Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs\u2014produced either by endothelial cells, platelets, leukocytes, and erythrocytes\u2014was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs\u2014which was measured in MP-depleted plasma\u2014was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications

Antithrombotic therapy and intracranial bleeding in subjects with sporadic brain arteriovenous malformations: preliminary results from a retrospective study.

Whether antithrombotic treatment is safe and/or affects the risk of intracranial bleeding in subjects with sporadic brain arteriovenous malformations (AVMs) is unknown. We conducted a retrospective analysis on the use of antithrombotics among patients affected by brain AVMs in follow-up at our institution. Attention was paid to the type of antithrombotic drug (either antiplatelets or anticoagulants), current or past use, dosage, and duration of treatment. Several clinical and angioarchitectural features of brain AVMs were also taken into consideration. The association between the use of antithrombotics and haemorrhagic onset was analyzed. A total of 77 patients were included in this study. Among them, ten patients were taking antithrombotic drugs at the time of AVM diagnosis. The rate of haemorrhagic onset was not significantly different between subjects who were and were not taking antithrombotic drugs (40 vs 55.2%, p = ns). Among the many clinical and angioarchitectural features analyzed, the only parameter that showed a statistically significant association with haemorrhagic onset was the size of the nidus. Patients who took antithrombotic treatments after being diagnosed with a brain AVM did not show an increased rate of intracranial haemorrhage over time considering a mean follow-up 4 years. In our study, antithrombotic treatment was not associated with increased intracranial bleeding among subjects with brain AVMs. In the presence of a strong clinical indication, antiplatelet and anticoagulant medications should not be denied a priori to patients with brain AVMs. Studies on larger populations are necessary to confirm these data

Acute kidney injury is associated with increased levels of circulating microvesicles in patients with decompensated cirrhosis

Background: Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. Aim: To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). Methods: We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. Results: Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8\u201310.7]), MELD (OR 1.13 [95%CI 1.02\u20131.27]), any bleeding (OR 9.07 [95%CI 2.02\u201340.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02\u20131.07]) were independently associated with 30-day mortality. Conclusion: AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation

Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.

AIM: Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data. METHODS: This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. RESULTS: This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients. CONCLUSIONS: In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien\u2013Dindo Grades III\u2013V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49\u20132.96, P &lt; 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46\u20130.75, P &lt; 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease