Comparative Outcomes Between Step-Cut Lengthening Calcaneal Osteotomy vs Traditional Evans Osteotomy for Stage IIB Adult-Acquired Flatfoot Deformity.

BACKGROUND: The forefoot abduction component of the flexible adult-acquired flatfoot can be addressed with lengthening of the anterior process of the calcaneus. We hypothesized that the step-cut lengthening calcaneal osteotomy (SLCO) would decrease the incidence of nonunion, lead to improvement in clinical outcome scores, and have a faster time to healing compared with the traditional Evans osteotomy. METHODS: We retrospectively reviewed 111 patients (143 total feet: 65 Evans, 78 SLCO) undergoing stage IIB reconstruction followed clinically for at least 2 years. Preoperative and postoperative radiographs were analyzed for the amount of deformity correction. Computed tomography (CT) was used to analyze osteotomy healing. The Foot and Ankle Outcome Scores (FAOS) and lateral pain surveys were used to assess clinical outcomes. Mann-Whitney U tests were used to assess nonnormally distributed data while χ2 and Fisher exact tests were used to analyze categorical variables (α = 0.05 significant). RESULTS: The Evans group used a larger graft size ( P < .001) and returned more often for hardware removal ( P = .038) than the SLCO group. SLCO union occurred at a mean of 8.77 weeks ( P < .001), which was significantly lower compared with the Evans group ( P = .02). The SLCO group also had fewer nonunions ( P = .016). FAOS scores improved equivalently between the 2 groups. Lateral column pain, ability to exercise, and ambulation distance were similar between groups. CONCLUSION: Following SLCO, patients had faster healing times and fewer nonunions, similar outcomes scores, and equivalent correction of deformity. SLCO is a viable technique for lateral column lengthening. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model.

BACKGROUND: While successful subtalar joint arthrodesis provides pain relief, resultant alterations in ankle biomechanics need to be considered, as this procedure may predispose the remaining hindfoot and tibiotalar joint to accelerated degenerative changes. However, the biomechanical consequences of isolated subtalar joint arthrodesis and additive fusions of the Chopart's joints on tibiotalar joint biomechanics remain poorly understood. QUESTIONS/PURPOSES: We asked: What is the effect of isolated subtalar fusion and sequential Chopart's joint fusions of the talonavicular and calcaneocuboid joints on tibiotalar joint (1) mechanics and (2) kinematics during loading for neutral, inverted, and everted orientations of the foot? METHODS: We evaluated the total force, contact area, and the magnitude and distribution of the contact stress on the articular surface of the talar dome, while simultaneously tracking the position of the talus relative to the tibia during loading in seven fresh-frozen cadaver feet. Each foot was loaded in the unfused, intact control condition followed by three randomized simulated hindfoot arthrodesis modalities: subtalar, double (subtalar and talonavicular), and triple (subtalar, talonavicular, and calcaneocuboid) arthrodesis. The intact and arthrodesis conditions were tested in three alignments using a metallic wedge insert: neutral (flat), 10° inverted, and 10° everted. RESULTS: Tibiotalar mechanics (total force and contact area) and kinematics (external rotation) differed owing to hindfoot arthrodeses. After subtalar arthrodesis, there were decreases in total force (445 ± 142 N, 95% CI, 340-550 N, versus 588 ± 118 N, 95% CI, 500-676 N; p < 0.001) and contact area (282 mm(2), 95% CI, 222-342 mm(2), versus 336 ± 96 mm(2), 95% CI, 265-407 mm(2); p < 0.026) detected during loading in the neutral position; these changes also were seen in the everted foot position. Hindfoot arthrodesis also was associated with increased external rotation of the tibiotalar joint during loading: subtalar arthrodesis in the neutral loading position (3.3° ± 1.6°; 95% CI, 2°-4.6°; p = 0.004) and everted loading position (4.8° ± 2.6°; 95% CI, 2.7°-6.8°; p = 0.043); double arthrodesis in neutral (4.4° ± 2°; 95% CI, 2.8°-6°; p = 0.003) and inverted positions (5.8° ± 2.6°; 95% CI, 3.7°-7.9°; p = 0.002), and triple arthrodesis in all loaded orientations including neutral (4.5° ± 1.8°; 95% CI, 3.1°-5.9°; p = 0.002), inverted (6.4° ± 3.5°; 95% CI, 3.6°-9.2°; p = 0.009), and everted (3.6° ± 2°; 95% CI, 2°-5.2°; p = 0.053) positions. Finally, after subtalar arthrodesis, additive fusions at Chopart's joints did not appear to result in additional observed differences in tibiotalar contact mechanics or kinematics with the number of specimens available. CONCLUSIONS: Using a cadaveric biomechanical model, we identified some predictable trends in ankle biomechanics during loading after hindfoot fusion. In our tested specimens, fusion of the subtalar joint appeared to exert a dominant influence over ankle loading. CLINICAL RELEVANCE: A loss or deficit in function of the subtalar joint may be sufficient to alter ankle loading. These findings warrant consideration in the treatment of the arthritic hindfoot and also toward defining biomechanical goals for ankle arthroplasty in the setting of concomitant hindfoot degeneration or arthrodesis.

