Low-intensity pulsed ultrasound shortens the treatment time in tibial distraction osteogenesis.

PURPOSE: Low-intensity pulsed ultrasound (LIPUS) has been used successfully to accelerate healing of fresh fractures and non-unions. It also improved callus maturation with distraction osteogenesis in animal trials. However, only few clinical studies are available to support its widespread use for the latter indication in humans. METHODS: Twenty-one patients undergoing callus distraction for posttraumatic tibial defects were randomized into two groups: the trial group (12 men; mean age 32 years) which received 20 minutes LIPUS daily during treatment and the control group (six men and three women; mean age 29 years) without LIPUS treatment. The Ilizarov ring fixator was used in all cases. Results were examined clinically and radiologically, analysing callus maturation with a computer-assisted measurement. RESULTS: Patients in the LIPUS group needed a mean of 33 days to consolidate every 1 cm of new bone in comparison to 45 days in the control group. The healing index was therefore shortened by 12 days/cm in the LIPUS group. This means that callus maturation was 27 % faster in the LIPUS group. The fixator time was shortened by 95 days in the LIPUS group. The overall daily increase in radiographic callus density was 33 % more in the LIPUS group than in the control group. CONCLUSIONS: LIPUS treatment is an effective non-invasive adjuvant method to enhance callus maturation in distraction osteogenesis. With the help of this treatment, the healing time and the duration of external fixation can be reliably shortened.

The predictive potential of the sweat chloride test in cystic fibrosis patients with the G551D mutation.

BACKGROUND: Ivacaftor, a cystic fibrosis transmembrane regulator (CFTR) potentiator, decreased sweat chloride concentrations and improved clinical measures in cystic fibrosis (CF) patients with the G551D mutation. RESULTS: Sweat chloride measurements at day 15 had an overall positive predictive value (PPV) of 86.3%, a negative predictive value (NPV) of 65.5%, sensitivity of 73.9%, and specificity of 80.9% for an FEV1 improvement of ≥5% from baseline at week 16. For ivacaftor patients the median FEV1 improvement was 16.7%; for placebo patients 0.4%. For patients aged 6-11 years who received ivacaftor and who had a sweat chloride decrease of ≥40 mmol/L from baseline at day 15, a median weight gain of 11.2% at week 16, compared to 6% for those with a smaller decrease was observed. CONCLUSIONS: Changes in sweat chloride concentration at day 15 following treatment with ivacaftor may have sufficient predictive potential to identify individuals that show improvement in pulmonary function and weight gain after 16 weeks of treatment.

Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial.

BACKGROUND: We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound (LIPUS) (n = 51) and subjects treated with a sham device (n = 50). Fracture age was ≥ 4 months in all cases. Study personnel and participants were blinded to random treatment assignment throughout the study. METHODS: This multi-center randomized sham-controlled trial was undertaken at six hospitals in Germany. Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing (i.e., delayed union) were enrolled and randomized to receive either LIPUS (Exogen 2000/2000+, Smith & Nephew GmbH, Schenefeld, Germany) or an identical nonoperative sham device. The daily treatment duration was 20 minutes, for a period of 16 weeks. Subjects randomly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters: 1.5 MHz frequency, 1 kHz repetition rate, 200 µs pulse duration, 30 mW/cm2 spatial intensity. Progress toward healing was estimated from changes in bone mineral density (BMD) and gap area as determined from computed tomography scans. Intention-to-treat analysis was conducted using a multiple imputation methodology. RESULTS: Based on log-transformed data, mean improvement in BMD was 1.34 (90% confidence interval (CI) 1.14 to 1.57) times greater for LIPUS-treated subjects compared to sham (p = 0.002). A mean reduction in bone gap area also favored LIPUS treatment (p = 0.014). CONCLUSIONS: These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia.

Treatment of Tossy III acromioclavicular joint injuries using hook plates and ligament suture.

OBJECTIVES: The management of acromioclavicular (AC) injuries has long been debated. We analyzed our results in treating such cases using hook plates and ligament suture. DESIGN: : Retrospective nonrandomized study. SETTING: Level I Trauma Center (University Hospital). PATIENTS: Twenty-five patients (mean age 41 years) with complete Tossy III AC joint disruptions. Using the Rockwood classification, 15 dislocations were classified as type V injuries, 9 as type III injuries, and 1 as a type IV injury. INTERVENTION: All patients were operatively treated using AC hook plates with ligament suturing after a median delay of 7 days. MAIN OUTCOME MEASURES: Clinical and radiographic evaluation using Constant-Murley functional score and Taft et al criteria. RESULTS: : A retrospective clinical and radiographic evaluation of 23 patients was performed after an average follow-up period of 30 months. The mean Constant score was 97 (range, 90-100) points, and the mean Taft score was 10.6 points. All but 1 patient were satisfied with their treatment outcome. Eight cases showed some loss of reduction after plate removal. A poor correlation existed, however, between clinical and radiographic results. CONCLUSIONS: The hook plate is a reliable fixation tool for complete AC joint dislocations, ensuring immediate stability and allowing early mobilization with good functional and cosmetic results. Routine plate removal should however be reevaluated.

Intramuscular pressure, tissue oxygenation, and muscle fatigue of the multifidus during isometric extension in elite rowers with low back pain.

CONTEXT: Chronic low back pain (LBP) has been reported with a high incidence in elite rowers. It results in less effective training, long interruptions in training, and a drop in performance. OBJECTIVE: The authors hypothesized that exercise-induced LBP in rowers is caused by a chronic functional compartment syndrome (CFCS) of the multifidus muscle. DESIGN: Controlled clinical trial. SETTING: The rowers were tested in their training camp. The control group was tested at a university hospital. PARTICIPANTS: 14 volunteer elite rowers complaining of LBP and 16 healthy volunteer amateur athletes. MAIN OUTCOME MEASUREMENTS: Intramuscular pressure (IMP), tissue oxygenation pressure (pO2), and median frequency (MF) shift in the electromyographic power density spectrum during isometric fatiguing extension at 60% of maximum voluntary contraction. RESULTS: At the beginning (controls 186.6 mm Hg vs rowers 60.2 mm Hg, P = .002) and the end (controls 224.1 mm HG vs rowers 77.1 mm Hg, P < .001) of the endurance exercise the median IMP was significantly higher in the healthy controls. Nearly identical resting pO2 was measured in both groups (controls 37.6 mm Hg vs rowers 37.3 mm Hg, P = .740). Rowers showed higher median MF shift (rowers -11.5 Hz vs controls -8.5 Hz, P = .079) during contraction. CONCLUSIONS: These observations cannot sufficiently be explained by the CFCS model and suggest that factors other than IMP have an additional effect on pain generation during exercise in elite rowers.

Low intensity pulsed ultrasound accelerates macrophage phagocytosis by a pathway that requires actin polymerization, Rho, and Src/MAPKs activity.

Phagocytosis is an essential event in the complex process of tissue repair. Here we examined the effect of low intensity pulsed ultrasound (US), which promotes fracture and wound healing, on phagocytosis by mouse macrophage cell line J774A.1 and human monocyte-derived macrophages. First, 10 to 40 min low intensity pulsed US increased uptake of serum opsonized E. coli by J774A.1 cells during a 50 min phagocytosis period. In addition, when the E. coli exposure time was varied between 35 to 80 min, the maximum increase in phagocytosis was observed in the first 35 min upon US exposure. In parallel, US induced robust actin polymerization in a time dependent manner in J774A.1 cells, showing the peak effect 30 min after stimulation. Interestingly, a low concentration of cytochalasin D (0.25-0.5 microM) prevented US-induced phagocytosis of E. coli. Furthermore, we demonstrated US enhanced activation of RhoA. Blocking its downstream effector Rho associated kinase (ROCK) with Y27632 abrogated US-induced phagocytosis. We also show that US induced activation of ERK and p38 MAPK. Pretreatment of the cells with the corresponding inhibitors PD98059 and SB203580 reduced US-induced phagocytosis. In addition, activity of tyrosine kinase Src was required for US-induced phagocytosis. Here Src represents an upstream activator of ERK and p38 MAPK. Depolymerization of actin by cytochalasin D prevented US-induced Src, ERK, and p38 activation. Our data provide a new insight into the cellular and molecular mechanisms by which low intensity pulsed US promotes tissue repair.

[Molecular mechanisms of low intensity pulsed ultrasound-mediated cellular behavior in human primary macrophages].

The aim of this study was to explore the molecular mechanisms of the effect of low intensity pulsed ultrasound (LIPUS) on human primary macrophage functions. Macrophage phagocytosis was analyzed using fluorescein isothiocyanate (FITC)-labelled Escherichia coli (E.Coli); focal complex and extracellular matrix metalloproteinase inducer (EMMPRIN) were observed by fluorescence microscopy; the secretion of metalloproteinases (MMPs) was examined by gelatin zymography, and the expressions of EMMPRIN and extracellular signal-regulated kinases (ERKs) were detected by Western blot. The results indicated that LIPUS accelerated macrophages to phagocytose E.Coli (29.81+/-0.36 vs 18.00+/-0.78), promoted the protein expressions of EMMPRIN and MMPs, increased the level of protein tyrosine phosphorylation, and induced the phosphorylation of ERKs. Furthermore, the above functions were only found in adherent macrophages, and were inhibited or decreased by mitogen activated protein kinase kinase (MAPK kinase, MEK) inhibitor PD98059 and RGD (Arg-Gly-Asp peptide), one of main integrin recognition sequences. It is concluded that the effect of LIPUS on macrophages depends on cell adhesion, and relates to integrin-MEK-ERK pathway.

