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Background and Aims: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium., Methods: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled. Patients were randomly assigned to undergo direct cardiac SWT or sham treatment in addition to coronary bypass surgery. The primary efficacy endpoint was the improvement in LVEF measured by cardiac magnetic resonance imaging from baseline to 360 days., Results: Overall, 63 patients were randomized, out of which 30 patients of the SWT group and 28 patients of the Sham group attained 1-year follow-up of the primary endpoint. Greater improvement in LVEF was observed in the SWT group (Δ from baseline to 360 days: SWT 11.3%, SD 8.8; Sham 6.3%, SD 7.4, P = .0146). Secondary endpoints included the 6-minute walking test, where patients randomized in the SWT group showed a greater Δ from baseline to 360 days (127.5 m, SD 110.6) than patients in the Sham group (43.6 m, SD 172.1) (P = .028) and Minnesota Living with Heart Failure Questionnaire score on day 360, which was 11.0 points (SD 19.1) for the SWT group and 17.3 points (SD 15.1) for the Sham group (P = .15). Two patients in the treatment group died for non-device-related reasons., Conclusions: In conclusion, the CAST-HF trial indicates that direct cardiac SWT, in addition to coronary bypass surgery improves LVEF and physical capacity in patients with ischaemic heart failure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This case report describes a novel and unique combination of both electromagnetic and electrohydraulic focused extracorporeal shockwave therapy (ESWT) and extracorporeal magnetotransduction therapy (EMTT) for accelerated healing in a calcaneus epiphyseal fracture with delayed healing in an adolescent Parkour athlete. After a 2.5m jump, the 14-year-old experienced significant heel pain, however avoided telling his parents. After eight weeks, the initial imaging using ultra low dose weight-bearing cone beam CT (WBCT) revealed a calcaneus non-union situation adjacent to the open calcaneal physis. To improve and accelerate bony healing substantially, we chose to apply both combined focused electromagnetic (Storz Ultra, Storz Medical AG, Tägerwillen, CH) and focused electrohydraulic (MTS, Konstanz, Germany) ESWT in a fractioned fashion plus EMTT (Storz Magnetolith, Tägerwillen, CH) in five consecutive weekly sessions while allowing the patient to fully weight bear. The follow-up WBCT after six weeks revealed a near to total healing of the delayed union and being pain-free. Notably, combination therapy with focused ESWT and EMTT did not result in early closure of the calcaneal epiphysis. We conclude that combined focused electromagnetic and electrohydraulic ESWT and EMTT facilitate bony healing in adolescent calcaneal apophyseal fractures without any adverse effects on the open physis. Evidence level IV (case report)., Competing Interests: KK is a lecturer for Storz Medical and reports non-financial support from MTS for providing test machine. AS has nothing to disclose. WS is a consultant for MTS and reports personal fees from SoftWave TRT, outside the submitted work., (© 2024 Knobloch et al.)

Introduction: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions., Materials and Methods: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT., Results: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002)., Conclusion: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A delay or failure to heal is the most common possible complication in clavicle fractures, especially in cases primarily treated conservatively. As the current standard therapy, surgical revision achieves good healing results, but is associated with potential surgery-related complications. Shockwave therapy as a non-invasive therapy shows similar reasonable consolidation rates in the non-union of different localizations, but avoids complications. Compromised clavicle fractures in the middle and lateral third treated with focused high-energy shockwave therapy were compared with those treated with surgical revision (ORIF). In addition, a three-dimensional computer simulation for evaluating the pressure distribution during shockwave application accompanied the clinical study. A comparable healing rate in bony consolidation was achieved in both groups. Significantly fewer complications, however, occurred in the shockwave group. The simulations showed safe application in this instance, particularly in avoiding lung tissue affection. When applied correctly, shockwaves represent a safe and promising therapy option for compromised clavicle fractures in the middle and lateral third.