Contributions of the University of Cape Town to medical science in the first 100 years: personal reflections.

The contributions of the University of Cape Town's Health Sciences Faculty to medical science through research over the past 100 years are reviewed. The application of contemporary techniques to common medical problems in the developing world had important implications globally. The faculty can be proud of its achievements in many areas important to the health of people in South Africa, Africa and beyond.

Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction.

BACKGROUND: Left ventricular (LV) remodeling following myocardial infarction (MI) is associated with increased levels of specific matrix metalloproteinases (MMPs) and relative reduction of endogenous tissue inhibitors of the MMPs (TIMPs). However, transcriptional mechanisms for the disparate post-MI MMP/TIMP expression remain unknown. Using murine constructs designed to report gene promoter activation, this study tested the hypothesis that distinctly different temporal profiles of MMP-2, MMP-9, and TIMP-1 transcription occurs post-MI. METHODS/RESULTS: Transcriptional activity (ß-galactosidase (ß-gal) reporter constructs) of MMP-2 (n = 49), MMP-9 (n = 62), or TIMP-1 (n = 40) was assayed at 1 h (acute), and 1-28 d after MI (coronary ligation) in transgenic reporter mice. At 7 d post-MI, the area of promoter activation normalized to LV area was increased from acute values for MMP-2 (63.4 ± 5.8 versus 1.1% ± 1.0%, P < 0.05) and MMP-9 (53.1 ± 6.1 versus 1.3% ± 0.9%, P < 0.05). While TIMP-1 promoter activation at 7 d post-MI increased from acute values (3.6 ± 1.3 versus 0.3% ± 0.5%, P < 0.05), this increase was smaller than that for MMP-2 or MMP-9 (both P < 0.05). MMP-2 promoter activation peaked in the MI region at 7 d post-MI and MMP-9 promoter activation was highest in the border region at 7 and 14 d post-MI. TIMP-1 promoter activation peaked within the MI region at 7 d post-MI and within the remote region at 14 d post-MI. CONCLUSIONS: These findings provided direct in vivo evidence that discordant changes in temporal and spatial patterns of MMP/TIMP transcription occurs with MI. Restoration of TIMP-1 promoter activation may represent a molecular therapeutic target to attenuate/prevent adverse post-MI LV remodeling.

Compartment syndrome after low-energy tibia fractures sustained during athletic competition.

OBJECTIVE: The purpose of this study was to determine whether patients who sustain tibia fractures during athletic competition are at an increased risk of developing acute compartment syndrome (ACS). DESIGN: Retrospective review. SETTING: University Level I trauma center. PARTICIPANTS/PATIENTS: Acute tibia fractures in 626 patients between July 2006 and June 2009. METHODS: A retrospective review of 626 consecutive tibia fractures treated by our department between July 2006 and June 2009 was performed. We recorded the mechanism and type of fracture as well as whether or not ACS developed. Soccer and football injuries were analyzed as specific groups. Chi square was used to analyze our results. MAIN OUTCOME MEASUREMENTS: The rate of ACS in patients injured during sporting events versus that of all patients with a tibia fracture. RESULTS: Thirty-four patients (5.4%) developed ACS, which is consistent with the published literature. Nine patients sustained the injury while playing soccer (1.4% of patients), whereas 11 patients (1.7%) were injured playing football. Five of the nine soccer players (55%; P < 0.001) and three of the football players (27%; P < 0.001) developed ACS. Collectively, tibia fractures sustained in football and soccer led to 25% of ACS cases despite accounting for only 3.1% of all tibia fractures. CONCLUSIONS: Tibia fractures sustained during soccer and football had a statistically significant association with development of ACS in our patient population during this time period. Such patients should be monitored closely and followed with high clinical suspicion for ACS.

