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BackgroundPostoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation.MethodsIn this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year.ResultsAmong 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups.ConclusionsDual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Introduction: The association between lipoprotein subparticles and atherosclerosis is not consistent in literature. For example, it is still unclear whether low-density lipoprotein particles (LDLP), high-density lipoprotein particles (HDLP), and triglyceride-rich lipoprotein particles (TRLP) were associated with carotid artery plaque (CAP) in adult population. Objective: We analyzed the cross-sectional association of LDLP, HDLP, and TRLP subparticles with CAP at ELSA-Brasil baseline. Methods: Data from 3801 participants (median age of 50.0[44.0-57.0] years, 54.3% of women) with no previous cardiovascular (CV) disease and without using lipid-lowering medications were analyzed. CAP presence was assessed by ultrasound images, while LDLP (total, large, medium and small), HDLP (total, large, medium and small) and TRLP (total, very large, large, medium, small and very small) were analyzed by nuclear magnetic resonance spectroscopy. Logistic regression models included all lipoprotein subparticles simultaneously and were adjusted by sociodemographic (age, sex, ethnicity, education, private health insurance) and CV risk factors (body mass index, smoking, alcohol consumption, family history of CV disease, diabetes, hypertension), with odds ratios (OR) and respective 95% confidence interval according to 1 standard deviation increase in the predictor. Results: The prevalence of CAP was 33.9% (n=1287). Participants with CAP had higher age (median 55.0 vs. 47.0, p Conclusion: The LDLP (large, medium and small) and TRLP (small and very small) were associated with CAP beyond sociodemographic and CV risk factors. This finding is in line with CV risk burden of large LDLP besides small LDLP and highlights a potential role of TRLP in atherosclerosis. However, further investigation between LDLP and TRLP with CAP progression is still needed.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P P =0.015). Lower performance was attributed largely to Word List Recall ( P P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.

OBJECTIVE We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences. SUMMARY BACKGROUND DATA GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinicopathological and oncological differences between the 2 have not been fully evaluated. METHODS We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared. RESULTS In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC (P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer (P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001). CONCLUSIONS GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies.

Those with diabetes are at an increased risk of cardiovascular disease (CVD). Safety net clinics serve populations that bear a significant burden of disease and disparities and are a key setting in which to focus on reducing CVD. An integrated health system provided funding and technical assistance (TA) to safety net organizations (community health centers and public hospitals) in Northern California to decrease the risk of cardiovascular events for patients with diabetes. This was a program called Preventing Heart Attacks and Strokes Everyday (PHASE), which combined an evidence-based medication protocol with population health management and team-based care strategies. The TA supported organizations by sharing best practices, providing quality improvement coaching, and facilitating peer learning. A mixed-methods evaluation found that organizations involved in PHASE improved rates of blood pressure control and cardioprotective medication prescriptions for patients with diabetes. They made progress on these measures through strategies such as leveraging team-based care, providing education on evidence-based protocols, and using data to drive improvements. The evaluation concluded that financially supporting and providing focused TA to safety net organizations can help them build capacity and leverage their strengths to improve outcomes and potentially decrease the risk of heart attacks and strokes in communities.

OBJECTIVE To compare the efficacy and safety of induction FOLFOX followed by PET-directed neoadjuvant chemoradiation therapy (nCRT), induction carboplatin plus paclitaxel (CP) followed by PET-directed nCRT, and nCRT with CP alone in patients with esophageal adenocarcinoma (EAC). SUMMARY BACKGROUND DATA nCRT with CP is a standard treatment for locally advanced EAC. The results of Cancer and Leukemia Group B 80803 support the use of induction chemotherapy followed by PET-directed chemoradiation therapy. METHODS We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher's exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression. RESULTS In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n=70; CP, n=239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs 16%, P=0.004), near-pCR (57% vs 33%, P

INTRODUCTION: Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. METHODS: We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. RESULTS: All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. CONCLUSION: The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.

BACKGROUND & AIMS: Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease associated with significant morbidity and mortality in patients with underlying liver disease, and confers a higher mortality in patients awaiting liver transplantation (LT). Although not a transplant indication, PoPH patients who undergo LT can experience significant clinical improvement, and those who maintain a mean pulmonary arterial pressure (mPAP) < 35mmHg and a pulmonary vascular resistance (PVR) < 5 Woods Units are granted Model for End Stage Liver Disease (MELD) exception points to expedite LT. The effect of PoPH on post-transplant outcomes such as mortality and graft failure, however, is not well defined. APPROACH & RESULTS: We performed a retrospective cohort study of the United States Organ Procurement and Transplant Network (OPTN) database of all adult patients who underwent LT between 1/1/2006 and 12/1/2020. Using adjusted Accelerated Failure Time models, we examined the relationship between a diagnosis of PoPH and outcomes following LT, and the relationship between pre-LT hemodynamics and post-LT survival (alive with a functioning graft) in PoPH patients. Compared to those undergoing transplants without exception points, PoPH patients had comparable post-LT survival, but were significantly more likely to have graft failure. Both pre-LT mPAP and PVR predicted post-LT survival in PoPH, with a pre-LT PVR of ≥ 1.6 WU more than doubling the hazard for mortality (death or a non-functioning graft) (coefficient=2.01, standard error=0.85, HR=2.21, p=0.02). CONCLUSIONS: PoPH may confer a significantly higher risk of post-LT graft failure as compared to cirrhotic patients without PoPH, and a pre-LT PVR of ≥ 1.6 WU may predict post-LT survival. Further investigation into the relationship between pre-LT hemodynamics, right ventricular function, and post-LT outcomes of mortality and graft failure in PoPH is needed.

