Citations

AbstractBackground: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls).Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the “effective” number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822.Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk.Impact: Further replication in independent samples is warranted. Cancer Epidemiol Biomarkers Prev; 22(11); 2094–101. ©2013 AACR.

ABSTRACT The clonal distribution of Escherichia coli across an unselected population in the current era of widespread antimicrobial resistance is incompletely defined. In this study, we used a newly described clonal typing strategy based on sequencing of fum C and fim H (i.e., CH typing) to infer multilocus sequence types (STs) for 299 consecutive, nonduplicate extraintestinal E. coli isolates from all cultures submitted to Olmsted County, MN, laboratories in February and March 2011 and then compared STs with epidemiological data. Forty-seven different STs were identified, most commonly ST131 (27%), ST95 (11%), ST73 (8%), ST127 (6%), and ST69 (5%). Isolates from these five STs comprised two-thirds of health care-associated (HA) isolates but only half of community-associated (CA) isolates. ST131 was represented overwhelmingly (88%) by a single recently expanded H30 subclone, which was the most extensively antimicrobial-resistant subclone overall and was especially predominant in HA infections and among adults >50 years old. In contrast, among patients 11 to 50 years old, ST69, -95, and -73 were more common. Because of the preponderance of the H30 subclone of ST131, ST diversity was lower among HA than CA isolates, and among antimicrobial-resistant than antimicrobial-susceptible isolates, which otherwise had similar ST distributions. In conclusion, in this U.S. Midwest region, the distribution and diversity of STs among extraintestinal E. coli clinical isolates vary by patient age, type of infection, and resistance phenotype. ST131 predominates among young children and the elderly, HA infections, and antimicrobial-resistant isolates, whereas other well-known pathogenic lineages are more common among adolescents and young adults, CA infections, and antimicrobial-susceptible isolates.

Introduction Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF). While it is known the severity of left atrial (LA) enlargement affect the success of AF ablation, little is known the impact of intracardiac pressure on the ablation outcome. Methods This prospective study consisted of 63 patients (mean age 57±9 years, 73% male) who underwent catheter-based pulmonary vein isolation for drug refractor symptomatic AF (48% paroxysmal, 52% persistent). All patients underwent simultaneous echocardiography and haemodynamic measurements including left ventricular end systolic pressure (LVEDP), mean left atrial pressure (LAP) and dP/dtmax using Millar catheter at the time of procedure during AF. Left atrial volume (LAV) was measure by biplane area length method. Recurrence of AF was defined as episodes of AF more than 5 min documented in 24h ambulatory ECG or event monitor. Results After a mean follow-up duration of 16±7 months, AF elimination off anti-arrhythmic drugs was achieved in 70 % (44/63) of patients. Among the echographic and haemodynamic measurements, the baseline LAV and mean LAP were 57.62±25.39 ml and 12.19±4.57 mm Hg in AF free patients compared to 81.20±40.88 ml (p=0.02) and 16.46±4.14 mm Hg (p=0.01) in AF recurrence groups. Univariate and multivariate analysis showed LAP was the only independent predictor of the recurrence with an adjusted odd ratio of 1.27 (95% CI 1.04 to 1.54, p=0.03, table). Conclusion LAP is a determinant of AF recurrence after AF ablation. Therapies towards reduction of LA filling pressure, especially in patients with elevated LAP, may improve the outcome of ablation. Table Baseline clinical characters in the recurrence group and non-recurrence group Non-recurrence (N=44) recurrence (N=19) Univariate Multivariate P 95% CI P 95% CI Age (ys) 57.39±9.92 59.26±10.47 0.49 0.97, 1.08 – – AF type, persistent AF no. (%) 23 (53%) 10 (50%) 0.97 0.34, 2.98 – – AF duration (ys) 5.84±5.43 8.08±7.66 0.20 0.99, 1.05 – – LA volume (mL) 57.62±25.39 81.20±40.88 0.02 1.01, 1.05 0.30 0.99, 1.05 LVEDP (mm Hg) 10.25±14.54 11.25±5.75 0.81 0.96, 1.06 – – dP/dt max (mm Hg/s) 1294.02±337.13 1211.77±225.36 0.47 0.99, 1.02 – – Mean LAPmean (mm Hg) 12.19±4.57 16.46±4.14 0.01 1.06, 1.50 0.02 1.04, 1.54 Pulmonary vein isolation is an effective therapy for curing symptomatic atrial fibrillation (AF) but the success rate ranged wide. This study aimed to investigate the effect of LAP on AF recurrence.