Calcaneal reconstruction with free fibular osteocutaneous flap.

Due to the role of the calcaneus in weight bearing, soft tissue coverage along with proper reduction of the fracture is the treatment following open calcaneal injury. Intra-articular calcaneal fractures present a very difficult management problem, as the lack of soft tissue and the intricate vascularity in this area pose a risk of complications. Coverage with local and free muscle flaps following excision of infected structures is a common approach for the treatment of chronic osteomyelitis. However, it is unknown which type of flap is optimal for the treatment of lateral foot wounds, especially when complicated by calcaneal osteomyelitis. A patient presented with an open wound over the lateral aspect of the heel with exposed hardware and chronic osteomyelitis of the calcaneus. Following multiple debridements, an ipsilateral osteocutaneous free fibular flap was transferred to the bony defect. Weight bearing was initiated at 2 months postoperatively, and he now ambulates with a normal gait, has normal plantar sensation, and has no difficulty maneuvering stairs. The patient has done well postoperatively and has recovered full range of motion and complete mobility. In this case report, an osteocutaneous free flap provided an excellent outcome for an active patient with a very complex and complicated condition.

Cardiac-restricted overexpression of membrane type-1 matrix metalloproteinase in mice: effects on myocardial remodeling with aging.

BACKGROUND: The direct consequences of a persistently increased myocardial expression of the unique matrix metalloproteinase (MMP) membrane type-1 (MT1-MMP) on myocardial remodeling remained unexplored. METHODS AND RESULTS: Cardiac-restricted MT1-MMPexp was constructed in mice using the full-length human MT1-MMP gene ligated to the myosin heavy chain promoter, which yielded approximately a 200% increase in MT1-MMP when compared with age/strain-matched wild-type (WT) mice. Left ventricular (LV) function and geometry was assessed by echocardiography in 3-month ("young") WT (n=32) and MT1-MMPexp (n=20) mice and compared with 14-month ("middle-aged") WT (n=58) and MT1-MMPexp (n=35) mice. LV end-diastolic volume was similar between the WT and MT1-MMPexp young groups, as was LV ejection fraction. In the middle-aged WT mice, LV end-diastolic volume and ejection fraction was similar to young WT mice. However, in the MT1-MMPexp middle-aged mice, LV end-diastolic volume was approximately 43% higher and LV ejection fraction 40% lower (both P<0.05). Moreover, in the middle-aged MT1-MMPexp mice, myocardial fibrillar collagen increased by nearly 2-fold and was associated with approximately 3-fold increase in the processing of the profibrotic molecule, latency-associated transforming growth factor binding protein. In a second study, 14-day survival after myocardial infarction was significantly lower in middle-aged MT1-MMPexp mice. CONCLUSIONS: Persistently increased myocardial MT1-MMP expression, in and of itself, caused LV remodeling, myocardial fibrosis, dysfunction, and reduced survival after myocardial injury. These findings suggest that MT1-MMP plays a mechanistic role in adverse remodeling within the myocardium.

Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs.

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) commonly causes infarct expansion (IE). This study sought to interrupt IE through microinjections of a biocompatible composite material into the post-MI myocardium. METHODS: MI was created in 21 pigs (coronary ligation). Radiopaque markers (2-mm diameter) were placed for IE (fluoroscopy). Pigs were randomized for microinjections (25 injections; 2- x 2-cm array; 200 microL/injection) at 7 days post-MI of a fibrin-alginate composite (Fib-Alg; fibrinogen, fibronectin, factor XIII, gelatin-grafted alginate, thrombin; n = 11) or saline (n = 10). RESULTS: At 7 days after injection (14 days post-MI), LV posterior wall thickness was higher in the Fib-Alg group than in the saline group (1.07 +/- 0.11 vs 0.69 +/- 0.07 cm, respectively, p = 0.002). At 28 days post-MI, the area within the markers (IE) increased from baseline (1 cm2) in the saline (1.71 +/- 0.13 cm2, p = 0.010) and Fib-Alg groups (1.44 +/- 0.23 cm2, p < 0.001). However, the change in IE at 21 and 28 days post-MI was reduced in the Fib-Alg group (p=0.043 and p=0.019). Total collagen content within the MI region was similar in the saline and Fib-Alg groups (12.8 +/- 1.7 and 11.6 +/- 1.5 microg/mg, respectively, p = NS). However, extractable collagen, indicative of solubility, was lower in the Fib-Alg group than the saline group (59.1 +/- 3.5 vs 71.0 +/- 6.1 microg/mL, p = 0.020). CONCLUSIONS: Targeted myocardial microinjection of the biocomposite attenuated the post-MI decrease in LV wall thickness and infarct expansion. Thus, intraoperative microinjections of biocompatible material may provide a novel approach for interrupting post-MI LV remodeling.

Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion.

The matrix metalloproteinases (MMPs), in particular, membrane type 1 MMP (MT1-MMP), are increased in the context of myocardial ischemia and reperfusion (I/R) and likely contribute to myocardial dysfunction. One potential upstream induction mechanism for MT1-MMP is endothelin (ET) release and subsequent protein kinase C (PKC) activation. Modulation of ET and PKC signaling with respect to MT1-MMP activity with I/R has yet to be explored. Accordingly, this study examined in vivo MT1-MMP activation during I/R following modification of ET signaling and PKC activation. With the use of a novel fluorogenic microdialysis system, myocardial interstitial MT1-MMP activity was measured in pigs (30 kg; n = 9) during I/R (90 min I/120 min R). Local ET(A) receptor antagonism (BQ-123, 1 microM) and PKC inhibition (chelerythrine, 1 microM) were performed in parallel microdialysis probes. MT1-MMP activity was increased during I/R by 122 +/- 10% (P < 0.05) and was unchanged from baseline with ET antagonism and/or PKC inhibition. Selective PKC isoform induction occurred such that PKC-betaII increased by 198 +/- 31% (P < 0.05). MT1-MMP phosphothreonine, a putative PKC phosphorylation site, was increased by 121 +/- 8% (P < 0.05) in the I/R region. These studies demonstrate for the first time that increased interstitial MT1-MMP activity during I/R is a result of the ET/PKC pathway and may be due to enhanced phosphorylation of MT1-MMP. These findings identify multiple potential targets for modulating a local proteolytic pathway operative during I/R.

Protein kinase C isoform activation and endothelin-1 mediated defects in myocyte contractility after cardioplegic arrest and reperfusion.

BACKGROUND: Endothelin-1 (ET-1) is released after hyperkalemic cardioplegic arrest (CA) and reperfusion and may contribute to contractile dysfunction. ET-1 receptor transduction causes activation of protein kinase C (PKC) isoforms, which can cause differential intracellular events. The goal of this study was to determine which PKC isoforms contribute to myocyte contractile dysfunction with ET-1 and CA. METHODS AND RESULTS: Percent shortening (PERSHORT) and the time to 50% relaxation (T50) were measured in porcine (n =22) left ventricular myocytes, randomized (minimum: 30 cells/group) to normothermia: (cell media for 2 hours/37 degrees C), and CA: (2 hours/4 degrees C, 24 mEq K+ solution followed by reperfusion in cell media), ET-1/CA: (100 pM ET-1 during CA). Studies were performed in the presence and absence of PKC inhibitors (500 nM) against the classical (Beta-I, Beta-II, Gamma) and novel (Epsilon, Eta) isoforms (myocytes from a minimum of 3 pigs per inhibitor). CA reduced PERSHORT by approximately 35% from normothermia (P<0.05), which was further reduced with ET-1. PKC-Beta-II or PKC-Gamma inhibition increased PERSHORT from ET-1/CA as well as CA only (P<0.05). CA prolonged T50 by approximately 19% from normothermia (P<0.05) and was further prolonged with ET-1. Inhibition of the classical PKC isoforms reduced T50 from ET-1/CA (P<0.05). Inhibition of novel PKC isoforms did not yield similar effects on either PERSHORT or T50 with ET-1/CA. CONCLUSIONS: Inhibition of the classical PKC isoforms relieved the negative inotropic and lusitropic effects of ET-1 after CA. These findings provide mechanistic support for developing targeted inhibitory strategies with respect to ET-1 signaling and myocyte contractile dysfunction with cardioplegic arrest and reperfusion.