Do MRI features at baseline predict radiographic joint space narrowing in the medial compartment of the osteoarthritic knee 2 years later?

This is the final version of the article. Available from Springer Verlag via the DOI in this record.PURPOSE: The purpose of the study was to relate magnetic resonance imaging (MRI) features at baseline with radiographically determined joint space narrowing (JSN) in the medial compartment of the knee after 2 years in a group of patients with symptomatic osteoarthritis at multiple joint sites. MATERIALS AND METHODS: MRI of the knee and standardized radiographs were obtained at baseline and after 2 years in 186 patients (81% female; aged 43-76 years; mean 60 years). MRI was analyzed for bone marrow lesions, cysts, osteophytes, hyaline cartilage defects, joint effusion, and meniscal pathology in the medial compartment. Radiographs were scored semiquantitatively for JSN in the medial tibiofemoral joint using the Osteoarthritis Research Society International (OARSI) atlas. Radiological progression was defined as > or =1 grade increase. Associations between baseline magnetic resonance (MR) parameters and subsequent radiographic JSN changes were assessed using logistic regression. Relative risk (RR) was then calculated. RESULTS: Radiographic progression of JSN was observed in 17 (9.1%) of 186 patients. Eleven patients had a Kellgren and Lawrence (KL) score of > or =2. A significant association was observed between all patients and meniscal tears (RR 3.57; confidence interval (CI) 1.08-10.0) and meniscal subluxation (RR 2.73; CI 1.20-5.41), between KL or = 2 and meniscus tears (RR 8.91; CI 1.13-22.84) and radiographic JSN 2 years later. Follow-up MR in 15 of 17 patients with progressive JSN showed only new meniscal abnormalities and no progression of cartilage loss. CONCLUSION: Meniscal pathology (tears and/or meniscal subluxation) was the only MRI parameter to be associated with subsequent radiographic progression of JSN in the medial tibiofemoral compartment on a radiograph 2 years later, as assessed by the OARSI score

Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features

It has been suggested that bone marrow edema-like (BME) lesions in the knee are associated with progression of osteoarthritis (OA). The purpose of our study in patients with OA was to evaluate prospectively changes of BME lesions over 2 years and their relationship with clinical features. Magnetic resonance (MR) images of the knee were obtained from 182 patients (20% male; aged 43–76 years; mean age 59 years) who had been diagnosed with familial symptomatic OA at multiple joint sites. MR images were made at baseline and at 2 years follow-up. BME lesions in 2 years were associated with clinical features assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores. A total of 327 BME lesions were recorded. Total size of BME lesions changed in 90 patients (66%). Size of individual lesions changed in 147 foci (45%): new lesions appeared in 69 (21%), existing lesions disappeared in 32 (10%), increased in size in 26 (8%) and decreased in size in 20 (6%) lesions. Increase or decrease of BME lesions, over a 2-year time period, was not associated with severity of WOMAC scores. BME lesions fluctuated in the majority of patients with OA over a 2-year time period. These changes were not associated with severity of WOMAC scores at the study end point

Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An OMERACT Agreement and Reliability Study

Objective: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). Methods: The Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with six sonographers testing inflammatory and structural features in twelve hand OA patients. We used Cohen's kappa (\u3ba) for intra-reader and Light's \u3ba for inter-reader reliability for all features except PD, in which Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) was applied. Percentage agreement was also assessed. Results: The web-based reliability exercise demonstrated substantial intra- and inter-reader reliability for all inflammatory features (\u3ba>0.64). In the patient-based exercise, intra- and inter-reader reliability varied: SH \u3ba=0.73 and 0.45; JE \u3ba=0.70 and 0.55; PD PABAK=0.90 and 0.88; PIP cartilage \u3ba=0.56 and 0.45; STT osteophytes \u3ba=0.62 and 0.36. Percentage close agreement was high for all features (>85%). Conclusion: With ultrasound, substantial to excellent intra-reader reliability was found for inflammatory features of hand OA. Inter-reader reliability was moderate, but overall high close agreement between readers suggest that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less good reliability and the latter is not endorsed. Keywords: Hand osteoarthritis; outcome measures; ultrasonography

The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis

Objective: To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA). Methods: An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary. Results: Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient’s global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention. Conclusion: The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain

Positive association between increased popliteal artery vessel wall thickness and generalized osteoarthritis: is OA also part of the metabolic syndrome?

This is the final version of the article. Available from Springer Verlag via the DOI in this record.PURPOSE: The purpose of the study was to determine if a positive association exists between arterial vessel wall thickness and generalized osteoarthritis (OA). Our hypothesis is that generalized OA is another facet of the metabolic syndrome. MATERIALS AND METHODS: The medical ethical review board of our institution approved the study. Written informed consent was obtained from each patient prior to the study. Magnetic resonance (MR) images of the knee were obtained in 42 patients who had been diagnosed with generalized OA at multiple joint sites. Another 27 MR images of the knee were obtained from a matched normal (non-OA) reference population. Vessel wall thickness of the popliteal artery was quantitatively measured by dedicated software. Linear regression models were used to investigate the association between vessel wall thickness and generalized OA. Adjustments were made for age, sex, and body mass index (BMI). Confidence intervals (CI) were computed at the 95% level and a significance level of alpha = 0.05 was used. RESULTS: Patients in the generalized OA population had a significant higher average vessel wall thickness than persons from the normal reference population (p < or = alpha), even when correction was made for sex, age, and BMI. The average vessel wall thickness of the popliteal artery was 1.09 mm in patients with generalized OA, and 0.96 mm in the matched normal reference population. CONCLUSION: The association found between increased popliteal artery vessel wall thickness and generalized osteoarthritis suggests that generalized OA might be another facet of the metabolic syndrome

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis

This document is the Accepted Manuscript version of the following article: Riessland et al., 'Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis', The American Journal of Human Genetics, Vol. 100 (2): 297-315, first published online 26 January 2017. The final, published version is available online at doi: http://dx.doi.org/10.1016/j.ajhg.2017.01.005 © 2017 American Society of Human Genetics.Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca(2+)-dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies.Peer reviewedFinal Accepted Versio

A Latin American Perspective to Agricultural Ethics

The mixture of political, social, cultural and economic environments in Latin America, together with the enormous diversity in climates, natural habitats and biological resources the continent offers, make the ethical assessment of agricultural policies extremely difficult. Yet the experience gained while addressing the contemporary challenges the region faces, such as rapid urbanization, loss of culinary and crop diversity, extreme inequality, disappearing farming styles, water and land grabs, malnutrition and the restoration of the rule of law and social peace, can be of great value to other regions in similar latitudes, development processes and social problems. This chapter will provide a brief overview of these challenges from the perspective of a continent that is exposed to the consequences of extreme inequality in multiple dimensions and conclude by arguing for the need to have a continuous South-South dialogue on the challenges of establishing socially and environmentally sustainable food systems

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation