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Background: Frailty assessment is an important marker of the older adult's fitness for cancer treatment independent of age. Pretreatment geriatric assessment (GA) is associated with improved mortality and morbidity outcomes but must occur in a time sensitive manner to be useful for cancer treatment decision making. Unfortunately, time, resources and other constraints make GA difficult to perform in busy oncology clinics. We developed the Cancer and Aging Interdisciplinary Team (CAIT) clinic model to provide timely GA and treatment recommendations independent of patient's physical location. Methods: The interdisciplinary CAIT clinic model was developed utilizing the surge in telemedicine during the COVID‐19 pandemic. The core team consists of the patient's oncologist, geriatrician, registered nurse, pharmacist, and registered dietitian. The clinic's format is flexible, and the various assessments can be asynchronous. Patients choose the service method—in person, remotely, or hybrid. Based on GA outcomes, the geriatrician provides recommendations and arrange interventions. An assessment summary including life expectancy estimates and chemotoxicity risk calculator scores is conveyed to and discussed with the treating oncologist. Physician and patient satisfaction were assessed. Results: Between May 2021 and June 2022, 50 patients from multiple physical locations were evaluated in the CAIT clinic. Sixty‐eight percent was 80 years of age or older (range 67–99). All the evaluations were hybrid. The median days between receiving a referral and having the appointment was 8. GA detected multiple unidentified impairments. About half of the patients (52%) went on to receive chemotherapy (24% standard dose, 28% with dose modifications). The rest received radiation (20%), immune (12%) or hormonal (4%) therapies, 2% underwent surgery, 2% chose alternative medicine, 8% were placed under observation, and 6% enrolled in hospice care. Feedback was extremely positive. Conclusions: The successful development of the CAIT clinic model provides strong support for the potential dissemination across services and institutions. [ABSTRACT FROM AUTHOR]

Objectives: To understand the magnitude of risk of health events, such as cardiovascular diseases (CVD), related to poor oral health, both relative and absolute risk measures should be reported. Our aim was to investigate the extent to which absolute and relative measures of risk are reported in longitudinal studies that assess the association between oral health indicators (OHIs) and CVD. Methods: A systematic search of longitudinal studies investigating the association of any OHI with CVD was carried out using the Embase, Medline and Cochrane library databases. The search covered each database from its inception date to August 2021. Data about reporting relative and absolute risks of the relationship between CVD and OHI from the abstract were extracted. If the relative risk for OHIs and CVD was reported in the abstract, then the underlying absolute risks were searched from the full text, and it was assessed whether it was similarly adjusted for confounding than was the relative risk in the abstract. Results: One hundred‐six articles were included. From these, 85 (80%) studies reported the association of OHIs and CVD with one or more relative risks in the abstract. Of those 85 studies, the underlying absolute risks were accessible or calculable from the abstract or full text of 60 studies. However, of these 60 studies, in only 10 (12%), the underlying absolute risks were similarly adjusted, as were the relative risks in the abstract. The absolute risks of CVD by OHIs were rarely reported without corresponding relative risks in the abstract (n = 2, 2%). Median absolute risk difference in the CVD risk between exposure levels to which the first relative risk in the abstract referred was 1.8% (interquartile range 0.6–4.6, n = 63). Conclusions: Focusing on relative risks over absolute risks was a common practice in literature. Reporting similarly adjusted underlying absolute risks of relative risks was rare in most studies, despite those being helpful for comprehending the magnitude of CVD‐risk increase related to poor oral health. Current reporting practices could lead to an overinterpretation of risk increase of CVD related to poor oral health. [ABSTRACT FROM AUTHOR]

Background: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST‐elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow‐up in STEMI patients. Methods: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow‐up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end‐diastolic volume compared to baseline at follow‐up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. Results: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow‐up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p <.001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (−7.4% [−10.1, −6.5] vs. −9.9% [−12.8, −8.1], p <.01), both on univariate and baseline LV volumes‐adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow‐up. Intra‐ and interobserver analysis showed good reproducibility of LA strain. Conclusions: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management. [ABSTRACT FROM AUTHOR]

Summary: Background: Neighbourhood socio‐economic environment (SEE) is associated with obesity in older children and adults, but little is known about this relationship in younger children. Breastfeeding is an important preventative of adiposity in childhood, but its relationship with neighbourhood SEE is unknown. Aims: We assessed differences in adiposity and obesity in children before age two by neighbourhood SEE, controlling for family socio‐demographics and breastfeeding duration. Materials and Methods: Family socio‐demographics, child body mass index z scores (BMIz), and breastfeeding duration were collected at periodic study visits from participants in PREVAIL (n = 245), a birth cohort in Cincinnati, OH. Addresses were assigned a Deprivation Index score, a validated measure of SEE, and dichotomized into highest SEE (least deprived quartile of scores) and not highest SEE (remaining quartiles). Longitudinal and Poisson models assessed differences in BMIz by SEE over the second year of life and obesity risk at age two, respectively (highest SEE, reference), while attenuation of obesity risk by breastfeeding duration was tested in mediation models. Results: Residing outside of the highest SEE neighbourhoods was associated with an increased BMIz of 0.04 (95%CI 0.02, 0.06) per month of life and increased obesity risk at age two (aRR: 3.7, 95%CI 1.2, 16.2), controlling for family socio‐demographics. Breastfeeding duration attenuated >9% of the obesity risk attributable to SEE (mediated RR: 3.4, 95%CI 1.1, 14.8). Discussion: In the PREVAIL Cohort, residing outside of the highest SEE neighbourhoods predicted a significant increase in BMIz and obesity risk in children before age two, a relationship that was partially mediated by breastfeeding duration. Conclusion: Breastfeeding support may play an important role in reducing obesity rates in children in lower SEE neighbourhoods. [ABSTRACT FROM AUTHOR]

Background: Many clinical and financial decisions for older adults depend on the future risk of disability and mortality. Prognostic tools for long‐term disability risk in a general population are lacking. We aimed to create a comprehensive prognostic tool that predicts the risk of mortality, of activities of daily living (ADL) disability, and walking disability simultaneously using the same set of variables. Methods: We conducted a longitudinal analysis of the nationally‐representative Health and Retirement Study (HRS). We included community‐dwelling adults aged ≥70 years who completed a core interview in the 2000 wave of HRS, with follow‐up through 2018. We evaluated 40 predictors encompassing demographics, diseases, physical functioning, and instrumental ADLs. We applied novel methods to optimize three models simultaneously while prioritizing variables that take less time to ascertain during backward stepwise elimination. The death prediction model used Cox regression and both the models for walking disability and for ADL disability used Fine and Gray competing‐risk regression. We examined calibration plots and generated optimism‐corrected statistics of discrimination using bootstrapping. To simulate unavailable patient data, we also evaluated models excluding one or two variables from the final model. Results: In 6646 HRS participants, 2662 developed walking disability, 3570 developed ADL disability, and 5689 died during a median follow‐up of 9.5 years. The final prognostic tool had 16 variables. The optimism‐corrected integrated area under the curve (iAUC) was 0.799 for mortality, 0.685 for walking disability, and 0.703 for ADL disability. At each percentile of predicted mortality risk, there was a substantial spread in the predicted risks of walking disability and ADL disability. Discrimination and calibration remained good even when missing one or two predictors from the model. This model is now available on ePrognosis (https://eprognosis.ucsf.edu/alexlee.php) Conclusions: Given the variability in disability risk for people with similar mortality risks, using individualized risks of disabilities may inform clinical and financial decisions for older adults. [ABSTRACT FROM AUTHOR]

Aims This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. Methods and results In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59±16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow-up (median 15.8 years, interquartile range: 11.3-16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow-up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01-1.47], p = 0.038). Conclusion In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). Methods: In this sub‐analysis of the HIJ‐PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut‐off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all‐cause death, non‐fatal myocardial infarction, non‐fatal stroke, and hospitalization for heart failure. Results: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut‐off point of 34 mL/m2. Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow‐up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19–7.22; P =.014). The tendency was similar after adjusting for several confounders (P =.025). Conclusion: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. Clinical trial registration: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742). [ABSTRACT FROM AUTHOR]

Objectives: Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%‐80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients. Methods: A total of 155 bone marrow samples from MM patients were collected from which RNA was analyzed by microarray. Sixteen previously developed GEP‐based markers were evaluated, combined with survival data, and studied using Cox proportional hazard regression. Results: Gene expression profiling‐based markers SKY92 and the PR‐cluster were shown to be independent prognostic factors for survival, with hazard ratios and 95% confidence interval of 3.6 [2.0‐6.8] (P <.001) and 5.8 [2.7‐12.7] (P <.01) for overall survival (OS). A multivariate model proved only SKY92 and the PR‐cluster to be independent prognostic factors compared to cytogenetic high‐risk patients, the International Staging System (ISS), and revised ISS. A substantial number of high‐risk individuals could be further identified when SKY92 was added to the cytogenetic, ISS, or R‐ISS. In the cytogenetic standard‐risk group, ISS I/II, and R‐ISS I/II, 13%, 23%, and 23% of patients with adverse survivals were identified. Conclusions: For the first time, this study confirmed the prognostic value of GEP markers outside clinical trials. Conventional prognostic models to define high‐risk MM are improved by the incorporation of GEP markers. [ABSTRACT FROM AUTHOR]

Objectives: Only 5% to 10% of patients who visit the emergency department (ED) with isolated dizziness without neurologic abnormalities may have central lesions; however, it is important to distinguish central lesions through brain imaging. This study was conducted to create a nomogram to provide an objective medical basis for selectively performing magnetic resonance imaging (MRI) among patients with isolated dizziness. Methods: This retrospective observational study enrolled patients who visited the ED of a tertiary hospital with isolated dizziness and underwent diffusion‐weighted MRI and subsequently consulted with the departments of neurology, neurosurgery, or otorhinolaryngology. Multivariable logistic regression analysis was performed to identify risk factors in patients diagnosed with central lesions to create a nomogram with the significant variables. Results: Of the 1,078 patients who were screened, 119 were diagnosed with central lesions. Significant variables in the multivariable logistic regression analysis were albumin levels (odds ratio [OR] = 0.339, 95% confidence interval [CI] = 0.188 to 0.610, p = 0.0003), inorganic phosphate levels (OR = 0.891, 95% CI = 0.832 to 0.954, p = 0.0010), history of ischemic stroke (OR = 3.170, 95% CI = 1.807 to 5.560, p < 0.0001), presyncope (OR = 3.152, 95% CI = 1.184 to 8.389, p = 0.0216), and nystagmus (OR = 0.365, 95% CI = 0.237 to 0.561, p < 0.0001). The area under the receiver operating characteristic curve of the nomogram created with these variables was 0.7315 (95% CI = 0.6842 to 0.7788, p < 0.0001). Conclusions: Albumin, inorganic phosphate, previous stroke, presyncope, and nystagmus were associated with the predictive diagnosis of central lesions among patients admitted to the ED with isolated dizziness. The novel nomogram created using these variables can help in objectively determining the need for MRI in patients presenting with isolated dizziness to the ED. [ABSTRACT FROM AUTHOR]

Objective: In aortic stenosis (AS), chronic pressure overload on left ventricle (LV) leads to LV hypertrophy, impaired relaxation, increased chamber stiffness, fibrosis and left atrial (LA) dilatation. An enlarged LA may be a marker of longstanding diastolic dysfunction (DD) and more advanced disease in AS. We aimed to assess the impact of LA volume index (LAVI) on events in patients with moderate or severe AS. Methods: A total of 324 patients (mean age 69 ± 13 years, 61% men) were included. LA volume was measured by biplane Simpson's method using apical four‐ and two‐chamber views and indexed to body surface area. An increased LAVI was defined as > 34 ml/m2. Results: The mean EF was 64 ± 8%, LAVI 35 ± 14 ml/m2 and flow rate 244 ± 70 ml/s. The number of total events was 275 (85%): 243 (75%) aortic valve replacement and 32 (10%) deaths. Mean follow‐up 23.7 ± 23.8 months (median 15.2 months). An increased LAVI (45% [n = 145]) was associated with adverse events (HR 1.86; 95% CI 1.24–2.82, p = 0.003) independent of age, smoking, diabetes, atrial fibrillation, LV ejection fraction, LV mass, aortic valve area, and low flow rate (<200 ml/s). In the same multivariate model, when increased LAVI was replaced by E/e′ ratio ≥14 cm, no association was found between E/e' ratio ≥14 cm and adverse events (HR 1.18; 95% CI.78–1.78, p = 0.430). Conclusion: LAVI was an independent predictor of adverse events in patients with moderate or severe AS and preserved ejection fraction. Including LAVI in the risk assessment of AS patients may further improve risk stratification. [ABSTRACT FROM AUTHOR]

Background/objectives: Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in the event‐free days. It remains uncertain whether communicating treatment benefit and harm using RMST‐based summary is more effective than conventional summary based on absolute and relative risk reduction. We compared the effect of RMST‐based approach and conventional approach on decisional conflict using an example of intensive versus standard blood pressure‐lowering strategies. Design: On‐line survey. Setting: A convenience sample of patients in the United States. Participants: Two hundred adults aged 65 and older with hypertension requiring anti‐hypertensive treatment (response rate 85.5%). Interventions: Participants were randomly assigned to either RMST‐based summary or conventional summary about the benefit and harm of blood pressure‐lowering strategies. Measurements: Decisional Conflict Scale (DCS), ranging from 0 (no conflict) to 100 (high conflict), and preference for intensive blood pressure‐lowering strategy. Results: Participants assigned to RMST‐based approach (n = 100) and conventional approach (n = 100) had similar age (mean [standard deviation, SD]: 72.3 [5.6] vs 72.8 [5.5] years) and proportions of female (50 [50.0%] vs 61 [61.0%]) and white race (92 [92.0%] vs 92 [92.0%]). The mean (SD) DCS score was 25.2 (15.0) for RMST‐based approach and 25.6 (14.1) for conventional approach (p = 0.84). The number (%) of participants who preferred intensive strategy was 10 (10.0%) for RMST‐based approach and 14 (14.0%) for conventional approach (p = 0.52). The results were consistent in subgroups defined by age, sex, education level, cardiovascular disease status, and predicted mortality risk categories. Conclusion: In a sample of relatively healthy older adults with hypertension, RMST‐based approach was as effective as conventional approach on decisional conflict about choosing a blood pressure‐lowering strategy. This study provides proof‐of‐concept evidence that RMST‐based approach can be used in conjunction with absolute and relative risk reduction for communicating treatment benefit and harm in a decision aid. [ABSTRACT FROM AUTHOR]

The baby‐friendly hospital initiative (BFHI) promotes exclusive breastfeeding (EBF) in hospitals, but this is not accessible in rural settings where mothers give birth at home, hence the need for a community intervention. We tested the effectiveness of the baby‐friendly community initiative (BFCI) on EBF in rural Kenya. This cluster randomized study was conducted in 13 community units in Koibatek sub‐county. Pregnant women aged 15–49 years were recruited and followed up until their children were 6 months old. Mothers in the intervention group received standard maternal, infant and young child nutrition counselling, support from trained community health volunteers, health professionals and community and mother support groups, whereas those in the control group received standard counselling only. Data on breastfeeding practices were collected longitudinally. The probability of EBF up to 6 months of age and the restricted mean survival time difference were estimated. A total of 823 (intervention group n = 351) pregnant women were recruited. Compared with children in the control group, children in the intervention group were more likely to exclusively breastfeed for 6 months (79.2% vs. 54.5%; P <.05). Children in the intervention group were also exclusively breastfed for a longer time, mean difference (95% confidence interval [CI]) 0.62 months (0.38, 0.85; P <.001). The BFCI implemented within the existing health system and including community and mother support groups led to a significant increase in EBF in a rural Kenyan setting. This intervention has the potential to improve EBF rates in similar settings. [ABSTRACT FROM AUTHOR]

Background: Although perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial. Here, we investigated the prognostic role of perineural invasion in surgically treated esophageal squamous cell carcinoma. Methods: We retrospectively reviewed the medical records of 316 patients who underwent esophagectomy and lymph node dissection for esophageal squamous cell carcinoma between 2007 and 2016. Results: Overall, 287 men (mean age: 62.73 ± 7.97 years) were included in the study. The median follow‐up period was 35.97 ± 30.99 months, perineural invasion was confirmed in 25 patients, and three‐year overall and disease‐free survival were significantly lower in the perineural invasion group than in the no‐perineural invasion group (75.9% vs. 40.0%, p < 0.001; 70.3% vs. 21.6%, p < 0.001). Cumulative incidences of locoregional recurrence and distant metastasis over three years were higher in the perineural invasion group (13.8% vs. 9.6%, p = 0.009 and 52.8% vs. 14.6%, p < 0.001). On performing multivariable analysis, perineural invasion, pathological stage, incomplete resection, and neoadjuvant therapy were adverse risk factors for disease‐free survival. The concordance index increased when perineural invasion was included in the model (0.712 vs. 0.723). On subgroup analysis, perineural invasion demonstrated a prognostic value in node‐negative patients (79.4% vs. 35.7%, p = 0.012). Conclusions: Perineural invasion was found to be an adverse risk factor for disease‐free survival in surgically treated patients with esophageal squamous cell carcinoma. Close observation and individualized adjuvant therapy may be helpful for patients with perineural invasion. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. Methods: We performed a cross‐sectional analysis of the Examinations of HIV‐Associated Lung Emphysema (EXHALE) study, including 162 HIV‐positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint‐years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. Results: In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non‐smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint‐years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. Conclusions: In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health. [ABSTRACT FROM AUTHOR]

Roxadustat (FG‐4592), an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end‐stage renal disease with anemia on hemodialysis. Seventeen patients, on epoetin‐alfa maintenance therapy with stable hemoglobin levels ≥10 g/dL, had epoetin‐alfa discontinued on day 3 and were enrolled in this double‐blind placebo‐controlled study. Two cohorts were randomized 3:1 (roxadustat: placebo). Patients received single doses of roxadustat (1 or 2 mg/kg) or placebo 1 hour after hemodialysis on day 1 and 2 hours before dialysis on day 8. Maximum plasma concentration and area under the plasma concentration–time curve for patients receiving roxadustat were slightly more than dose proportional and elimination half‐life ranged from 14.7 to 19.4 hours. Roxadustat was highly protein bound (99%) in plasma, and dialysis contributed a small fraction of the total clearance: only 4.56% and 3.04% of roxadustat recovered from the 1 and 2 mg/kg dose groups, respectively. Roxadustat induced transient elevations of endogenous erythropoietin that peaked between 7 and 14 hours after dosing and returned to baseline by 48 hours after dosing. Peak median endogenous erythropoietin levels were 96 mIU/mL and 268 mIU/mL for the 1‐ and 2‐mg/kg doses, respectively, within physiologic range of endogenous erythropoietin responses to hypoxia at high altitude or after blood loss. No serious adverse events were reported, and there were no treatment‐ or dose‐related trends in adverse event incidence. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate right ventricle (RV) dyssynchrony and its relation with mortality using speckle‐tracking echocardiography (STE) in patients with acute inferior myocardial infarction (IMI). Methods: One hundred and fifty‐eight consecutive patients with acute IMI treated with primary percutaneous coronary intervention, and 44 healthy subjects were included. RV myocardial involvement (RVMI) was defined as an elevation >1 mm in V1 or V4R and/or the presence of a culprit lesion at the proximal portion of the first RV marginal branch after reviewing coronary angiography. Patients were followed for 3 years to determine the cardiovascular mortality. Results: Overall, 70 patients with IMI had RVMI. IMI patients had significantly higher RV peak systolic longitudinal strain dyssynchrony (PLSSD) index, lower peak longitudinal systolic strain (PLSS), longer time to PLSS, and time to PLSS differences compared to healthy controls while the patients with RVMI had significantly worse values compared to patients without RVMI and healthy controls. Twenty‐seven patients (17.1%) died within 2 years. RVMI was more prevalent in mortality group, and they had significantly higher RV PSSD index, whereas they had lower RV free wall PLSS and longer time to PLSS differences. Receiver operating characteristics (ROC) analysis revealed that a RV PLSSD index > 65 ms predicted mortality with a sensitivity of 88.9% and specificity of 71.8% in IMI patients. Conclusions: Intra‐ and inter‐ventricular dyssynhcrony may develop in patients with acute IMI, especially in those with RV involvement, which might have a negative effect on the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Background: There are two main choices of administration route of recombinant human endostatin (Endostar) available and the treatment options of concurrent chemoradiotherapy (CCRT) have changed over time. The aim of this study was to observe the long‐term efficacy and safety of different administration routes of Endostar combined with CCRT. Methods: Patients with unresectable stage III non‐small cell lung cancer (NSCLC) from two phase II trials were included as two cohorts. Both were treated with Endostar combined with CCRT. Endostar was administrated by intravenous injection (7.5 mg/m2/day, seven days) in the IV arm and by continuous intravenous pumping (7.5 mg/m2/24 hours, 120 hours) in the CIV arm. Results: A total of 48 patients were included in the IV arm and 67 patients in the CIV arm. The median progression‐free survival (PFS), overall survival (OS), local recurrence‐free survival (LRFS) and distant metastasis‐free survival (DMFS) in the IV arm and CIV arm were 9.9 months versus 15.4 months (HR = 0.751, 95% CI 0.487–1.160, P = 0.200), 24.0 months versus 38.5 months (HR = 0.746, 95% CI 0.473–1.178, P = 0.209), 32.3 months versus 27.1 months (HR = 1.193, 95% CI 0.673–2.115, P = 0.546), 20.1 months versus 49.7 months (HR = 0.603, 95% CI 0.351–1.036, P = 0.067). The one, three, five‐year PFS in the IV arm and CIV arm was 45.8% versus 52.9%, 18.3% versus 31.4%, and 18.3% versus 27.7% and the one, three, five‐year OS was 81.2% versus 82.1%, 31.1% versus 50.3%, and 31.1% versus 41%, respectively. Incidence of hematological adverse reactions were numerically lower in the CIV arm than the IV arm. Conclusions: Endostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC. Key points: Significant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Variation in the workup of rectal bleeding may result in guideline-discordant care and delayed diagnosis of colorectal cancer. Accordingly, we undertook this study to characterize primary care clinicians' initial rectal bleeding evaluation. Methods We studied 438 patients at 10 adult primary care practices affiliated with three Boston, Massachusetts, academic medical centres and a multispecialty group practice, performing medical record reviews of subjects with visit codes for rectal bleeding, haemorrhoids or bloody stool. Nurse reviewers abstracted patients' sociodemographic characteristics, rectal bleeding-related symptoms and components of the rectal bleeding workup. Bivariate and multivariable logistic regression models examined factors associated with guideline-discordant workups. Results Clinicians documented a family history of colorectal cancer or polyps at the index visit in 27% of cases and failed to document an abdominal or rectal examination in 21% and 29%. Failure to order imaging or a diagnostic procedure occurred in 32% of cases and was the only component of the workup associated with guideline-discordant care, which occurred in 27% of cases. Compared with patients at hospital-based teaching sites, patients at urban clinics or community health centres had 2.9 (95% confidence interval 1.3-6.3) times the odds of having had an incomplete workup. Network affiliation was also associated with guideline concordance. Conclusion Workup of rectal bleeding was inconsistent, incomplete and discordant with guidelines in one-quarter of cases. Research and improvements strategies are needed to understand and manage practice and provider variation. [ABSTRACT FROM AUTHOR]

