MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Ankle osteoarthritis: comprehensive review and treatment algorithm proposal.

Ankle osteoarthritis (OA) is much less frequent than knee or hip OA, but it can be equally disabling, greatly affecting the quality of life of the patients. Approximately 80% of ankle OA is post-traumatic, mainly secondary to malleolar fractures, being another of the main causes untreated in chronic instability. The average age of the patient affected by ankle OA is around 50 years, being therefore active patients and in working age who seek to maintain mobility and remain active. The authors conducted a comprehensive review of the conservative, medical, and surgical treatment of ankle OA. Initial conservative treatment is effective and should be attempted in any stage of OA. From a pharmacological point of view, non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular infiltrations can produce temporary relief of symptoms. After the failure of conservative-medical treatment, two large groups of surgical treatment have been described: joint-preserving and joint-sacrificing procedures. In the early stages, only periarticular osteotomies have enough evidence to recommend in ankle OA with malalignment. Both ankle arthrodesis and ankle replacement can produce satisfactory functional results if correctly indicated in the final stages of the disease. Finally, the authors propose a global treatment algorithm that can aid in the decision-making process.

Ankle Osteoarthritis Aetiology.

Ankle osteoarthritis affects 1% of the population and, unlike gonarthrosis or coxarthrosis, is secondary to previous trauma in more than 75% of cases. Another peculiarity of this disease is that it affects a younger and active population, with socio-occupational implications. Mechanical factors, such as incongruity, instability, malalignment, and impacts, which increase stress on isolated areas of the ankle cartilage, have been clearly associated with the development of osteoarthritis. However, we cannot ignore the importance of pro-inflammatory mediators present from the moment of fracture as triggers of the cascade that eventually causes chondrocyte cell death, ultimately responsible for ankle osteoarthritis.

Comparison between cotton test and tap test for the assessment of coronal syndesmotic instability: A cadaveric study.

INTRODUCTION: In surgically treated rotational malleolar fractures, residual syndesmotic instability is typically assessed following fixation with the widely used intraoperative Cotton test. However, due to its dynamic nature, there are inconsistencies of the magnitude and direction of the distraction force when attempting to pull the fibula away from the tibia using a bone hook. The novel Tap test advances a cortical tap through a drilled hole in the fibula with a stable, unidirectional distraction force applied to the tibia. The objective of this cadaveric study was to compare the Cotton and Tap tests as diagnostic tools for coronal plane syndesmotic instability. METHODS: Tibiofibular Clear Space (TFCS) of 10 cadaveric specimens was measured for: intact, non-stressed; intact, stressed; injured, non-stressed; and injured, stressed (Tap and Cotton tests). In injured conditions, the syndesmotic ligamentous complex was sectioned using an anterolateral longitudinal approach. Perfect fluoroscopic Mortise images were acquired for all conditions. Two independent and blinded Orthopaedic Foot and Ankle Surgeons measured TFCS 1 cm proximal to the ankle joint line. Intra and interobserver reliabilities were assessed by Intraclass Correlation Coefficient. Syndesmotic TFCS values for all conditions were compared by paired Wilcoxon. Diagnostic performance of the Cotton and Tap tests was assessed using a relative increase of TFCS > 2 mm when comparing intact stressed and injured stressed conditions. P-values <0.05 were considered significant. RESULTS: The intraclass correlation coefficient for intraobserver and interobserver reliability was respectively 0.96 and 0.79. TFCS measurements were similar in intact non-stressed, intact stressed (both Cotton and Tap tests) and injured non-stressed conditions, with mean values and 95% Confidence Intervals of: intact non-stressed, 3.5 mm; intact stressed, 3.6 mm (Cotton test) and 4.0 mm (Tap test); injured non-stressed, 3.8 mm. The Cotton test and Tap test had, respectively, 73.3% and 70% sensitivity, 100% and 90% specificity, 86.7% and 80% diagnostic accuracy. CONCLUSIONS: Our cadaveric study compared the Cotton and Tap tests for detection of coronal plane syndesmotic instability. Both tests demonstrated similar increases in the TFCS measurements in stressed injured conditions when compared to intact non-stressed and stressed conditions, as well as injured non-stressed conditions.

