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1.
JSES Int ; 4(2): 272-279, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32490413

ABSTRACT

BACKGROUND: Surgical management of displaced midshaft clavicle fractures in adults leads to better union rates, improved early functional outcomes, and increased patient satisfaction compared with nonoperative treatment. However, both intramedullary fixation and plate osteosynthesis are subject to a specific array of disadvantages and complications. The Anser Clavicle Pin is a novel intramedullary device designed to address these disadvantages and complications. The aim of this study was to evaluate the union rate, functional outcomes, and complications of the Anser Clavicle Pin at 1-year follow-up. METHODS: A prospective explorative case series including 20 patients with displaced midshaft clavicle fractures was performed in 2 hospitals. The primary outcomes were union rate, functional outcomes (Constant-Murley score and Disabilities of the Arm, Shoulder and Hand score), and complications. The secondary outcomes were closed reduction rate, operative time, image-intensifier time, hospital stay, incision length, time to radiologic union, postoperative pain reduction, reoperation rate, health-related quality-of-life score, and patient satisfaction. RESULTS: There was a 100% union rate. The Constant-Murley score at 1 year was 96.7 (standard deviation [SD], 5). The Disabilities of the Arm, Shoulder and Hand score was 5.1 (SD, 10). There were no infections, neuropathy of the supraclavicular nerve, or hardware irritation requiring removal of hardware. Three device-related complications (15%) occurred, including plastic deformation, protrusion, and hardware failure. The satisfaction score was 8.9 (SD, 1) on the visual analog scale at the 1-year follow-up. CONCLUSION: Managing displaced midshaft clavicle fractures with the Anser Clavicle Pin results in a 100% union rate and excellent functional outcomes and patient satisfaction. It has a low non-device-related complication rate, and the device-related complications that occurred in this series may be prevented in the future.

2.
Rheumatology (Oxford) ; 56(3): 351-361, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27940589

ABSTRACT

Objective: A crucial feature of OA is cartilage degradation. This process is mediated by pro-inflammatory cytokines, among other factors, via induction of matrix-degrading enzymes. Interleukin 37 (IL37) is an anti-inflammatory cytokine and is efficient in blocking the production of pro-inflammatory cytokines during innate immune responses. We hypothesize that IL37 is therapeutic in treating the inflammatory cytokine cascade in human OA chondrocytes and can act as a counter-regulatory cytokine to reduce cartilage degradation in OA. Methods: Human OA cartilage was obtained from patients undergoing total knee or hip arthroplasty. Immunohistochemistry was applied to study IL37 protein expression in cartilage biopsies from OA patients. Induction of IL37 expression by IL1ß, OA synovium-conditioned medium and TNFα was investigated in human OA chondrocytes. Adenoviral overexpression of IL37 followed by IL1ß stimulation was performed to investigate the anti-inflammatory potential of IL37. Results: IL37 expression was detected in cartilage biopsies of OA patients and induced by IL1ß. After IL1ß stimulation, increased IL1ß, IL6 and IL8 expression was observed in OA chondrocytes. Elevated IL37 levels diminished the IL1ß-induced IL1ß , IL6 and IL8 gene levels and IL1ß and IL8 protein levels. In addition to the reduction in pro-inflammatory cytokine expression, IL37 reduced MMP1 , MMP3 , MMP13 and disintegrin and metalloproteinase with thrombospondin motifs 5 gene levels and MMP3 and MMP13 protein levels. Conclusion: IL37 is induced by IL1ß, and IL37 itself reduced IL1ß, IL6 and IL8 production, indicating that IL37 is able to induce a counter-regulatory anti-inflammatory feedback loop in chondrocytes. In addition, IL37 dampens catabolic enzyme expression. This supports IL37 as a potential therapeutic target in OA.


Subject(s)
Chondrocytes/metabolism , Interleukin-1/metabolism , Interleukin-1beta/pharmacology , Osteoarthritis , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Adenoviridae , Blotting, Western , Chondrocytes/drug effects , Disintegrins/drug effects , Disintegrins/genetics , Disintegrins/metabolism , Humans , Immunohistochemistry , Interleukin-1/genetics , Interleukin-1beta/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/drug effects , Interleukin-8/genetics , Interleukin-8/metabolism , Matrix Metalloproteinase 1/drug effects , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 13/drug effects , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/drug effects , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , RNA, Messenger/drug effects , Real-Time Polymerase Chain Reaction
3.
Int Orthop ; 39(5): 859-63, 2015 May.
Article in English | MEDLINE | ID: mdl-25408489

ABSTRACT

PURPOSE: The purpose of this study is predicting the clinical and radiological long-term outcome and identifying prognostic factors of Legg-Calvé-Perthes disease (LCPD) in Catterall 2 and 3 hips. METHODS: Sixty hips (59 patients) were diagnosed with LCPD between 1959 to 1974 and were followed prospectively. Forty-two of these 60 hips were classified as Catterall 2 or 3. In 2002, 33 hips (32 patients) with Catterall type 2 or 3 were evaluated clinically and radiographically. In 2010, 27 hips (26 patients) were re-evaluated. RESULTS: In 2002, 15 hips had Catterall 2 type LCPD and 18 hips Catterall 3. Twelve of the 33 hips (36%) had signs of osteoarthritis. In 2010, 14 hips were classified as Catterall 2 and 13 hips as Catterall 3. Catterall 2 hips had a significantly better Harris Hip Score (HHS) (p = 0.001). There were 15 hips (55%) with signs of osteoarthritis. CONCLUSION: The long-term prognosis of LCPD Catterall type 2 and 3 is relatively benign. However, more than 50% of the patients will develop signs of osteoarthritis between the 4th and 5th decades. At the latest follow-up a strong increase in the number of cases with osteoarthritis was seen. Sphericity of the femoral head is an important predicting factor in the development of osteoarthritis.


