Clarifying the ghrelin system’s ability to regulate feeding behaviours despite enigmatic spatial separation of the GHSR and its endogenous ligand

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours

Clinical and Economic Impact of Diabetes Mellitus on Percutaneous and Surgical Treatment of Multivessel Coronary Disease Patients

BACKGROUND: Our aims were to compare coronary artery bypass grafting (CABG) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study (ARTS) trial and to determine the

Impact of occlusion duration on the success rate and outcomes of percutaneous coronary intervention in chronic total occlusions

ABSTRACTBackgroundInitial studies have shown that old occlusions or those with indeterminate occlusion duration have been associated with percutaneous coronary intervention (PCI) failure and a worse prognosis. This study aimed to determine the impact of occlusion duration on the success and outcomes of contemporary PCI on chronic total occlusion (CTO).MethodsThe authors analyzed a retrospective cohort of consecutive patients submitted to PCI in CTO, who were compared according to the confirmed occlusion duration (COD) < 12 months, ≥ 12 months, or indeterminate occlusion duration (IOD).ResultsA total of 168 patients were treated, 122 (72.6%) with COD (80 < 12 months, 42 ≥ 12 months) and 46 (24.7%) with an IOD. Lesion extension was 17.0 ± 13.6mm, in 2.90 ± 0.58mm vessels, and the anterograde approach was used in 98.8% of cases. Angiographic success was attained in 79.2% of patients (80.0% vs. 73.8% vs. 82.6%; p = 0.73). The main cause of failure was the inability to cross the lesion with the guidewire (68.6%). Occlusion duration had no impact on in-hospital events (4.8% vs. 7.1% vs. 6.0%; p = 0.73), which were almost entirely explained by periprocedural myocardial infarction, or on late outcomes (18.8% vs. 7.1% vs. 15.3%; p = 0.23). At the multivariate analysis, lesion length ≥ 20mm (odds ratio - OR = 7.27; 95% confidence interval - 95% IC 1.94-29.1; p = 0.003), calcification (OR = 4.72; 95% CI 1.19-19.1; p = 0.02), and tortuosity of the occluded segment (OR = 15.98; 95% CI 2.18-144.7; p = 0.007) were predictors of failure.ConclusionsOcclusion duration was not associated with increased failure rate of the procedure or worse PCI outcomes in CTO

Impact of Side Branch Predilation on Percutaneous Coronary Intervention in Complex Coronary Bifurcation Lesions

ABSTRACTBackgroundThe treatment of coronary bifurcation lesions with single stenting in the main vessel and provisional side branch stenting may be limited by the degree of anatomical/morphological complexity. Side branch predilation, a procedural step that is typically avoided, may be required to maintain side branch patency. The impact of side branch predilation on the immediate results of percutaneous coronary intervention in complex coronary bifurcation lesions was investigated.MethodsBetween May, 2008 and August, 2009, 59 patients with single coronary bifurcation lesions and significant involvement of the main and side branches were included in the study. The main exclusion criteria were the involvement of the left main coronary artery, ST-elevation acute myocardial infarction (< 72 hours) and in-stent restenosis.ResultsThe mean age of patients was 61.2±11 years, 25.4% were female, and 30.1% had diabetes mellitus. Lesions were most prevalent in the left anterior descending artery/diagonal branch (86.4%). During the procedure, 8.5% (5/59) of lesions had unsuccessful side branch predilation, and four of these bifurcations were treated with two stents. In the multivariate model, side branch stenosis at baseline was the only significant predictor of unsuccessful side branch predilation (odds ratio 1.15, 95%CI: 1.01–1.30; P=0.04), and side branch stenosis > 87.6% was identified as the most accurate cut-off value to predict failure in the receiver operating characteristic (ROC) curve.ConclusionsSide branch predilation was associated with immediate side branch failure in < 10% of cases, and the only significant predictor in the multivariate model was side branch stenosis severity (> 85%) at baseline

Predictors of long-term adverse events after Absorb bioresorbable vascular scaffold implantation: a 1,933-patient pooled analysis from international registries

Aims: The aim of this study was to investigate the predictors of long-term adverse clinical events after implantation of the everolimus-eluting Absorb bioresorbable vascular scaffold (BVS). Methods and results: We pooled patient-level databases derived from the large-scale ABSORB EXTEND study and five high-volume international centres. Between November 2011 and November 2015, 1,933 patients underwent PCI with a total of 2,372 Absorb BVS implanted. The median age was 61.0 (IQR 53.0 to 68.6) years, 24% had diabetes, and 68.2% presented with stable coronary artery disease. At a median follow-up of 616 days, MACE occurred in 93 (4.9%) patients, all-cause death in 36 (1.9%) patients, myocardial infarction in 47 (2.5%) patients, and target vessel revascularisation in 72 (3.8%) patients. Definite or probable scaffold thrombosis occurred in 26 (1.3%) patients. On multivariable logistic regression analysis, acute coronary syndromes (hazard ratio [HR] 2.79, 95% confidence interval [CI]: 1.47 to 5.29; p=0.002), dyslipidaemia (HR 1.43, 95% CI: 1.23 to 1.79; p=0.007), scaffold/reference diameter ratio &gt;1.25 (HR 1.49, 95% CI: 1.18 to 1.88; p=0.001), and residual stenosis &gt;15% (HR 1.67, 95% CI: 1.34 to 2.07; p&lt;0.001) were independent predictors of MACE, whereas the use of intravascular imaging was independently associated with a reduction in MACE (HR 0.13, 95% CI: 0.06 to 0.28; p&lt;0.001). Conclusions: Optimal Absorb BVS implantation and the use of intravascular imaging guidance are associated with lower rates of adverse events at long-term follow-up