Operative or Nonoperative Treatment is Predicted Accurately for Patients Who Have Hip Complaints Consulting an Orthopedic Surgeon Using Machine Learning Algorithms Trained With Prehospital Acquired History-Taking Data.

BACKGROUND: Increasing numbers of patients suffering from hip osteoartritis will lead to increased orthopaedic health care consumption. Artificial intelligence might alleviate this problem, using Machine learning (ML) to optimize orthopaedic consultation workflow by predicting treatment strategy (non-operative or operative) prior to consultation. The purpose of this study was to assess ML accuracy in clinical practice, by comparing ML predictions to the outcome of clinical consultations. METHODS: In this prospective clinical cohort study, adult patients referred for hip complaints between January 20th to February 20th 2023 were included. Patients completed a computer-assisted history taking (CAHT) form and using these CAHT answers, a ML-algorithm predicted non-operative or operative treatment outcome prior to in-hospital consultation. During consultation, orthopaedic surgeons and physician assistants were blinded to the prediction in 90 and unblinded in 29 cases. Consultation outcome (non-operative or operative) was compared to ML treatment prediction for all cases, and for blinded and unblinded conditions separately. Analysis was done on 119 consultations. RESULTS: Overall treatment strategy prediction was correct in 101 cases (accuracy 85%, P < .0001). Non-operative treatment prediction (n = 71) was 97% correct versus 67% for operative treatment prediction (n = 48). Results from unblinded consultations (86.2% correct predictions,) were not statistically different from blinded consultations (84.4% correct, P > .05). CONCLUSIONS: Machine Learning algorithms can predict non-operative or operative treatment for patients with hip complaints with high accuracy. This could facilitate scheduling of non-operative patients with physician assistants, and operative patients with orthopaedic surgeons including direct access to pre-operative screening, thereby optimizing usage of health care resources.

Morphological risk factors for scaphoid fracture: a case-control study.

PURPOSE: Most patients with a clinically suspected scaphoid fracture and normal initial radiograph are unnecessarily treated. Previously developed prediction rules using demographic and clinical risk are unable to accurately predict occult fractures. Adding other risk factors could enhance this. Therefore, we aim to explore if there are morphological risk factors of the wrist for sustaining a scaphoid fracture. METHODS: We retrospectively included adult patients with a clinically suspected scaphoid fracture between 2013 and 2019 in our case-control study. There were 82 patients with a scaphoid fracture and 158 patients with a wrist contusion. Morphological risk factors were identified using statistical shape modelling (SSM) and linear measurements. Independent wrist shape variations on posteroanterior and lateral radiographs were captured in modes using SSM. Associations between outcomes and a scaphoid fracture were explored using logistic regression and the reliability was assessed. RESULTS: Of the 15 posteroanterior modes and 8 lateral modes identified and linear measurements performed, 1 PA mode was associated with a scaphoid fracture (PA mode 4; OR 1.40, CI 1.04-1.93, p = 0.031). We described this mode as an ulna plus and narrower distal radius with more volar tilt and radial inclination. The reliability of the posteroanterior modes and linear measurements was mostly good/excellent and moderate/poor for the lateral modes. CONCLUSION: There was one complex wrist shape significantly associated with a scaphoid fracture. Since the association was weak and the shape is difficult to identify radiographs, we believe this morphological risk factor would not enhance identifying occult scaphoid fractures in the future.

A 20 mg dose of dexamethasone does not reduce the proportion of joint replacement patients needing rescue analgesia: a matched cohort study.

Background: Consistent pain control after total joint replacement (TJR) has not yet been reached in all patients managed with a multimodal analgesia regime. Questions remain on dosage and timing of analgesics. Glucocorticoids such as dexamethasone are considered most powerful in reducing the surgery-induced inflammatory response with most pain studies using a 6-12 mg dose. Reviews agree that additional glucocorticoids may provide more analgesia, but a dose-finding analysis is limited. The primary aim of this study was to determine if a high, single preoperative dose of dexamethasone resulted in a reduced need for rescue analgesics during the first 24 hours after TJR when compared to a standard 8 mg dose of dexamethasone. Methods: A cohort study in which 59 patients who received 20 mg dexamethasone intravenously just prior to incision were matched 1:1 to patients who received a standard 8 mg dose. Consecutive elective hip and knee replacement patients managed by one anaesthesiologist were included in the high dose group between June 2019 and March 2020. Patients were matched for arthroplasty type, gender, age, anaesthesia type and pre-operative pain. Patients with opioid use before surgery or with diabetes mellitus were excluded. Oxynorm rescues analgesics (number of times given and dosage) usage during hospitalization was retrieved from the electronic nursing files. Results: There were no significant differences between groups in gender distribution, mean age and body mass index (BMI), in American Society of Anesthesiologists (ASA), type of arthroplasty, anaesthesia type and pre-operative pain score. In the 20 mg group 54 patients (91.5%) needed oxynorm during hospitalization versus 58 (98.3%) in the 8 mg group (P=0.09). High dose group patients received a median of 5 mg [interquartile range (IQR): 0] oxynorm versus 5 mg (IQR: 0) in the standard dose group (P=0.70). Conclusions: In this matched cohort study there was no difference in the proportion of patients needing rescue analgesics during hospitalization between the group of patients who preoperatively received 20 mg dexamethasone and the group of patients who received 8 mg. Future blinded randomized controlled trials are needed to further investigate the effect of different glucocorticoids dosages on pain after joint replacement surgery.