Ankle arthrodesis using Ilizarov ring fixators: a review of 22 cases.

BACKGROUND: Orthopaedic surgeons are being increasingly confronted with complex ankle problems that cannot be reliably treated by conventional arthrodesis procedures. The Ilizarov technique can be an alternative salvage method in such cases. METHODS: Twenty-two Ilizarov tibiotalar arthrodeses were retrospectively reviewed. There were 16 men and six women (mean age 49 years). The underlying pathology was infection after internal fixation of ankle or plafond fractures in 16 patients, posttraumatic ankle arthritis in five, and septic arthritis after an infected Achilles tendon repair in one. Five patients had at least one failed previous arthrodesis. Primary iliac crest bone grafting was done in two patients. Proximal tibial lengthening was done in six patients. RESULTS: Twenty-one patients were followed for an average of 29 months. A solid fusion was achieved in all patients by the end of treatment. The external fixation time averaged 27.7 (range 12 to 84) weeks. The mean time spent in a foot frame was 22.3 weeks. Complications occurred in 11 patients, including two nonunions that healed after revision and renewed frame application and four pin track infections. CONCLUSIONS: The use of the Ilizarov frame provides a successful salvage method that offers solid bony fusion, optimal leg length, and eradication of infection in complex ankle pathology or failed previous arthrodesis.

Injuries of the cervical spine in patients with ankylosing spondylitis: experience at two trauma centers.

OBJECT: The cervical spine in a patient with ankylosing spondylitis (AS) (Bechterew disease) is exposed to maximal risk due to physical load. Even minor trauma can cause fractures because of the spine's poor elasticity (so-called bamboo spine). The authors conducted a study to determine the characteristics of cervical fractures in patients with AS to describe the standard procedures in the treatment of this condition at two trauma centers and to discuss complications of and outcomes after treatment. METHODS: Between 1990 and 2006, 37 patients were surgically treated at two institutions. All patients were examined preoperatively and when being discharged from the hospital for rehabilitation. Single-session (11 cases) and two-session anterior-posterior (13 cases), anterior (11 cases), posterior (two cases), and laminectomy (one case) procedures were performed. The injury pattern, segments involved, the pre- and postoperative neurological status, and complications were analyzed. Preoperative neurological deficits were present in 36 patients. All patients experienced improvement postoperatively, and there was no case of surgery-related neurological deterioration. In patients in whom treatment was delayed because of late diagnosis, preoperative neurological deficits were more severe and improvement worse than those treated earlier. The causes of three deaths were respiratory distress syndrome due to a rigid thorax and cerebral ischemia due to rupture of the vertebral arteries. There were 12 perioperative complications (32%), three infections, one deep venous thrombosis, five early implant failures, and the three aforementioned fatalities. There were no cases of epidural hematoma. In all five cases in which early implant failure required revision surgery, the initial stabilization procedure had been anterior only. A comparison of complications and the outcomes at the two centers revealed no significant differences. CONCLUSIONS: The standard intervention for these injuries is open reduction, anterior decompression and fusion, and anterior-posterior stabilization; these procedures may be conducted in one or two stages. Based on the early implant failures that occurred exclusively after single-session anterior stabilizations (five of 10--a failure rate of 50%), the authors have performed only posterior and anterior procedures since 1997 at both centers. Diagnostic investigations include computed tomography scanning or magnetic resonance imaging of the whole spine, because additional injuries are common. The causative trauma may be very slight, and diagnosis may be delayed because plain radiographs can be initially misinterpreted. In cases in which diagnosis is delayed, patients present with more severe neurological deficits, and postoperative improvement is less pronounced than that in patients in whom a prompt diagnosis is established. Because of postoperative pulmonary and ischemic complications, the mortality rate is high. In the present series the mortality rate was lower than the mean rate reported in the literature.

Hybrid external fixation for arthrodesis in knee sepsis.

