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1.
Artigo em Inglês | MEDLINE | ID: mdl-32025764

RESUMO

PURPOSE: To compare return to sport and knee function 1 year after anterior cruciate ligament (ACL) reconstruction using autografts with and without vancomycin presoaking. METHODS: A case-control study based on a retrospective analysis of prospective data included athletes over the age of 16 operated from 2012 to 2018 for ACL reconstruction. There were two groups of patients due to a change in treatment protocols: Group 1 « without vancomycin ¼ before November 2016 and Group 2 « with vancomycin¼ after this date. In Group 2, the graft was soaked in a vancomycin solution for 10 min and then fixed into the bone tunnels. The primary evaluation criterion was the return to sport 1 year after surgery. The secondary criteria were various knee scores. The number of patients needed to perform a non-inferiority study was calculated. RESULTS: 1674 patients fulfilled the selection criteria, 1184 in Group 1 and 490 in Group 2. The series included 1112 men and 562 women, mean age 30 ± 9.7 years, 68 professional athletes, 674 competitive athletes and 932 recreational athletes. While seven patients presented with post-operative septic arthritis in Group 1, this complication was not found in Group 2. No significant difference was identified in the return to running between the two groups 1 year after surgery (75.9% vs. 76.1%, n.s.). Significantly more of the patients in Group 2 returned to their preinjury sport (p = 0.04). Knee function was comparable between the groups. CONCLUSION: Vancomycin-soaked grafts during ACL reconstruction reduce the risk of post-operative infection of the knee without affecting the return to sport or knee function. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: https://clinicaltrials.gov/, ClinicalTrials.gov Identifier: NCT02511158.

2.
Pharmacol Ther ; : 107475, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926200

RESUMO

Metabolic diseases have a tremendous impact on human morbidity and mortality. Numerous targets regulating adenosine monophosphate kinase (AMPK) have been identified for treating the metabolic syndrome (MetS), and many compounds are being used or developed to increase AMPK activity. In parallel, the cyclic nucleotide phosphodiesterase families (PDEs) have emerged as new therapeutic targets in cardiovascular diseases, as well as in non-resolved pathologies. Since some PDE subfamilies inactivate cAMP into 5'-AMP, while the beneficial effects in MetS are related to 5'-AMP-dependent activation of AMPK, an analysis of the various controversial relationships between PDEs and AMPK in MetS appears interesting. The present review will describe the various PDE families, AMPK and molecular mechanisms in the MetS and discuss the PDEs/PDE modulators related to the tissues involved, thus supporting the discovery of original molecules and the design of new therapeutic approaches in MetS.

3.
Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

4.
Clin Exp Rheumatol ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820722

RESUMO

Idiopathic inflammatory myopathies (IIM) are a group of rare connective tissue diseases (CTDs) deeply affecting patients' prognosis. Extra-muscular involvement is not rare and skin, joints and lung are the most common targets. However, also dyserythropoiesis has been described, carrying relevant issues on patients' management and follow-up, as for example, lymphopenia has been associated with an increased risk of rapid progressive interstitial lung disease in anti-MDA5 positive dermatomyositis. Conversely to systemic lupus erythematosus, thrombocytopenia has been only rarely described in IIM and very few authors focused on its potential prognostic implications. We describe five cases of thrombocytopenia in IIM patients positive for myositis specific (MSA) or associated (MAA) autoantibodies. These reports extend the spectrum of haematological features associated to IIM, focusing also on potential risk factors for thrombocytopenia occurrence.

6.
J Clin Med ; 8(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810355

RESUMO

Peripheral arterial disease (PAD) is a frequent and serious condition, potentially life-threatening and leading to lower-limb amputation. Its pathophysiology is generally related to ischemia-reperfusion cycles, secondary to reduction or interruption of the arterial blood flow followed by reperfusion episodes that are necessary but also-per se-deleterious. Skeletal muscles alterations significantly participate in PAD injuries, and interestingly, muscle mitochondrial dysfunctions have been demonstrated to be key events and to have a prognosis value. Decreased oxidative capacity due to mitochondrial respiratory chain impairment is associated with increased release of reactive oxygen species and reduction of calcium retention capacity leading thus to enhanced apoptosis. Therefore, targeting mitochondria might be a promising therapeutic approach in PAD.