Folate Receptor Expression by Human Monocyte-Derived Macrophage Subtypes and Effects of Corticosteroids.

OBJECTIVE: Folate receptor beta (FR-ß) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-ß+ macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-ß expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid. DESIGN: Human monocyte-derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-ß expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: FR-ß expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-ß expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-ß+ phenotype. CONCLUSIONS: As corticosteroids skewed monocytes toward an FR-ß-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-ß has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-ß expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-ß+ macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity.

Machine learning algorithms trained with pre-hospital acquired history-taking data can accurately differentiate diagnoses in patients with hip complaints.

Background and purpose - Machine learning (ML) techniques are a form of artificial intelligence able to analyze big data. Analyzing the outcome of (digital) questionnaires, ML might recognize different patterns in answers that might relate to different types of pathology. With this study, we investigated the proof-of-principle of ML-based diagnosis in patients with hip complaints using a digital questionnaire and the Kellgren and Lawrence (KL) osteoarthritis score.Patients and methods - 548 patients (> 55 years old) scheduled for consultation of hip complaints were asked to participate in this study and fill in an online questionnaire. Our questionnaire consists of 27 questions related to general history-taking and validated patient-related outcome measures (Oxford Hip Score and a Numeric Rating Scale for pain). 336 fully completed questionnaires were related to their classified diagnosis (either hip osteoarthritis, bursitis or tendinitis, or other pathology). Different AI techniques were used to relate questionnaire outcome and hip diagnoses. Resulting area under the curve (AUC) and classification accuracy (CA) are reported to identify the best scoring AI model. The accuracy of different ML models was compared using questionnaire outcome with and without radiologic KL scores for degree of osteoarthritis.Results - The most accurate ML model for diagnosis of patients with hip complaints was the Random Forest model (AUC 82%, 95% CI 0.78-0.86; CA 69%, CI 0.64-0.74) and most accurate analysis with addition of KL scores was with a Support Vector Machine model (AUC 89%, CI 0.86-0.92; CA 83%, CI 0.79-0.87).Interpretation - Analysis of self-reported online questionnaires related to hip complaints can differentiate between basic hip pathologies. The addition of radiological scores for osteoarthritis further improves these outcomes.

Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement? A methodological study.

OBJECTIVES: To determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement (2013), and any association with author, trial or journal factors. DESIGN: Methodological study. DATA SOURCES: MEDLINE, Embase and CENTRAL were electronically searched using optimised search strategies. ELIGIBILITY CRITERIA: Protocols written for an RCT of living humans, published in full text in a peer-reviewed journal and published in the English language. MAIN OUTCOME: Primary outcome was the overall proportion of checklist items which were adequately reported in RCT protocols published before and after the SPIRIT statement. RESULTS: 300 RCT protocols were retrieved; 150 from the period immediately before the SPIRIT statement (9 July 2012 to 28 December 2012) and 150 from a recent period after the SPIRIT statement (25 January 2019 to 20 March 2019). 47.9% (95% CI, 46.5% to 49.3%) of checklist items were adequately reported in RCT protocols before the SPIRIT statement and 56.7% (95% CI, 54.9% to 58.5%) after the SPIRIT statement. This represents an 8.8% (95% CI, 6.6% to 11.1%; p<0.0001) mean improvement in the overall proportion of checklist items adequately reported since the SPIRIT statement. While 40% of individual checklist items had a significant improvement in adequate reporting after the SPIRIT statement, 11.3% had a significant deterioration and there were no RCT protocols in which all individual checklist items were complete. The factors associated with higher reporting quality of RCT protocols in multiple regression analysis were author expertise or experience in epidemiology or statistics, multicentre trials, longer protocol word length and publicly reported journal policy of compliance with the SPIRIT statement. CONCLUSION: The overall reporting quality of RCT protocols has significantly improved since the SPIRIT statement, although a substantial proportion of individual checklist items remain poorly reported. Continued and concerted efforts are required by journals, editors, reviewers and investigators to improve the completeness and transparency of RCT protocols.