Background: The pathological mechanism in acute spinal cord injury (SCI) is dual sequential: the primary mechanical lesion and the secondary injury due to a cascade of biochemical and pathological changes initiated by the primary lesion. Therapeutic approaches have focused on modulating the mechanisms of secondary injury. Despite extensive efforts in the treatment of SCI, there is yet no causal, curative treatment approach available. Extracorporeal shock wave therapy (ESWT) has been successfully implemented in clinical use. Biological responses to therapeutic shock waves include altered metabolic activity of various cell types due to direct and indirect mechanotransduction leading to improved migration, proliferation, chemotaxis, modulation of the inflammatory response, angiogenesis, and neovascularization, thus inducing rather a regeneration than repair. The aim of this clinical study is to investigate the effect of ESWT in humans within the first 48 h after an acute traumatic SCI, with the objective to intervene in the secondary injury phase in order to reduce the extent of neuronal loss., Methods: This two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled study has been initiated in July 2020, and a total of 82 patients with acute traumatic SCI will be recruited for the first stage in 15 participating hospitals as part of a two-armed three-stage adaptive trial design. The focused ESWT (energy flux density: 0.1-0.19 mJ/mm 2 , frequency: 2-5 Hz) is applied once at the level of the lesion, five segments above/below, and on the plantar surface of both feet within the first 48 h after trauma. The degree of improvement in motor and sensory function after 6 months post-injury is the primary endpoint of the study. Secondary endpoints include routine blood chemistry parameters, the degree of spasticity, the ability to walk, urological function, quality of life, and the independence in everyday life., Discussion: The application of ESWT activates the nervous tissue regeneration involving a multitude of various biochemical and cellular events and leads to a decreased neuronal loss. ESWT might contribute to an improvement in the treatment of acute traumatic SCI in future clinical use., Trial Registration: ClinicalTrials.gov NCT04474106., (© 2022. The Author(s).)

Background: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening., Method: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days., Results: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ 2  = 23.848, df = 2, p < 0.001) was observed (χ 2  = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3., Conclusions: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies., (© 2021. The Author(s).)

Extracorporeal shockwave therapy is a treatment modality, originally introduced into the clinic as lithotripsie, which has also been successfully used in the last two decades in the non-invasive treatment of delayed or non-healing fractures. Initially, the mechanism of action was attributed to microfracture-induced repair, but intensive basic research has now shown that the shockwave generates its effect in tissue via mechanotransduction. Numerous signal transduction pathways have already been demonstrated, which in their entirety trigger an endogenous regeneration process via cell proliferation, migration and differentiation. Clinically, these shockwave-conveyed biological signals support healing of acute, delayed and non-union fractures. The attainable outcome is comparable to surgery but avoiding an open approach with associated potential complications. These advantageous properties with a clearly positive cost-benefit ratio make shockwave therapy a first line treatment in delayed and non-union fractures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed., Objective: We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making., Methods: We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury., Results: The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking., Conclusions: Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

Extracorporeal shockwave therapy showed a pronounced effect on bone mass in previous animal studies. We showed in this pilot study that a single treatment with unfocused shockwave therapy in unselected patients does not show side effects. Although our study did not show any effect of shockwave on BMD, the limited sample size does not definitively exclude this and a study with 174 subjects per group would be needed to show an effect size of 0.3 with a power of 80%., Purpose: Unfocused extracorporeal shockwave therapy might stimulate bone formation to reduce the fracture risk. In this study, we assessed the safety of unfocused extracorporeal shockwave therapy and its effects on bone mass., Methods: A clinical pilot study with twelve female patients free of bone disease undergoing elective surgery of the lower extremity or elective spinal surgery under general anesthesia received 3.000 electrohydraulic-generated unfocused extracorporeal shockwaves (energy flux density 0.3 mJ/mm 2 ) to one distal forearm. The contralateral forearm served as a control. We examined the effect on bone mass with the use of repeated dual energy X-ray absorptiometry measurements and we measured patient discomfort around the therapy., Results: No difference in bone mineral content and density was measured 6 and 12 weeks after therapy. shockwave therapy occasionally caused transient erythema or mild hematoma, but no discomfort in daily life or (late) adverse events., Conclusions: Unfocused extracorporeal shockwave therapy is a safe treatment, but no increase in bone mass on the forearm was found at 0.3 mJ/mm 2 energy flux density. In this study, we were not able to demonstrate that a single treatment with unfocused shockwave therapy in unselected patients had any effect in terms of bone mineral density (BMD) or bone mineral content (BMC). A power analysis indicated that 174 patients per group are required to show an effect size of 0.3 with a power of 80%.

