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Objectives: To validate reliability of slice-encoding for metal artefact correction (SEMAC)-MRI findings in prosthesis loosening detection by comparing them to surgical outcomes (gold standard) in symptomatic patients following hip arthroplasties. To evaluate periprosthetic anatomical structures in symptomatic patients to identify an alternative cause of hip symptoms. Methods: We prospectively followed 47 symptomatic patients (55 hips, 39 painful hips – group P and 16 control hips – group C) at our institution from 2011 to 2016. We acquired 1.5 T MRI conventional and SEMAC-MRI images for all patients. Two consultants scored MRI for osteolysis and marrow oedema zone-wise using predefined signal characteristics and settled scoring variations by consensus. We used Spearman Rank-Order Correlation for correlation analysis and used OMERACT (Outcome Measures in Rheumatology) filter pillars to validate SEMAC-MRI findings. Results: Eleven patients needed revision surgery, all from group P. None from group C required revision surgery. Remaining 28 hips in the group P were managed conservatively pain completely resolved in 21 hips, eight hips had trochanteric bursitis, eight had extraarticular cause and the remaining five hips had spontaneous pain resolution. We found moderate-to-weak correlation between SEMAC-MRI findings for prosthesis loosening and revision surgery outcomes. Sensitivity, Specificity, PPV and NPV in Group P were (72.7, 64.3, 44.4, 85.7%) in T1W-SEMAC, (90.9, 46.4, 40.0, 92.9%) in STIR-SEMAC and (36.3, 78.5, 40.0, 75.8%) in PDW-SEMAC. Conclusion: Negative SEMAC-MRI results can effectively exclude prosthesis loosening confirmed on revision surgery and SEMAC-MRI can detect alternative cause of hip pain accurately. Advances in knowledge: Negative SEMAC-MRI in painful THA patients can effectively exclude prosthesis loosening as a cause.

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype. Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.

Objective To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi). Methods A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths. Results Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041. Conclusion The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.

Diabetes is a chronic condition that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. People having type 1 diabetes require insulin (10% of all diabetics). People with type 2 diabetes can be treated with oral medication, but may also require insulin; 10% of all type 2 diabetics require insulin. Among the actual different methods to administer insulin (syringes, pens and conventional infusion pumps) a possibility to increase infuser performances is offered by the utilization of silicon based MEMS pumps (Micro- Electro Mechanical Systems). The main two pump families are classified as mechanical and non-mechanical pumps. The former contains check-valve, peristaltic, rectification without valves and rotary ones (“Displacement Pumps”) or Ultrasonic and Centrifugal (“Dynamic Pumps”); the latter consists in Pressure, Concentration, Electrical Potential gradients and Magnetic Potential micro-pumps. The micro-pump described here is an electro-mechanical device actuated with a piezoelectric-element and based on MEMS technology, able to minimize size and costs, offering a high precision pharmacological dispense. Three slices are bonded to reach the final results: top and bottom caps and an intermediate SOI. In case of anodic bonding, top and bottom caps are constituted of micromachined borophosphosilicate wafers, whereas in case of metallic bonding three silicon slices are used. The paper deals with the fabrication evolution of the device according to the different items that had to be faced during development: design, fluidic, mechanical and electrical simulations and characterization, safety requirements and final testing. Built-in reliability is ensured by two inner sensors able to detect any occlusion or malfunctioning and informing so the patient. The result is a compact, core pump chip that can deliver from 0.02 Units of insulin up to 3.6 Units per minute with accuracy better than 5%.