Congenital Forearm Pseudarthrosis, a Systematic Review for a Treatment Algorithm on a Rare Condition.

BACKGROUND: A congenital forearm pseudarthrosis is a rare condition and is strongly associated with neurofibromatosis type 1. Several surgical techniques are described in the literature, but the most optimal treatment strategy remains unclear. This systematic review aims to develop a treatment algorithm that may aid in clinical decision making. METHODS: The PROSPERO registration number for this study was CRD42018099602 and adheres to the PRISMA guidelines for systematic reviews. Embase, MEDLINE, Cochrane Central, Web of Science, and Google Scholar databases were searched for published studies reporting on congenital forearm pseudarthrosis not related to other underlying pathologies like bacterial infection or fibrous dysplasia. Results were not restricted by date or study type, only English literature was allowed. Studies were assessed for quality using the critical appraisal checklist for case reports from the Joanna Briggs Institute. Patient characteristics, underlying disease, type of surgery, union rate, and functional outcome were extracted from included studies. RESULTS: Of 829 studies identified, 47 were included in this review (17 case series and 30 case reports, a total of 84 cases). A one-bone forearm procedure showed highest union rates (92%), however, it results in loss of forearm rotation. Free vascularized fibula grafting showed high union rates (87%) and was related to good functional outcome of elbow flexion and forearm rotations. Other procedures showed disappointing outcomes. CONCLUSIONS: Congenital forearm pseudarthrosis is best treated with a free vascularized fibula grafting, a one-bone forearm procedure should be used as a salvage procedure. Evidence extracted from the case reports was sufficient to generate a treatment algorithm to be used in clinical pediatric practice. LEVEL OF EVIDENCE: Level IV-therapeutic.

Ultrasound-Guided Nerve Blocks as Analgesia for Nonoperative Management of Distal Radius Fractures-Two Consecutive Randomized Controlled Trials.

OBJECTIVES: To investigate whether a conventional fracture hematoma block (FHB) or an ultrasound-guided peripheral nerve block has more superior analgesic effect during nonoperative management of distal radius fractures in an emergency department setting. Two peripheral nerve block types were investigated, one at the level of the elbow, or cubital nerve block (CNB), and another an axillary nerve block (ANB). DESIGN: Two prospective randomized controlled studies were performed to compare the difference in pain intensity during closed reduction of a distal radius fracture between FHB-, CNB-, and, ANB-treated patients. SETTING: Level 2 trauma center. PATIENTS: One hundred ten patients with radiographic displaced distal radius fractures were randomized. Fifty patients were randomized between FHB and CNB, and 60 patients were randomized between CNB and ANB. INTERVENTION: FHB, CNB, or ANB. These were performed by 3 physicians new to ultrasound-guided peripheral nerve blocks and trained before onset of this study. MAIN OUTCOME MEASUREMENT: Pain was sequentially measured using an NRS during closed distal radius fracture reduction. RESULTS: CNB patients experienced less pain during block procedure (P = 0.002), finger trap traction (P = 0.007), fracture reduction (P = 0.00001), after plaster cast application (P = 0.01), and after control radiography (P = 0.01). In our second study, ANB-treated patients reported less pain during block procedure (P = 0.04), during finger trap traction (P < 0.0001), fracture reduction (P < 0.0001), after plaster cast application (P = 0.0001), and after control radiography (P = 0.0005). CONCLUSIONS: Although participating clinicians had minimal expertise using ultrasound-guided peripheral nerve blocks, nonoperative management of distal radius fracture using an ANB was less painful. These block types are expected to completely eradicate sensation the best. Future studies should address technical factors including adequate placement and time to let the block set up, as well as issues such as resource utilization including time and clinician availability to better determine the relative advantages and disadvantages to other analgesia techniques such as the FHB. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Chronic kidney failure mineral bone disorder leads to a permanent loss of hematopoietic stem cells through dysfunction of the stem cell niche.

In chronic kidney disease (CKD), endothelial injury, is associated with disease progression and an increased risk for cardiovascular complications. Circulating cells with vascular reparative functions are hematopoietic and also reduced in CKD. To explore the mechanistic basis behind these observations, we have investigated hematopoietic stem cell (HSC) homeostasis in a mouse model for non-progressive CKD-mineral and bone disorder with experimentally induced chronic renal failure (CRF). In mice subjected to 12 weeks of CRF, bone marrow HSC frequencies were decreased and transplantation of bone marrow cells from CRF donors showed a decrease in long-term HSC repopulation compared to controls. This loss was directly associated with a CRF-induced defect in the HSC niche affecting the cell cycle status of HSC and could not be restored by the PTH-reducing agent cinacalcet. In CRF, frequencies of quiescent (G0) HSC were decreased coinciding with an increase in hematopoietic progenitor cells (HPC) in the S-and G2-phases of cell cycle. Moreover, in CRF mice, HSC-niche supporting macrophages were decreased compared to controls concomitant to impaired B lymphopoiesis. Our data point to a permanent loss of HSC and may provide insight into the root cause of the loss of homeostatic potential in CKD.

Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

INTRODUCTION: Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. METHODS: Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (µCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor ß (FRß)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced µCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRß expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. RESULTS: Our in vivo study showed that intra-articular injections with TA strongly enhanced FRß(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRß(+) macrophages. Furthermore, TA-stimulated M2 macrophages showed enhanced IL-10 expression at the mRNA level. CONCLUSIONS: TA injections potently induce a CD163(+)- and FRß(+)-activated macrophage with anti-inflammatory characteristics such as reduced IL-10 production in vitro and lack of osteophytosis in vivo.

Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis.

We studied the effects of intra-articularly injected bone marrow derived mesenchymal stem cells (MSCs), as well as freshly isolated bone marrow mononuclear cells (BMMNCs), on pain, cartilage damage, bone changes and inflammation in an in-vivo rat osteoarthritis (OA) model. OA was induced unilaterally by injection of mono-iodoacetate (MIA) and allowed to develop for 3 weeks. Then, animals were treated by intra-articular injection with MSCs, BMMNCs, or saline as a control. Four weeks later, pain was assessed with an incapitance tester, subchondral bone alterations were measured with µCT and cartilage quality and joint inflammation were assessed by histological analysis. Animals treated with MSCs distributed significantly more weight to the affected limb after treatment, which was not observed in the other groups. No statistically significant differences between treatment groups regarding cartilage damage, subchondral bone alterations and synovial inflammation were observed. Additional cell tracking experiments indicated adequate intra-articular cell injection and cell survival up to 2 weeks. In our OA model, injected MSCs were able to reduce MIA induced pain, as measured by an increased weight distribution to the affected limb. No statistically significant effects of the cellular therapies on structural damage and synovial inflammation were found.

Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage.

INTRODUCTION: Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. METHODS: sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (µCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced µCT and histology to measure sGAG content and cartilage thickness. RESULTS: All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. CONCLUSIONS: Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced subchondral sclerosis, synovial macrophage activation, and osteophyte formation.

Enhanced bone regeneration of cortical segmental bone defects using porous titanium scaffolds incorporated with colloidal gelatin gels for time- and dose-controlled delivery of dual growth factors.

Porous titanium scaffolds are a promising class of biomaterials for grafting large bone defects, because titanium provides sufficient mechanical support, whereas its porous structure allows bone ingrowth resulting in good osseointegration. To reinforce porous titanium scaffolds with biological cues that enhance and continue bone regeneration, scaffolds can be incorporated with bioactive gels for time- and dose-controlled delivery of multiple growth factors (GFs). In this study, critical femoral bone defects in rats were grafted with porous titanium scaffolds incorporated with nanostructured colloidal gelatin gels. Gels were loaded with bone morphogenetic protein-2 (BMP-2, 3 µg), fibroblast growth factor-2 (FGF-2, 0.6 µg), BMP-2, and FGF-2 (BMP-2/FGF-2, ratio 5:1) or were left unloaded. GF delivery was controlled by fine tuning the crosslinking density of oppositely charged nanospheres. Grafted femurs were evaluated using in vivo and ex vivo micro-CT, histology, and three-point bending tests. All porous titanium scaffolds containing GF-loaded gels accelerated and enhanced bone regeneration: BMP-2 gels gave an early increase (0-4 weeks), and FGF-2 gels gave a late increase (8-12 weeks). Interestingly, stimulatory effects of 0.6 µg FGF-2 were similar to a fivefold higher dose of BMP-2 (3 µg). BMP-2/FGF-2 gels gave more bone outside the porous titanium scaffolds than gels with only BMP-2 or FGF-2, resulted in bridging of most defects and showed superior bone-implant integrity in three-point bending tests. In conclusion, incorporation of nanostructured colloidal gelatin gels capable of time- and dose-controlled delivery of BMP-2 and FGF-2 in porous titanium scaffolds is a promising strategy to enhance and continue bone regeneration of large bone defects.

