Is Knee joint distraction a viable treatment option for knee OA? - a literature review and meta-analysis

Knee joint distraction (KJD) is a new application of an established technique to regenerate native cartilage using an external fixator. The purpose of this study is to perform a systematic review and meta-analysis of the literature to determine whether KJD is beneficial for knee osteoarthritis and how results compare with established treatments. Studies assessing the outcomes of KJD were retrieved, with three studies (one cohort and two randomized controlled trials), 62 knees, meeting the inclusion criteria. The primary outcome was functional outcome, assessed using a validated outcome score, at 1 year. Secondary outcomes included pain scores, structural assessment of the joint, and adverse events. KJD is associated with improvements in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from baseline to 1 year as well as reductions in pain scores and improvements in structural parameters assessed radiographically and by magnetic resonance imaging. KJD is not associated with decreased knee flexion, but is associated with a high risk of pin site infection. In patients aged 65 years or under at 1 year, no differences in WOMAC or pain scores was detected between patients managed with KJD compared with high tibial osteotomy or total knee arthroplasty. KJD may represent a potential treatment for knee arthritis, though further trials with longer term follow-up are required to establish its efficacy compared with contemporary treatments. This is a Level I (systematic review and meta-analysis) study

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use

Background aims: Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid–derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury. Methods: SF-MSCs were obtained during knee arthroscopic procedures (N = 7). Colony forming unit–fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions. Results: PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium. Conclusions: This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage

Gene expression signatures of synovial fluid multipotential stromal cells (MSCs) in advanced knee osteoarthritis and following knee joint distraction

Osteoarthritis (OA) is the most common musculoskeletal disorder. Although joint replacement remains the standard of care for knee OA patients, knee joint distraction (KJD), which works by temporarily off-loading the joint for 6–8 weeks, is becoming a novel joint-sparing alternative for younger OA sufferers. The biological mechanisms behind KJD structural improvements remain poorly understood but likely involve joint-resident regenerative cells including multipotent stromal cells (MSCs). In this study, we hypothesized that KJD leads to beneficial cartilage-anabolic and anti-catabolic changes in joint-resident MSCs and investigated gene expression profiles of synovial fluid (SF) MSCs following KJD as compared with baseline. To obtain further insights into the effects of local biomechanics on MSCs present in late OA joints, SF MSC gene expression was studied in a separate OA arthroplasty cohort and compared with subchondral bone (SB) MSCs from medial (more loaded) and lateral (less loaded) femoral condyles from the same joints. In OA arthroplasty cohort (n = 12 patients), SF MSCs expressed lower levels of ossification- and hypotrophy-related genes [bone sialoprotein (IBSP), parathyroid hormone 1 receptor (PTH1R), and runt-related transcription factor 2 (RUNX2)] than did SB MSCs. Interestingly, SF MSCs expressed 5- to 50-fold higher levels of transcripts for classical extracellular matrix turnover molecules matrix metalloproteinase 1 (MMP1), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and tissue inhibitor of metalloproteinase-3 (TIMP3), all (p < 0.05) potentially indicating greater cartilage remodeling ability of OA SF MSCs, compared with SB MSCs. In KJD cohort (n = 9 patients), joint off-loading resulted in sustained, significant increase in SF MSC colonies’ sizes and densities and a notable transcript upregulation of key cartilage core protein aggrecan (ACAN) (weeks 3 and 6), as well as reduction in pro-inflammatory C–C motif chemokine ligand 2 (CCL2) expression (weeks 3 and 6). Additionally, early KJD changes (week 3) were marked by significant increases in MSC chondrogenic commitment markers gremlin 1 (GREM1) and growth differentiation factor 5 (GDF5). In combination, our results reveal distinct transcriptomes on joint-resident MSCs from different biomechanical environments and show that 6-week joint off-loading leads to transcriptional changes in SF MSCs that may be beneficial for cartilage regeneration. Biomechanical factors should be certainly considered in the development of novel MSC-based therapies for OA

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Development and validation of the motivations for selection of medical study (MSMS) questionnaire in India

Background and Objective Understanding medical students' motivation to select medical studies is particularly salient to inform practice and policymaking in countries-such as India-where shortage of medical personnel poses crucial and chronical challenges to healthcare systems. This study aims to develop and validate a questionnaire to assess the motivation of medical students to select medical studies. Methods A Motivation for Selection of Medical Study (MSMS) questionnaire was developed using extensive literature review followed by Delphi technique. The scale consisted of 12 items, 5 measuring intrinsic dimensions of motivations and 7 measuring extrinsic dimensions. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), validity, reliability and data quality checks were conducted on a sample of 636 medical students from six medical colleges of three North Indian states. Results The MSMS questionnaire consisted of 3 factors (subscales) and 8 items. The three principal factors that emerged after EFA were the scientific factor (e.g. research opportunities and the ability to use new cutting edge technologies), the societal factor (e.g. job security) and the humanitarian factor (e.g. desire to help others). The CFA conducted showed goodnessof-fit indices supporting the 3-factor model. Conclusion The three extracted factors cut across the traditional dichotomy between intrinsic and extrinsic motivation and uncover a novel three-faceted motivation construct based on scientific factors, societal expectations and humanitarian needs. This validated instrument can be used to evaluate the motivational factors of medical students to choose medical study in India and similar settings and constitutes a powerful tool for policymakers to design measures able to increase selection of medical curricula