Increased Infarct Wall Thickness by a Bio-Inert Material Is Insufficient to Prevent Negative Left Ventricular Remodeling after Myocardial Infarction

Several injectable materials have been shown to preserve or improve cardiac function as well as prevent or slow left ventricular (LV) remodeling post-myocardial infarction (MI). However, it is unclear as to whether it is the structural support or the bioactivity of these polymers that lead to beneficial effects. Herein, we examine how passive structural enhancement of the LV wall by an increase in wall thickness affects cardiac function post-MI using a bio-inert, non-degradable synthetic polymer in an effort to better understand the mechanisms by which injectable materials affect LV remodeling.Poly(ethylene glycol) (PEG) gels of storage modulus G' = 0.5±0.1 kPa were injected and polymerized in situ one week after total occlusion of the left coronary artery in female Sprague Dawley rats. The animals were imaged using magnetic resonance imaging (MRI) at 7±1 day(s) post-MI as a baseline and again post-injection 49±4 days after MI. Infarct wall thickness was statistically increased in PEG gel injected vs. control animals (p<0.01). However, animals in the polymer and control groups showed decreases in cardiac function in terms of end diastolic volume, end systolic volume and ejection fraction compared to baseline (p<0.01). The cellular response to injection was also similar in both groups.The results of this study demonstrate that passive structural reinforcement alone was insufficient to prevent post-MI remodeling, suggesting that bioactivity and/or cell infiltration due to degradation of injectable materials are likely playing a key role in the preservation of cardiac function, thus providing a deeper understanding of the influencing properties of biomaterials necessary to prevent post-MI negative remodeling

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1.14 billion (95% uncertainty interval 1.13-1.16) individuals were current smokers, who consumed 7.41 trillion (7.11-7.74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27.5% [26. 5-28.5] reduction) and females (37.7% [35.4-39.9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0.99 billion (0.98-1.00) in 1990. Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16-8.20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3-21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7.69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a dear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1·14 billion (95% uncertainty interval 1·13–1·16) individuals were current smokers, who consumed 7·41 trillion (7·11–7·74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27·5% [26·5–28·5] reduction) and females (37·7% [35·4–39·9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0·99 billion (0·98–1·00) in 1990. Globally in 2019, smoking tobacco use accounted for 7·69 million (7·16–8·20) deaths and 200 million (185–214) disability-adjusted life-years, and was the leading risk factor for death among males (20·2% [19·3–21·1] of male deaths). 6·68 million [86·9%] of 7·69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7·69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a clear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Funding Bloomberg Philanthropies and the Bill & Melinda Gates Foundation

Pathologic outcomes during the learning curve for robotic-assisted laparoscopic radical prostatectomy

OBJECTIVE: We report our initial experience with 62 patients undergoing robotic-assisted laparoscopic prostatectomy (RALP), focusing on the primary parameter of positive surgical margins. The authors demonstrate that excellent oncologic outcomes can be attained with a less steep learning curve than previously hypothesized. MATERIALS AND METHODS: The first 62 patients undergoing RALP by a single physician (DPD) at our institution between November 2005 and August 2007 were retrospectively assessed. Surgical pathology records were reviewed for Gleason score, pathologic tumor stage, nodal status, location of prostate cancer within the specimen, extracapsular extension, surgical margin status, presence of perineural invasion, tumor volume, and weight of the surgical specimen. Margin status was determined using surgical specimens only, and not intraoperative frozen sections. All cases in this series were completed using the four-arm da Vinci Robotic System (Intuitive Surgical, Sunnyvale, California). RESULTS: Sixty-one patients had prostate cancer on their final surgical pathology specimens. Pathologic stage T2 and stage T3 patients were 88.7% and 9.7% of all cases, respectively. The pathologic Gleason score was 7 or greater in 62.3%. Our overall positive surgical margin rate was 3.3%. Patients with pathologic T2 and T3 disease had a positive surgical margin rate of 1.8% and 16.7%, respectively. CONCLUSIONS: Our study suggests that RALP can have equal if not better pathologic outcomes compared to open radical prostatectomy even during the initial series of cases. We argue that the learning curve for RALP is shorter than previously thought with respect to oncologic outcomes, and concerns asserting that lack of tactile feedback leads to poor oncologic outcomes are unfounded

Inflammatory response.

<p>Inflammatory response in polymer and saline injected hearts 7 weeks after MI. (A) PEG injected heart (inset shows high magnification image of PEG region showing no cell infiltration in the polymer, scale bar 20 µm) (B) saline injected heart. Scale bars are 100 µm. PEG area is demarcated by an asterisk (*). CD68 stained macrophages in (C) PEG injected heart (D) saline injected heart. PEG area outlined with a dotted line. Scale bars are 20 µm.</p

Histological assessment.

<p>Histological assessment of polymer and saline injections 7 weeks after MI. Representative slides stained with H&E: (A) PEG hydrogel (G′ = 0.5 kPa) injected in infarct region and (B) saline injected in infarct region. (C) Infarct wall thickness at 7 weeks post-MI. Wall thinning was prevented in the PEG injected group compared to the control. (*<i>p</i><0.01, PEG: n = 7, saline: n = 8 ) Photomicrographs are taken at 10Х and scale bars are 1 mm. PEG area outlined with dotted line and demarcated by an asterisk (*).</p

3-D representation of the LV.

<p>Finite element representation of the LV pre and post-injection in both PEG and saline injected groups. Arrow denotes region of infarction. Infarct wall thickening is seen in the PEG injected heart while infarct wall thinning is depicted in the saline injected heart compared to baseline. Also note the dilation of LV lumen pre and post-injection in both groups.</p

Cardiac function.

<p>Comparison of cardiac function baseline (1 week post-MI, pre-injection) and post-treatment (7 weeks post-MI) in PEG (0.5 kPa) injected and saline injected groups. (A) Ejection fraction. (B) End diastolic volume. (C) End systolic volume. Statistical significance determined using paired two-tailed <i>t</i>-test between pre and post-injection groups. (*<i>p</i><0.01 PEG compared to baseline, § <i>p</i><0.01 saline compared to baseline, PEG: n = 6, saline: n = 6).</p