Subject(s)
Legg-Calve-Perthes Disease/surgery , Osteoarthritis, Hip/epidemiology , Postoperative Complications/epidemiology , Age of Onset , Child , Child, Preschool , Female , Femur Head/diagnostic imaging , Follow-Up Studies , Humans , Infant , Legg-Calve-Perthes Disease/diagnostic imaging , Legg-Calve-Perthes Disease/epidemiology , Male , Prognosis , Prospective Studies , Radiography , Treatment Outcome
4.
Tissue Eng Part A ; 20(15-16): 2243-52, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24547725

ABSTRACT

OBJECTIVE: To rescue chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in osteoarthritic conditions by inhibition of protein kinases. METHODS: hMSCs were cultured in pellets. During early chondrogenic differentiation, these were exposed to osteoarthritic synovium-conditioned medium (OAS-CM), combined with the Janus kinase (JAK)-inhibitor tofacitinib and/or the transforming growth factor ß-activated kinase 1 (TAK1)-inhibitor oxozeaenol. To evaluate effects on chondrogenesis, the glycosaminoglycan (GAG) content of the pellets was measured at the time that chondrogenesis was manifest in control cultures. Moreover, mRNA levels of matrix molecules and enzymes were measured during this process, using real-time polymerase chain reaction (RT-PCR). Initial experiments were performed with hMSCs from a fetal donor, and results of these studies were confirmed with hMSCs from adult donors. RESULTS: Exposure to OAS-CM resulted in pellets with a much lower GAG content, reflecting inhibited chondrogenic differentiation. This was accompanied by decreased mRNA levels of aggrecan, type II collagen, and Sox9, and increased levels of matrix metalloproteinase (MMP)1, MMP3, MMP13, ADAMTS4, and ADAMTS5. Both tofacitinib (JAK-inhibitor) and oxozeaenol (TAK1 inhibitor) significantly increased the GAG content of the pellets in osteoarthritis (OA)-like conditions. The combination of both protein kinase inhibitors showed an additive effect on GAG content. In agreement with this, in the presence of OAS-CM, both tofacitinib and oxozeaenol increased mRNA expression of sox9. The expression of aggrecan and type II collagen was also up-regulated, but this only reached significance for aggrecan after TAK1 inhibition. Both inhibitors decreased the mRNA levels of MMP1, 3, and 13 in the presence of OAS-CM. Moreover, oxozeaenol also significantly down-regulated the mRNA levels of aggrecanases ADAMTS4 and ADAMTS5. When combined, the inhibitors caused additive reduction of OA-induced MMP1 mRNA expression. Counteraction of OAS-CM-induced inhibition of chondrogenesis by these protein kinase inhibitors was confirmed with hMSCs of two different adult donors. Both tofacitinib and oxozeaenol significantly improved GAG content in cell pellets from these adult donors. CONCLUSIONS: Tofacitinib and oxozeaenol partially prevent the inhibition of chondrogenesis by factors secreted by OA synovium. Their effects are additive. This indicates that these protein kinase inhibitors can potentially be used to improve cartilage formation under the conditions occurring in osteoathritic, or otherwise inflamed, joints.


Subject(s)
Cell Differentiation/drug effects , Chondrogenesis/drug effects , Janus Kinases/antagonists & inhibitors , MAP Kinase Kinase Kinases/antagonists & inhibitors , Mesenchymal Stem Cells/pathology , Osteoarthritis/pathology , Protein Kinase Inhibitors/pharmacology , Adult , Cartilage, Articular/drug effects , Cartilage, Articular/growth & development , Cartilage, Articular/pathology , Fetus/cytology , Humans , Janus Kinases/metabolism , MAP Kinase Kinase Kinases/metabolism , Mesenchymal Stem Cells/enzymology , Piperidines/pharmacology , Pyrimidines/pharmacology , Pyrroles/pharmacology , Time Factors , Zearalenone/pharmacology
5.
J Clin Microbiol ; 47(9): 3038-40, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19571033

ABSTRACT

We present descriptions of two human Mycobacterium microti infections: one of a patient with pulmonary disease and one of a patient with osteomyelitis of the hip. Both patients had acid-fast bacilli and a positive Mycobacterium tuberculosis complex PCR from clinical specimens, but mycobacterial cultures remained negative. The microbiological diagnosis was established by molecular methods.


Subject(s)
Mycobacterium/isolation & purification , Tuberculosis, Osteoarticular/diagnosis , Tuberculosis, Osteoarticular/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Hip/microbiology , Humans , Lung/microbiology , Male , Middle Aged , Mycobacterium/classification , Polymerase Chain Reaction/methods
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