Background and Purpose: Despite a higher incidence of stroke and a more adverse cardiovascular risk factor profile in Blacks and Hispanics compared with Whites, carotid artery revascularization is performed less frequently among these subpopulations. We assessed racial differences in high-grade (≥70% diameter-reducing) carotid stenosis. Methods: Consecutive clients in a Nationwide Life Line for-Profit Service to screen for vascular disease, 2005 to 2019 were evaluated in a cross-sectional study. The prevalence of high-grade stenosis, defined by a carotid ultrasound peak systolic velocity of ≥230 cm/s, was assessed. Participants self-identified as White, Black, Hispanic, Asian, Native American, or other. Race/ethnic differences were assessed using Poisson regression. The number of individuals in the United States with high-grade stenosis was estimated by applying prevalence estimates to 2015 US Census population estimates. Results: The prevalence of high-grade carotid stenosis was estimated in 6 130 481 individuals. The prevalence of high-grade stenosis was higher with increasing age in all race-sex strata. Generally, Blacks and Hispanics had a lower prevalence of high-grade stenosis compared with Whites, while Native Americans had a higher prevalence. For example, for men aged 55 to 65, the relative risk of stenosis compared with Whites was 0.40 (95% CI, 0.29–0.55) and 0.61 (95% CI, 0.46–0.81) for Blacks and Hispanics, respectively; and 1.53 (95% CI, 1.12–2.10) for Native Americans. When these prevalence estimates were applied to the Census estimates of the US population, an estimated 327 721 individuals have high-grade stenosis, of whom 7% are Black, 7% Hispanic, and 43% women. Conclusions: Despite their having a more adverse cardiovascular risk profile, there was a lower prevalence of high-grade carotid artery stenosis for both the Black and Hispanic relative to the White clients. This lower prevalence of high-grade stenosis is a potential contributor to the lower use of carotid revascularization procedures in these minority populations.

Background Deep brain stimulation (DBS) electrode placement utilizing a frame-based technique requires registration of the stereotactic frame with computed tomography (CT) or magnetic resonance (MR) imaging. This traditionally has been accomplished with a conventional CT scanner. In recent years, intraoperative CT has become more prevalent. Objective To compare the coordinates obtained with intraoperative CT and conventional CT for registration of the stereotactic frame for DBS. Methods Patients undergoing DBS electrode placement between 2015 and 2017, who underwent both conventional and intraoperative CT for registration of the stereotactic frame, were included for analysis. The coordinates for the stereotactic target, anterior commissure, and posterior commissure for each CT method were recorded. The mean, maximum, minimum, and standard deviation of the absolute difference for each of the paired coordinates was calculated. Paired t-tests were performed to test for statistical significance of the difference. The directional difference as well as the vector error between the paired coordinates was also calculated. Results The mean absolute difference between conventional and intraoperative CT for the coordinate pairs was less than 0.279 mm or 0.211 degrees for all coordinate pairs analyzed. This was not statistically significant for any of the coordinate pairs. Moreover, the maximum absolute difference between all coordinate pairs was 1.04 mm. Conclusion Intraoperative CT imaging provides stereotactic frame registration coordinates that are similar to those obtained by a standard CT scanner. This may save time and hospital resources by obviating the need for the patient to go to the radiology department for a CT scan.

Objective We sought to determine the extent of lymphadenectomy that optimizes staging and survival in patients with locally advanced esophageal adenocarcinoma (EAC) treated with neoadjuvant chemoradiotherapy followed by esophagectomy. Summary background data Several studies have found that a more extensive lymphadenectomy leads to better disease-specific survival in patients treated with surgery alone. Few studies, however, have investigated whether this association exists for patients treated with neoadjuvant chemoradiotherapy. Methods We examined our prospective database and identified patients with EAC treated with neoadjuvant chemoradiotherapy followed by esophagectomy between 1995 and 2017. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods, and a multivariable Cox proportional hazards model was used to identify independent predictors of OS and DFS. The relationship between the total number of nodes removed and 5-year OS or DFS was plotted using restricted cubic spline functions. Results In total, 778 patients met the inclusion criteria. The median number of excised nodes was 21 (interquartile range, 16-27). A lower number of excised lymph nodes was independently associated with worse OS and DFS (OS: hazard ratio [HR], 0.98; confidence interval [CI], 0.97-1.00; P = 0.013; DFS: HR, 0.99; CI, 0.98-1.00; P = 0.028). Removing 25 to 30 lymph nodes was associated with a 10% risk of missing a positive lymph node. Both OS and DFS improved with up to 20 to 25 lymph nodes removed, regardless of treatment response. Conclusions The optimal extent of lymphadenectomy to enhance both staging and survival following chemoradiotherapy, regardless of treatment response, is approximately 25 lymph nodes.

