An Innovative Faster R-CNN-Based Framework for Breast Cancer Detection in MRI.

Replacing lung cancer as the most commonly diagnosed cancer globally, breast cancer (BC) today accounts for 1 in 8 cancer diagnoses and a total of 2.3 million new cases in both sexes combined. An estimated 685,000 women died from BC in 2020, corresponding to 16% or 1 in every 6 cancer deaths in women. BC represents a quarter of a total of cancer cases in females and by far the most commonly diagnosed cancer in women in 2020. However, when detected in the early stages of the disease, treatment methods have proven to be very effective in increasing life expectancy and, in many cases, patients fully recover. Several medical imaging modalities, such as X-rays Mammography (MG), Ultrasound (US), Computer Tomography (CT), Magnetic Resonance Imaging (MRI), and Digital Tomosynthesis (DT) have been explored to support radiologists/physicians in clinical decision-making workflows for the detection and diagnosis of BC. In this work, we propose a novel Faster R-CNN-based framework to automate the detection of BC pathological Lesions in MRI. As a main contribution, we have developed and experimentally (statistically) validated an innovative method improving the "breast MRI preprocessing phase" to select the patient's slices (images) and associated bounding boxes representing pathological lesions. In this way, it is possible to create a more robust training (benchmarking) dataset to feed Deep Learning (DL) models, reducing the computation time and the dimension of the dataset, and more importantly, to identify with high accuracy the specific regions (bounding boxes) for each of the patient's images, in which a possible pathological lesion (tumor) has been identified. As a result, in an experimental setting using a fully annotated dataset (released to the public domain) comprising a total of 922 MRI-based BC patient cases, we have achieved, as the most accurate trained model, an accuracy rate of 97.83%, and subsequently, applying a ten-fold cross-validation method, a mean accuracy on the trained models of 94.46% and an associated standard deviation of 2.43%.

Fetal Supraventricular Tachycardia: What the Adult Cardiologist Needs to Know.

Fetal supraventricular tachycardia management is challenging, with consequences for both the fetus and the mother. If left untreated, fetal hydrops may ensue, at which point delivery and treatment of the arrhythmia is preferred. However, if the fetus is not at term nor near-term, significant doses of antiarrhythmics may be needed to achieve adequate transplacental bioavailability. Although digoxin has classically been the mainstay of treatment, the use of flecainide or sotalol as monotherapy or in combination with digoxin is being studied. Interdisciplinary team management and shared decision-making between the physician and patient are key to achieving successful outcomes. Adult cardiologists, particularly inpatient consultation services or through burgeoning cardio-obstetrics programs, may, in some practice settings, be asked to evaluate or comanage pregnant women with fetal arrhythmia.

BAGS: An automated Barcode, Audit & Grade System for DNA barcode reference libraries.

Biodiversity studies greatly benefit from molecular tools, such as DNA metabarcoding, which provides an effective identification tool in biomonitoring and conservation programmes. The accuracy of species-level assignment, and consequent taxonomic coverage, relies on comprehensive DNA barcode reference libraries. The role of these libraries is to support species identification, but accidental errors in the generation of the barcodes may compromise their accuracy. Here, we present an R-based application, Barcode, Audit & Grade System (BAGS) (https://github.com/tadeu95/BAGS), that performs automated auditing and annotation of cytochrome c oxidase subunit I (COI) sequences libraries, for a given taxonomic group of animals, available in the Barcode of Life Data System (BOLD). This is followed by implementing a qualitative ranking system that assigns one of five grades (A to E) to each species in the reference library, according to the attributes of the data and congruency of species names with sequences clustered in barcode index numbers (BINs). Our goal is to allow researchers to obtain the most useful and reliable data, highlighting and segregating records according to their congruency. Different tests were performed to perceive its usefulness and limitations. BAGS fulfils a significant gap in the current landscape of DNA barcoding research tools by quickly screening reference libraries to gauge the congruence status of data and facilitate the triage of ambiguous data for posterior review. Thereby, BAGS has the potential to become a valuable addition in forthcoming DNA metabarcoding studies, in the long term contributing to globally improve the quality and reliability of the public reference libraries.