7.
Neurology ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882529

RESUMO

OBJECTIVE: To refine the predictive significance of muscle granuloma in patients with myositis. METHODS: A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM). RESULTS: All but 2 granuloma-myositis patients had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of granuloma-myositis patients matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining granuloma-myositis patients did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis. CONCLUSION: Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.

8.
J Clin Med ; 8(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752231

RESUMO

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

9.
J Clin Med ; 8(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640161

RESUMO

Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are synthesized in response to atrial cardiomyocyte stretch, increase natriuresis, diuresis, and vascular permeability through binding of the second intracellular messenger's guanosine 3',5'-cyclic monophosphate (cGMP) to specific receptors. During heart failure (HF), the beneficial effects of the enhanced cardiac hormones secretion are reduced, in connection with renal resistance to NP. In addition, there is a BNP paradox characterized by a physiological inefficiency of the BNP forms assayed by current methods. In this context, it appears interesting to improve the efficiency of the cardiac natriuretic system by inhibiting cyclic nucleotide phosphodiesterases, responsible for the degradation of cGMP. Recent data support such a therapeutic approach which can improve the quality of life and the prognosis of patients with HF.

11.
J Clin Med ; 8(10)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623409

RESUMO

Asthma is a chronic inflammatory lung syndrome with an increasing prevalence and a rare but significant risk of death. Its pathophysiology is complex, and therefore we investigated at the systemic level a potential implication of oxidative stress and of peripheral blood mononuclear cells' (PBMC) mitochondrial function. Twenty severe asthmatic patients with severe exacerbation (GINA 4-5) and 20 healthy volunteers participated at the study. Mitochondrial respiratory chain complexes activities using different substrates and reactive oxygen species (ROS) production were determined in both groups by high-resolution respirometry and electronic paramagnetic resonance, respectively. Healthy PBMC were also incubated with a pool of plasma of severe asthmatics or healthy controls. Mitochondrial respiratory chain complexes activity (+52.45%, p = 0.015 for VADP) and ROS production (+34.3%, p = 0.02) were increased in asthmatic patients. Increased ROS did not originate mainly from mitochondria. Plasma of severe asthmatics significantly increased healthy PBMC mitochondrial dioxygen consumption (+56.8%, p = 0.031). In conclusion, such asthma endotype, characterized by increased PMBCs mitochondrial oxidative capacity and ROS production likely related to a plasma constituent, may reflect activation of the immune system. Further studies are needed to determine whether increased PBMC mitochondrial respiration might have protective effects, opening thus new therapeutic approaches.

17.
Antioxidants (Basel) ; 8(6)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181751

RESUMO

Cycles of ischemia-reperfusion (IR) that occur during peripheral arterial disease (PAD) are associated with significant morbi-mortality, and aging is an irreversible risk factor of PAD. However, the effects of advanced age on IR-induced skeletal muscle mitochondrial dysfunction are not well known. Young and aged mice were therefore submitted to hindlimb IR (2 h ischemia followed by 2 h reperfusion). Skeletal muscle mitochondrial respiration, calcium retention capacity (CRC) and reactive oxygen species (ROS) production were determined using high resolution respirometry, spectrofluorometry and electronic paramagnetic resonance. IR-induced impairment in mitochondrial respiration was enhanced in old animals (VADP; from 33.0 ± 2.4 to 18.4 ± 3.8 and 32.8 ± 1.3 to 5.9 ± 2.7 pmol/s/mg wet weight; -44.2 ± 11.4% vs. -82.0 ± 8.1%, in young and aged mice, respectively). Baseline CRC was lower in old animals and IR similarly decreased the CRC in both groups (from 11.8 ± 0.9 to 4.6 ± 0.9 and 5.5 ± 0.9 to 2.1 ± 0.3 µmol/mg dry weight; -60.9 ± 7.3 and -60.9 ± 4.6%, in young and aged mice, respectively). Further, IR-induced ROS production tended to be higher in aged mice. In conclusion, aging exacerbated the deleterious effects of IR on skeletal muscle mitochondrial respiration, potentially in relation to an increased oxidative stress.

18.
J Clin Med ; 8(6)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208093

RESUMO

Endothelial dysfunction (ED), often linked to hypertriglyceridemia, is an early step of atherosclerosis. We investigated, in a randomized cross-over study, whether high-fat meal (HFM)-induced ED might be reduced by fruit juice or champagne containing polyphenols. Flow-mediated dilatation (FMD) and biological parameters (lipid profile, glycemia, inflammation, and oxidative stress markers) were determined before and two and three hours after the HFM in 17 healthy young subjects (24.6 ± 0.9 years) drinking water, juice, or champagne. Considering the entire group, despite significant hypertriglyceridemia (from 0.77 ± 0.07 to 1.41 ± 0.18 mmol/L, p < 0.001) and a decrease in Low Density Lipoprotein (LDL), the FMD was not impaired. However, the FMD decreased in 10 subjects (from 10.73 ± 0.95 to 8.1 3± 0.86 and 8.07 ± 1.16%; p < 0.05 and p < 0.01; 2 and 3 hours, respectively, after the HFM), without concomitant change in concentration reactive protein or reactive oxygen species, but with an increase in glycemia. In the same subjects, the FMD did not decrease when drinking juice or champagne. In conclusion, HFM can impair the endothelial function in healthy young subjects. Fruit juice, rich in anthocyanins and procyanidins, or champagne, rich in simple phenolic acids, might reduce such alterations, but further studies are needed to determine the underlying mechanisms, likely involving polyphenols.

19.
Eur Radiol ; 29(12): 6858-6866, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31175414

RESUMO

OBJECTIVES: Diagnostic performance and potential radiation dose reduction of wide-area detector CT sequential acquisition ("wide-volume" acquisition (WV)) in unenhanced chest examination are unknown. This study aims to assess the image quality, the diagnostic performance, and the radiation dose reduction of WV mode compared with the classical helical acquisition for lung parenchyma analysis in an ultra-low-dose (ULD) protocol. METHODS: After Institutional Review Board Approval and written informed consent, 64 patients (72% men; 67.6 ± 9.7 years old; BMI 26.1 ± 5.3 kg/m2) referred for a clinically indicated unenhanced chest CT were prospectively included. All patients underwent, in addition to a standard helical acquisition (120 kV, automatic tube current modulation), two ULD acquisitions (135 kV, fixed tube current at 10 mA): one in helical mode and one in WV mode. Image noise, subjective image quality (5-level Likert scale), and diagnostic performance for the detection of 9 predetermined parenchymal abnormalities were assessed by two radiologists and compared using the chi-square or Fisher non-parametric tests. RESULTS: Subjective image quality (4.2 ± 0.7 versus 4.2 ± 0.8, p = 0.56), image noise (41.7 ± 8 versus 40.9 ± 8.7, p = 0.3), and diagnostic performance were equivalent between ULD WV and ULD helical. Radiation dose was significantly lower for the ULD WV acquisition (mean dose-length product 14.1 ± 1.3 mGy cm versus 15.8 ± 1.3, p < 0.0001). CONCLUSION: An additional 11% dose reduction is achieved with the WV mode in ULD chest CT with fixed tube current, with equivalent image quality and diagnostic performance when compared with the helical acquisition. KEY POINTS: • Image quality and diagnostic performance of ultra-low-dose unenhanced chest CT are identical between wide-volume mode and the reference helical acquisition. • Wide-volume mode allows an additional radiation dose reduction of 11% (mean dose-length product 14.1 ± 1.3 mGy cm versus 15.8 ± 1.3, p < 0.0001).

20.
J Clin Med ; 8(5)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083472

RESUMO

Peripheral arterial disease (PAD), leading to intermittent claudication, critical ischemia with rest pain, and/or tissue damage, is a public health issue associated with significant morbidity and mortality. Little is known about the link between PAD, cognitive function, and whether exercise might reduce cognitive dysfunction in PAD patients, as previously observed concerning both quality of life and prognosis. This review highlights the fact that patients suffering from PAD often demonstrate cognitive dysfunction characterized by reduced performance in nonverbal reasoning, reduced verbal fluency, and decreased information processing speed and a greater risk for progression toward dementia. Further, the data presented support that physical exercise, likely through myokine secretion and microglial anti-inflammatory phenotype enhancement, might participate in the cognition protection in common clinical settings.

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