of children followed only until early school age. Our objective was to determine the cumulative incidence of attention deficit/hyperactivity disorder (ADHD) and learning disabilities (LD) in former late preterm versus term infants in a population-based birth cohort. METHODS: Subjects included all children born 1976 to 1982 in Rochester, MN who remained in the community after 5 years. This study focused on the comparison of subjects in 2 subgroups, late preterm (34 to &lt;37 weeks) and term (37 to &lt;42 weeks). School and medical records were available to identify individuals who met research criteria for ADHD and LD in reading, written language, and math. The Kaplan-Meier method was used to estimate the cumulative incidence of each condition by 19 years of age. Cox models were fit to evaluate the association between gestational age group and condition, after adjusting for maternal education and perinatal complications. RESULTS: We found no statistically significant differences in the cumulative incidence of ADHD or LD between the late preterm (N = 256) versus term (N = 4419) groups: ADHD (cumulative incidence by age 19 years, 7.7% vs 7.2%; P = .84); reading LD (14.2% vs 13.1%; P = .57); written language LD (13.5% vs 15.7%; P = .36), and math LD (16.1% vs 15.5%; P = .89). CONCLUSIONS: These data from a population-based birth cohort indicate that former late preterm infants have similar rates of LD and ADHD as term infants.

Medical professionalism is a multifaceted paradigm and is an essential component of medical education. Gross anatomy is a laboratory to teach professionalism, and promoting critical reflection in medical students is a prerequisite to furthering professionalism. The aim of this study was to determine if professionalism case discussions during a Gross Anatomy course improve students' reflections using a validated reflection instrument (12 items; five‐point Likert scale where 1 = Disagree, 2 = Disagree with reservation, 3 = Neutral, 4 = Agree with reservation, 5 = Agree). Four facilitated reflection sessions were aimed at fostering reflective capacity through reflection on elements of professionalism. Results did not show a significant change between pre‐and postintervention reflection scores (3.45 ± 0.61 vs. 3.48 ± 0.51; P = 0.82). Historical control students were found to have significantly higher reflection scores when compared with postintervention students (3.91 ± 0.53 vs. 3.48 ± 0.51; P < 0.001). However, the historical control students were found to have significantly higher professionalism scores (P = 0.001) as compared with the intervention students. Student satisfaction was high, with 25 of 28 (89.2%) students reporting that the sessions should be included as a component of future anatomy courses. While reflection scores were not significantly increased as a result of the intervention, students expressed appreciation for the opportunity to discuss professionalism issues related to the dissection of cadavers. Additionally, the intervention students had both lower professionalism scores and lower reflection scores, which supports the idea that highly professional students are more capable of reflecting on professionalism. Future studies should determine whether this case discussion intervention improves objective measures of professionalism. Anat Sci Educ 7: 191–198. © 2013 American Association of Anatomists.

Objective To assess recommendations for prostate‐specific antigen ( PSA ) screening in a national survey of radiation oncologists and urologists following the recent USA P reventive S ervices T ask F orce ( USPSTF ) grade D recommendation. Methods A random sample of 1366 radiation oncologists and urologists were identified from the A merican M edical A ssociation P hysician M asterfile. From N ovember 2011 to A pril 2012, a mail survey was sent to query PSA screening recommendations for men at average risk of prostate cancer for the following age groups: 40–49, 50–59, 60–69, 70–74, 75–79 and ≥80 years. Multivariable logistic regression was used to test for differences in PSA ‐based screening recommendations by physician characteristics. Results Response rates were similar at 52% for radiation oncologists and urologists ( P = 0.92). Overall, 51.5% of respondents recommended PSA ‐based screening for men aged 40–49 years, while nearly all endorsed it for those aged 50–74 years (96.1% for 50–59, 97.3% for 60–69, and 87.7% for 70–74 years). However, screening recommendations decreased to 43.9% and 12.8% for men aged 75–79 and ≥80 years, respectively. On multivariable analysis, urologists were more likely to recommend screening for men aged 40–49 (odds ratio [ OR ] 3.09; P < 0.001) and 50–59 years ( OR 3.81; P = 0.01), but less likely for men aged 75–79 ( OR 0.66; P = 0.01) and ≥80 years ( OR 0.45; P = 0.002) compared with radiation oncologists. Conclusion While radiation oncologists and urologists recommended PSA screening for men aged 50–69 years, there was less agreement about screening for younger (40–49 years old) and older (≥70 years) men at average risk for prostate cancer.

Background— A patent foramen ovale (PFO) may permit arterial embolization of thrombi that accumulate on the leads of cardiac implantable electronic devices in the right-sided cardiac chambers. We sought to determine whether a PFO increases the risk of stroke/transient ischemic attack (TIA) in patients with endocardial leads. Methods and Results— We retrospectively evaluated all patients who had endocardial leads implanted between January 1, 2000, and October 25, 2010, at Mayo Clinic Rochester. Echocardiography was used to establish definite PFO and non-PFO cohorts. The primary end point of stroke/TIA consistent with a cardioembolic etiology and the secondary end point of mortality during postimplantation follow-up were compared in PFO versus non-PFO patients with the use of Cox proportional hazards models. We analyzed 6075 patients (364 with PFO) followed for a mean 4.7±3.1 years. The primary end point of stroke/TIA was met in 30/364 (8.2%) PFO versus 117/5711 (2.0%) non-PFO patients (hazard ratio, 3.49; 95% confidence interval, 2.33–5.25; P <0.0001). The association of PFO with stroke/TIA remained significant after multivariable adjustment for age, sex, history of stroke/TIA, atrial fibrillation, and baseline aspirin/warfarin use (hazard ratio, 3.30; 95% confidence interval, 2.19–4.96; P <0.0001). There was no significant difference in all-cause mortality between PFO and non-PFO patients (hazard ratio, 0.91; 95% confidence interval, 0.77–1.07; P =0.25). Conclusions— In patients with endocardial leads, the presence of a PFO on routine echocardiography is associated with a substantially increased risk of embolic stroke/TIA. This finding suggests a role of screening for PFOs in patients who require cardiac implantable electronic devices; if a PFO is detected, PFO closure, anticoagulation, or nonvascular lead placement may be considered.

Objective To evaluate survival in patients after radical cystectomy ( RC ) who presented with non‐muscle‐invasive urothelial carcinoma and progressed to muscle invasion during surveillance. Our secondary objective was to evaluate the association between clinical factors before RC and survival. Patients and Methods In all, 981 consecutive M ayo C linic RC patients without a history of radiation or systemic chemotherapy were reviewed. Of these, 190 had RC after they progressed from non‐muscle invasive disease to muscle invasion (progressed to ≥ pT2 ). These patients were compared to 310 patients who had RC before muscle invasion (≤ pT1 ), and 481 patients who had muscle invasion at initial presentation (presented with ≥ pT2 ). Survival estimates were generated using the K aplan– M eier method and compared using the log‐rank test, while adjusted analyses were performed using C ox proportional hazard regression models. Results Patients who progressed to muscle invasion on surveillance had a higher risk of death than patients who initially presented with muscle invasion (overall survival hazard ratio [ HR ] 1.3; 95% confidence interval [ CI ] 1.0, 1.5). The estimated 5‐year cancer‐specific survival was 85.4% for patients presenting with ≤ pT1 , 52.9% for patients who progressed to ≥ pT2 , and 62.4% for patients who presented with ≥ pT2 ( P < 0.001). The corresponding 5‐year overall survival rates were 70.0%, 42.1%, and 49.5% ( P < 0.001). Of the patients who initially presented with non‐muscle‐invasive disease, progression to muscle invasion was associated with increased risk of cancer‐specific death (adjusted HR 2.38; 95% CI 1.6, 3.5). Lack of information about patients who presented without muscle invasion and never received RC is the major limitation of this study. Conclusions Despite close surveillance, many patients who progress to muscle invasion will die from bladder cancer. Patients who progress to muscle invasion on surveillance seem to have particularly aggressive disease and may benefit from multimodal treatments.

Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 −4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10 −5 ), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

ABSTRACTIntroduction: We assessed proficiency (accuracy and intra‐ and intertest reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic sensorimotor polyneuropathy (DSPN). Methods: Technologists from 3 medical centers using different but identical QSTs independently assessed 6 modalities of sensation of the foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. Results: Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intraclass correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra‐ or intertest differences were observed. Conclusions: These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra‐ or intertest differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length‐dependent sensorimotor polyneuropathies. Muscle Nerve 49: 645–653, 2014

Coronary Artery Ventricular Tachycardia. Background The coronary cusps have been well described as a successful site for ablation in patients with symptomatic outflow tract ventricular tachycardia. The earliest site of activation is rarely found at the ostia or into the main coronary arteries. The exact anatomic substrate, diagnostic characteristics, and therapeutic approaches for such instances are poorly understood. Methods We retrospectively reviewed outflow tract ventricular arrhythmia (OTVA) ablations done at Mayo Clinic Rochester from 2003 to 2011 (total VT: 414; outflow tract VT: 106). Three cases were identified where the earliest site of activation was not within the cusp but rather at or within the coronary ostia (3/414 for all VT: 0.7%; 3/106 for all OTVT: 2.8%). Results In 1 patient, the left main coronary artery (LMCA) was found to have electrograms (EGMs) recorded with bipolar mapping that preceded activation in the cusps or the left ventricular outflow tract. In 2 cases, the right coronary ostium and proximal right coronary artery recorded the earliest signals. Intracardiac echocardiographic guidance was used to successfully ablate these arrhythmias targeting the aortic route (1 patient) or the right coronary cusp (2 patients), and essentially isolated the focus of origin from the ventricular outflow tracts. Detailed mapping of surrounding structures, including the atrial appendages, the contralateral outflow tract, and the coronary venous system excluded far‐field mapping in the artery as a cause for early activation at the ostial location. Local EGM characteristics suggested an unusually lengthy supravalvar myocardial extension as the likely arrhythmogenic substrate. Ablation was successful without coronary arterial or valvular injury and without valvular or root stenosis. Conclusions Endocardial ablation isolating foci of origin in the vicinity of the coronary ostia is a challenging procedure but can be performed safely with appropriate visualization and is effective in the treatment of OTVA.