OBJECTIVE We sought to quantify and characterize long-term consequences of pneumonectomy, with particular attention to nononcologic mortality. SUMMARY OF BACKGROUND DATA Pneumonectomy is associated with profound changes in cardiopulmonary physiology. Studies of long-term outcomes after pneumonectomy typically report generalized measures, such as disease-free and overall survival. METHODS Patients undergoing lobectomy or pneumonectomy for lung cancer at our institution from 2000 to 2018 were reviewed. Propensity-score matching was performed for 12 clinicopathologic factors. Ninety-day complications and deaths were compared. Five-year cumulative incidence of oncologic and nononcologic mortality were compared using competing risks approaches. RESULTS From 3339 lobectomy and 355 pneumonectomy patients identified, we derived 318 matched pairs. At 90 days, rates of overall complications were similar (46% for pneumonectomy vs 43% for lobectomy; P = 0.40), but rates of major complications (21% vs 13%; P = 0.005) and deaths (6.9% vs 1.9%; P = 0.002) were higher the pneumonectomy cohort. The cumulative incidence of oncologic mortality was not significantly different between cohorts (P = 0.9584). However, the cumulative incidence of nononcologic mortality was substantially higher in the pneumonectomy cohort for both date of surgery and 1-year landmark analyses (P < 0.0001 and P = 0.0002, respectively). Forty-five pneumonectomy patients (18%) died of nononcologic causes 1-5 years after surgery; pneumonia (n = 21) and myocardial infarction (n = 10) were the most common causes. In pneumonectomy patients, preexisting cardiac comorbidity and low diffusion capacity of the lungs for carbon monoxide were predictive of nononcologic mortality. CONCLUSIONS Compared to lobectomy, excess mortality after pneumonectomy extends beyond 1 year and is driven primarily by nononcologic causes. Pneumonectomy patients require lifelong monitoring and may benefit from expeditious assessment and intervention at the initial signs of illness.

Background Research evaluating the efficacy of multimodal therapy for the treatment of keloids has reported combination regimens are most effective. Objective To compare recurrence rates for keloids treated with surgery plus one adjuvant intervention (dual therapy) versus surgery plus 2 or more adjuvant interventions (triple therapy). Materials and methods Systematic literature review and meta-analysis of combination treatment for keloids. Results After full-text review, we included 60 articles representing 5,547 keloids: 5,243 received dual therapy, 259 received triple therapy, and 45 received quadruple therapy (the latter 2 groups were combined for analysis). The difference in recurrence rates between dual (19%) and triple therapy (11.2%) was not significant (p = .343). However, the difference in recurrence rates between dual therapy using surgery and radiation (18.7%) and triple therapy using surgery, radiation, and a third intervention (7.7%) was significant (p = .002). The differences for surgery and intralesional triamcinolone (TAC) showed trends toward significance, because keloids treated with dual therapy (21.7%) had a higher recurrence rate than those treated with triple therapy comprised of surgery, TAC, and another intervention (13.7%; p = .099). Conclusion Triple therapy using surgery plus radiation and/or TAC as one of the adjuvant treatment modalities may achieve the lowest recurrence rates for keloids.

OBJECTIVE: We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) undergoing resection and multidisciplinary management at a high-volume institution. SUMMARY BACKGROUND DATA: Outcomes following resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival. METHODS: We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression. RESULTS: In total, 113 patients were included (median age, 28 years [range, 16–65]). Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/− necrosis (20%), viable nonteratomatous germ cell tumor +/− teratoma (41%), and secondary somatic-type malignancy +/− teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P

Objective Limited data are available regarding the relationship between anti-tumor necrosis factor (TNF) drug/antibody levels and perianal fistula outcomes in Crohn's disease. The aims of this study were to assess the relationship between maintenance anti-TNF levels and perianal fistula outcomes. Methods This was a retrospective cross-sectional study of patients receiving maintenance adalimumab or infliximab therapy (minimum 24 weeks) for the treatment of Crohn's disease with associated perianal fistulas, who had anti-TNF drug/antibody levels (trough for infliximab) measured within 4 weeks of clinical assessment. The primary outcome was the association of anti-TNF levels with perianal fistula healing defined as the absence of drainage. The secondary outcome was the association of anti-TNF levels with complete perianal fistula closure. Results A total of 64 patients (adalimumab, n = 35; infliximab, n = 29) were included. Patients with fistula healing had higher levels of anti-TNF vs. those without fistula healing (adalimumab: 12.6 vs. 2.7 μg/mL, P 6.8 μg/mL and >9.8 μg/mL for fistula healing and closure, respectively. For infliximab, receiver operator characteristic analysis identified an optimum trough level of >7.1 μg/mL for both fistula healing and closure. Conclusion Higher maintenance anti-TNF levels are associated with perianal fistula healing and closure in Crohn's disease.

Background N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. Methods Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake. Results Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07). Conclusions Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

Introduction: Early diagnosis of atrial fibrillation (AF) leading to early therapy can improve clinical outcomes (e.g., stroke). Current approaches for AF risk stratification are limited. Dynamic ECG analysis during sleep is an alternate, underexplored approach for AF risk stratification. Hypothesis: Dynamic ECG analysis during sleep predicts AF incidence in community adults, and adds major independent prognostic value to conventional AF risk factors and scores. Methods: In the multi-center prospective Sleep Heart Health Study, we studied consecutive, asymptomatic, ostensibly healthy, middle-aged and older community adults without a history of AF who were in sinus rhythm during home polysomnography. We performed comprehensive and systematic univariate and multivariate analyses of all available clinical, ECG and polysomnography parameters for association with AF incidence over follow-up. Results: Over 5.3±0.29 years, 315 (11.2%) of 2,807 people had new onset AF. We identified the major independent significant AF predictors, including established risk factors and ECG dynamics, and derived a multivariate prediction model entitled, the Cincinnati AF score (CAFS) ( FIGURE 1 ). Addition of CAFS to a multivariate model with (1) CHA 2 DS 2 -VASc score increased ROC curve area by 9% and yielded net reclassification improvement (NRI) of 90% [43+47% for cases and non-cases, respectively]; or with (2) CHARGE-AF score increased ROC curve area by 3.5% and yielded NRI of 54% [23+31%]. These improvements were driven primarily by the ECG dynamics, independent of sleep apnea and other risk factors. Conclusion: Dynamic ECG analysis during sleep adds major independent prognostic value to established AF risk factors and scores. The ability to better identify individuals who will and will not develop AF has potential for broad clinical impact. We are currently validating CAFS in another multi-center cohort of asymptomatic ambulatory adults with a diverse demographic profile.

Background and importance Chronic neuropathic facial pain is a debilitating disease that can be approached with multiple different treatment modalities. Cervical spinal cord stimulation has been demonstrated to be effective for patients suffering from neuropathic facial pain. Consensus does not exist in the literature regarding technique for placement. Clinical presentation A 49-yr-old female presented with chronic intractable neuropathic facial pain. She underwent a successful percutaneous spinal cord stimulation trial, followed by placement of a paddle electrode for permanent implantation. The paddle electrode failed to duplicate the pain relief of her trial. Measurement of the width of the paddle demonstrated that it was 2 mm smaller than the separation of the percutaneous trial electrodes. Electrodes with wider interelectrode distance were then placed with satisfactory pain relief. Conclusion Although conventional spinal cord stimulation targets the dorsal columns, cervical spinal cord stimulation for facial pain targets the spinal trigeminal nucleus. The effectiveness of stimulation may be increased with a more laterally positioned electrode in order to recruit the more laterally positioned spinal trigeminal nucleus. This case report illustrates the importance of this anatomic consideration.

Objective We reviewed our experience with pediatric chest wall tumors (CWTs) to identify variables associated with survival, scoliosis development, and need for corrective scoliosis surgery. Background Chest wall neoplasms in children or adolescents are rare. Consequently, there are few large series that detail survival or quality of life indicators, like scoliosis. Methods Medical records were reviewed for all chest wall resections for primary and metastatic CWT performed from October 1, 1986 to September 30, 2016 on patients 21 years or younger at diagnosis. Kaplan-Meier distributions were compared using the log-rank test. Variables correlated with survival, scoliosis development, or need for corrective surgeries were analyzed using competing-risk analysis. Results Seventy-six cases [57 (75%) primary, 19 (25%) metastatic] were identified. Median age at diagnosis was 15.6 years (range: 0.5-21 years). Tumor types were Ewing sarcoma family tumors (54%), other soft tissue sarcomas (21%), osteosarcoma (11%), rhabdomyosarcoma (7%), and other (8%). A median of 3 (range: 1-5) contiguous ribs were resected. Surgical reconstruction included composite Marlex mesh and methyl-methacrylate, Gore-Tex, or primary closure in 57%, 28%, and 14% of procedures, respectively. Overall 5-year survival was 61% (95% confidence interval: 50%-75%). Scoliosis developed in 19 (25%) patients; 6 patients required corrective surgery. Variables associated with overall survival were the presence of metastatic disease at diagnosis, and whether the chest tumor itself was a primary or metastatic lesion. Younger age at chest wall resection was associated with the need for corrective surgery in patients who developed scoliosis. Conclusions Among pediatric and adolescent patients with CWTs, survival depends primarily on the presence of metastases. Age, type of chest wall reconstruction, and tumor size are not associated with scoliosis development. Among patients who develop scoliosis, younger patients are more likely to require corrective surgery.

ObjectiveTo determine the frontal lobe proton magnetic resonance spectroscopy (1H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau (MAPT) mutations.MethodsWe recruited patients with MAPT mutations from 5 individual families, who underwent single voxel 1H MRS from the medial frontal lobe at 3T (n = 19) from the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Study at the Mayo Clinic site. Asymptomatic MAPT mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic MAPT mutation carriers (n = 10) had a median FTLD-CDR SOB score of 5. Noncarriers from healthy first-degree relatives of the patients were recruited as controls (n = 25). The demographic aspects and 1H MRS metabolite ratios were compared by use of the Fisher exact test for sex and linear mixed models to account for within-family correlations. We used Tukey contrasts for pair-wise comparisons.ResultsAsymptomatic MAPT mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) (p = 0.001) and lower NAA/myo-inositol (mI) (p = 0.026) than noncarriers after adjustment for age. Symptomatic MAPT mutation carriers had lower NAA/Cr (p = 0.01) and NAA/mI (p = 0.01) and higher mI/Cr (p = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr (p = 0.006) and NAA/mI (p < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio (p = 0.001), as the ages of carriers approached and passed the age at symptom onset.ConclusionFrontal lobe neurochemical alterations measured with 1H MRS precede the symptom onset in MAPT mutation carriers. Frontal lobe 1H MRS is a potential biomarker for early neurodegenerative processes in MAPT mutation carriers.

BACKGROUND AND OBJECTIVES: Frailty, a syndrome distinct from comorbidity and disability, is clinically manifested as a decreased resistance to stressors and is present in up to 35% of patient with ESKD. It is associated with falls, hospitalizations, poor cognitive function, and mortality. Also, frailty is associated with poor outcomes after kidney transplant, including delirium and mortality. Frailty is likely also associated with decreased access to kidney transplantation, given its association with poor outcomes on dialysis and post-transplant. Yet, clinicians have difficulty identifying which patients are frail; therefore, we sought to quantify if frail kidney transplant candidates had similar access to kidney transplantation as nonfrail candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 7078 kidney transplant candidates (2009–2018) in a three-center prospective cohort study of frailty. Fried frailty (unintentional weight loss, grip strength, walking speed, exhaustion, and activity level) was measured at outpatient kidney transplant evaluation. We estimated time to listing and transplant rate by frailty status using Cox proportional hazards and Poisson regression, adjusting for demographic and health factors. RESULTS: The mean age was 54 years (SD 13; range, 18–89), 40% were women, 34% were black, and 21% were frail. Frail participants were almost half as likely to be listed for kidney transplantation (hazard ratio, 0.62; 95% confidence interval, 0.56 to 0.69; P

Objective This study compares and contrasts new graduate nurse attributes and perceptions using findings from a 2010 study and a recent analysis of new graduate nurses participating in the same residency program. Background As millennials saturate the healthcare work environment, their unique views and needs will influence the evolution of new graduate nurse residencies. Methods This study used previously reported data on new graduate nurses between 1999 and 2009 and compared it with a secondary analysis of data collected on new graduate nurses between 2011 and 2016. Results This study provides evidence that millennial new graduate nurses' levels of commitment and satisfaction do not moderate turnover intentions in the 1st 2 years of practice as they did in the previous group of new graduate nurses. Conclusions Job embeddedness, a construct that measures the likelihood of whether a person is going to stay, may be a better measurement among new graduate nurses than commitment or satisfaction because millennials, a generation that is predominant in current new graduate nurses, are more engaged than loyal.

OBJECTIVE To improve understanding of sex differences in clinicopathologic characteristics, treatment and outcomes between male and female patients undergoing esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA Esophageal cancer is a male predominant disease, and sex has not been considered in previous studies as an important factor in diagnosis or management. Sex differences in demographics, clinicopathologic characteristics, and postoperative outcomes remain largely undefined. METHODS Retrospective review of 1958 patients (21% female) with esophageal cancer who underwent esophagectomy at a single institution between 1995 and 2017. RESULTS Most patients had adenocarcinoma (83%); however, the rate of squamous cell carcinoma was significantly higher in females (35% vs 11%, respectively; P

Background: Dyslipidemia and inflammation independently contribute to atherosclerosis. The associations between different lipid parameters and inflammatory markers is not fully understood. Hypothesis: LDL-C, triglycerides, and HDL-C do not predict inflammation equally. Methods: We analyzed data from 784,233 patients from the second harvest of the Very Large Database of Lipid study with lipids and hsCRP measured. The prevalence of having hsCRP≥2 mg/L was compared in 20 quantiles of non-HDL-C, LDL-C, HDL-C and triglycerides. Using linear regression, we estimated the correlations between hsCRP and lipids and to what degree individual lipid components explain the variation in hsCRP values. We then examined these association by sex and age (≥65 vs Results: The median hsCRP of the population was 2.3 mg/L (IQR, 1.0-5.7). The proportion of patients with hsCRP≥2 mg/L progressively increased with higher non-HDL-C, LDL-C, triglycerides quintiles, but decreased with higher HDL-C quintiles. All lipid measures directly correlated with hsCRP value except HDL-C which was inversely correlated (P2 = 0.5% and 0.1%, respectively). Triglyceride levels were the strongest predictor of hsCRP (standardized β, 0.21; P Conclusion: Of major lipid and lipoprotein cholesterol fractions, triglycerides and HDL-C correlated most strongly and non-HDL-C and LDL-C contributed the least to hsCRP.

Introduction: Emerging evidence suggests that remnant cholesterol (RC) promotes future atherosclerotic cardiovascular disease (ASCVD) events. Our aim was to estimate the risk associated with RC beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Hypothesis: RC provides incremental prognostic information regarding incident ASCVD, independent of LDL-C and apoB. Methods: We pooled data from 17,532 individuals from Atherosclerosis Risk in Communities study (n=9,748), Multi-Ethnic Study of Atherosclerosis (n=3,049) and Coronary Artery Risk Development in Young Adults (n=4,735), who were ASCVD-free at baseline and had measurements of lipids, apoB and apolipoprotein A1. RC was calculated as non-high-density cholesterol (non-HDL-C) minus LDL-C estimated by the Martin/Hopkins equation. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in discordant/concordant groups of RC and LDL-C across median cutpoints and cutpoints of percentile equivalence to LDL-C targets (70 and 100 mg/dL). Results: Mean age of participants was 52.3±17.9 years, 56.7% women and 34% black. There were 2,143 ASCVD events over median follow-up of 18.7 years. After multivariable adjustment including apoB and HDL-C, logRC was associated with higher ASCVD risk [HR 1.42, 95% CI (1.23-1.63)]. In discordance analyses, the high RC and low LDL-C group (≥/ Conclusion: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors and LDL-C and apoB levels. RC assessment and management in primary prevention, beyond LDL-C and apoB, is useful and requires further scrutiny.

Introduction: The Friedewald equation (F-LDL-C) and the Martin-Hopkins algorithm (MH-LDL-C) estimate direct LDL-C from a standard lipid panel. Discordant LDL-C estimates by the two methods may carry significant clinical implications. We evaluated the clinical variables associated with discordant LDL-C estimates and the association of discordance with risk of incident atherosclerotic cardiovascular disease (ASCVD) in the Dallas Heart Study (DHS), a multi-ethnic, population based prospective cohort. Methods: We estimated F-LDL-C and MH-LDL-C in 2824 DHS participants (42% male; mean age 43.5 years) with TG ≤ 400 mg/dL, who were not on baseline lipid lowering therapy and were free of prior ASCVD. We divided the cohort into quintiles of LDL-C discordance (MH-LDL-C minus F-LDL-C, in mg/dL) and assessed associations with ASCVD risk factors. We evaluated associations between discordance and incident ASCVD by sequentially adjusted Cox regression models, and we generated restricted cubic spline plots of discordance and hazard for ASCVD. Results: There were 228 ASCVD events over a median of 12.3 years. Clinical characteristics across discordance quintiles are shown in the Table . After adjustment for traditional ASCVD risk factors, there was a linear association between higher LDL-C discordance and increased risk of ASCVD events ( Figure ) with the highest hazard in Quintile 5 (HR 1.5, 95% CI 1.1 - 2.0). Conclusions: Discordant LDL-C estimates were largely associated with male sex, White and Hispanic races, and characteristics of the metabolic syndrome. Individuals in the highest quintile of discordant LDL-C estimates, with MH-LDL-C > F-LDL-C, had greater risk for incident ASCVD.

Introduction: Adding N-acetylcysteine (NAC) to amiodarone may mitigate inflammation and oxidative stress, preventing postoperative atrial fibrillation (POAF). NAC, reported to reduce cardiac surgery POAF, has not been tested in major thoracic surgery. Methods: Patients at high risk for POAF (BNP≥25pg/ml, male, age≥75, or history of AF) who underwent major thoracic surgery (n=154) were randomized to amiodarone + NAC (n=78) or amiodarone + placebo (n=76). Begun on arrival to the PACU were amiodarone 150 mg iv then 1 g/24 h iv x 48 h, and NAC or placebo bolus 50 mg/kg iv then 50 mg/kg/24 h iv x 48 h. The primary endpoint was sustained AF >30 s by telemetry (first 72 h) or symptoms within 7 days of surgery; patients with the primary endpoint underwent home ECG monitoring. Secondary endpoints were AF up to 1-year post discharge and systemic markers of inflammation. Results: Baseline characteristics were similar between arms (Table). POAF occurred in 15/78 NAC patients (19%) and 13/76 placebo patients (17%) (p=0.8). The trial was stopped at the interim analysis for futility. Regardless of treatment, of 28 patients with POAF, 3/28 (11%) were discharged in AF, and 1/28 (4%) met the primary endpoint after discharge. At 1-year, 7/28 patients with POAF (25%) had recurrent episodes of AF, and 1 developed persistent AF—none developed stroke. Inflammatory markers were similar between treatment arms; however, regardless of NAC, on postoperative day 2, patients with POAF (n=28) had higher CRP (p=0.008) and IL-6 (p=0.001) than patients without POAF (n=126). Conclusions: Compared to amiodarone alone, NAC + amiodarone did not reduce the incidence of POAF nor markers of inflammation early after major thoracic surgery. Recurrent AF episodes are common among patients with POAF within 1-year of surgery.