Background Mechanical stimulation of acute ischemic myocardium by shock wave therapy ( SWT ) is known to improve cardiac function by induction of angiogenesis. However, SWT in chronic heart failure is poorly understood. We aimed to study whether mechanical stimulation upon SWT improves heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis and to dissect underlying mechanisms. Methods and Results SWT was applied in a mouse model of chronic myocardial ischemia. To study effects of SWT on postnatal vasculogenesis, wild-type mice received bone marrow transplantation from green fluorescence protein donor mice. Underlying mechanisms were elucidated in vitro in endothelial cells and murine aortic rings. Echocardiography and pressure/volume measurements revealed improved left ventricular ejection fraction, myocardial contractility, and diastolic function and decreased myocardial fibrosis after treatment. Concomitantly, numbers of capillaries and arterioles were increased. SWT resulted in enhanced expression of the chemoattractant stromal cell-derived factor 1 in ischemic myocardium and serum. Treatment induced recruitment of bone marrow-derived endothelial cells to the site of injury. In vitro, SWT resulted in endothelial cell proliferation, enhanced survival, and capillary sprouting. The effects were vascular endothelial growth factor receptor 2 and heparan sulfate proteoglycan dependent. Conclusions SWT positively affects heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis. SWT upregulated pivotal angiogenic and vasculogenic factors in the myocardium in vivo and induced proliferative and anti-apoptotic effects on endothelial cells in vitro. Mechanistically, these effects depend on vascular endothelial growth factor signaling and heparan sulfate proteoglycans. SWT is a promising treatment option for regeneration of ischemic myocardium.

Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm 2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p < 0.001) and control (41 ± 4%, p = 0.012) groups. LVEF markedly improved in shock-wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd., (Copyright © 2014 John Wiley & Sons, Ltd.)

Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures. A retrospective multivariant analysis of a prospective open, single-centre, clinical trial of tibia non-union was conducted. 56 patients with 58 eligible fractures who met the FDA criteria were included. All patients received 3000-4000 impulses of electrohydraulic shockwaves at an energy flux density of 0.4mJ/mm(2) (-6dB). On average patients underwent 1.9 times (±1.3SD) surgical interventions prior to ESWT displaying the rather negatively selected cohort and its limited therapy responsiveness. In 88.5% of patients receiving ESWT complete bone healing was observed after six months irrespective of underlying pathology. The multivariant analysis showed that time of application is important for therapy success. Patients achieving healing received ESWT earlier: mean number of days between last surgical intervention and ESWT (healed - 355.1 days±167.4SD vs. not healed - 836.7 days±383.0SD; p<0.0001). ESWT proved to be a safe, effective and non-invasive treatment modality in tibial non-unions recalcitrant to standard therapies. The procedure is well tolerated, time-saving, lacking side effects, with potential to significantly decrease health care costs. Thus, in our view, ESWT should be considered the treatment of first choice in established tibial non-unions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: The effect of non-invasive extracorporeal shockwaves on pulpal blood flow in orthodontic patients who have undergone active treatment was investigated., Materials and Methods: Seventy-two adult patients were enrolled in the clinical trial and allocated by block randomization to a treatment or a placebo group at a 1:1 ratio. The patients were required to be otherwise healthy. Blinding was performed for the subjects and the outcome assessor. The region of interest was the mandibular incisors and canines, which were vital, unrestored, and had experienced no trauma. The active treatment group received a single shockwave treatment with 1000 impulses at 0.19-0.23 mJ/mm(2) while the placebo group was treated with a deactivated shockwave applicator but acoustic sham. Pulpal blood flow was evaluated four times over a period of 6 months starting from the day of bracket removal, using a laser Doppler device., Results: Thirty patients were evaluated in each group. Orthodontic patients who have undergone active treatment tend to have high levels of pulpal blood flow which decrease over a period of 6 months. Pulpal blood flow did not differ significantly over 6 months between the placebo and treatment group. Shockwave treatment was associated with no significant effect in respect of tooth type, age, sex, or mean blood pressure, and had no unintended pernicious effects., Conclusions: Extracorporeal shockwaves had no statistically significant effect on pulpal blood flow. Multiple applications of ESWT in a pathological setup may be needed in future studies to demonstrate significant differences., Clinical Relevance: The absence of any adverse effects justifies further principal investigations of the use of shockwave treatment in the oral cavity.

Fracture non-unions are still a challenging problem in orthopedics. The treatment of non-unions remains highly individualized, complex, and demanding. In most countries the surgical approach with debridement of the non-union gap, anatomical reduction and appropriate osteosynthesis along with autologous bone grafting is considered as the standard of care. One of the very first non-urologic applications of extracorporeal shockwave treatment (ESWT) concerned non-healing fractures. Since the early 1990ties the knowledge of the working mechanism has increased enormously. The purpose of this review article is to demonstrate by peer-reviewed literature in conjunction with our own experiences that ESWT can be an efficient, non-invasive, almost complication-free and cost effective alternative to surgical treatment of non-healing fractures., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Diabetic foot ulcers (DFUs) are among the most common foot disorders with ulceration, infection, and gangrene that may ultimately lead to lower extremity amputation. The goals of treatment include the control of diabetes and proper shoe wear. An effective therapy and appropriate foot care are important in wound healing in DFUs. Recently, extracorporeal shockwave therapy (ESWT) was reported to significantly promote and accelerate the healing of complex soft tissue wounds as compared to the standard methods of treatment in DFUs. ESWT showed positive results in short-term and long-term outcomes in diabetic patients suffering from foot ulcers. In this article, we review the clinical results of ESWT in DFUs., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Aim: This RCT investigated the effect of non-invasive extracorporeal shockwaves on tooth mobility in orthodontic patients after active treatment., Materials and Methods: Seventy-two adult patients were included in the study. Immediately after active orthodontic treatment, patients were assigned to a treatment or a placebo group based on block randomization. The orthodontic patients were required to be otherwise healthy. The region of interest was the anterior portion of the mandible. The treatment group received a single shockwave treatment with 1000 impulses while the placebo group was treated with an acoustic sham. Tooth mobility was evaluated over a period of 6 months using a Periotest and manual testing. Pocket probing depths, bleeding on probing and the irregularity index were also assessed., Results: Tooth mobility reduced significantly over 6 months in both groups, but shockwaves achieved significantly more rapid reduction on manual testing. Probing depth was significantly reduced while the irregularity index remained stable. Bleeding on probing was significantly reduced in the treatment group. No anti-inflammatory effect could be derived due to possible initial group differences., Conclusions: The mobility of teeth aligned by orthodontic treatment reduces over time. Shockwave treatment appeared to reduce tooth mobility more rapidly., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This randomized clinical trial investigated the effect of extracorporeal shock waves on the amount of orthodontic tooth movement and periodontal parameters., Material and Methods: Twenty-six adult orthodontic patients participated in this clinical trial; all of them receiving lower second molar mesially directed movement. The fixed orthodontic device included superelastic coil springs (200 cN) and miniscrews as temporary anchorage device. The active treatment group received a single shock wave treatment with 1,000 impulses in the region of tooth movement. The placebo group was treated with deactivated shock wave applicator with an acoustic sham. The study period lasted 4 months with a monthly data exploration., Results: No statistically significant difference in posterior-anterior tooth movement between the treatment and placebo group was seen during observation period. Gender had no significant influence on tooth movement in either group. No significant difference occurred in mesio-distal tipping and rotation, but a significant difference (p = 0.035) in bucco-lingual tipping of the molars was found. Periodontal status of the patients (sulcus probing depth, gingival index) did not significantly differ in both groups. The plaque index showed a significant difference (p = 0.003)., Conclusions: Single application of extracorporeal shock wave treatment was associated neither with a statistically significant acceleration of tooth movement nor with an altered periodontal status in vivo., Clinical Relevance: Shock waves showed no harmful effects in the investigated area. Their clinical use for lithotripsy during orthodontic therapy might be permitted.

