Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study

BackgroundThe itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice.HypothesisThe safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines.MethodsAdults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two‐thirds of the enrollment period are presented.ResultsA total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor.ConclusionsThe interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.     

Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis

Supplementation with Citrulline (Cit) has been shown to have a positive impact on aerobic exercise performance and related outcomes such as lactate, oxygen uptake (VO₂) kinetics, and the rate of perceived exertion (RPE), probably due to its relationship to endogenous nitric oxide production. However, current research has shown this to be controversial. The main objective of this systematic review and meta-analysis was to analyze and assess the effects of Cit supplementation on aerobic exercise performance and related outcomes, as well as to show the most suitable doses and timing of ingestion. A structured literature search was carried out by the PRISMA^® (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PICOS guidelines in the following databases: Pubmed/Medline, Scopus, and Web of Science (WOS). A total of 10 studies were included in the analysis, all of which exclusively compared the effects of Cit supplementation with those of a placebo group on aerobic performance, lactate, VO₂, and the RPE. Those articles that used other supplements and measured other outcomes were excluded. The meta-analysis was carried out using Hedges’ g random effects model and pooled standardized mean differences (SMD). The results showed no positive effects of Cit supplementation on aerobic performance (pooled SMD = 0.15; 95% CI (−0.02 to 0.32); I², 0%; p = 0.08), the RPE (pooled SMD = −0.03; 95% CI (−0.43 to 0.38); I², 49%; p = 0.9), VO₂ kinetics (pooled SMD = 0.01; 95% CI (−0.16 to 0.17); I², 0%; p = 0.94), and lactate (pooled SMD = 0.25; 95% CI (−0.10 to 0.59); I², 0%; p = 0.16). In conclusion, Cit supplementation did not prove to have any benefits for aerobic exercise performance and related outcomes. Where chronic protocols seemed to show a positive tendency, more studies in the field are needed to better understand the effects.     

IL-1β–dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1β–mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.     

Herbal medicinal products for inflammatory bowel disease: A focus on those assessed in double‐blind randomised controlled trials

Inflammatory bowel disease patients frequently use herbal products as complementary or alternative medicines to current pharmacotherapies and obtain information on them mainly from the internet, social media, or unlicensed practitioners. Clinicians should therefore take a more active role and become knowledgeable of the mechanisms of action and potential drug interactions of herbal medicines for which evidence of efficacy is available. The therapeutic efficacy and safety of several herbal medicines have been studied in double‐blind randomised controlled trials (RCTs). Evidence of efficacy is available for Andrographis paniculata extract; curcumin; a combination of myrrh, extract of chamomile flower, and coffee charcoal; and the Chinese herbal medicines Fufangkushen colon‐coated capsule and Xilei san in patients with ulcerative colitis; and Artemisia absinthium extract and Boswellia serrata resin extract in patients with Crohn's disease. However, most of this evidence comes from single small RCTs with short follow‐up, and the long‐term effects and safety of their use have not yet been established. Thus, our findings indicate that further appropriately sized RCTs are necessary prior to the recommended use of these herbal medicines in therapy. In the meantime, increasing awareness of their use, and potential drug interactions among physicians may help to reduce unwanted effects and adverse disease outcomes.     

Human milk and formulae: neurotrophic and new biological factors

Mother milk is widely accepted to be a unique product believed to contain biological factors involved in the regulation of newborn optimal growth including brain when compared to milk-formula milks. In this setting, there is growing evidence that in milk-formula neuro-oxidative stress biomarkers, neurotrophic proteins and calcium binding proteins, known to be involved in a cascade of events leading to brain, cardiac and vascular development/damage, are to date lacking or at a lower concentration than breast milk. Therefore, this review is aimed at offering additional insights to the role in human milk of some selected biomarkers such as: i) neurotrophic factors such as Activin A; ii) Calcium binding protein such as S100B and, iii) heat shock protein known to be involved in oxidative stress response (namely hemeoxygenase-1, HO-1 or Heat shock Protein 32, HSP32).     

Non-Union Scoring System (NUSS): Is It Enough in Clinical Practice?

IntroductionBone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this study is to evaluate the appropriateness of the Non-Union Scoring System NUSS treatment protocol in the management of long bone non-unions by comparing it to the experience-based therapeutic approach carried out in our facility.Materials and MethodsWe conducted a comparative outcome study of a retrospective series of 89 patients surgically treated for long bone non-union in our facility vs. clinical results reported by Calori et al. obtained following the NUSS treatment protocol.ResultsRadiographic healing was reached in 13/13 non-unions (100%) in group NUSS 1, in 58/62 (93.5%) in group NUSS 2, and in 13/14 (92.9%) in group NUSS 3. The mean time to radiographic healing was 5.69 ± 2.09 months in group 1, 7.38 ± 3.81 months in group 2 and 9.23 ± 2.31 months in group 3. 91% of patients in group I, 69% in group II and 48% in group III received what would be considered by the NUSS treatment protocol an “overtreatment”, especially from a biological stand point. The comparative outcome analysis shows that our case series achieved significantly higher global healing rates (p value = 0.017) and shorter radiological healing times in groups NUSS 1 and 2 (p value < 0.001).ConclusionFrom the results obtained, we can assume that the NUSS treatment protocol might underestimate the necessary therapies, particularly from a biological point of view.