Objective
To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.
Methods
Knees replaced between 36 and ...60 months’ follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T
0
) and 2 years before T
0
(T
-2
) were compared using conditional logistic regression.
Results
One hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 ± 8.7 mean ± SD years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control cc OR = 1.57; 95 % CI: 1.23–2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11–1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement.
Conclusions
Discrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement.
Key Points
•
Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW.
•
MRI predicts knee replacement with similar accuracy to radiographic JSW.
•
MRI reveals greater cartilage thinning and thickening prior to knee replacement.
ObjectivesOsteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA ...patients with a likely NP component, and those without a likely NP component.MethodsBaseline data from the Innovative Medicines Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway knee OA cohort study were used. Patients with a painDETECT score ≥19 (with likely NP component, n=24) were matched on a 1:2 ratio to patients with a painDETECT score ≤12 (without likely NP component), and similar knee and general pain (Knee Injury and Osteoarthritis Outcome Score pain and Short Form 36 pain). Pain, physical function and radiographic joint damage of multiple joints were determined and compared between OA patients with and without a likely NP component.ResultsOA patients with painDETECT scores ≥19 had statistically significant less radiographic joint damage (p≤0.04 for Knee Images Digital Analysis parameters and Kellgren and Lawrence grade), but an impaired physical function (p<0.003 for all tests) compared with patients with a painDETECT score ≤12. In addition, more severe pain was found in joints other than the index knee (p≤0.001 for hips and hands), while joint damage throughout the body was not different.ConclusionsOA patients with a likely NP component, as determined with the painDETECT questionnaire, may represent a specific OA phenotype, where local and overall joint damage is not the main cause of pain and disability. Patients with this NP component will likely not benefit from general pain medication and/or disease-modifying OA drug (DMOAD) therapy. Reserved inclusion of these patients in DMOAD trials is advised in the quest for successful OA treatments.Trial registration numberThe study is registered under clinicaltrials.gov nr: NCT03883568.
This paper aims to investigate the potential interest of using a Vessel Monitoring System (VMS) based on GPRS/GSM (Global System for Mobile Communications) technology to obtain a better estimation of ...fishing activity and distribution of a small-scale artisanal fleet, for which the European satellite-based system is not available. Since the early 1980s, the artisanal fishery targeting blackspot seabream (Pagellus bogaraveo), commonly known as “voraz”, has been developing along the Strait of Gibraltar area. Up to now the fishing effort was estimated using the number of sales, a proxy for the number of fishing days. This measure does not, however, capture the “missing effort”, i.e., fishing days resulting in no catch or not enough catch to be sold at public auction. The European satellite-based VMS provides information about the dynamics of different fishing fleets, but is not installed on small vessels (<15 m), such as those used by the artisanal “voracera” fleet targeting blackspot seabream in the Strait of Gibraltar. The Andalucía Regional Government installed its own vessel monitoring system on several artisanal fleets using GPRS/GSM cellular network technology that sends data on vessel positions and speed every three minutes. Data collected from 2009 to 2011 using this system were filtered and analysed to estimate fishing effort, catch rates and the spatial distribution of the blackspot seabream fishery. The estimates obtained seem to provide a good representation of fishery reality. As expected, the missing effort increases as the resource levels decrease. Additionally, expert knowledge of the fishery allowed application of an algorithm for splitting these daily trips into estimated fishing hauls. Afterwards the spatial distribution of catches and Catch per Unit Effort (CPUE) could be obtained linking VMS locations with landings information. This study provides a considerably finer spatial scale view of the fishery than data available in the past.
Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations and ...mis-splicing fuel therapy-resistant leukemia stem cell (LSC) generation in adults, splicing deregulation has not been extensively studied in pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses of FACS-purified hematopoietic stem and progenitor cells followed by differential splicing analyses, dual-fluorescence lentiviral splicing reporter assays, and the potential of a selective splicing modulator, Rebecsinib, in pAML. Using these methods, we discover transcriptomic splicing deregulation typified by differential exon usage. In addition, we discover downregulation of splicing regulator RBFOX2 and CD47 splice isoform upregulation. Importantly, splicing deregulation in pAML induces a therapeutic vulnerability to Rebecsinib in survival, self-renewal, and lentiviral splicing reporter assays. Taken together, the detection and targeting of splicing deregulation represent a potentially clinically tractable strategy for pAML therapy.
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•Pediatric acute myeloid leukemia stem cells harbor increased exon skipping events•Decreased RBFOX2 induces embryonic splicing and CD47 splice isoform upregulation•Lentiviral splicing reporter studies show exon skipping reversal with Rebecsinib•Rebecsinib inhibits pediatric acute myeloid leukemia stem cell propagation
Pediatric acute myeloid leukemia stem cells (LSCs) harbor increased exon skipping events and decreased RBFOX2 expression, which is linked to embryonic splicing patterns and CD47 splice isoform upregulation. van der Werf et al. show that the reversal of malignant exon skipping with Rebecsinib, a selective splicing modulator, prevents pediatric LSC propagation.
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