The absence of detectable ADAMTS-4 (aggrecanase-1) activity in synovial fluid is a predictive indicator of autologous chondrocyte implantation success

Background: Autologous chondrocyte implantation (ACI) is used worldwide in the treatment of cartilage defects in the knee. Several demographic and injury-specific risk factors have been identified that can affect the success of ACI treatment. However, the discovery of predictive biomarkers in this field has thus far been overlooked. Purpose: To identify potential biomarkers in synovial fluid and plasma that can be used in the preoperative setting to help optimize patient selection for cell-based cartilage repair strategies. Study Design: Controlled laboratory study. Methods: Fifty-four ACI-treated patients were included. Cartilage oligomeric matrix protein (COMP), hyaluronan, soluble CD14 levels, and aggrecanase-1 (ADAMTS-4) activity in synovial fluid and COMP and hyaluronan in plasma were measured. Baseline and postoperative functional outcomes were determined using the patient-reported Lysholm score. To find predictors of postoperative function, linear and logistic regression analyses were performed. The dependent variables were the baseline and postoperative Lysholm score; the independent variables were patient age and body mass index, defect location, defect area, having a bone-on-bone defect, type of defect patch (periosteum or collagen), requirement of an extra procedure, and baseline biomarker levels. Results: The mean baseline Lysholm score was 47.4 ± 17.0, which improved to 64.6 ± 21.7 postoperatively. The activity of ADAMTS-4 in synovial fluid was identified as an independent predictor of the postoperative Lysholm score. Indeed, simply the presence or absence of ADAMTS-4 activity in synovial fluid appeared to be the most important predictive factor. As determined by contingency analysis, when ADAMTS-4 activity was detectable, the odds of being a responder were 3 times smaller than when ADAMTS-4 activity was not detectable. Other predictive factors were the baseline Lysholm score, age at ACI, and defect patch type used. Conclusion: The absence of ADAMTS-4 activity in the synovial fluid of joints with cartilage defects may be used in conjunction with known demographic risk factors in the development of an ACI treatment algorithm to help inform the preclinical decision

The absence of detectable ADAMTS-4 (aggrecanase-1) activity in synovial fluid is a predictive indicator of autologous chondrocyte implantation success

Background: Autologous chondrocyte implantation (ACI) is used worldwide in the treatment of cartilage defects in the knee. Several demographic and injury-specific risk factors have been identified that can affect the success of ACI treatment. However, the discovery of predictive biomarkers in this field has thus far been overlooked. Purpose: To identify potential biomarkers in synovial fluid and plasma that can be used in the preoperative setting to help optimize patient selection for cell-based cartilage repair strategies. Study Design: Controlled laboratory study. Methods: Fifty-four ACI-treated patients were included. Cartilage oligomeric matrix protein (COMP), hyaluronan, soluble CD14 levels, and aggrecanase-1 (ADAMTS-4) activity in synovial fluid and COMP and hyaluronan in plasma were measured. Baseline and postoperative functional outcomes were determined using the patient-reported Lysholm score. To find predictors of postoperative function, linear and logistic regression analyses were performed. The dependent variables were the baseline and postoperative Lysholm score; the independent variables were patient age and body mass index, defect location, defect area, having a bone-on-bone defect, type of defect patch (periosteum or collagen), requirement of an extra procedure, and baseline biomarker levels. Results: The mean baseline Lysholm score was 47.4 ± 17.0, which improved to 64.6 ± 21.7 postoperatively. The activity of ADAMTS-4 in synovial fluid was identified as an independent predictor of the postoperative Lysholm score. Indeed, simply the presence or absence of ADAMTS-4 activity in synovial fluid appeared to be the most important predictive factor. As determined by contingency analysis, when ADAMTS-4 activity was detectable, the odds of being a responder were 3 times smaller than when ADAMTS-4 activity was not detectable. Other predictive factors were the baseline Lysholm score, age at ACI, and defect patch type used. Conclusion: The absence of ADAMTS-4 activity in the synovial fluid of joints with cartilage defects may be used in conjunction with known demographic risk factors in the development of an ACI treatment algorithm to help inform the preclinical decision

Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat.

Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes. We have confirmed that there is a chondrogenic potency hierarchy ranging across these cell types, with the most potent being chondrocytes, followed by FP-MSCs, BM-MSCs, and lastly SCF-MSCs. We have also examined gene expression and surface marker profiles in a predictive model to identify cells with enhanced chondrogenic potential. In doing so, we have shown that Sox-9, Alk-1, and Coll X expressions, as well as immunopositivity for CD49c and CD39, have predictive value for all of the cell types tested in indicating chondrogenic potency. The findings from this study have significant clinical implications for the refinement and development of novel cell-based cartilage repair strategies

Characterization of the cells in repair tissue following autologous chondrocyte implantation in mankind: a novel report of two cases

