Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial.

BACKGROUND: DNA methylation-based estimators of biological age are reliable biomarkers of the ageing process. We aimed to investigate a range of epigenetic ageing biomarkers in a substudy of the NEAT001/ANRS143 clinical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxil fumarate and emtricitabine in antiretroviral therapy (ART)-naive adults. METHODS: We analysed frozen whole blood samples from 168 ART-naive participants with HIV from the NEAT001/ANRS143 trial, before ART initiation and after 2 years of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtricitabine). We also included 44 participants without HIV with a similar age and sex distribution. We analysed DNA methylation. Epigenetic age estimators (Horvath's clock, Hannum's clock, GrimAge, and PhenoAge) and estimated leucocyte compositions were generated using Horvath's New Online Methylation Age Calculator and Houseman's method. We calculated epigenetic age acceleration measures for each estimator of epigenetic age. The NEAT001/ANRS143 trial is registered with ClinicalTrials.gov, NCT01066962. FINDINGS: Compared with the HIV-uninfected group, ART-naive participants with HIV showed higher epigenetic age acceleration (EAA) according to all EAA estimators (mean 2·5 years, 95% CI 1·89-3·22 for Horvath-EAA; 1·4 years, 0·74-1·99 for Hannum-EAA; 2·8 years, 1·97-3·68 for GrimAge-EAA; and 7·3 years, 6·40-8·13 for PhenoAge-EAA), with all differences being statistically significant except for Hannum-EAA (Horvath-EAA p=0·0008; Hannum-EAA p=0·059; GrimAge-EAA p=0·0021; and PhenoAge-EAA p<0·0001). Epigenetic ageing was more pronounced in participants who had CD4 counts less than 200 cells per µL (significant for PhenoAge and Hannum's clock, p=0·0015 and p=0·034, respectively) or viral loads over 100 000 copies per mL at baseline (significant for PhenoAge, p=0·017). After 2 years of ART, epigenetic age acceleration was reduced, although PhenoAge and GrimAge remained significantly higher in participants with HIV compared with participants without HIV (mean difference 3·69 years, 95% CI 1·77-5·61; p=0·0002 and 2·2 years, 0·47-3·99; p=0·013, respectively). There were no significant differences in the ART effect on epigenetic ageing between treatment regimens. At baseline, participants with HIV showed dysregulation of DNA methylation-based estimated leucocyte subsets towards more differentiated T-cell phenotypes and proinflammatory leucocytes, which was also partly restored with ART. INTERPRETATION: ART initiation partly reversed epigenetic ageing associated with untreated HIV infection. Further studies are needed to understand the long-term dynamics and clinical relevance of epigenetic ageing biomarkers in people with HIV. FUNDING: NEAT-ID Foundation.

Arthroscopic management of proximal tibial fractures: technical note and case series presentation.

BACKGROUND AND AIMS: The purpose of this article is to describe a new surgical method of arthroscopy assisted treatment of intraarticular proximal tibial fractures (ARIF - arthroscopic reduction and internal fixation), analyzing its efficiency and safety on a series of patients. Tibial plateau fractures affect the proximal tibial metaphyseal and articular surface, representing 1.2% of all fractures and up to 8% of all fractures in elderly. PATIENTS AND METHOD: Our case series consists of 6 patients with Schatzker types I-III tibial plateau fractures, treated in the Orthopedic and Traumatology Clinic of Cluj-Napoca from July 2012 to August 2014. Patients included in the study presented Schatzker type I-III tibial plateau fracture. RESULTS: The results obtained with the arthroscopic method were excellent in 5 cases (mean Rasmussen score 27.60 points) and good in 1 case (mean score 23.75). The radiological consolidation appeared after a mean of 12 weeks. No major complication was noted. CONCLUSIONS: Diagnosis and treatment of associated lesions, shortening of hospitalization length and postoperative rehabilitation, but also the lower rate of complications, can make arthroscopic reduction and internal fixation the method of choice for the operative treatment of selected Schatzker I-III types of proximal tibial fractures.

The traumatic rupture of the Achilles' tendon - an analysis of the modern methods of evaluation and treatment.

AIMS: The main aim of this article is an analysis of both advantages and disadvantages of the modern solutions of treatment - percutaneous surgery, in comparison with the classic methods of treatments described in the surgery of Achilles' tendon. PATIENTS AND METHOD: The study was conducted on 23 patients admitted to the Orthopedics and Traumatology Clinic of Cluj-Napoca between January 2011-June 2012. Nineteen (19) patients were diagnosed with a complete rupture of the Achilles tendon and 4 patients with a partial rupture. The diagnosis of traumatic Achilles tendon ruptures was usually clinical, the Ultrasound (common or 3D) and the MRI confirmed the lesion and determined its location and extension. We analyzed the diagnostic methods, the elapsed time before surgery, the treatment options depending on lesion's location, technical difficulties, costs, postoperative care, the average healing time, complications. RESULTS: The Ultrasound was performed in 65.2% of the patients (15 patients) for confirming the extension of the lesion and it served for pre-operative planning. In most of the cases, the classical methods of Achilles tendon reconstruction were used (18 cases). The complications rate was about 8%. We diagnosed an iterative Achilles tendon rupture (the patient was initially treated using the percutaneous methods) and a delay in cicatrisation. CONCLUSIONS: The percutaneous surgical techniques are a viable alternative for the acute ruptures of Achilles tendon, the classic intervention has clear indications in lesions diagnosed late, in the recurrent tendon ruptures.