Radiographic Assessment of First Tarsometatarsal Joint Shape and Orientation.

BACKGROUND: Hypermobility within the first tarsometatarsal (TMT) joint is a predisposing factor for hallux valgus. The purpose of this study was to assess whether the shape and angulation of the first TMT joint are affected by the positioning of the foot in radiographs. METHODS: Ten adult above-knee fresh-frozen cadaveric specimens were placed into a radiolucent apparatus that allowed controlled angulation of each foot at 0, 5, 10, 15, and 20 degrees in dorsiflexion, plantarflexion, inversion, and eversion. For each specimen, the first TMT joint angle (1TMTJA), shape of the distal articular surface of the medial cuneiform (flat or curved), and image quality of the first TMT joint were measured. RESULTS: The mean value for 1TMTJA was 22.9 degrees (95% confidence interval [CI] 21.9-24). Individual anatomical variations of the specimens as well as the different angulations due to foot positioning significantly influenced the 1TMTJA (both P < .001). Joints that were found to have a flat configuration showed significantly increased 1TMTJA on average when compared to the ones with curved articular surface, 25.9 (95% CI 24.4-27.4) and 20.8 degrees (95% CI 19.5-22.0) (P < .001), respectively. Image quality for visualization of the first TMT joint was progressively better for increased angles of dorsiflexion and inversion. CONCLUSION: The shape and angulation of the first TMT joint on radiographic evaluation are affected by the positioning of the foot. CLINICAL RELEVANCE: Clinical usefulness of these radiographic characteristics is limited and should not influence operative planning in patients with possible instability of the first TMT joint.

The use of bioactive glass S53P4 in the treatment of an infected Charcot foot: a case report.

OBJECTIVE:: To report a case of successful limb-salvage staged treatment in the treatment of an infected diabetic Charcot foot. CASE SUMMARY:: A 45-year-old male with long-term, uncontrolled type 2 diabetes, six months' history of progressive deformity on the right foot and 45 days of purulent drainage in the lateral aspect of the foot. Patient was diagnosed with an infected Charcot foot with extensive midfoot bone involvement as shown by radiographic and MRI images. We used a multidisciplinary approach to treatment with early antibiotic therapy, tight glycaemic control and staged surgical treatment. Initial treatment was adequate irrigation and debridement, bone-void filling with bioactive glass, external fixation and provisional negative pressure wound therapy (NPWT). Later progressed to total contact casting and progressive protect weight bearing. At final follow-up, patient was full weight-bearing in stiff soled footwear, with no clinical signs of infection, no gross alteration of gait pattern and demonstrating complete bone healing and integration of the bioactive glass. CONCLUSION:: The bioactive glass S53P4 was successfully used in the limb-salvage staged treatment of a patient with an infected Charcot foot. Here, full integration with the surrounding bone and its supportive action in the combat of bone infection was demonstrated.

Increased cytokine levels and histological changes in cartilage, synovial cells and synovial fluid after malleolar fractures.

BACKGROUND: Malleolar fractures are among the most common fractures in the human skeleton with a high risk of later development of post-traumatic osteoarthritis (OA). The acute ankle injury initiates a sequence of events potentially leading to progressive articular surface damage resulting from inflammatory changes in cartilage, synovial tissue and synovial fluid. We hypothesised that in the acute phase of ankle fracture, these changes occur at the same time in the different tissues. METHODS: Specimens of chondral tissue, synovial tissue and synovial fluid were collected from 16 patients with acute articular ankle fracture (study group). Additional samples were obtained from five male fresh cadavers within 12 hours of death (control group). Chondral tissue was assessed for cellularity, irregularities and chondrocyte disarray. Synovial tissue was assessed for synovitis, proteoglycans and collagen deposition. Synovial fluid was assessed for cytokines IL-2, IL-6, IL-10, IL-17, IFN-γ and TGF-ß1. RESULTS: Chondral tissue showed discontinuity in the tidemark between cartilage and subchondral bone, chondrocyte disarray, increased cellularity (both at the cartilage surface and subchondral bone), articular surface irregularities and increased deposition of proteoglycans and collagen fibres. Synovial tissue showed a statistically significant difference between the study and control groups in the concentration per tissue area of both thin collagen fibres (p=0.0274) and thick collagen fibres (p<0.0001). Cytokine concentrations in synovial fluid samples were significantly higher in ankle fracture tissue compared with controls for IL-2 (p=0.0002), IL-6 (p<0.0001), IL-10 (p=0.002) and IL-17 (p<0.0001). No statistically significant differences were observed for IFN-γ (p=0.06303) and TGF-ß1 (p=0.8832). CONCLUSION: We observed a pattern of simultaneous and interrelated pathological changes in cartilage, subchondral bone, synovial tissue and synovial fluid after acute malleolar fracture. As the observed inflammatory changes could lead to the development of OA, a more thorough knowledge of these early processes could be helpful to find strategies for prevention or delay of this common complication.

Diabetic limb salvage procedure with bone allograft and free flap transfer: a case report.

The aim of this case report was to describe a successful diabetic limb salvage procedure in the treatment of an infected diabetic foot ulcer through a multidisciplinary team approach and complex surgical reconstruction involving a femoral head bone allograft and musculocutaneous latissimus dorsi free flap. The decision to proceed with aggressive staged efforts at diabetic limb salvage should be made only after careful consultation with the patient, his or her family, and the rest of the multidisciplinary healthcare team.

Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear.

BACKGROUND: Studies suggest that the collagen degeneration and disordered arrangement of collagen fibers in rotator cuff tears are associated with an increase in activity of matrix metalloproteases 1 and 3 (MMP-1 and MMP-3), and that MMP activity may be in part genetically mediated. The degree to which this might be clinically relevant in patients with rotator cuff tears has not been well characterized. QUESTIONS/PURPOSES: (1) Is genetic polymorphism of MMP-1 and MMP-3 associated with rotator cuff tears? (2) Are there haplotypes of MMP-1 and MMP-3 correlated with rotator cuff tears? (3) Compared with control subjects, do patients with rotator cuff tears have a higher proportion of relatives with the same disease? METHODS: We evaluated 64 patients with full-thickness rotator cuff tears and 64 asymptomatic control subjects. Patients younger 65 years, with nontraumatic tears, were included. The tear or integrity of the rotator cuff tear was evaluated by MRI or ultrasonography in all individuals. The patients and control subjects were paired by age. MMP-1 and MMP-3 genotypes were determined using the PCR-restriction fragment length polymorphism assays. RESULTS: Genetic polymorphisms in MMP-1 and MMP-3 are associated with rotator cuff tear, in which individuals with rotator cuff tears have associated genotypes 1G/2G (patients, 32 of 64 [50%], control subjects, 16 of 64 [25%]; odds ratio [OR], 4.8; 95% CI, 2.1-11.0; p < 0.001) and 2G/2G were at great risk (patients, 15 of 64 [23%], control subjects, seven of 64 [11%]; OR, 5.2; 95% CI,1.8-14.9; p < 0.001), and patients with rotator cuff tears were associated with a higher proportion of 2G allele distribution (62 of 128 [48%] versus 30 of 128 [23%]; p < 0.001). Patients with the 5A/5A genotype are at greater risk of rotator cuff tear (patients, 15 of 64 [23%]; control subjects, four of 64 [6%]; OR, 5.5; 95% CI, 1.4-20.9; p = 0.021), and there was higher 5A allele distribution in patients with rotator cuff tears (patients, 68 of 128 [53%]; control subjects, 52 of 128 [41%]; p = 0.045). Individuals with the haplotype 2G/5A were more likely to have rotator cuff tears develop (patients, 42 of 64 [66%]; control subjects, 17 of 64 [27%]; OR, 5.3; 95% CI, 2.5-11.3; p < 0.001). Patients with rotator cuff tears reported, in higher number, the existence of relatives who previously had treatment for rotator cuff tears (19 of 64 [30%] versus four of 64 [6%]; OR, 6.3; 95% CI, 2.0-19.9; p = 0.001). CONCLUSIONS: The genetic polymorphism of MMP-1 and MMP-3 is associated with rotator cuff tear. Individuals with haplotype 2G/5A were more susceptible to rotator cuff tears in the population studied. CLINICAL RELEVANCE: Knowledge of the genetic markers related to rotator cuff tears can enable identification of susceptible individuals and increase understanding of the pathogenesis of tendon degeneration.