No effect of hole geometry in microfracture for talar osteochondral defects.

BACKGROUND: Débridement and bone marrow stimulation is an effective treatment option for patients with talar osteochondral defects. However, whether surgical factors affect the success of microfracture treatment of talar osteochondral defects is not well characterized. QUESTIONS/PURPOSES: We hypothesized (1) holes that reach deeper into the bone marrow-filled trabecular bone allow for more hyaline-like repair; and (2) a larger number of holes with a smaller diameter result in more solid integration of the repair tissue, less need for new bone formation, and higher fill of the defect. METHODS: Talar osteochondral defects that were 6 mm in diameter were drilled bilaterally in 16 goats (32 samples). In eight goats, one defect was treated by drilling six 0.45-mm diameter holes in the defect 2 mm deep; in the remaining eight goats, six 0.45-mm diameter holes were punctured to a depth of 4 mm. All contralateral defects were treated with three 1.1-mm diameter holes 3 mm deep, mimicking the clinical situation, as internal controls. After 24 weeks, histologic analyses were performed using Masson-Goldner/Safranin-O sections scored using a modified O'Driscoll histologic score (scale, 0-22) and analyzed for osteoid deposition. Before histology, repair tissue quality and defect fill were assessed by calculating the mean attenuation repair/healthy cartilage ratio on Equilibrium Partitioning of an Ionic Contrast agent (EPIC) micro-CT (µCT) scans. Differences were analyzed by paired comparison and Mann-Whitney U tests. RESULTS: Significant differences were not present between the 2-mm and 4-mm deep hole groups for the median O'Driscoll score (p = 0.31) and the median of the µCT attenuation repair/healthy cartilage ratios (p = 0.61), nor between the 0.45-mm diameter and the 1.1-mm diameter holes in defect fill (p = 0.33), osteoid (p = 0.89), or structural integrity (p = 0.80). CONCLUSIONS: The results indicate that the geometry of microfracture holes does not influence cartilage healing in the caprine talus. CLINICAL RELEVANCE: Bone marrow stimulation technique does not appear to be improved by changing the depth or diameter of the holes.

In situ forming acyl-capped PCLA-PEG-PCLA triblock copolymer based hydrogels.

Sustained intra-articular drug delivery opens up new opportunities for targeted treatment of osteoarthritis. In this study, we investigated the in vitro and in vivo properties and performance of a newly developed hydrogel based on acyl-capped PCLA-PEG-PCLA specifically designed for intra-articular use. The hydrogel formulation consisted of a blend of polymers either capped with acetyl, or with 2-(2',3',5',-triiodobenzoyl, TIB) moieties. TIB was added to visualize the gel using µCT, enabling longitudinal quantification of its degradation. Blends containing TIB-capped polymer degraded in vitro (37 °C; pH 7.4 buffer) through dissolution over a period of ~20 weeks, and degraded slightly faster (~12 weeks) after subcutaneous injection in rats. This in vivo acceleration was likely due to active (enzymatic) degradation, shown by changes in polymer composition and molecular weight as well as the presence of macrophages. After intra-articular administration in rats, the visualized gel gradually lost signal intensity over the course of 4 weeks. Good cytocompatibility of acetyl-capped polymer based hydrogel was proven in vitro on erythrocytes and chondrocytes. Moreover, intra-articular biocompatibility was demonstrated using µCT-imaging and histology, since both techniques showed no changes in cartilage quality and/or quantity.

Hsp90 inhibition protects against biomechanically induced osteoarthritis in rats.