Introduction: In this randomized, placebo-controlled clinical trial, we investigated the effect of noninvasive extracorporeal shock waves on the stability of temporary anchorage devices (TADs) under orthodontic loading., Methods: Thirty adult orthodontic patients of the Bernhard Gottlieb University Clinic in Vienna, Austria, were enrolled in this clinical trial and allocated by block randomization (size, 4) in a 1:1 ratio to either the treatment or the placebo group. Randomization was performed with software, and the allocations were concealed in sealed envelopes. Eligibility criteria included healthy adult patients with mesially directed orthodontic movement of the mandibular second molar into the extraction site of the mandibular first molar. The fixed orthodontic devices included active superelastic coil springs (200 cN) and TADs in the mandibular alveolar bone. Blinding was performed for the subjects and the outcome assessor. The treatment group received 1 shock-wave application with 1000 impulses at 0.19 to 0.23 mJ per square millimeter in the region of the TADs. The placebo group was treated with a deactivated shock-wave applicator and acoustic sham. The TADs positions were evaluated at placement and after 4 months. The reliability and precision of the impression process of the TADs were evaluated in an in-vitro model., Results: Thirteen participants finished the investigation successfully in the treatment group but only 12 finished in the placebo group because 1 TAD loosened. The difference of the total TAD displacement for the 4-month time period between the placebo and treatment groups was 0.17 ± 0.95 mm (95% CI: -0.96, 0.62). No statistically significant difference between the 2 groups was found when sex was evaluated. Primary stability of the TADs as measured by placement torque, amount of tooth movement, and age of the patients did not influence displacement of the TADs. The reliability and precision of TAD impressions were confirmed. No unintended pernicious effects occurred after shock-wave treatment during the study period., Conclusions: A single application of extracorporeal shock-wave treatment did not improve the stability of the TADs during orthodontic loading. Sufficient interradicular space should be provided to minimize the risk of periodontal and dental root defects., Registration: This trial was registered at https://clinicaltrials.gov., Protocol: The protocol was published before trial commencement, NCT01695928., Funding: No funding or conflict of interest to be declared., (Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objectives: Shock waves have been shown to induce recruitment of intravenously injected endothelial progenitor cells to ischemic hind limbs in rats. We hypothesized that shock wave treatment as sole therapy would induce angiogenesis in this ischemia model and would lead to mobilization of endogenous endothelial (progenitor) cells., Methods: A total of 18 rats, aged 5 weeks old, were subdivided into 3 groups: sham (n = 6), ischemic muscle with shock wave treatment (shock wave treatment group, n = 6), and without shock wave treatment (control, n = 6). Hind limb ischemia was induced by ligation of the femoral artery. Three weeks later, shock wave treatment (300 impulses at 0.1 mJ/mm(2)) was applied to the adductor muscle; the controls were left untreated. Muscle samples were analyzed using real-time polymerase chain reaction for angiogenic factors and chemoattractants for endothelial progenitor cell mobilization. Fluorescence activated cell sorting analysis of the peripheral blood was performed for CD31/CD34-positive cells. Perfusion was measured using laser Doppler imaging. Functional improvement was evaluated by walking analysis., Results: Angiogenic factors/endothelial progenitor cell chemoattractants, stromal cell-derived factor-1 and vascular endothelial growth factor, were increased in the treatment group, as shown by real-time polymerase chain reaction, indicating the mobilization of endothelial progenitor cells. Fluorescence activated cell sorting analysis of the peripheral blood revealed high numbers of CD31/CD34-positive cells in the treatment group. Greater numbers of capillaries were found in the treated muscles. Blood perfusion increased markedly in the treatment group and led to functional restoration, as shown by the results from the walking analysis., Conclusions: Shock wave therapy therefore could develop into a feasible alternative to stem cell therapy in regenerative medicine, in particular for ischemic heart and limb disease., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

It has long been thought that the effectiveness and efficiency of physical therapy would improve if our understanding of the cell biology/biochemistry that participates in mechanics could be improved. Traditional physical therapy focuses primarily on rehabilitation, but recent developments in mechanobiology that illuminated the effects of physical forces on cells and tissues have led to the realization that the old therapy model should be updated. To achieve this here, the term mechanotherapy is proposed and recent studies showing how mechanotherapies target particular cells, molecules, and tissues are reviewed. These studies show how mechanical force modulates integrin-mediated processes and other mechanosensors such as gap junctions, hemichannels, primary cilia, transient receptor potential channels (cell targeting), and intracellular mechanosignaling pathways (molecule targeting). The role of mechanical force in various therapies, including microdeformation, shockwave, tissue expansion, distraction osteogenesis, and surgical tension reduction (tissue targeting) therapies, is reviewed. This review aims to jumpstart research into this field, which promises to generate a new era of viable and novel pharmacological and engineering interventions that can overcome human diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unfocused extracorporeal shock waves (UESW) have been shown to have an anabolic effect on bone mass. Therefore we investigated the effects of UESW on bone in osteoporotic rats with and without anti-resorptive treatment. Twenty-week-old rats were ovariectomized (n = 27). One group was treated with saline and another group with Alendronate (ALN) 2.4 µg/kg, 3×/week. UESW were applied 2 weeks after ovariectomy. Thousand UESW were applied to one hind leg, the contra-lateral hind leg was not treated and served as control. With the use of in vivo micro-CT scanning it was shown that in saline treated rats trabecular bone volume fraction (BV/TV) was higher at 2 weeks follow-up in UESW treated legs compared to control legs. However, at 4 and 10 weeks no difference was found. In ALN treated animals UESW led to a pronounced anabolic response resulting in an increase in BV/TV at all time-points. Furthermore, UESW resulted in increased cortical volume (CtV), higher trabecular connectivity and, more plate-like and thicker trabeculae. Biomechanical testing showed that UESW lead to a higher maximum force before failure and higher stiffness in all treatment groups. With histology abundant areas of intramembranous bone formation along the periosteal cortex and within the bone marrow were observed. In conclusion this study shows promising results for the use of UESW in the treatment of osteoporosis, especially when this treatment is combined with an anti-resorptive treatment., (Copyright © 2012 Orthopaedic Research Society.)

