Various clinical scenarios leading to development of the string sign of the internal thoracic artery after coronary bypass surgery: the role of competitive flow, a case series

<p>Abstract</p> <p>Background</p> <p>The left internal mammary artery (LIMA) is the choice for grafting of the left anterior descending coronary artery (LAD). One possible mechanism of the rare graft failure involve the presence of competitive flow.</p> <p>Method</p> <p>105 patients who had undergone coronary bypass grafting between 1998 and 2000 were included in this observational study. The recatheterizations were performed 28 months after the operations. The rate of patency the LIMA grafts was determined, and the cases with graft failure were analyzed.</p> <p>Results</p> <p>The LIMA graft was patent in 99 patients (94%). Six patients (6%) exhibited diffuse involution of the graft (string sign). The string sign was always associated with competitive flow as the basis of the LIMA graft involution. In one case quantitative re-evaluation of the preoperative coronary angiography revealed merely less than 50% diameter stenosis on the LAD with a nonligated side-branch of the LIMA. At recatheterization in two patients the pressure wire measurements demonstrated only a non-significant decrease of the fractional flow reserve (0.83 and 0.89), despite the 53% and 57% diameter stenosis in the angiogram. Another patient displayeda significant regression of the LAD lesion between the pre- and postoperative coronary angiography (from 76% to 44%) as the cause of the development of the competitive flow. In one instance, a radial artery graft on the LAD during a redo bypass operation resulted in competitive flow in the radial graft due to the greater diameter than that of the LIMA. In a further patient, competitive flow developed from a short sequential part of the LIMA graft between the nonsignificantly stenosed diagonal branch and the LAD, with involution of the main part of the graft to the diagonal branch.</p> <p>Conclusions</p> <p>The most common cause of the development of the string sign of a LIMA graft due to competitive flow is overassessment of the lesion of the LAD. Regression of a previous lesion or some other neighboring graft can also cause the phenomenon.</p

Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells

The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes (T2D) and obesity, undergoes rapid endocytosis after stimulation by endogenous and therapeutic agonists. We have previously highlighted the relevance of this process in fine-tuning GLP-1R responses in pancreatic beta cells to control insulin secretion. In the present study, we demonstrate an important role for the translocation of active GLP-1Rs into liquid-ordered plasma membrane nanodomains, which act as hotspots for optimal coordination of intracellular signaling and clathrin-mediated endocytosis. This process is dynamically regulated by agonist binding through palmitoylation of the GLP-1R at its carboxyl-terminal tail. Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. Downstream effects on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable

The muon Smasher's guide

We lay out a comprehensive physics case for a future high-energy muon collider, exploring a range of collision energies (from 1 to 100 TeV) and luminosities. We highlight the advantages of such a collider over proposed alternatives. We show how one can leverage both the point-like nature of the muons themselves as well as the cloud of electroweak radiation that surrounds the beam to blur the dichotomy between energy and precision in the search for new physics. The physics case is buttressed by a range of studies with applications to electroweak symmetry breaking, dark matter, and the naturalness of the weak scale. Furthermore, we make sharp connections with complementary experiments that are probing new physics effects using electric dipole moments, flavor violation, and gravitational waves. An extensive appendix provides cross section predictions as a function of the center-of-mass energy for many canonical simplified models

Prophylactic N-acetylcysteine decreases serum CRP but not PCT levels and microalbuminuria following major abdominal surgery. A prospective, randomised, double-blinded, placebo-controlled clinical trial

Objective Our objective was to investigate whether short-term infusion of the oxygen free radical scavenger N-acetylcysteine (NAC) administered before and during extensive abdominal surgery could ameliorate the progression of early systemic inflammatory response. Design Prospective, randomised, double-blinded, placebo-controlled clinical trial. Setting Twenty-bed intensive care unit in a university hospital. Patients Following written informed consent, 100 patients were randomised into NAC and placebo groups. Three patients from the NAC group and four from the placebo group withdrew before the final analysis. Intervention The treatment group (n=47) received NAC (150 mg/kg–1 bolus followed by a continuous infusion of 12 mg/kg–1/h–1) and the placebo group (n=46) received the same volume of 5% dextrose during surgery. Measurements and results Serum procalcitonin (PCT), C-reactive protein (CRP) and microalbuminuria was monitored preoperatively, on admission to ICU, then daily during the first 3 postoperative days. For statistical analysis Mann Whitney and Chi-squared tests were used. Patients' clinical course was similar in each group as monitored by the Multiple Organ Dysfunction Scores. There was no significant difference between the two groups regarding PCT and microalbuminuria at any assessment point. Significantly lower CRP levels were found in the NAC group on days 1 and 2 (t24: median: 84.5 interquartile range: [62–120] vs. 118 [86–137] mg/l; p=0.020; t48: 136 [103–232] vs. 195 [154–252] mg/l; p=0.013, NAC vs. placebo respectively). Conclusion In this study, short-term NAC treatment decreased CRP levels, but failed to attenuate any other inflammatory response, as monitored by serum PCT and microalbuminuria. Overall, our results do not support the routine prophylactic use of NAC as a free radical scavenger in abdominal surgery