Several techniques for knee fusion have been described with success rates ranging from 29% to 100%, with worse results occurring in patients with joint sepsis. We treated 21 patients with persistent infections using knee arthrodesis with a hybrid Ilizarov frame at our institution. There were 13 men and eight women ranging from 21 to 75 years (mean, 49.7 years). Sixteen patients had chronic osteomyelitis and five had previous fusion trials. Two patients required bone transport using the same arthrodesis frame. We corrected associated malalignment in three patients. Solid knee fusion was achieved in all but one patient after a mean external fixation time of 22.7 weeks (range, 11-47 weeks). Limb shortening averaged 2.8 cm (range, 1.5-5 cm). No patients required secondary bone grafting to achieve fusion. Nine patients had complications develop, three of whom required reresection and frame application to treat persistent infection or delayed union. Our results emphasize the clinical success of using the Ilizarov fixator for knee arthrodesis after persistent sepsis.

Circular external fixation in knee arthrodesis following septic trauma sequelae: preliminary report.

Deep infection is one of the most devastating complications after knee fractures. It may be related to the initial fracture status or, more commonly, the surgical intervention. From 1991 to 2003, 12 patients underwent knee fusion to treat resistant infection after complex knee fractures or arthrodesis fractures using the Ilizarov method and frame. There were 9 men and 3 women (mean age, 39.7 years). Two-thirds of the patients had long-standing infection and 5 patients had undergone earlier attempts at knee arthrodesis. Correction of concurrent malalignment was achieved in 2 patients. Bone transport using the same arthrodesis frame was necessary in 2 patients to overcome large bony defects. Solid fusion was achieved in all patients by the end of treatment. The average duration of external fixation was 22 weeks (range: 11-44 weeks). No patients required secondary bone grafting to achieve union. Complications occurred in 6 (50%) patients. The most common problem seen was pin tract infection, but only 2 patients required surgical intervention for its treatment. The study emphasizes the clinical success of the Ilizarov method in knee arthrodesis after infected fractures.

Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing.

OBJECTIVE: To achieve analgesic, anti-inflammatory and antipyretic effects in traumatology and orthopedic surgery without side effects or with the least possible side effects, with special emphasis on bone healing. INDICATIONS: Acute and chronic inflammatory conditions, e. g., rheumatoid arthritis, ankylosing spondylitis. Degenerative joint disease. Posttraumatic and postoperative pain, edema, or fever. Prevention of heterotopic bone formation. CONTRAINDICATIONS: Hypersensitivity. Gastrointestinal ulceration or bleeding. Severe hepatic or renal impairment. RESULTS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are invaluable in treating a variety of musculoskeletal conditions. As well as their excellent analgesic potency their anti-inflammatory effects are beneficial in treating posttraumatic and postoperative edema. In addition, NSAIDs inhibit heterotopic bone formation after hip arthroplasty. Animal studies, however, have demonstrated that they cause delayed fracture healing. Although clinical studies have not yet supplied unequivocal evidence of this effect in human subjects, the authors recommend that in the presence of other risk factors which may adversely affect fracture healing, such as smoking, diabetes mellitus or peripheral arterial occlusive disease, the indication of NSAID use for analgesia should be strictly limited. Therapeutic alternatives such as centrally acting agents (e. g., weak opioids) should be considered in these patients.

Molecular mechanisms of low intensity pulsed ultrasound in human skin fibroblasts.

Soluble factors such as polypeptide growth factors, mitogenic lipids, inflammatory cytokines, and hormones are known regulators of cell proliferation. However, the effect of mechanical stimuli on cell proliferation is less well understood. Here we examined the effect of low intensity pulsed ultrasound (US), which is used to promote wound healing, on the proliferation of primary human foreskin fibroblasts and the underlying signaling mechanisms. We show that a single 6-11-min US stimulation increases bromodeoxyuridine incorporation. In addition, an increase in the total cell number is observed after sequential US stimulation. US induced stress fiber and focal adhesion formation via activation of Rho. We further observed that US selectively induced activation of extracellular signal-regulated kinase (ERK) 1/2. Inhibition of Rho-associated coiled-coil-containing protein kinase (ROCK) prevented US-induced ERK1/2 activation, demonstrating that the Rho/ROCK pathway is an upstream regulator of ERK activation in response to US. Consequently, activation of ROCK and MEK-1 was required for US-induced DNA synthesis. Finally, an integrin beta(1) blocking antibody as well as a RGD peptide prevented US-induced DNA synthesis. In addition, US slightly increased phosphorylation of Src at Tyr(416), and Src activity was found to be required for ERK1/2 activation in response to US. In conclusion, our data demonstrate for the first time that US promotes cell proliferation via activation of integrin receptors and a Rho/ROCK/Src/ERK signaling pathway.