Saddle pulmonary embolism and thrombus-in-transit straddling the patent foramen ovale 28 days after COVID symptom onset.

We present a late presentation of saddle pulmonary embolism and thrombus-in-transit straddle the patent foramen on patient who successfully recovered from severe acute respiratory syndrome coronavirus-2 (COVID-19) pneumonia. Seven days postdischarge (ie, 28 days after initial COVID-19 symptom onset), she was readmitted to hospital for severe dyspnea. Computer tomography angiogram and echocardiography confirmed the diagnosis. Severe pro-inflammatory and pro-thrombotic states with endothelial involvement have been reported associated with severe COVID-19 infection. However, the duration of hypercoagulable state has not yet known. This case highlights the risk of thromboembolic phenomena for prolonged periods of times after recovering from COVID-19 pneumonia.

Association Between Atrial Fibrillation and Cognitive Impairment in Individuals With Prior Stroke: A Meta-Analysis and Meta-Regression Analysis.

Background and Purpose- Atrial fibrillation (AF) is the most common chronic arrhythmia. Dementia and cognitive impairment (CI) are major burdens to public health. The prevalence of all 3 entities is projected to increase due to population aging. Previous reports have linked AF with a higher risk of CI and dementia in patients without prior stroke. Stroke is known to increase the risk for dementia and CI. It is unclear if AF in patients with history of stroke can further increase the risk for dementia or CI. Our purpose was to evaluate the impact of AF on risk for dementia or CI among patients with history of stroke. Methods- Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Pubmed, Scopus, and Cochrane central were searched. The outcomes of interest were dementia, CI, and the composite end point of dementia or CI. A random-effect model meta-analysis was performed. Meta-regression analysis was also performed. Publication bias was assessed with the Egger test and with funnel plots. Results- Fourteen studies and 14 360 patients (1363 with AF) were included in the meta-analysis. In the meta-analysis of adjusted odds ratio, AF was associated with increased risk of CI (odds ratio, 1.60 [95% CI, 1.20-2.14]), dementia (odds ratio, 3.11 [95% CI, 2.05-4.73]), and the composite end point of CI or dementia (odds ratio, 2.26 [95% CI, 1.61-3.19]). The heterogeneity for the composite end point of dementia or CI was moderate (adjusted analysis). The heterogeneity for the analysis of the end point of CI only was substantial in the unadjusted analysis and moderate in the adjusted analysis. The heterogeneity for the end point of dementia only was moderate in the unadjusted analysis and zero in the adjusted analysis. Conclusions- Our results indicate that an association between AF and CI or dementia is patients with prior strokes is possible given the persistent positive associations we noticed in the unadjusted and adjusted analyses. The heterogeneity levels limit the certainty of our findings.

Hospital and clinical care costs associated with atrial fibrillation for Medicare beneficiaries in the Cardiovascular Health Study and the Framingham Heart Study.

BACKGROUND: Atrial fibrillation is increasingly prevalent as the US population ages and is associated with significant morbidity and mortality. Care for patients with atrial fibrillation can be costly, US health care costs are comparatively high, and there are few cost estimates available that incorporate detailed measurement of comorbidities and their effects on costs. METHODS AND RESULTS: In the Cardiovascular Health Study and the Framingham Heart Study, participants aged 65 years or older with newly diagnosed atrial fibrillation were matched on age and follow-up time to referents free of atrial fibrillation. The total clinical and hospital medical costs paid by Medicare Parts A and B (drug costs from Medicare Part D costs were not included) in the year prior to diagnosis (or matching) were compared with costs in the following year. Estimates were adjusted for other medical conditions and adjusted to 2009 dollars. In the Cardiovascular Health Study, 513 participants were diagnosed with new-onset atrial fibrillation and survived 30 days post-atrial fibrillation diagnosis, and 513 referents (as a control cohort) were identified, with a mean age of 77 years. In the Framingham Heart Study, we identified 336 participants diagnosed with atrial fibrillation, who survived 30 days post-atrial fibrillation diagnosis and matched these participants to 336 referents. We compared these new-onset atrial fibrillation participants with referents, using a difference in difference design to account for both time trends and differences between the two groups. The adjusted incremental cost for participants with atrial fibrillation, compared with referents, was US$18,060 (95% confidence interval: US$14,965-US$21,155) in the Cardiovascular Health Study and US$20,012 (95% confidence interval: US$15,057-US$24,966) in the Framingham Heart Study. The pooled estimate was US$18,601 (95% confidence interval: US$15,981-US$21,234). CONCLUSION: Atrial fibrillation was associated with increased costs in the year after diagnosis in two community-based cohorts, even after careful accounting for age, time period, and systematically measured comorbidities.

Lethal and Sublethal Effects of Various Pesticides on Trichogramma achaeae (Hymenoptera: Trichogrammatidae).

Little information is available regarding the lethal and sublethal effects of pesticides on Trichogramma achaeae (Nagaraja and Nagarkatti; Hymenoptera: Tricogrammatidae) during integrated management of Tuta absoluta (Meyrick; Lepidoptera: Gelechiidae), an important pest for tomato production. Twenty-two pesticides sprayed on Ephestia kuehniella (Zeller; Lepidoptera: Pyralidae) eggs were evaluated on the mortality of adult parasitoids upon contact with the hosts 24 h after the treatments and their sublethal effects on the parasitoids were assessed in laboratory conditions. Tests were carried out with fresh solutions at the recommended concentration. According to the International Organisation for Biological and Integrated Control (IOBC) standards, chlorpyrifos is harmful to the parasitoid; merthiocarb, methomyl, spinosad lambda-cyhalothrin, and acrinatrin are moderately harmful; and chlorantraniliprole, lufenuron, hexythiazox, cyromazine and Bacillus thuringiensis have no effect on the parasitoid. Sulfur is slightly harmful, and azoxystrobin is harmless. Chlorpyrifos was the most lethal among these pesticides and killed all females in less than 24 h. All other pesticides affected the biological parameters of T. achaeae to varying degrees. Regarding the lethal and sublethal effects, merthiocarb and spinosad killed all female offspring in less than 24 h; lambda-cyhalothrin and sulfur reduced the number of parasitized eggs; and acrinatrin, deltamethrin and azoxystrobin affected the emergence rate. After that, we can recommend the use of chlorantraniliprole and B. thuringiensis to control Lepidoptera, cyromazine to control Diptera, pirimicarb to control Homoptera, hexythiazox to control mites and azoxystrobin can be used as fungicide in an integrated pest management program with mass released of T. achaeae.

Potential of Trichogramma achaeae (Hymenoptera: Trichogrammatidae) in Biological Control of Tuta absoluta (Lepidoptera: Gelechiidae) in Azorean Greenhouse Tomato Crops.

Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is an important pest of tomato crops. It is native to South America and has rapidly extended its range into Mediterranean countries. The parasitoid Trichogramma achaeae Nagaraja and Nagarkatti (Hymenoptera: Trichogrammatidae) has been recommended as a possible biological control agent of this invasive pest. The pest and parasitoid were accidentally introduced into the Azores Islands and became well-established owing to the climate conditions of the region. During an undertaken survey to determine the presence of natural parasitism, 2.5% of the T. absoluta eggs were found to be parasitized by Tr. achaeae, and no other egg parasitoid was observed. Other Trichogramma species, Trichogramma cordubensis Vargas & Cabello, was also selected to test, along with Tr. achaeae, against T. absoluta on caged tomato plants (microhabitats), and the effectiveness of these parasitoids in limiting the T. absoluta populations was assessed. The results revealed that Tr. achaeae had a high parasitism and emergence rate (29.6% and 65.9%, respectively), relative to those rates observed for T. cordubensis (6.1% and 39.3%, respectively). Greenhouse assays were also carried out between May and July in 2013 and 2014 on commercially produced tomatoes with the aim of evaluating the potential of Tr. achaeae mass releases for the control of T. absoluta under these conditions. In the second year, we observed a reduction in the mean number of leaf mines and of eggs, larvae, and pupae of T. absoluta per leaflet, and an increase in the Tr. achaeae parasitism rate.

Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study).

BACKGROUND: The epidemiology of atrial fibrillation (AF) without comorbidities, known as 'lone AF', is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF. METHODS: We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex- and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality. RESULTS: Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71±12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95%CI 0.55-0.81, P < .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P < .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P < .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P < .001) were higher than age-, sex-, and cohort-matched individuals without AF. CONCLUSIONS: The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF.

Five-Year Outcome in Stroke Patients Submitted to Thrombolysis.

BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74-0.90) were independently associated with a lower likelihood of an excellent 5-year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12-0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome.

Red blood cell fatty acids and biomarkers of inflammation: a cross-sectional study in a community-based cohort.

INTRODUCTION: Inflammation and inflammatory biomarkers have emerged as integral components and predictors of incident cardiovascular (CV) disease. Omega-3 fatty acids, particularly eicosapentaenoic and docosahexaenoic acids (EPA and DHA) have anti-inflammatory properties, and have been variably associated with lower blood pressure, favorable blood lipid changes, and reduced CV events. METHODS AND RESULTS: We examined the cross-sectional association of red blood cell (RBC) fatty acids, representative of body membrane fatty acid composition, with 10 biomarkers active in multiple inflammatory pathways in 2724 participants (mean age 66 ± 9 years, 54% women, 8% minorities) from the Framingham Offspring and minority Omni Cohorts. After multivariable adjustment, the RBC EPA and DHA content was inversely correlated (all P ≤ 0.001) with 8 biomarkers: urinary isoprostanes (r = -0.16); and soluble interleukin-6 (r = -0.10); C-reactive protein (r = -0.08); tumor necrosis factor receptor 2 (r = -0.08); intercellular adhesion molecule-1 (r = -0.08); P-selectin (r = -0.06); lipoprotein-associated phospholipase-A2 mass (r = -0.11) and activity (r = -0.08). The correlations for monocyte chemoattractant protein-1 was -0.05, P = 0.006 and osteoprotegerin (r = -0.06, P = 0.002) were only nominally significant. CONCLUSION: In our large community-based study, we observed modest inverse associations between several types of inflammatory biomarkers with RBC omega-3 fatty acid levels. Our findings are consistent with the hypothesis that omega-3 fatty acids have anti-inflammatory properties.

Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease).

Dramatic recovery after IV thrombolysis in anterior circulation ischemic stroke: predictive factors and prognosis.

BACKGROUND AND PURPOSE: Dramatic recovery (DR) after thrombolysis is dependent of vessel recanalization and is predictive of favorable clinical outcome. Successful recanalization is not equivalent to DR. Our objective was to assess its frequency and evaluate clinical and biochemical predictors and their prognosis. METHODS: We analyzed prospectively registered data from January 2007 to September 2012. All patients with anterior circulation stroke and NIHSS≥10 were included. Improvement of ≥10 or a score ≤3 24h after thrombolysis was defined as DR. RESULTS: In the 230 patients included, DR frequency was 23% (53 patients). DR group had lower admission NIHSS (14 vs 17, p=0.024), less total anterior circulation infarcts (p=0.009), more partial anterior circulation infarcts (p=0.003) and lower blood glucose on admission (118 vs 128mg/dL, p=0.013). All patients with DR had an Alberta Stroke Program Early CT Score (ASPECTS) ≥7, vs 89.3% without DR (p=0.013). Arterial recanalization, defined as hyperdense middle cerebral artery sign disappearance on control CT, was more frequent in the DR group (68.4% vs 14.1%, p<0.001). Intracranial hemorrhage on 24h-control CT scan was less frequent in the DR group (p<0.001). Multinomial logistic regression analysis showed that ASPECTS score was an independent predictor of DR (OR=2.35, 95%CI=1.32-4.16, p=0.003) and CT evidence of recanalization was independently associated with DR (OR=11.60, 95%CI, 3.02-44.53, p<0.001). CONCLUSION: DR is a frequent occurrence. ASPECTS score is an independent predictor of DR, which is also independently associated with CT evidence of middle cerebral artery recanalization.