AIM: Autologous chondrocyte implantation (ACI) is used worldwide for the treatment of cartilage defects. This study has aimed to assess for the first time the cells that are contained within human ACI repair tissues several years post-treatment. We have compared the phenotypic properties of cells from within the ACI repair with adjacent chondrocytes and subchondral bone-derived mesenchymal stromal/stem cells (MSCs). MATERIALS & METHODS: Two patients undergoing arthroplasty of their ACI-treated joint were investigated. Tissue and cells were isolated from the repair site, adjacent macroscopically normal cartilage and MSCs from the subchondral bone were characterized for their growth kinetics, morphology, immunoprofile and differentiation capacity. RESULTS: ACI repair tissue appeared fibrocartilaginous, and ACI repair cells were heterogeneous in morphology and size when freshly isolated, becoming more homogeneous, resembling chondrocytes from adjacent cartilage, after culture expansion. The same weight of ACI repair tissue resulted in less cells than macroscopically normal cartilage. During expansion, ACI repair cells proliferated faster than MSCs but slower than chondrocytes. ACI repair cell immunoprofiles resembled chondrocytes, but their differentiation capacity matched MSCs. CONCLUSION: This novel report demonstrates that human ACI repair cell phenotypes resemble both chondrocytes and MSCs but at different stages of their isolation and expansion in vitro

Divergent drivers of leaf trait variation within species, among species, and among functional groups.

Understanding variation in leaf functional traits-including rates of photosynthesis and respiration and concentrations of nitrogen and phosphorus-is a fundamental challenge in plant ecophysiology. When expressed per unit leaf area, these traits typically increase with leaf mass per area (LMA) within species but are roughly independent of LMA across the global flora. LMA is determined by mass components with different biological functions, including photosynthetic mass that largely determines metabolic rates and contains most nitrogen and phosphorus, and structural mass that affects toughness and leaf lifespan (LL). A possible explanation for the contrasting trait relationships is that most LMA variation within species is associated with variation in photosynthetic mass, whereas most LMA variation across the global flora is associated with variation in structural mass. This hypothesis leads to the predictions that (i) gas exchange rates and nutrient concentrations per unit leaf area should increase strongly with LMA across species assemblages with low LL variance but should increase weakly with LMA across species assemblages with high LL variance and that (ii) controlling for LL variation should increase the strength of the above LMA relationships. We present analyses of intra- and interspecific trait variation from three tropical forest sites and interspecific analyses within functional groups in a global dataset that are consistent with the above predictions. Our analysis suggests that the qualitatively different trait relationships exhibited by different leaf assemblages can be understood by considering the degree to which photosynthetic and structural mass components contribute to LMA variation in a given assemblage

Measuring patient-perceived quality of care in US hospitals using Twitter

BACKGROUND: Patients routinely use Twitter to share feedback about their experience receiving healthcare. Identifying and analysing the content of posts sent to hospitals may provide a novel real-time measure of quality, supplementing traditional, survey-based approaches. OBJECTIVE: To assess the use of Twitter as a supplemental data stream for measuring patient-perceived quality of care in US hospitals and compare patient sentiments about hospitals with established quality measures. DESIGN: 404 065 tweets directed to 2349 US hospitals over a 1-year period were classified as having to do with patient experience using a machine learning approach. Sentiment was calculated for these tweets using natural language processing. 11 602 tweets were manually categorised into patient experience topics. Finally, hospitals with ≥50 patient experience tweets were surveyed to understand how they use Twitter to interact with patients. KEY RESULTS: Roughly half of the hospitals in the US have a presence on Twitter. Of the tweets directed toward these hospitals, 34 725 (9.4%) were related to patient experience and covered diverse topics. Analyses limited to hospitals with ≥50 patient experience tweets revealed that they were more active on Twitter, more likely to be below the national median of Medicare patients (p<0.001) and above the national median for nurse/patient ratio (p=0.006), and to be a non-profit hospital (p<0.001). After adjusting for hospital characteristics, we found that Twitter sentiment was not associated with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) ratings (but having a Twitter account was), although there was a weak association with 30-day hospital readmission rates (p=0.003). CONCLUSIONS: Tweets describing patient experiences in hospitals cover a wide range of patient care aspects and can be identified using automated approaches. These tweets represent a potentially untapped indicator of quality and may be valuable to patients, researchers, policy makers and hospital administrators

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

Human Articular Chondrocytes Retain Their Phenotype in Sustained Hypoxia While Normoxia Promotes Their Immunomodulatory Potential.

Objective To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2) or continuous hypoxia (2% O2). Design Chondrocytes were extracted from patients undergoing total knee replacement ( n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (3D) pellet culture and compared with freshly isolated chondrocytes (FC). Cells were assessed by flow cytometry for markers indicative of mesenchymal stromal cells (MSCs), chondrogenic-potency and dedifferentiation. Chondrogenic potency and immunomodulatory gene expression was assessed in NC and HC by reverse transcription quantitative polymerase chain reaction. Immunohistochemistry was used to assess collagen II production following 3D pellet culture. Results NC were positive (>97%, n = 5) for MSC markers, CD73, CD90, and CD105, while HC demonstrated 60%) compared with HC and FC in which production was <2%. Hypoxic conditions upregulated expression of SOX9, frizzled-related protein ( FRZB), fibroblast growth factor receptor 3 ( FGFR3), and collagen type II ( COL2A1) and downregulated activin receptor-like kinase 1 ( ALK1) in 3 out of 4 patients compared with normoxic conditions for monolayer cells. Conclusions Hypoxic conditions encourage retention of a chondrogenic phenotype with some immunomodulatory potential, whereas normoxia promotes dedifferentiation of chondrocytes toward an MSC phenotype with loss of chondrogenic potency but enhanced immunomodulatory capacity

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel