by
Saraschandra Vallabhajosyula;
Dhiran Verghese;
Malcolm R Bell;
Dennis H Murphree;
Wisit Cheungpasitporn;
Paul Elliott Miller;
Shannon M Dunlay;
Abhiram Prasad;
Gurpreet S Sandhu;
Rajiv Gulati;
Mandeep Singh;
Amir Lerman;
Bernard J Gersh;
David R Holmes Jr;
GW Bersness
Aims
There are limited contemporary data on the use of initial fibrinolysis in ST‐segment elevation myocardial infarction cardiogenic shock (STEMI‐CS). This study sought to compare the outcomes of STEMI‐CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI).
Methods
Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (>18 years) STEMI‐CS admissions receiving pre‐hospital/in‐hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI‐CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in‐hospital mortality, development of non‐cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do‐not‐resuscitate status.
Results
During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non‐White, with lower co‐morbidity, and admitted on weekends and to small rural hospitals (all P < 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P < 0.001). The fibrinolysis group had comparable all‐cause in‐hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity‐matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do‐not‐resuscitate status use, and lesser hospitalization costs.
Conclusions
The use of initial fibrinolysis had comparable in‐hospital mortality than those receiving PPCI in STEMI‐CS in the contemporary era in this large national observational study.
Background: Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI. Methods: In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed. Results: The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75–0.99) and in a matched subset (HR 0.75, 95%CI 0.63–0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79–1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75–1.39). Conclusions: Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.
Background:Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes.
Methods: Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed (1) endothelial function as flow-mediated dilation of the brachial artery, (2) arterial stiffness and central augmentation index using applanation tonometry, (3) vascular function as fingertip reactive hyperemia index, (4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, (5) oxidative stress by measuring plasma aminothiols, and (6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period.
Results: Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells.
Conclusions: Our findings suggest a solitary antiplatelet effect of clopidogrel therapy in patients with stable coronary artery disease, with no effect on other subclinical markers of cardiovascular disease risk.
Background: Frontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown. Methods: We evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality. Results: Of 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101–180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1–50° had higher survival (85.6%) compared with FQRST = 51–100° (72.3%) and FQRST = 101–180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31–13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1–50° = 0 points, 51–100° = 2 points, 101–180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813–0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001). Conclusion: FQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.
by
Vardhmaan Jain;
Arman Qamar;
Kunihiro Matsushita;
Muthiah Vaduganathan;
Kellan E Ashley;
Muhammad Shahzeb Khan;
Deepak L Bhatt;
Sameer Arora;
Melissa C Caughey
BACKGROUND: Diabetes is associated with increased risk of acute myocardial infarction (AMI). The demographic trends, clinical presentation, management, and outcomes of patients with diabetes who are hospitalized with AMI have not been recently reported. METHODS AND RESULTS: The ARIC (Atherosclerosis Risk in Communities) study conducted hospital surveillance of AMI in 4 US communities. AMI was classified by physician review using a validated algorithm. Medications and procedures were abstracted from the medical record. From 2000 to 2014, 21 094 weighted hospitalizations for AMI were sampled. The prevalence of diabetes steadily increased, from 35% to 41% to 43% (P-trend<0.0001) across 2000 to 2004, 2005 to 2009, and 2010 to 2014, respectively. Patients with diabetes were older (61 versus 59 years of age), more often Black (44% versus 31%), and more commonly women (42% versus 34%). The burden of cardiovascular comorbidities was higher with diabetes and increased temporally. Patients with diabetes less often presented with ST-segment elevation (9% versus 17%) or acute chest pain (72% versus 80%), and had higher mean GRACE (Global Registry of Acute Coronary Syndrome) score (123 versus 109), Thrombolysis in Myocardial Ischemia (TIMI) score (4.3 versus 4.0), and Killip class (1.9 versus 1.5). Patients with diabetes had a lower adjusted probability of receiving aspirin (relative probability, 0.95 [95% CI, 0.91– 0.99]), nonaspirin antiplatelets (0.93 [95% CI, 0.86– 0.99]), coronary angiography (0.85 [95% CI, 0.78– 0.92]), and coronary revascularization (0.85 [95% CI, 0.76– 0.92]). Diabetes was associated with a 52% higher hazard of all-cause 1-year mortality (hazard ratio, 1.52 [95% CI, 1.23–1.89]). CONCLUSIONS: Diabetes is associated with higher risk of death in patients hospitalized with AMI, highlighting the need for ad-herence to evidence-based therapies in this high-risk population.
Objective
The Thoracic Surgery Residents Association (TSRA) is a resident-led organization established in 1997 under the guidance of the Thoracic Surgery Directors Association to represent the interests and educational needs of cardiothoracic surgery residents. We aim to describe the past contributions, current efforts, and future directions of the TSRA within a conceptual framework of the TSRA mission.
Methods
Primary review of educational resources was performed to report goals and content of past contributions. TSRA Executive Committee input was used to describe current resources and activities, as well as the future goals of the TSRA. Podcast analytics were performed to report national and global usage.
Results
Since 2011, the TSRA has published 3 review textbooks, 5 reference guides, 3 test-preparation textbooks, 1 supplementary publication, and 1 multiple-choice question bank and mobile application, all written and developed by cardiothoracic surgery trainees. In total 108 podcasts have been recorded by mentored trainees, with more than 175,000 unique listens. Most recently, the TSRA has begun facilitating trainee submissions to Young Surgeon's Notes, fostered a trainee mentorship program, developed the monthly TSRA Newsletter, and established a wide-reaching presence on Facebook, Twitter, and Instagram to help disseminate educational resources and opportunities for trainees.
Conclusions
The TSRA continues to be the leading cardiothoracic surgery resident organization in North America, providing educational resources and networking opportunities for all trainees. Future directions include development of an integrated disease-based resource and continued collaboration within and beyond our specialty to enhance the educational opportunities and career development of cardiothoracic trainees.
Objectives: Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. Methods: We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. Results: Escalation of premorbid use in the 5 years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR = 3.6, p < 0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR = 2.2, p < 0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (= 0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. Conclusions: These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations.
by
Sergio Ramírez-Pérez;
Luis Alexis Hernández-Palma;
Edith Oregon-Romero;
Brian Uriel Anaya-Macías;
Samuel García-Arellano;
Guillermo González-Estevez;
José Francisco Muñoz-Valle
The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.
We evaluated the relationship of drinking water salinity to neonatal and infant mortality using Bangladesh Demographic Health Surveys of 2000, 2004, 2007, 2011, and 2014. Point data of groundwater electrical conductivity (EC)— a measure of salinity—were collated from the Bangladesh Water Development Board and digitizing salinity contour map. Data for groundwater dissolved elements (sodium, calcium, magnesium, and potassium) data came from a national hydrochemistry survey in Bangladesh. Point EC and dissolved minerals data were then interpolated over entire Bangladesh and extracted to each cluster location, the primary sampling unit of Bangladesh Demographic Health Surveys. We used restricted cubic splines and survey design-specific logistic regression models to determine the relationship of water salinity to neonatal and infant mortality. A U-shaped association between drinking water salinity and neonatal and infant mortality was found, suggesting higher mortality when salinity was very low and high. Compared to mildly saline (EC ≥0.7 and < 2 mS/cm) water drinkers, freshwater (EC < 0.7 mS/cm) drinkers had 1.37 (95% CI: 1.01, 1.84) times higher neonatal mortality and 1.43 (95% CI: 1.08, 1.89) times higher infant mortality. Compared to mildly saline water drinkers, severe-saline (EC ≥10 mS/cm) water drinkers had 1.77 (95% CI: 1.17, 2.68) times higher neonatal mortality and 1.93 (95% CI: 1.35, 2.76) times higher infant mortality. We found that mild-salinity water had a high concentration of calcium and magnesium, whereas severe-salinity water had a high concentration of sodium. Freshwater had the least concentrations of salubrious calcium and magnesium.
by
Eric O. Ohuma;
Melissa Young;
Reynaldo Martorell;
Leila Cheikh Ismail;
Juan Pablo Pena-Rosas;
Manorama Purwar;
Maria Nieves Garcia-Casal;
Michael G. Gravett;
Mercedes de Onis;
QinQing Wu;
Maria Carvalho;
Yasmin A. Jaffer;
Ann Lambert;
Enrico Bertino;
Aris T. Papageorghiou;
Fernando C. Barros;
Zulfiqar A. Bhutta;
Stephen H. Kennedy;
Jose Villar
Background: Anaemia in pregnancy is a global health problem with associated morbidity and mortality. Methods: A secondary analysis of prospective, population-based study from 2009 to 2016 to generate maternal haemoglobin normative centiles in uncomplicated pregnancies in women receiving optimal antenatal care. Pregnant women were enrolled <14 weeks’ gestation in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project which involved eight geographically diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, United Kingdom and United States. At each 5 ± 1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care that complemented the study's requirements, including haemoglobin values. Findings: A total of 3502 (81%) of 4321 women who delivered a live, singleton newborn with no visible congenital anomalies, contributed at least one haemoglobin value. Median haemoglobin concentrations ranged from 114.6 to 121.4 g/L, 94 to 103 g/L at the 3rd centile, and from 135 to 141 g/L at the 97th centile. The lowest values were seen between 31 and 32 weeks’ gestation, representing a mean drop of 6.8 g/L compared to 14 weeks’ gestation. The percentage variation in maternal haemoglobin within-site was 47% of the total variance compared to 13% between sites. Interpretation: We have generated International, gestational age-specific, smoothed centiles for maternal haemoglobin concentration compatible with better pregnancy outcomes, as well as adequate neonatal and early childhood morbidity, growth and development up to 2 years of age. Funding: Bill & Melinda Gates Foundation Grant number 49038.