Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients.

BACKGROUND: Detecting right heart failure post left ventricular assist device (LVAD) is challenging. Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. METHODS: Thirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial coupling (ratio of Ees/Ea). RESULTS: LVAD patients had lower RV Ees (0.20 ± 0.08 vs 0.30 ± 0.15 mm Hg/ml, p = 0.01) and lower RV Ees/Ea (0.37 ± 0.14 vs 1.20 ± 0.54, p < 0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r = 0.68, p = 0.004) as well as the LVAD cohort itself (r = 0.78, p = 0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p = 0.048), driven by an inability to augment RV Ees (0.22 ± 0.11 vs 0.19 ± 0.02 mm Hg/ml, p = 0.95) to accommodate higher RV Ea (0.82 ± 0.38 vs 0.39 ± 0.08 mm Hg/ml, p = 0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients ((area under the curve) AUC = 0.80); during the ramp study, change in PAPi also correlated with change in RV Ees/Ea (r = 0.58, p = 0.04). CONCLUSIONS: LVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD left ventricular unloading, which reduces septal contractility.

Understanding and effectively addressing disparities in obesity: A systematic review of the psychological determinants of emotional eating behaviours among Black women.

Emotional eating may be a particularly important contributor to differences in body weight and weight loss response to behavioural interventions among non-Hispanic Black women. We performed a systematic review on the impact of psychological factors (stress, anxiety, depression, and discrimination) upon emotional eating and weight among non-Hispanic Black women, applying the Preferred Reporting Items for Systematic Reviews and Meta-analysis for relevant studies. The initial search yielded 4593 articles with 15 accepted for review. Based on this review, there is a suggestion that negative emotions, in particular, perceived stress, may be predictive of emotional eating among non-Hispanic Black women. Results from the only two longitudinal studies identified by the review indicate that stress influences emotional eating, and emotional eating predicts weight gain over time. Findings from this review highlight the need for more studies that examine various negative emotions that may lead to emotional eating and weight gain among non-Hispanic Black women. Findings from this review also highlight the need for more rigorous studies to differentiate the effects of emotional eating from that of the physiologic (ie, activation of the hypothalamic-pituitary axis) responses to stress and its impact on high-risk groups.

Analysis of near crashes among teen, young adult, and experienced adult drivers using the SHRP2 naturalistic driving study.

OBJECTIVE: Motor vehicle crashes are the leading cause of death among young drivers. Though previous research has focused on crash events, near crashes offer additional data to help identify driver errors that could potentially lead to crashes as well as evasive maneuvers used to avoid them. The Strategic Highway Research Program 2 (SHRP2) Naturalistic Driving Study (NDS) contains extensive data on real-world driving and offers a reliable methodology to quantify and study near crashes. This article presents findings on near crashes and how they compare to crash events among teen, young adult, and experienced adult drivers. METHODS: A subset from the SHRP2 database consisting of 1,653 near crashes for teen (16-19 years, n = 550), young adult (20-24 years, n = 748), and experienced adult (35-54 years, n = 591) drivers was used. Onboard instrumentation including scene cameras, accelerometers, and Global Positioning System logged time series data at 10 Hz. Scene videos were reviewed for all events to classify near crashes based on 7 types: rear-end, road departure, intersection, head-on, side-swipe, pedestrian/cyclist, and animal. Near crash rates, incident type, secondary tasks, and evasive maneuvers were compared across age groups and between crashes and near crashes. For rear-end near crashes, vehicle dynamic variables including near crash severity, headway distance, time headway, and time to collision at the time of braking were compared across age groups. Crashes and near crashes were combined to compare the frequency of critical events across age. RESULTS: Teen drivers exhibited a significantly higher (P <.01) near crash rate than young adult and experienced adult drivers. The near crash rates were 81.6, 56.6, and 37.3 near crashes per million miles for teens, young adults, and experienced adults, respectively. Teens were also involved in significantly more rear-end (P <.01), road departure (P <.01), side-swipe (P <.01), and animal (P <.05) near crashes compared to young and experienced adults. Teens exhibited a significantly greater (P <.01) critical event rate of 102.2 critical events per million miles compared to 72.4 and 40.0 critical events per million miles for young adults and experienced adults, respectively; the critical event rate ratio was 2.6 and 1.8 for teens and young adults, respectively. CONCLUSIONS: To our knowledge, this is the first study to examine near crashes among teen, young adult, and experienced adult drivers using SHRP2 naturalistic data. Near crash and critical event rates significantly decreased with increasing age and driver experience. Overall, teens were more than twice as likely to be involved in critical events compared to experienced adults. These data can be used to develop more targeted driver training programs and help manufacturers design active safety systems based on the most common driving errors for vulnerable road users.

Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer (NSCLC) in a KRas/p53 transgenic mouse model.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities. In this study, we explored the use of a recently described small molecule agent, STA-8666, as a potential agent for controlling early stage tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and has been shown to have high efficacy and low toxicity, associated with efficient tumor targeting, in preclinical studies using patient-derived and other xenograft models for pancreatic, bladder, and small cell lung cancer. Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth, and was well tolerated over this extended dosing period. STA-8666 induced DNA damage and apoptosis, and reduced proliferation and phosphorylation of the proliferation-associated protein ERK1/2, selectively in tumor tissue. In contrast, STA-8666 did not affect tumor features, such as degree of vimentin staining, associated with epithelial-mesenchymal transition (EMT), or downregulate tumor expression of HSP90. These data suggest STA-8666 and other similar targeted compounds may be useful additions to control the growth of early stage NSCLC in patient populations.