B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies.

AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. CONCLUSION: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation.

BACKGROUND: We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP). METHODS: We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP. RESULTS: The mean age of the 3,217 participants was 59 ± 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age- and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model. CONCLUSION: In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers.

Association between inflammatory biomarkers and bone mineral density in a community-based cohort of men and women.

OBJECTIVE: Based upon evidence in animal and in vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and the inflammatory marker C-reactive protein (CRP) would be inversely associated with bone mineral density (BMD) in a community-based cohort of men and women, with the strongest associations among postmenopausal women not receiving menopause hormonal therapy (MHT). METHODS: We ascertained fasting serum concentrations of IL-6, TNFα, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual x-ray absorptiometry in 2,915 members of the Framingham Offspring Study (1996-2001). We used multivariable linear regression to estimate the difference (ß) in BMD at each bone site associated with a 1-unit increase in log-transformed serum concentrations of IL-6, TNFα, and CRP separately for men (n = 1,293), premenopausal women (n = 231), postmenopausal women receiving MHT (n = 498), and postmenopausal women not receiving MHT (n = 893). RESULTS: Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (ß = -0.030, P < 0.01) and between CRP and femoral neck (ß = -0.015, P = 0.05) and trochanter BMD (ß = -0.014, P = 0.04). TNFα was positively associated with spine BMD (ß = 0.043, P = 0.01). In postmenopausal women receiving MHT, CRP was positively associated with femoral neck BMD (ß = 0.011, P = 0.04). There were no associations among postmenopausal women not receiving MHT. CONCLUSION: The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.

Atherosclerotic biomarkers and aortic atherosclerosis by cardiovascular magnetic resonance imaging in the Framingham Heart Study.

BACKGROUND: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. METHODS AND RESULTS: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). CONCLUSIONS: In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors.

Atrial fibrillation patterns and risks of subsequent stroke, heart failure, or death in the community.

BACKGROUND: Atrial fibrillation (AF) patterns and their relations with long-term prognosis are uncertain, partly because pattern definitions are challenging to implement in longitudinal data sets. We developed a novel AF classification algorithm and examined AF patterns and outcomes in the community. METHODS AND RESULTS: We characterized AF patterns between 1980 and 2005 among Framingham Heart Study participants who survived ≥ 1 year after diagnosis. We classified participants based on their pattern within the first 2 years after detection as having AF without recurrence, recurrent AF, or sustained AF. We examined associations between AF patterns and 10-year survival using proportional hazards regression. Among 612 individuals with AF, mean age was 72.5 ± 10.8 years, and 53% were men. Of these, 478 participants had ≥ 2 electrocardiograms (median, 3; limits 2 to 23) within 2 years after initial AF and were classified as having AF without 2-year recurrence (n = 63, 10%), recurrent AF (n = 162, 26%) or sustained AF (n = 207, 34%), although some (n = 46, 8%) were indeterminate. Of 432 classified participants, 363 died, 75 had strokes, and 110 were diagnosed with heart failure during the next 10 years. Relative to individuals without AF recurrence, the multivariable-adjusted mortality was higher among people with recurrent AF (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.26 to 3.29) and sustained AF (HR, 2.36; 95% CI, 1.49 to 3.75). CONCLUSIONS: In our community-based AF sample, only 10% had AF without early-term (2-year) recurrence. Compared with individuals without 2-year AF recurrences, the 10-year prognosis was worse for individuals with either sustained or recurrent AF. Our proposed AF classification algorithm may be applicable in longitudinal data sets.