OBJECTIVE: Although articular cartilage has evolved to facilitate joint mobilization, severe loading can induce chondrocyte apoptosis, which is related to the progression of osteoarthritis (OA). To avoid apoptosis, chondrocytes synthesize heat-shock proteins (HSPs). This study was undertaken to examine the roles of Hsp70 and Hsp90 in biomechanically induced OA, and the possibility of using Hsp90 inhibition as an intervention strategy for OA management. METHODS: OA was biomechanically induced in rats by means of strenuous running. Disease progression was compared between running rats treated with Hsp90 inhibitor and untreated running controls. Hsp70 and Hsp90 protein levels in articular cartilage were determined by Western blotting. OA progression was monitored using contrast-enhanced micro-computed tomography to measure cartilage degradation and subchondral bone changes and single-photon-emission computed tomography to examine synovial macrophage activation and histologic features. RESULTS: Chronic cartilage loading led to early OA development, characterized by degeneration of cartilage extracellular matrix. In vivo Hsp90 inhibition resulted in increased Hsp70 synthesis, which suggests that Hsp90 activity limits Hsp70 production. Hsp90 inhibitor treatment increased cartilage sulfated glycosaminoglycan levels to concentrations even beyond baseline and protected against cartilage degradation, stimulated subchondral bone thickness, and suppressed macrophage activation. CONCLUSION: Our findings indicate that Hsp90 plays a pivotal role in biomechanically induced chondrocyte stress responses. Intervention strategies that inhibit Hsp90 can potentially protect or improve cartilage health and might prevent OA development.

Quantifying osteoarthritic cartilage changes accurately using in vivo microCT arthrography in three etiologically distinct rat models.

In vivo microCT arthrography (µCTa) can be used to measure both quantity (volumetric) and quality (glycosaminoglycan content) of cartilage. This study investigated the accuracy of four segmentation techniques to isolate cartilage from µCTa datasets and then used the most accurate one to investigate if the µCTa method could show osteoarthritic changes in rat models during longitudinal follow-up. Volumetric measurements and glycosaminoglycan contents of patellar cartilage from in vivo µCTa-scans were compared with an ex vivo gold standard µCT-scan. Cartilage was segmented with three global thresholds and one local threshold algorithm. Comparisons were made for healthy and osteoarthritic cartilage. Next, three rat models were investigated for 24 weeks using µCTa. Osteoarthritis was induced by injection with a chemical (mono-iodoacetate), a surgical intervention (grooves applied in articular cartilage), and via exercise (strenuous running). After euthanasia, all knee joints were isolated for histology. Local thresholds accurately segmented cartilage from in vivo µCTa scans and best measured cartilage quantity and glycosaminoglycan content. Each of the three osteoarthritic rat models showed a specific pattern of osteoarthritis progression. All µCTa results were comparable to histology. In vivo µCTa is a sensitive technique for imaging cartilage degradation. Local thresholds enhanced the sensitivity of this method and will probably more accurately detect disease-modulating effects from interventional strategies. The data from rat models may serve as a reference for the time sequence of cartilage degeneration during in vivo testing of new strategies in osteoarthritis treatment.

Citation analysis of orthopaedic literature; 18 major orthopaedic journals compared for Impact Factor and SCImago.

BACKGROUND: One of the disadvantages of the Impact Factor (IF) is self-citation. The SCImago Journal Rank (SJR) indicator excludes self-citations and considers the quality, rather than absolute numbers, of citations of a journal by other journals. The present study re-evaluated the influence of self-citation on the 2007 IF for 18 major orthopaedic journals and investigated the difference in ranking between IF and SJR. METHODS: The journals were analysed for self-citation both overall and divided into a general group (n = 8) and a specialized group (n = 10). Self-cited and self-citing rates, as well as citation densities and IFs corrected for self-citation (cIF), were calculated. The rankings of the 18 journals by IF and by SJR were compared and the absolute difference between these rankings (DeltaR) was determined. RESULTS: Specialized journals had higher self-citing rates (p = 0.01, Deltamedian = 9.50, 95%CI -19.42 to 0.42), higher self-cited rates (p = 0.0004, Deltamedian = -10.50, 95%CI -15.28 to -5.72) and greater differences between IF and cIF (p = 0.003, Deltamedian = 3.50, 95%CI -6.1 to 13.1). There was no significant correlation between self-citing rate and IF for both groups (general: r = 0.46, p = 0.27; specialized: r = 0.21, p = 0.56). When the difference in ranking between IF and SJR was compared between both groups, sub-specialist journals were ranked lower compared to their general counterparts (DeltaR: p = 0.006, Deltamedian = 2.0, 95%CI -0.39 to 4.39). CONCLUSIONS: Citation analysis shows that specialized orthopaedic journals have specific self-citation tendencies. The correlation between self-cited rate and IF in our sample was large but, due to small sample size, not significant. The SJR excludes self-citations in its calculation and therefore enhances the underestimation in ranking of specialized journals.