Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Shaping Ability and Debris Extrusion of New Rotary Nickel-Titanium Root Canal Instruments

The aim was to evaluate the canal straightening and the amount of apically extruded debris associated with five rotary nickel-titanium when preparing curved root canals. A total of 100 root canals in extracted human teeth (angles of curvatures 20°–30°; radii 5.9–13.5 mm) were divided into five groups (n = 20/group). The groups were balanced with respect to the angle and the radius of canal curvature. The root canals were prepared using conventional austenite 55-NiTi alloy instruments F360, F6 SkyTaper (both Komet, Lemgo, Germany), and the heat-treated NiTi Jizai, Silk-Complex and Silk-Standard instruments (all Mani, Tochigi, Japan) to an apical size 25. The amount of extruded debris was assessed with a micro balance. Statistical analysis was performed using Kruskal–Wallis test with Bonferroni correction at a significance level of p < 0.05. During canal preparation, neither instrument fractures nor procedural preparation errors were noticed. Regarding canal straightening, the use of Jizai instruments resulted in the significantly lowest straightening (p < 0.05), while no significant differences were obtained between all other groups (p > 0.05). Regarding the amount of apically extruded debris, no significant differences between all groups were obtained (p > 0.05). Within the limitations of this study, all instruments performed well, and especially the Jizai instruments showed an excellent shaping ability.     

Drug‐Coated Balloons: A Safe and Effective Alternative to Drug‐Eluting Stents in Small Vessel Coronary Artery Disease

Background

Drug‐coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug‐eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year.

Methods

We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB‐only angioplasty was performed in 172 patients, whereas 163 patients were treated with second‐generation DES.

Results

DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES‐treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1‐year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601).

Conclusions

In this high‐risk cohort of patients, DCB‐only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES‐treated patients, but had the added benefit of a shorter DAPT regime.

     

Childhood‐onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus

Objective

To examine childhood‐onset disease as a predictor of mortality in a cohort of adult patients with systemic lupus erythematosus (SLE).

Methods

Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 957 adult subjects with SLE that includes 98 subjects with childhood‐onset SLE. Baseline and followup data were obtained via telephone interviews conducted in 2002–2007. The number of deaths during 5 years of followup was determined and standardized mortality ratios (SMRs) for the cohort, and across age groups, were calculated. Kaplan‐Meier life table analysis was used to compare mortality rates between childhood‐ (defined as SLE diagnosis at <18 years of age) and adult‐onset SLE. Multivariate Cox proportional hazard models were used to determine predictors of mortality.

Results

During the median followup period of 48 months, 72 deaths (7.5% of subjects) occurred, including 9 deaths (12.5%) in subjects with childhood‐onset SLE. The overall SMR was 2.5 (95% confidence interval [95% CI] 2.0–3.2). In Kaplan‐Meier survival analysis, after adjusting for age, childhood‐onset subjects were at increased risk for mortality throughout the followup period (P< 0.0001). In a multivariate model adjusting for age, disease duration, and other covariates, childhood‐onset SLE was independently associated with an increased mortality risk (hazard ratio [HR] 3.1, 95% CI 1.3–7.3), as was low socioeconomic status measured by education (HR 1.9, 95% CI 1.1–3.2), and end stage renal disease (HR 2.1, 95% CI 1.1–4.0).

Conclusion

Childhood‐onset SLE was a strong predictor of mortality in this cohort. Interventions are needed to prevent early mortality in this population.     

At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation

Background

Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).

Methods

In a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.

Results

Serum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R² = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.

Conclusions

A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.     

