The anti-ageing molecule sirt1 mediates beneficial effects of cardiac rehabilitation

Background An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. Results A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation. In fifty elderly HF patients with preserved ejection fraction (HFpEF), levels of sirtuin 1 (Sirt1) in peripheral blood mononuclear cells (PBMCs) and of its targets, the antioxidants catalase (Cat) and superoxide dismutase (SOD) in serum were measured before (Patients, P) and at the end of the CRP (Rehabilitated Patients, RP), showing a rise of their activities after rehabilitation. Endothelial cells (ECs) were conditioned with serum from P and RP, and oxidative stress was induced using hydrogen peroxide. An increase of Sirt1 and Cat activity was detected in RP-conditioned ECs in both the absence and presence of oxidative stress, together with a decrease of senescence, an effect not observed during Sirt1 and Cat inhibition. Conclusions In addition to the improvement in functional and hemodynamic parameters, a supervised exercise-based CRP increases Sirt1 activity and stimulates a systemic antioxidant defence in elderly HFpEF patients. Moreover, CRP produces antioxidant and anti-senescent effects in human endothelial cells mediated, at least in part, by Sirt1 and its target Cat

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke

BACKGROUND: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. AIMS: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. METHODS: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. RESULTS: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. CONCLUSIONS: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend &lt; 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma

Arthroscopic management of chronic patellar tendinopathy.

BACKGROUND: In patients with patellar tendinopathy in whom nonoperative management is unsuccessful, surgery is an option to return to high levels of physical activity. Although open surgery is traditionally advocated, an arthroscopic approach may be safe and effective. PURPOSE: This study was undertaken to analyze medium- and long-term outcome of 64 patients undergoing arthroscopic surgery for the management of patellar tendinopathy after failing nonoperative treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 64 patients (73 knees), 27 of whom were professional athletes, with patellar tendinopathy refractory to nonoperative management underwent arthroscopic debridement of the adipose tissue of the Hoffa's body posterior to the patellar tendon, debridement of abnormal patellar tendon, and excision of the lower pole of the patella. Preoperative and postoperative evaluation was undertaken using the International Knee Documentation Committee (IKDC), Lysholm knee scale, and Victorian Institute of Sport Assessment-Patella (VISA-P) scores for all patients at 1 and 3 years. No patients were lost to follow-up. Forty-three and 29 patients were similarly assessed at 5 and 10 years, respectively, after surgery. Return to sports and rehabilitation was also assessed. RESULTS: The IKDC, Lysholm, and VISA-P scores all significantly improved at 1 and 3 years' follow-up. The average preoperative IKDC score of 51.6 improved to 86.4 at both the 1- and 3-year stage. The average preoperative Lysholm score of 52.3 improved to 94.7 at 1-year follow-up and was 95.5 at 3-year follow-up. The average preoperative VISA-P score of 35.3 improved to 69.8 at the 1-year stage and was 70.7 at the 3-year follow-up. These scores remained significantly better for the patients assessed at 5 and 10 years' follow-up. There were no postoperative complications. Nineteen of the 27 professional athletes returned to sports at the same level. Seven patients developed pain after sports within 3 years after the operation, a failure rate of 7 of 73 knees (9.6%). All patients were able to return to sports by 3 months. CONCLUSION: Arthroscopic surgery for patients with patellar tendinopathy, refractory to nonoperative management, appears to provide significant improvements in symptoms and function, with improvements maintained for at least 3 years. These results suggest that some patients may not be able to achieve their presymptom sporting level; or if they do, they may participate in sports with some degree of residual symptoms. Limited data show that these improvements are maintained for up to 10 years. Early return to sports may also be achieved

Ptprg and BCR/ABL1 Expression In CML Patients At Diagnosis and Upon TKI Treatment: Preliminary Results

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