For almost 30 years, extracorporeal shock wave therapy has been clinically implemented as an effective treatment to disintegrate urinary stones. This technology has also emerged as an effective noninvasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life. Intensive wound care is required, and this places an enormous burden on society in terms of lost productivity and healthcare costs. Therefore, cost-effective, noninvasive, and efficacious treatments are imperative to achieve both (accelerated and complete) healing of problematic wounds and reduce treatment-related costs. Several experimental and clinical studies show efficacy for extracorporeal shock wave therapy as means to accelerate tissue repair and regeneration in various wounds. However, the biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains unclear. Potential mechanisms, which are discussed herein, include initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves. This review aims to provide an overview of shock wave therapy, its history and development as well as its current place in clinical practice. Recent research advances are discussed emphasizing the role of extracorporeal shock wave therapy in soft tissue wound healing., (© 2012 by the Wound Healing Society.)

Background: As extracorporeal shock wave therapy (ESWT) can enhance healing of skin graft donor sites, this study focused on shock wave effects in burn wounds., Methods: A predefined cohort of 50 patients (6 with incomplete data or lost to follow-up) with acute second-degree burns from a larger study of 100 patients were randomly assigned between December 2006 and December 2007 to receive standard therapy (burn wound debridement/topical antiseptic therapy) with (n = 22) or without (n = 22) defocused ESWT (100 impulses/cm at 0.1 mJ/mm) applied once to the study burn, after debridement. Randomization sequence was computer-generated, and patients were blinded to treatment allocation. The primary endpoint, time to complete burn wound epithelialization, was determined by independent, blinded-observer. A worst case scenario was applied to the missing cases to rule out the impact of withdrawal bias., Results: Patient characteristics across the 2 study groups were balanced (P > 0.05) except for older age (53 ± 17 vs. 38 ± 13 years, P = 0.002) in the ESWT group. Mean time to complete (≥95%) epithelialization (CE) for patients that did and did not undergo ESWT was 9.6 ± 1.7 and 12.5 ± 2.2 days, respectively (P < 0.0005). When age (continuous variable) and treatment group (binary) were examined in a linear regression model to control the baseline age imbalance, time to CE, age was not significant (P = 0.33) and treatment group retained significance (P < 0.0005). Statistical significance (P = 0.001) was retained when ESWT cases with missing follow-up were assigned the longest time to CE and when controls with missing follow-up were assigned the shortest time to CE., Conclusions: In this randomized phase II study, application of a single defocused shock wave treatment to the superficial second-degree burn wound after debridement/topical antiseptic therapy significantly accelerated epithelialization. This finding warrants confirmation in a larger phase III trial (ClinicalTrials.gov identifier: NCT01242423).

Objective. Soft tissue wound healing is a complex and well-orchestrated sequence of events on multiple biological levels involving systemic, cellular, and molecular signals. The physiological process of wound healing leads to full tissue repair and regeneration with nearly complete restoration of tissue integrity and functionality. Wounds, particularly among the elderly population, can show delayed or disturbed healing; however, delayed or disturbed healing is also evident in patients with comorbidities such as diabetes, atherosclerosis, venous/arterial insufficiency, reduced mobility due to chronic infirmity, and hypercholesterolemia. Chronic wounds are conditions, which include a wide range of inflammatory and degenerative conditions of the musculoskeletal system. Management of chronic, difficult to heal, or non-healing soft tissue wounds requires a multidisciplinary approach. Often these treatment options have inconsistent and irregular outcomes. Poor response or failure to conservative treatments places a substantial burden on patients, their families, the healthcare system, and society in general. Therefore, the development of a new, effective method of treatment to improve healing of problematic wounds and reduce treatment-related costs is extremely valuable. One such therapy is Extracorporeal Shockwave Therapy (ESWT). ESWT acts through mechanotransduction, which produces therapeutic benefits through complex biological pathways including neovascularization and tissue regeneration in the therapeutic target. Published data thus far suggest that the application of ESWT for soft tissue indications is safe, reliable, cost-effective, and clinically efficacious. The exact biological effects of ESWT on human cells are not completely understood, but are currently undergoing further study. The aim of this review is to provide a general overview of shockwave therapy and its role in the treatment of acute and chronic soft tissue wounds. .