Background This study aimed to determine the myocardial damage (infarct size provided by cardiac single-photon emission tomography) in early stages of the infarction using longitudinal strain and rotational parameters of the left ventricle. Methods The study included 66 patients with anterior myocardial infarction ( AMI) and 62 patients with inferior myocardial infarction ( IMI) who underwent primary percutaneous intervention as well as a control group consisting of 50 healthy subjects. LV rotational parameters based on parasternal short-axis views in basal and apical planes and global longitudinal strain were measured with apical four-chamber, apical two-chamber, and apical long-axis views. Results There was a significant positive correlation between infarct size and GLPSavg ( r=−.55 <.001), GTOR angle ( r=−.52, P<.001), apical rotation angle ( r=−.40 <.001, and EF ( r=−.43, <.001). While cutoff values were GLPSavg: 11.9 ( AUC=0.78), GTOR angle: 11.4° ( AUC=0.77), apical rotation angle: 7.1° ( AUC=0.76) for patients with an infarct size greater than 20%, the cutoff values were GLPSavg: 10.7 ( AUC=0.75), GTOR angle: 8.7° ( AUC=0.86), apical rotation angle: 4.35° ( AUC=0.87) for those with an infarct size greater than 40%. Conclusion GLPSavg, GTOR angle, and apical rotation angle values may be used to determine the extent of infarction in early post- MI period, thereby allowing precautions to be taken for remodeling in early stages. [ABSTRACT FROM AUTHOR]

Pediatric Resynchronization Patients Introduction Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children. Methods Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared. Results From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups. Conclusion ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization. [ABSTRACT FROM AUTHOR]

Introduction Although left atrium ( LA) has played an important role in diastole, ischemic insult of atrium in acute myocardial infarction ( AMI) has not been clearly evaluated. Methods We hypothesized that LA function would be further decreased in AMI patients with a culprit lesion in the left circumflex branch ( LCX). This was an observational cohort study in a single university hospital. Echocardiography was performed to evaluate left ventricular diastolic function, LA volume, and LA function. Systolic ( LAS) and late diastolic ( LAA) LA strain were measured using speckle tracking echocardiography. Results Sixty-eight AMI patients treated with emergent or urgent percutaneous coronary intervention were enrolled. Global LAS strain was significantly lower in patients with a culprit lesion in the LCX than culprit lesions in other vessels (left anterior descending, 27.3 ± 6.8%; left circumflex, 20.1 ± 8.9%; right coronary artery, 23.3 ± 6.5%; P = 0.007). LA volume index did not differ significantly (P = 0.093). Other clinical and conventional echocardiographic parameters, including Doppler measurements, did not differ significantly. Conclusions Global LAS strain was lower in AMI patients with a culprit lesion in the LCX than those with culprit lesions in other vessels, without any significant difference in LA volume index. The lower global LAS strain might suggest decreased LA function resulting from ischemic insult by AMI with culprit lesions in the LCX. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the predictive value of longitudinal, circumferential, and radial strains by two-dimensional speckle tracking echocardiography ( 2DSTE) for improvement in cardiac function after acute myocardial infarction ( AMI) compared with that of contrast-enhanced cardiac magnetic resonance imaging (ce MRI). Methods In 35 patients with first-time AMI, myocardial viability was assessed to predict recovery of function at follow-up (7 ± 2 months), prospectively. For each left ventricular segment, each peak strains were determined using 2DSTE, and the relative extent of hyperenhancement was assessed using ce MRI. Results Of 176 segments with impaired function early after AMI, 99 segments showed regional recovery. Compared with segments showing functional improvement, those that failed to recover had lower peak radial (20 ± 16% vs. 32 ± 21%; P < 0.001), circumferential (−10 ± 5% vs. −20 ± 6%; P < 0.001), and longitudinal (−10 ± 5% vs. −14 ± 5%; P < 0.001) strain and a greater extent of hyperenhancement (71 ± 22% vs. 27 ± 20%; P < 0.001). Among strain parameters, circumferential strain yielded greater area under the curve ( AUC; 0.899) than radial and longitudinal strain (0.682 and 0.718, respectively). The predictive value of circumferential strain (sensitivity 81.0%, specificity 79.6%, at a cutoff value of −14.3%) could be comparable to that of hyperenhancement (sensitivity 86.2%, specificity 83.9%, AUC 0.921, at a cutoff value of 47%) (P = 0.439). Conclusion Circumferential strain can identify reversible myocardial dysfunction after AMI with a diagnostic ability comparable to that of ce MRI. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to evaluate the left ventricle ( LV) function with speckle tracking echocardiography ( STE) and to assess its relation to prognosis in patients after acute myocardial infarction ( AMI). Methods Sixty-three patients (F/M = 16/47 pts; 62.33 ± 11.85 years old) with AMI ( NSTEMI/ STEMI 24/39 pts) and successful percutaneous coronary intervention ( PCI) with stent implantation (thrombolysis in myocardial infarction; TIMI 3 flow) were enrolled in this study. All patients underwent baseline two-dimensional conventional echocardiography and STE 3 days (baseline) and 30 days after PCI. All patients were followed up for cardiovascular clinical endpoints, major adverse cardiovascular endpoint ( MACE), and functional status (Canadian Cardiovascular Society and New York Heart Association). Results During the follow-up (31.9 ± 5.1 months), there were 3 cardiovascular deaths, 15 patients had AMI, 2 patients had cerebral infarction, 24 patients reached the MACE. Baseline LV torsion (P = 0.035), but none of the other strain parameters were associated with the time to first unplanned cardiovascular hospitalization. Univariate analysis showed that baseline longitudinal two-chamber and four-chamber strain ( sLa2 0 and sLa4 0) and the same parameters obtained 30 days after the AMI together with transverse four-chamber strain ( sLa2 30, sLa4 30, and sTa4 30) were significantly associated with combined endpoint (MACE). The strongest association in the univariate analysis was found for the baseline sLa2. However, in multivariable analysis only a left ventricular remodeling (LVR - 27% pts) was significantly associated with MACE and strain parameters were not associated with the combined endpoint. Conclusion The assessment of LV function with STE may improve cardiovascular risk prediction in postmyocardial infarction patients. [ABSTRACT FROM AUTHOR]

Objective Quantitative left ventricular mass ( LVM) as well as regional strain values may be obtained from full-volume real time 3D echocardiography data via semi-automated feature tracking and represent indices of heart function, both in health and disease. Methods Fresh adult porcine and ovine hearts were passively pumped to simulate normal cardiac motion at stroke volumes ( SVs) varying from 30 to 70 mL. A 3V-D Matrix probe, interfaced with a GE Vivid E9 ultrasound system, was used to image each heart at baseline conditions and after simulated myocardial infarction ( MI). The 4D LV quantification function of Echo PAC PC was used to quantify the LVM and longitudinal and circumferential strain ( LS & CS) of LV segments at each SV prior and subsequent to simulated MI. LVM was validated by volumetric displacement, while LS and CS values were compared to sonomicrometry-based strain. Results Linear regression analyses show excellent correlations in LVM, LS, and CS between the 4D echo and volumetric/sonomicrometric displacement with R2 values of 0.99, 0.88, and 0.67, respectively. Bland-Altman analyses for all variables validate the compatibility of both methods. It was also determined that Echo PAC PC was able to detect a decrease in LS and CS in the relevant segments between pre- and post- MI at all SVs (P < 0.05). Conclusions Echo PAC PC is a robust utility with the ability to accurately obtain quantitative LVM, LS, and CS values from 4D echo volumes and has the potential to improve the yield of clinical studies in cases of suspected MI. [ABSTRACT FROM AUTHOR]

Introduction Myocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known. Materials and Methods We studied a total of 77 subjects, comprising 37 thalassemia patients (mean age: 24.2 ± 5.5 years) with a history of repeated blood transfusions, in addition to 40 age- and gender-matched controls (mean age: 24 ± 4.5 years). Serum ferritin levels were checked in all subjects, as well as semiautomated quantification of left ventricular ( LV) longitudinal, circumferential, and radial deformations assessed by two-dimensional (2D) speckle tracking analysis. Results Compared with the control group, thalassemia patients showed significantly larger LV mass index and lower myocardial deformations (P < 0.05), but left ventricular ejection fraction ( LVEF) did not differ significantly (P = 0.233). There was a significant linear correlation between serum ferritin level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = −0.46, P = 0.0051), with optimal cutoff provided to be −15.48%, −21.31%, and 26.67% for longitudinal, circumferential, and radial strain in predicting clinical events, respectively. During a median of 802.5 days follow-up, 11 clinical composites (HF incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects); subjects with composites had significantly reduced longitudinal and radial strain compared to those without (both P < 0.05). After adjusting for age, sex, serum ferritin level, and LV mass index, a worsening of longitudinal strain remained as an independent predictor of clinical events and death ( HR: 6.05, P = 0.033). Conclusion Subclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions, which further correlated with serum ferritin levels. In addition, worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population. [ABSTRACT FROM AUTHOR]

Background While speckle imaging has been shown to predict outcome in patients with heart failure ( HF), it remains unclear whether speckle strain predicts outcome in patients with HF with preserved ejection fraction ( HFPEF). Methods Four hundred twenty patients with HF by Framingham criteria and either: left ventricular ( LV) EF <50%, or elevated LV filling pressure by comprehensive echo Doppler study in the setting of left ventricular ejection fraction ( LVEF) ≥50%, were enrolled. Speckle tracking was used to measure strain and strain rate in multiple vectors. The primary endpoint was HF hospitalization or cardiovascular death. Results Follow-up was completed in 380/420 patients (90%). The mean age was 55.7 ± 0.8 years, 191/380 (50%) were male, 319/380 (84%) were hypertensive, 183/380 (48%) were diabetic, and 152/380 (40%) had known coronary artery disease. At a mean follow-up of 369 ± 30 days, 107/380 patients (28%) reached the primary endpoint: 97 HF rehospitalizations and 10 cardiac deaths. The best univariate predictors of outcome were global longitudinal peak strain ( GLPS) (χ2 = 25.6, P < 0.001), mitral DT (χ2 = 16.8, P < 0.001), LVEF (χ2 = 16.7, P < 0.0001), longitudinal early diastolic strain (χ2 = 8.7, P = 0.003), and circumferential peak strain (χ2 = 7.9, P = 0.005). On multivariate analysis, GLPS (P < 0.0001), LVEF (P = 0.0002), and mitral DT (P = 0.005) were independent predictors of outcome. In the 100 HF patients with preserved LVEF, there were 17 events. Patients with GPLS ≤−15 had significantly better event-free survival than patients with GPLS >−15 (χ2 = 4.1, P = 0.04), whereas LVEF did not predict event-free survival. Conclusion Speckle strain echocardiography is an important predictor of outcome in HF patients with both depressed and preserved LVEF. [ABSTRACT FROM AUTHOR]

Objective To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate, and/or prolonged dexamethasone therapy for immune-mediated congenital atrioventricular heart block (CAVB) on the cognitive and academic performance of these children at school age. Methods We performed a prospective, blinded assessment of the cognitive functioning of 3 cohorts of children ages 6-16 years with in utero exposure to maternal anti-Ro antibodies in the following groups: no CAVB and no prenatal dexamethasone treatment (n = 14), CAVB without prenatal treatment (n = 10), and CAVB with prenatal dexamethasone treatment (n = 16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function, and behavior. Results All cohorts scored within the normal range and were not significantly different in terms of intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For children with CAVB who were treated prenatally, there were no significant associations between the neurocognitive function scores, the minimal fetal heart rate (range 47-80 beats per minute), and either the duration (range 2-15 weeks) or dosage (range 56-824 mg) of dexamethasone therapy. Conclusion CAVB and transplacental treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers of children are needed to validate our observation, and assessment of other cognitive abilities is warranted. [ABSTRACT FROM AUTHOR]

Background Patients with alcohol dependence ( AD) and pathological gambling ( PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning. Methods Thirty-three alcohol-dependent patients ( ADs), 28 pathological gamblers ( PGs), and 18 healthy controls ( HCs) performed a contingency learning task in which they learned stimulus-reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal-Wallis rank-sum tests. Regression analyses were performed to compare learning curves. Results PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task. Conclusions Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI)- or Cockcroft− Gault ( CG)-based estimated glomerular filtration rates ( eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease ( CKD) or end-stage renal disease ( ESRD). Methods A total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m2, respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs. Results Of 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them ( CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m2 in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area ( BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up ( PYFU); 95% confidence interval ( CI) 8.0-9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD ( n = 36) and death ( n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio ( aIRR) 7.17; 95% CI 2.65-19.36 and aIRR 23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs ( aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03, respectively). Conclusions Differences between e GFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons. [ABSTRACT FROM AUTHOR]

Background Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys, we examined whether moderate-level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition ( PPI) of the acoustic startle. PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders. Methods Acoustic startle and PPI of the acoustic startle were tested in 37 adult rhesus monkeys ( Macaca mulatta) from 4 experimental conditions: (i) moderate-level prenatal alcohol-exposed, (ii) prenatally stressed, (iii) moderate-level prenatal alcohol-exposed + prenatally stressed, and (iv) sucrose controls. Results Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher hypothalamic-pituitary-adrenocortical ( HPA) axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI. Conclusions Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is 1 effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the comorbidity between fetal alcohol spectrum disorder and mental health conditions. [ABSTRACT FROM AUTHOR]

Background Several meta-analyses of the implantable cardioverter-defibrillator (ICD) clinical trials have demonstrated that while men derived a mortality reduction with prophylactic ICD implantation, women did not. These trials also observed that women receive less appropriate ICD shock therapy compared to men. We aimed to investigate this 'gender-paradox' among a heterogeneous community cohort of patients receiving ICDs. Methods We identified 1,445 consecutive patients undergoing ICD implantation from 1997 to 2007. The study population consisted of 582 patients, of whom 291 were women who could be propensity matched to 291 men, based on age, ejection fraction, implantation indication (primary or secondary), etiology of cardiomyopathy (ischemic or nonischemic), and the presence of a cardiac resynchronization therapy-defibrillator (CRT-D) device. The impact of gender difference on the probability of death and appropriate ICD shocks for ventricular arrhythmias was calculated using multivariable Cox proportional hazards analyses. Results During a mean follow-up of 909 ± 901 days, compared to men, women demonstrated a similar risk of death (25% vs 25%, adjusted hazard ratio [AHR] 1.05 [95% confidence interval (CI) 0.81-1.35], P = 0.74). In contrast, women demonstrated a decreased probability of appropriate ICD-shock therapy (14% vs 19%, AHR 0.80 [95% CI 0.59-0.88], P = 0.03) compared to men, and among cohorts with a nonischemic cardiomyopathy (10% vs 20%, P < 0.001) and CRT-D devices (7% vs 19%, P = 0.01). Conclusion Among a community cohort with ICDs, women have a similar mortality compared to men while experiencing less appropriate ICD therapy. These results support the findings of a lower arrhythmic mortality among women. [ABSTRACT FROM AUTHOR]