Introduction: Elevated Lipoprotein(a) [Lp(a)] is associated with an increased risk of coronary heart disease (CHD). Although Lp(a) is mostly heritable, and controlled by the apo(a) gene, acute increases are described in small studies following acute coronary syndrome (ACS). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition modestly reduces Lp(a) in people with stable CHD but its effects during the early phase of an ACS are unknown. Hypothesis: Early administration of a PCSK9 inhibitor prevents a rise in Lp(a) following an ACS/NSTEMI. Methods: Participants from the EVACS trial (Evolocumab in Acute Coronary Syndrome; NCT03515304), all with a NSTEMI and a troponin-I of > 5 ng/ml were randomized to placebo or to evolocumab. Serum Lp(a) was obtained at study entry prior to study drug and at 30 days. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges. Results: Fifty-six participants were randomized to placebo (27) or to evolocumab (29). Mean age was 55±13 years, 41% were women and 27% were African American. The Scatterplots (Fig.1) demonstrate for those with a baseline Lp(a) of ≤75 nmol/L (the previously described optimal level) there was no increase in Lp(a) over the 30-day study period in either group. However, for those with a baseline Lp(a) of >75 nmol/L there was a significant increase in the placebo group (Panel A), from a baseline of 176.5 nmol/L [131.5, 245.0] to 266 nmol/L [195.8, 302.5] at 30 days, p=0.02, but no increase in the evolocumab group (Panel B; baseline of 142 nmol/L [93, 177] to 137 nmol/L [96.8, 178.3], p=NS). The baseline values of those with Lp(a) of >75 nmol/L did not differ between the groups; at 30 days, however, Lp(a) was higher in the placebo than in the evolocumab group (p=0.02; Panel C). Conclusions: Early administration of evolocumab prevents the acute increase in Lp(a) in those with a baseline Lp(a) of over 75 nmol/L following an ACS/NSTEMI.

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) is well recognized for its important role in cholesterol metabolism. Elevated levels are associated with increased cardiovascular risk and inhibition with PCSK9 antibodies (PCSK9i) lowers cardiovascular events in patients with coronary artery disease. PCSK9 levels are also elevated in people living with HIV (PLWH) and those with dyslipidemia. Because increased PCSK9 in PLWH is associated with impaired coronary endothelial function, a barometer of coronary vascular health, we tested the hypothesis that PCSK9i improves impaired coronary endothelial function in dyslipidemia without coronary artery disease and in PLWH with nearly optimal/above goal low‐density lipoprotein cholesterol levels. Methods and Results We performed a single‐center study in 19 PLWH and 11 with dyslipidemia to evaluate the effects of the PCSK9i evolocumab on coronary endothelial function using cine 3T MRI to noninvasively measure coronary endothelial function, assessed as the changes in coronary cross‐sectional area and coronary blood flow from rest to that during isometric handgrip exercise, a known endothelial‐dependent vasodilator. Before evolocumab, there was a decrease or no coronary vasodilation and no increase in coronary blood flow (the normal responses) to isometric handgrip exercise in either group. Following 6 weeks of evolocumab, 480 mg q4 weeks, the % cross‐sectional area changes from rest to isometric handgrip exercise were +5.6±5.5% and +4.5±3.1% in the PLWH and dyslipidemia groups, respectively, both P Conclusions To our knowledge, these data represent the first evidence that PCSK9 inhibition improves coronary artery health in PLWH and people with dyslipidemia. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03500302.

Effective teaching methods are critical to the acquisition of physical assessment skills. This article describes the combined use of deliberate practice, standardized patient simulation, and peer evaluation in improving physical assessment skills among first-semester nursing students. Students prepared for a physical assessment check-off by using deliberate practice throughout the semester; they then received peer feedback after a standardized patient simulation. Students felt the integrated experience improved their physical assessment performance. Incorporating this innovative educational trio can provide opportunities for physical assessment skill enhancement.

