Clinical utility of dual energy computed tomography in gout: Current concepts and applications

Summary. Gout is the most common inflammatory arthritis and is increasing in prevalence and incidence in many countries worldwide. Dual Energy Computed Tomography (DECT) has a high diagnostic accuracy in established gout, but its diagnostic sensitivity is low in subjects with recent-onset gout. A meta-analysis of 17 studies showed a pooled sensitivity and specificity of 0.85 and 0.88, respectively. DECT is a useful diagnostic tool for patients with contraindications for joint aspiration or for those who refuse joint aspiration. This article aims to give an up to date review and summary of existing literature on the role and accuracy of DECT in the imaging of gout. (www.actabiomedica.it)

Advanced diagnostic imaging and intervention in tendon diseases

Degenerative tendon pathology represents one of the most frequent and disabling musculoskeletal disorders. Diagnostic radiology plays a fundamental role in the clinical evaluation of tendon pathologies. Moreover, several minimally invasive treatments can be performed under imaging guidance to treat tendon disorders, maximizing the efficacy and reducing procedural complications. In this review article we describe the most relevant diagnostic features of conventional and advanced US and MRI imaging in tendon disorders, along with the main options for image-guided intervention. (www.actabiomedica.it)

Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA).</p> <p>Methods</p> <p>Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model.</p> <p>Results</p> <p>After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044).</p> <p>Conclusions</p> <p>These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.</p

The fate of children with microdeletion 22q11.2 syndrome and congenital heart defect: clinical course and cardiac outcome

BACKGROUND: This study aimed to evaluate the cardiac outcome for children with microdeletion 22q11.2 and congenital heart defect (CHD). METHODS: A total of 49 consecutive children with 22q11.2 and CHD were retrospectively identified. The CHD consisted of tetralogy of Fallot and variances (n = 22), interrupted aortic arch (n = 10), ventricular septal defect (n = 8), truncus arteriosus (n = 6), and double aortic arch (n = 1). Extracardiac anomalies were present in 46 of 47 children. RESULTS: The median follow-up time was 8.5 years (range, 3 months to 23.5 years). Cardiac surgical repair was performed for 35 children, whereas 5 had palliative surgery, and 9 never underwent cardiac surgery. The median age at repair was 7.5 months (range, 2 days to 5 years). The mean hospital stay was 35 days (range, 7-204 days), and the intensive care unit stay was 15 days (range, 3-194 days). Significant postoperative complications occurred for 26 children (74%), and surgery for extracardiac malformations was required for 21 patients (43%). The overall mortality rate was 22% (11/49), with 1-year survival for 86% and 5-year survival for 80% of the patients. A total of 27 cardiac reinterventions were performed for 16 patients (46%) including 15 reoperations and 12 interventional catheterizations. Residual cardiac findings were present in 25 patients (71%) at the end of the follow-up period. CONCLUSIONS: Children with microdeletion 22q11.2 and CHD are at high risk for mortality and morbidity, as determined by both the severity of the cardiac lesions and the extracardiac anomalies associated with the microdeletion

A Chemocentric Approach to the Identification of Cancer Targets

A novel chemocentric approach to identifying cancer-relevant targets is introduced. Starting with a large chemical collection, the strategy uses the list of small molecule hits arising from a differential cytotoxicity screening on tumor HCT116 and normal MRC-5 cell lines to identify proteins associated with cancer emerging from a differential virtual target profiling of the most selective compounds detected in both cell lines. It is shown that this smart combination of differential in vitro and in silico screenings (DIVISS) is capable of detecting a list of proteins that are already well accepted cancer drug targets, while complementing it with additional proteins that, targeted selectively or in combination with others, could lead to synergistic benefits for cancer therapeutics. The complete list of 115 proteins identified as being hit uniquely by compounds showing selective antiproliferative effects for tumor cell lines is provided

The genetic interaction network of CCW12, a Saccharomyces cerevisiae gene required for cell wall integrity during budding and formation of mating projections

<p>Abstract</p> <p>Background</p> <p>Mannoproteins construct the outer cover of the fungal cell wall. The covalently linked cell wall protein Ccw12p is an abundant mannoprotein. It is considered as crucial structural cell wall component since in baker's yeast the lack of <it>CCW12 </it>results in severe cell wall damage and reduced mating efficiency.</p> <p>Results</p> <p>In order to explore the function of <it>CCW12</it>, we performed a Synthetic Genetic Analysis (SGA) and identified genes that are essential in the absence of <it>CCW12</it>. The resulting interaction network identified 21 genes involved in cell wall integrity, chitin synthesis, cell polarity, vesicular transport and endocytosis. Among those are <it>PFD1</it>, <it>WHI3</it>, <it>SRN2</it>, <it>PAC10</it>, <it>FEN1 </it>and <it>YDR417C</it>, which have not been related to cell wall integrity before. We correlated our results with genetic interaction networks of genes involved in glucan and chitin synthesis. A core of genes essential to maintain cell integrity in response to cell wall stress was identified. In addition, we performed a large-scale transcriptional analysis and compared the transcriptional changes observed in mutant <it>ccw12</it>Δ with transcriptomes from studies investigating responses to constitutive or acute cell wall damage. We identified a set of genes that are highly induced in the majority of the mutants/conditions and are directly related to the cell wall integrity pathway and cell wall compensatory responses. Among those are <it>BCK1</it>, <it>CHS3</it>, <it>EDE1</it>, <it>PFD1</it>, <it>SLT2 </it>and <it>SLA1 </it>that were also identified in the SGA. In contrast, a specific feature of mutant <it>ccw12</it>Δ is the transcriptional repression of genes involved in mating. Physiological experiments substantiate this finding. Further, we demonstrate that Ccw12p is present at the cell periphery and highly concentrated at the presumptive budding site, around the bud, at the septum and at the tip of the mating projection.</p> <p>Conclusions</p> <p>The combination of high throughput screenings, phenotypic analyses and localization studies provides new insight into the function of Ccw12p. A compensatory response, culminating in cell wall remodelling and transport/recycling pathways is required to buffer the loss of <it>CCW12</it>. Moreover, the enrichment of Ccw12p in bud, septum and mating projection is consistent with a role of Ccw12p in preserving cell wall integrity at sites of active growth.</p> <p>The microarray data produced in this analysis have been submitted to NCBI GEO database and GSE22649 record was assigned.</p