Cardiac Resynchronization Therapy and QRS Axis. Background: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) as shown in MADIT-CRT. The presence of QRS axis deviation may influence response to CRT-D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT-D. Methods : Baseline electrocardiograms of 1,820 patients from MADIT-CRT were evaluated for left axis deviation (LAD: quantitative QRS axis -30 to -90) or right axis deviation (RAD: QRS axis 90-180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all-cause mortality as in MADIT-CRT. Results: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non-LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT-D in the non-LBBB subgroups, there was no significant difference in hazard ratios for CRT-D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26-0.53 and with LAD: 0.54, 95% CI: 0.36-0.79; P value for interaction = 0.18). Conclusions: LAD in non-LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT-D than those with LAD. (J Cardiovasc Electrophysiol, Vol. 24, pp. 442-448, April 2013) [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the acute and chronic effect of smoking on left ventricular function in healthy heavy smokers by conventional Doppler flow, tissue Doppler, and two-dimensional speckle tracking echocardiography (2 D- STE). Methods: Echocardiograms were performed in 42 healthy heavy (>20 cigarettes/day) smokers (age 34 ± 5 years), before (group SM-1), 15 minutes ( SM-2) and 30 minutes ( SM-3) after starting smoking 2 cigarettes. Nonsmokers (n = 41, age 33 ± 4 years) served as controls. Transmitral flow, isovolumetric relaxation time ( IVRT), and myocardial performance index ( MPI) were measured. Tissue velocity measurements were averaged from lateral and septal mitral annulus. Longitudinal strain ( GS), systolic ( SRs), early diastolic ( SRe), late diastolic ( SRa), and isovolumetric relaxation ( SRivr) strain rate were measured. The percent change in strain from end-systole to the first one-third of diastole ( SI- DI = [( GS − strain at one-third diastole)/ GS] × 100) was also measured. Results: IVRT and MPI were increased and early diastolic mitral annular velocity was decreased in SM-2; they returned to baseline in SM-3. There was no difference in GS and SRs. SRe and SRivr were reduced in SM-1 (P < 0.05), and remained significantly reduced in SM-2 and SM-3. SI- DI was lower in SM-1 (P = 0.011) and was further reduced in SM-2 and SM-3 (P < 0.001). Conclusion: Acute and chronic smoking inhalation has adverse effects on myocardial function in healthy heavy smokers. 2D- STE is able to detect both baseline differences and late acute effects of smoking. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This investigation aimed to conduct a case-control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein beta (CEBPB). MATERIALS AND METHODS: Skulls of CEBPB-/-, CEBPB+/- and CEBPB+/+ mice were inspected with micro-computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. RESULTS: Elongation of the coronoid process was identified in CEBPB+/- (P ≤ 0.046) and CEBPB-/- 12-month-olds (P ≤ 0.028) but not in 14-day-olds (P ≥ 0.217) and 0-day-olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB-/- adult mice was demonstrated (χ² = 6.00, df = 1, P = 0.014). CONCLUSIONS:CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed. [ABSTRACT FROM AUTHOR]

Intrinsic QRS Narrowing with CRT. Background: Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown. Objective: We sought to determine (1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), (2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT, and (3) to identify predictors of iQRS width shortening. Methods: We prospectively included 85 consecutive patients with left bundle-branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF, and left ventricular volumes were assessed before and 1 year after CRT implantation. Clinical and echocardiographic CRT responders were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 ms. Results: Baseline and 1-year follow-up mean iQRS durations were, respectively, 168.0 ± 19.7 ms and 149.6 ± 31.6 ms (P < 0.0001). Electrocardiographic response, observed in 43/85 patients (51%), was associated with a greater rate of clinical (P = 0.035) and echocardiographic (P = 0.023) response. Younger age, male gender, and longer baseline QRS width were independent predictors of electrocardiographic response. Conclusion: CRT decreases iQRS duration. A reduction of at least 20 ms in iQRS duration is associated with better clinical and echocardiographic response. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1219-1227, November 2012) [ABSTRACT FROM AUTHOR]

Aims: Right ventricular (RV) dysfunction is a frequent consequence of pulmonary embolism (PE) and a marker of increased risk. However, current qualitative methods assessing RV function are imprecise. We sought to determine whether RV strain analysis would have clinical utility in patients with PE compared with normal controls. Methods and results: We compared 75 acute PE subjects (mean age 54 ± 16) with 30 normal controls (mean age 50 ± 15). Regional RV longitudinal strain was assessed using offline speckle tracking software to obtain strain and strain rate data from the basal, mid, and apical free wall and septum. Global RV free wall and septal strain was significantly reduced in PE subjects (−14.17 (±5.96) vs −24.92 (±4.16), P < 0.0001; −14.99 (±5.55) vs −18.54 (±7.34), P = 0.0082). Regional RV strain was markedly reduced in PE subjects in all regions of the free wall and in the mid and basal septum (P < 0.05). Strain rates of PE subjects were significantly reduced in all segments of the RV free wall (P < 0.05). In 36 PE subjects with regional RV dysfunction ('McConnell sign'), strain in the apical free wall was significantly reduced in comparison to those without (−10.08 vs −13.51; P = 0.0420), in parallel with higher RV:LV ratios (1.30, ±1.01 vs 0.78, ±0.16; P = 0.0035) and lower RV fractional area change (32.06, ±14.42 vs 42.52, ±11.61; P = 0.0021). Conclusions: Regional RV longitudinal strain is altered in the free wall and mid and basal septum in subjects with acute PE. Strain rates are only reduced in the RV free wall. (Echocardiography 2012;29:464-470) [ABSTRACT FROM AUTHOR]

Background: One of the most prognostically significant consequences of acute myocardial infarction (AMI) is the development of an adverse left ventricular (LV) remodeling. Objectives: The purpose of our study was to evaluate a feasibility of speckle tracking imaging (STI), in particular, global longitudinal strain (Ls) in predicting LV remodeling after AMI. Methods: A total of 82 AMI patients (mean age 57.6 ± 9.4) were included in the study. Within 48-72 hours of the onset of AMI and at a 4-month follow-up, two-dimensional echocardiography was performed. The apical two- and four-chamber views of the heart were analyzed offline using Echo Pac software for the assessment of strain by the STI method. LV remodeling was defined as a 15% increase from the baseline in LV end-diastolic volume. Results: Twenty-eight patients (34.1%) with LV remodeling at 4-month follow-up had comparable baseline clinical and echocardiographic characteristics with 54 patients (without LV remodeling), except for a predominance of the anterior wall MI (P < 0.01), higher leukocyte count value at admission (P < 0.01), lower ejection fraction (P < 0.05), increased end-systolic volume (P < 0.05), and reduced global systolic Ls (P < 0.05). Multivariable logistic regression analysis revealed the systolic Ls as an independent determinant of LV remodeling after AMI. A receiver operating characteristic curve analysis showed that a cutoff value of −11.6% for the systolic Ls yielded a 78% sensitivity and a 73% specificity to predict LV remodeling in 4 months. Conclusions. Our study has shown that LV longitudinal strain assessed by STI is an independent predictor of LV remodeling after AMI. (Echocardiography 2012;29:419-427) [ABSTRACT FROM AUTHOR]