Introduction Lateral or posteriolateral coronary vein has been considered the optimal location of left ventricular (LV) lead placement for cardiac resynchronisation therapy (CRT). However, the long-term clinical outcomes of CRT based on LV lead location have not been sufficiently addressed. Methods Seven hundred and eighteen CRT-P/CRT-D recipients from Jan 2002 to Dec 2008 were studied. At the CRT implant, the LV lead placement was prioritised as posterolateral/lateral (PL, 50%), anterior lateral (AL, 31%), anterior interventricular (AI, 12%) or middle cardiac veins (MC, 7%). NYHA class and echocardiography were assessed before and after CRT. Clinical outcomes of CRT were compared among 4 LV lead locations. Results Patient baseline demographics, except the gender (P=0.03), were similar among four groups. After CRT, the improvement in NYHA class, LV ejection fraction (EF), and LV diastolic diameter were significantly improved comparably across four LV lead locations (table). The increase in LVEF by >5% were 46%, 47%, 41% and 42% in PL, AL, AI and MC groups (p=0.87). Conclusion The present study suggests that LV lead positioned in the alternative coronary veins, other than posteriolateral or lateral location, achieve comparable benefit in improvement of HF symptoms, and LV function after CRT. Table Comparison of clinic outcomes before and after CRT in different LV lead locations Lateral vein (N=359) Anterolateral vein (N=226) middle cardiac vein (N=49) anterior interventricular vein (N=84) Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT NYHA 3.02±0.46 2.34±0.81* 2.92±0.53 2.34±0.89* 3.10±0.45 2.70±0.85* 2.98±0.52 2.43±0.86* LVEF (%) 23.57±7.28 30.82±11.67* 24.19±7.96 30.44±12.06* 24.97±7.62 30.72±11.43* 22.45±7.25 28.40±11.73* LVEDD (mm) 65.71±9.12 63.00±9.73* 65.79±8.87 63.88±9.88* 65.39±9.32 62.61±10.25* 68.48±8.92 64.86±9.67* LVESD (mm) 57.91±9.89 52.83±11.68* 56.69±10.23 53.03±12.01* 56.18±11.56 52.24±13.11* 59.09±10.04 55.32±13.30 RVD (mm) 0.90±0.86 0.82±0.85 0.85±0.92 0.82±0.85 0.86±0.83 1.01±0.84 0.56±0.77 0.78±0.91 RV dysfunction 1.05±0.92 0.88±0.92* 1.03±0.93 0.93±0.91 1.06±0.97 1.06±0.90 0.74±0.86 0.79±0.96 MR (m/s) 1.54±0.78 1.30±0.75* 1.57±0.83 1.35±0.75* 1.53±0.71 1.15±0.70* 1.36±0.69 1.19±0.68 * P<0.05 compared to pre-CRT.

BACKGROUNDDrug choice and delivered dose of treatment potentially influence outcome in patients treated for follicular lymphoma (FL). Historically, observational studies have evaluated drug choice. The National LymphoCare Study (NLCS) is a prospective, observational study of patients with FL who were enrolled at academic and community practice sites in the United States between 2004 and 2007. In the current study, the authors report on measures of delivered dose and its impact on outcomes for the most common first‐line regimens.METHODSAll evaluable patients with FL who were treated with initial rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP); rituximab plus cyclophosphamide, vincristine, and prednisone (R‐CVP); or rituximab plus a fludarabine‐containing regimen (R‐Flu) were included. Associations between baseline factors, choice of treatment, number of cycles received, completion of therapy, and patient outcomes were assessed.RESULTSA total of 646 patients received R‐CHOP, 297 received R‐CVP, and 222 received R‐Flu. Characteristics were similar between the 3 groups with the following exceptions. Patients receiving R‐CHOP were more often found to have grade 3 FL and patients receiving R‐CVP were older and had higher Follicular Lymphoma International Prognostic Index scores. The majority of patients (80%) received ≥ 5 cycles of treatment. Toxicity, but not disease progression, was commonly cited as the reason for the early discontinuation of treatment (51% vs 6%). Time to retreatment was shorter for patients receiving ≤ 4 cycles, regardless of the treatment regimen used. The number of cycles was associated with overall survival, progression‐free survival, and lymphoma‐related mortality for patients receiving R‐CVP.CONCLUSIONSThe majority of patients with FL receiving chemoimmunotherapy in the NLCS completed ≥ 5 cycles of treatment. Strategies to improve dose delivery appear unlikely to impact outcomes, except possibly in patients receiving R‐CVP. Although early treatment discontinuation appears to be associated with survival, this analysis does not implicate causality. Cancer 2013;119:4129–4136. © 2013 American Cancer Society.

Objective To investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry. Methods Subjects meeting the modified Bohan and Peter criteria for definite juvenile DM were analyzed from the cross‐sectional Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between 2010 and 2012 from 55 US pediatric rheumatology centers. Demographics, disease characteristics, diagnostic assessments, and medication exposure data were collected at enrollment. Results A total of 384 subjects met the criteria for analysis. At enrollment, the median Childhood Myositis Assessment Scale score was 51 (interquartile range [IQR] 46–52), the median Childhood Health Assessment Questionnaire score was 0 (IQR 0–0.5), and the median physician and subject global assessment scores were 1 (IQR 0–2) and 1 (IQR 0–3), respectively, out of a maximum of 10. Of the diagnostic assessments, magnetic resonance imaging was more likely than electromyography or muscle biopsy to show abnormalities. A total of 329 subjects had ≥2 diagnostic studies performed, and >34% of these subjects reported ≥1 negative study. Ninety‐five percent had been treated with corticosteroids and 92% with methotrexate, suggesting that these medications were almost universally prescribed for juvenile DM in the US. Conclusion In 2 years, the ongoing CARRA Registry has collected clinical data on 384 children with juvenile DM and has the potential to become one of the largest juvenile DM cohorts in the world. More research is needed about prognostic factors in juvenile DM, and differences in therapy based on manifestations of disease need to be explored by practitioners. This registry provides the infrastructure needed to advance clinical and translational research and represents a major step toward improving outcomes of children with juvenile DM.