Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. Objectives: The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Design: Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Methods: Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Results: Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used. Conclusion: Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.

OBJECTIVE To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Partial Achilles Tendon Rupture - A Neglected Entity : A Narrative Literature Review on Diagnostics and Treatment Options

Partial ruptures in the Achilles tendon are rather uncommon and are often misinterpreted as aggravated Achilles tendinopathy, and not always considered as a differential diagnosis. The aim of this literature review was to characterize typical symptoms, to provide an overview of available diagnosis and treatment options, and to give reference points for future research. There were few studies and sparse knowledge of scientific value, making it difficult to give evidence-based recommendations. Based on the few studies and the authors' clinical experience, a diagnosis should be based on a patient's history with a typical sharp onset of pain and inability to fully load the tendon. Previous intratendinous cortisone injections might be present. Clinical findings are a localized tender region in the tendon and often weakness during heel raises. Ultrasound and Doppler examinations show a region with an irregular and bulging superficial tendon line, often together with localized high blood flow. Magnetic resonance Imaging (MRI) shows a hyperintense signal in the tendon on T1 and T2-weighted sequences. First-line therapy should be a conservative approach using a 2 cm heel lift for the first 6 weeks and avoiding tendon stretching (for 12 weeks). This is followed by a reduced heel lift of 1 cm and progressive tendon loading at weeks 7-12. After 12 weeks, the heel lift can be removed if pain-free, and the patient can gradually start eccentric exercises lowering the heel below floor level and gradually returning to previous sport level. If conservative management has a poor effect, surgical exploration and the excision of the partial rupture and suturing is required. Augmentation procedures or anchor applications might be useful for partial ruptures in the Achilles insertion, but this depends on the size and exact location. After surgery, the 12 to 14-week rehabilitation program used in conservative management can be recommended before the patient's return to full tendon loading activities

Arthroscopic surgery versus physiotherapy for femoroacetabular impingement: a meta-analysis study

Introduction!#!Femoroacetabular impingement (FAI) is thought to play an important role in the development of hip osteoarthritis. However, there is no consensus about the optimal treatment options, since non-operative therapy such as physiotherapy and surgical treatment such as arthroscopic hip surgery can both improve symptoms. Therefore, the aim of the present meta-analysis was to compare the outcomes between two different treatment regimes; physiotherapy versus arthroscopic treatment for FAI.!##!Methods!#!The present meta-analysis was carried out according to the PRISMA guidelines. In November 2019, the main online databases were accessed. All the randomized clinical trials (RCTs) comparing surgical arthroscopic treatment versus physiotherapy for FAI were considered for inclusion. Only articles reporting quantitative data under the outcomes of interest were included. For the all analysis, we used Review Manager Software. Data from 644 patients were analysed.!##!Results!#!Data from 644 patients were evaluated with a mean follow-up of 14.67 ± 8.3 months. The unpaired t test detected an optimal baseline comparability in terms of side, gender, years, duration of symptoms and BMI (p = 0.08-0.9). The VAS subscale of the score EQ-5D and the mean iHOT33 reported favourable values in the arthroscopic group (p = 0.03 and p &amp;lt; 0.0001, respectively). Similar findings were evidenced in the iHOT33 subgroup 6-months (p = 0.70) and 12-months (p = 0.0002). The HOS score, the ADL (p &amp;lt; 0.0001) and the sport (p = 0.0003) subscales reported both greater values in the arthroscopic group. No statistical significance was found concerning the risk to incur in further total hip arthroplasty (p = 0.72).!##!Conclusion!#!Based on only three high-quality RCTs, arthroscopic hip surgery is an effective therapeutic treatment for FAI revealing superior results than a non-surgical approach with physiotherapy

Do hip-abduction braces work?—A biomechanical evaluation of a commercially available hip brace

Introduction!#!Dislocations of the hip joint are a common and clinically relevant complication following total hip arthroplasty (THA). Hip-abduction braces are currently used following operative or non-operative treatment of THA dislocations to prevent re-dislocations. However, the clinical and biomechanical effectiveness of such braces is still controversial.!##!Material and methods!#!A total of 30 volunteers were measured during standing and during sitting up and down from a chair task wearing a hip brace set at 70°, 90° or no hip flexion limitation. Range of motion of the hip joint was measured in all directions by an inertial sensor system. Further it has been evaluated if the range of motion would be reduced by the additional use of an arthrodesis cushion.!##!Results!#!The use of a hip brace set up with flexion limitation did reduce hip ROM in all directions significantly compared to unhinged brace (p &amp;lt; 0.001-0.035). Performing the 'sit down and stand-up task' the brace set up at 70° flexion limitation did reduce maximum hip flexion significantly (p = 0.008). However, in most cases the measured hip flexion angles were greater than the settings of the hip brace should have allowed. The additional use of a cushion can further limit hip motion while sitting up and down from a chair.!##!Conclusion!#!This study has demonstrated that hip-abduction braces reduce hip range of motion. However, we also found that to achieve a flexion limitation of the hip to 90°, the hip brace should be set at a 70° hip flexion limitation

Dynamic spinal posture and pelvic position analysis using a rasterstereographic device

Background Until recently, rasterstereographic analysis of the spine was limited to static measurements. However, understanding and evaluating the motion of the spine under dynamic conditions is an important factor in the diagnosis and treatment of spinal pathologies. The aim of this study was to study the spinal posture and pelvic position under dynamic conditions and compare it to static measurements using a dynamic rasterstereographic system. Methods A total of 121 healthy volunteers (56 females; 65 males) were included in this observational study. The parameters trunk inclination, trunk imbalance, pelvic obliquity, kyphotic angle, lordotic angle, surface rotation, and lateral deviation were studied and compared under static and dynamic (1, 2, 4, 5 km/h) conditions using the system Formetric 4D Motion (R) (DIERS International GmbH, Germany). Results Female volunteers had a higher lordotic angle than males under static conditions (p< 0.001). Trunk inclination (5.31 degrees vs. 6.74 degrees), vertebral kyphotic angle (42.53 degrees vs. 39, 59 degrees), and surface rotation (3.35 degrees vs. 3.81 degrees) increase under dynamic conditions (p< 0.001). Trunk inclination and lordotic angle both show significant changes during walking compared to static conditions (p< 0.001). Conclusion The spinal posture differs between females and males during standing and during walking. Rasterstereography is a valuable tool for the dynamic evaluation of spinal posture and pelvic position, which can also be used to quantify motion in the spine and therefore it has the potential to improve the understanding and treatment of spinal pathologies