Primary percutaneous coronary intervention of native chronic total occlusions to treat ST elevation myocardial infarction secondary to acute vein graft occlusion

Primary percutaneous coronary intervention (PCI) is the treatment modality of choice in patients presenting with ST elevation myocardial infarction (STEMI). Clinical outcomes have dramatically improved with the wide adoption of primary PCI in patients with STEMI because of acute thrombotic native coronary artery occlusion. However, patients with prior coronary artery bypass graft (CABG) surgery who present with STEMI because of acute saphenous vein graft (SVG) occlusion continue to have worse outcomes because of poor acute and long‐term results of SVG stenting. Therefore, it may be preferable to treat the native coronary artery supplied by the occluded graft although this can be challenging if the native vessel is a chronic total occlusion (CTO). Recent advances in technology and techniques in CTO PCI have significantly improved the success rate and efficiency of CTO procedures. At our institution we have developed a high volume CTO programme with high success rates. We present three cases of acute inferior STEMI because of SVG occlusion which were treated with successful retrograde PCI of the native vessel CTO, utilising the occluded graft as a retrograde channel in two cases and native septal collaterals in the other. Thrombolysis In Myocardial Infarction (TIMI) 3 flow in the native coronary artery was achieved in all three cases with good acute outcomes. Our case series highlights the benefits of a high volume CTO programme. With recent advances in CTO techniques, acute PCI to native vessel CTO is feasible and may be the treatment of choice in selected cases of acute SVG failure. © 2017 Wiley Periodicals, Inc.     

Targeting the vascular endothelial growth factor in hematologic malignancies

There exists increasing evidence that apart from solid tumors, angiogenic growth factors also play important roles in the development and/or maintenance of hematolymphoid malignancies. Thus, in these cancers, angiogenesis and bone marrow microvessel density often correlate with prognosis and disease burden. Several reports speculated on the role of angiogenesis and the resulting possible therapeutic options in hematologic malignancies. The most prominent angiogenic factor, vascular endothelial growth factor (VEGF), is expressed in a number of established leukemic cell lines as well as in freshly isolated human leukemias and lymphomas, and several human leukemias express VEGF receptor 1 and/or VEGF receptor 2. VEGF/VEGF‐receptor interactions are also involved in proliferation, migration, and survival of leukemic cells by autocrine and paracrine mechanisms. As a consequence, a possible drugable effect by inhibiting VEGF signaling in different hematologic malignancies has been discussed. This review focuses on angiogenesis‐independent effects of VEGF on survival and proliferation of leukemic or lymphoma cells and on possible therapeutic approaches using anti‐VEGF/VEGF‐receptor therapies to inhibit proliferation or induce apoptosis of malignant cells in hematologic diseases.     

Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis

Fluoroquinolones such as ofloxacin are promising drugs to treat drug-resistant tuberculosis (TB) and have been proposed for shortening the treatment of TB. The objectives were to study the synergistic effect of the combinations of three drugs and to evaluate the in?vitro interactions of the following combinations against Mycobacterium tuberculosis: A) isoniazid, rifampicin, and ethambutol and B) ofloxacin, rifampicin, and ethambutol using an adaptation of the two-dimensional chequerboard assay. A total of 12 isolates resistant to isoniazid or to isoniazid-streptomycin and 11 drug-susceptible isolates were tested. The fractional inhibitory concentration (FICI) was calculated as follows: FICI?=?FIC(A)?+?FICB?+?FIC(C)?=?A/MIC(A)?+?B/MIC(B)?+?C/MIC(C) where A, B and C were the MICs of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) were the individual MICs. The FICI was interpreted as synergism when the value was ≤0.75. In combination A, 11 drug-susceptible isolates decreased the individual MIC one to three dilutions, showing indifferent activity in 81.8% (FICI?=?0.88-1.6) and synergistic activity in 18.1% (FICI?=?0.6). In combination B, 21 out of the 23 isolates studied (91.3%) showed synergism (FICI?=?0.31-0.62). In conclusion, adaptation of the two-dimensional chequerboard assay is a reliable method to study in?vitro three-drug combinations. Both three-drug combinations tested may be useful against drug-resistant isolates, although the combination including ofloxacin showed better efficacy, being of potential use in drug-susceptible and isoniazid-resistant isolates.