Background: Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. Subclinical hypothyroidism is associated with higher levels of total cholesterol and Low-density lipoprotein cholesterol as well as high levels of triglycerides and low levels of high-density lipoprotein cholesterol. Triglyceride-rich Lipoprotein Particles concentration (TRLP) have recently emerged as a causal factor for atherogenesis. Aim: To evaluate the relationship between Subclinical Hypothyroidism and Subclinical Hyperthyroidism and Triglyceride-rich Lipoprotein Particles. Methods: Participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were classified according to the baseline thyroid function as Subclinical Hypothyroidism, Euthyroidism, and Subclinical Hyperthyroidism. Conventional lipid concentrations (total, HDL cholesterol, and triglycerides were determined by a nonprecipitated colorimetric method. The TRLP subfractions were analyzed through Nuclear Magnetic Resonance spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted a multivariate linear regression model adjusted for demographic characteristics (race, gender, and educational level), body-mass index, diabetes, smoking status, and alcoholic beverages intake. Results: Of 3,550 individuals free of cardiovascular or thyroid diseases (54%, women; median age 51 years; 51% White, and 53% with at least college education) 92%of them were euthyroid, 6.8% had subclinical hypothyroidism, and 1.2% had subclinical hyperthyroidism. No differences were observed concern the levels of total, HDL, and LDL-cholesterol, but triglycerides were higher for people with Subclinical Hypothyroidism. After adjustment by the covariates described above and using subjects with normal thyroid function as the reference group, for people with Subclinical hypothyroidism a difference of means ( and 95% Confidence Interval) for Total TRLP levels (in ng/L) obtained was 0.06 (-0.00 to 0.13), and for the TRLP subfractions elevated for Very-Small [0.16 (0.02 to 0.28)] and Very-Large [0.21 (0.05 to 0.36)], and similar values for Small [-0.01 (-0.13 to 0.12)]; Medium [0.05 (-0.08 to 0.17)] and Large [0.16 (-0.06 to 0.38)] subfractions. In Subclinical Hyperthyroidism, there was a reduction in Total TRLP (-0.24 (-0.40 - -0.08)), seemingly driven by reduced Very Small-TRLP (0.23 (-0.11 - 0.57). Conclusion: This study suggests that subclinical hypothyroidism is associated with high levels of Very-Small and Very-Large TRLP, which are related to an unfavorable atherogenic profile. Subclinical Hyperthyroidism is associated with low concentrations of Very-Small TRLP.

Introduction: Despite more accurate low-density lipoprotein cholesterol (LDL-C) estimates by the Martin (mLDL-C) method, most laboratories still use the Friedewald (fLDL-C) equation. Low non-high density lipoprotein (non-HDL-C) and high triglycerides (TG) drive inaccuracy in LDL-C estimation. We compared a strategy of identifying errors in fLDL-C using non-HDL-C/TG ratios with subsequent reflex direct LDL-C testing to a strategy of using mLDL-C. Methods: We included 4,939,542 individuals (2/3 derivation, 1/3 validation dataset) with TG Results: Nearly 8% of fLDL-C results deviated >12% from direct LDL-C compared with only 2.5% of mLDL-C results in the entire population. Non-HDL-C/TG ratios of 0.6-0.9 performed best in the derivation dataset. In the validation dataset, a non-HDL-C/TG ratio of 0.7 had the highest area under the curve for identifying >12% error in fLDL-C estimates (Table). At this ratio, 14.5% of fLDL-C samples would need direct LDL-C measurement at an increase in costs of lipid testing by 10%. Conclusions: Use of non-HDL-C/TG ratio

Background Arsenic‐related cardiovascular effects at exposure levels below the US Environmental Protection Agency's standard of 10 μg/L are unclear. For these populations, food, especially rice, is a major source of exposure. We investigated associations of rice intake, a marker of arsenic exposure, with subclinical cardiovascular disease (CVD) markers in a multiethnic population. Methods and Results Between 2000 and 2002, MESA (Multi‐Ethnic Study of Atherosclerosis) enrolled 6814 adults without clinical CVD . We included 5050 participants with baseline data on rice intake and markers of 3 CVD domains: inflammation (hsCRP [high‐sensitivity C‐reactive protein], interleukin‐6, and fibrinogen), vascular function (aortic distensibility, carotid distensibility, and brachial flow‐mediated dilation), and subclinical atherosclerosis at 3 vascular sites (carotid intima‐media thickness, coronary artery calcification, and ankle‐brachial index). We also evaluated endothelial‐related biomarkers previously associated with arsenic. Rice intake was assessed by food frequency questionnaire. Urinary arsenic was measured in 310 participants. A total of 13% of participants consumed ≥1 serving of rice/day. Compared with individuals consuming CVD risk factor adjustment (eg, geometric mean ratio [95% CI ] for hs CRP , 0.98 [0.86–1.11]; aortic distensibility, 0.99 [0.91–1.07]; and carotid intima‐media thickness, 0.98 [0.91–1.06]). Associations with urinary arsenic were similar to those for rice intake. Conclusions Rice intake was not associated with subclinical CVD markers in a multiethnic US population. Research using urinary arsenic is needed to assess potential CVD effects of low‐level arsenic exposure. Understanding the role of low‐level arsenic as it relates to subclinical CVD may contribute to CVD prevention and control.

Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of stroke among diabetic patients, we explored associations between lipoprotein subfractions and risk for stroke in the FIELD trial. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation. Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for all stroke. LDL and its subfractions and Lp(a)-C did not. VLDL and its subfractions, non-HDL-C, triglycerides, apo B, apo En, various ratios incorporating apo C3, and the ratios of apoB/A1 and apoB/apoA2 all correlated with increased risk for stroke. Conclusions: VAP identifies multiple lipoprotein subclasses, apoproteins, and VAP subclass/apoprotein ratios associated with stroke. Many of these measures improved with fenofibrate therapy.