A prediction rule for lack of achievement of inactive disease with methotrexate as the sole disease-modifying antirheumatic therapy in juvenile idiopathic arthritis

Background: To investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID. Methods: The clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (\u3b2) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for lack of achievement of ID. Results: A total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) > 1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was > 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association. Conclusion: A conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset

Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development

Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging.

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction

Mini-Laparoscopic Repair of Apical Pelvic Organ Prolapse (POP) by Lateral Suspension with Mesh

Background: The aim of the present study is to analyze the feasibility, safety and learning curve of MiniLaparoscopic Lateral suspension (LLS) for the treatment of apical and anterior defects following pelvic organ prolapse. Methods: this is a cohort study on a retrospective series of 35 consecutive patients who underwent Mini-LLS for symptomatic POP between January 2014 and July 2016. All 35 patients were operated at the Gynaecological Unit in S. Chiara Hospital by two senior surgeons (S. Tateo and L. Mereu) and by a team with optimal skills in laparoscopic surgery. Patients were divided in two groups according to two different chronological phases: phase 1 identified the initial 12 cases, phase 2 the last 23 cases. We collected pre-, peri- and post-operative information to analyze the surgical outcomes and learning curve after Mini-LLS procedures. Results: The mean LLS-Overall Time (OT) was 107.6 min (range, 185- 63 min). None of the patients had intraoperative complications. No conversion to laparotomy was necessary. The mean post-operative hospital stay was 58 hours in total (SD +/-22). Only in 3 cases (8.6 %) post-operative grade I complications were observed. Recurrence of POP was observed in 3 cases (8.6 %) during a mean follow up of 18 months. The mean OT decreased with experience, in particular after the first 12 cases (phase 1: 113.54 minutes versus phase 2: 104.43 minutes). In consequence, the reduction of time per procedure was statistically significant considering the Cusum Time (CT) (P &lt; .05). Conclusions: Mini-LLS with mesh is a safe and reproducible technique with good anatomical results, low complication rates and a short learning curve

APOE influences vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage

OBJECTIVE: To determine the influence of the APOE genotype on functional and cognitive outcome and on the incidence and prognosis of clinical vasospasm (delayed ischemic neurologic deficit [DIND]) in noncomatose patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors reviewed the data of patients admitted for SAH to the Neurosurgical Departments of the San Gerardo Hospital of Monza (January 1996 to December 2001) and the Ospedali Riuniti of Bergamo (January 2002 to September 2003). The authors considered only noncomatose patients and evaluated outcome by means of the Rankin Disability Index and the Mini-Mental State Examination at least 6 months after the SAH. Statistical analysis: Uni- and multivariate logistic regression. RESULTS: The authors included 101 patients. They found the epsilon4 allele in 26 patients (25.7%). The presence of the epsilon4 allele negatively affected the overall outcome (functional morbidity or cognitive morbidity, or both) (p = 0.0087) and, particularly, cognitive morbidity (p = 0.0028). Those with an epsilon4 allele had delayed ischemic neurologic deficit DINDs more frequently (p = 0.024) and, in the presence of DIND, they were more likely to show permanent neurologic deficits (p = 0.0051). CONCLUSIONS: ApoE4 negatively affects cognitive morbidity and delayed ischemic neurologic deficit recovery. The presence of an epsilon4 allele increases the risk of delayed ischemic neurologic deficit

Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation

BACKGROUND: Studies attempting to precisely define the range of fragile mental retardation 1 (FMR1) expansions and its inf luence in premature ovarian failure (POF) manifestation are partially lacking. To this aim, we evaluated a large cohort of POF patients for the size and, in selected cases, for the sequence of the CGG expansion. Furthermore, the correlation between POF and X-inactivation was investigated in FRAXA families. METHODS: By fluorescent PCR, 190 POF and 200 control women were sized for the CGG tract; some subjects were also characterized by sequencing and for the FMR1 activation ratio. RESULTS AND CONCLUSION: We found a significant association (19/190, 10%, P < 1 x 10(-6)) between POF and FMR1 premutation (range 63-163 repeats) and a significant enrichment (9/190, 4.7%, P = 0.021) of POF carriers of intermediate expansions (range 41-58 repeats). Interestingly, intermediate alleles were entirely composed of CGG repeats. Furthermore, the analysis of three pairs of siblings with similar FMR1 expansions and discordant for the POF phenotype showed a direct correlation between the expression of the intermediate/premutated allele and POF manifestation. The results obtained strengthen the correlation between FMR1 expansion and POF and suggest that the manifestation of the ovarian dysfunction could be influenced both by the pattern of interruption of the CGG repeat and by X-inactivation

Collaborative and distributed computing applied to biomedicine with the FightAIDS@Home

Distributed computing systems are used for high performance computing tasks, taking advantage of join processing power of multiple independent computers, but they are interconnected by network. These high performance systems can be divided into two classes of distributed computing systems: computer cluster and grid computing. The FightAIDS@Home is a distributed system toward the search for solutions for the AIDS treatment, and this project is led by the Olson Laboratory, California. Nowadays, this project use computing resources of the Grid World Community Grid, which consist mostly of computers of ordinary users, using open and non-specific standard protocols and interfaces to ensure interoperability between different systems. These paper presents informations from a case study about FightAIDS@Home and its implementation, using aspects of distributed systems such as grid computer and cloud computing to support implementation of collaborative computing