Possible effects of comorbidities and of different wound etiologies on the success of extracorporeal shock wave therapy (ESWT) of chronic soft tissue wounds were investigated. From September 2003 until February 2007, 282 patients, being previously treated unsuccessfully were enrolled. Treatment consisted of ESWT occurring at defined intervals. At each treatment session a wound bed score was recorded, also at initial presentation a detailed patient history and wound etiology. Observed comorbidities were pooled according to the chapters of the ICD-10 system. Two hunderd fifty-eight patients were analyzed (91.49%) and underwent follow-up for a median of 31.8 months. Wound closure occurred in 191 patients (74.03%) by a median of two treatment sessions. No wound reappeared at the same location. A multivariate logistic regression model showed that pooled comorbidities and wound etiologies did not have a significant influence on success. Comorbidities and wound etiologies have surprisingly no significant influence on the success of ESWT., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the time-dependent treatment effects of extracorporeal shock wave therapy (ESWT) in a standard rodent ischemic epigastric flap model., Background: ESWT has been shown to accelerate tissue repair in acute and chronic wounds and improve graft survival, but the mechanism remains incompletely understood., Methods: Shock waves at 0.1 mJ/mm and 5 impulses/s (total 300 impulses) were applied to the epigastric flap ischemic region at various times pre-, immediately and 24 hours postischemic insult. Flap survival; vascular perfusion; vessel number; von Willebrand factor and smooth muscle actin protein expression as well as in vivo vascular endothelial growth factor receptor 2 expression were evaluated at 1, 3, and 7 days postoperatively in ESWT-treated and untreated controls., Results: Flap perfusion, microvessel number, and survival (through reduced flap contraction and necrosis) were significantly enhanced in the treated groups compared with controls, irrespective of timing of shock wave treatment (preischemia vs. postischemia). Vascular endothelial growth factor receptor 2 expression was dynamically upregulated in response to ESWT., Conclusion: Shock wave preconditioning and treatment postischemic insult improves skin flap survival through neovascularization and early upregulation of angiogenesis-related growth factors.

Background: predictive models permitting individualized prognostication for patients with fracture nonunion are lacking. The objective of this study was to train, test, and cross-validate a Bayesian classifier for predicting fracture-nonunion healing in a population treated with extracorporeal shock wave therapy., Methods: prospectively collected data from 349 patients with delayed fracture union or a nonunion were utilized to develop a naïve Bayesian belief network model to estimate site-specific fracture-nonunion healing in patients treated with extracorporeal shock wave therapy. Receiver operating characteristic curve analysis and tenfold cross-validation of the model were used to determine the clinical utility of the approach., Results: predictors of fracture-healing at six months following shock wave treatment were the time between the fracture and the first shock wave treatment, the time between the fracture and the surgery, intramedullary stabilization, the number of bone-grafting procedures, the number of extracorporeal shock wave therapy treatments, work-related injury, and the bone involved (p < 0.05 for all comparisons). These variables were all included in the naïve Bayesian belief network model., Conclusions: a clinically relevant Bayesian classifier was developed to predict the outcome after extracorporeal shock wave therapy for fracture nonunions. The time to treatment and the anatomic site of the fracture nonunion significantly impacted healing outcomes. Although this study population was restricted to patients treated with shock wave therapy, Bayesian-derived predictive models may be developed for application to other fracture populations at risk for nonunion., Level of Evidence: prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Background: Extracorporeal shock wave therapy may enhance revascularization and repair of healing soft tissue., Methods: Between January 2006, and September 2007, 28 patients with acute traumatic wounds and burns requiring skin grafting were randomly assigned in a 1:1 fashion to receive standard topical therapy (nonadherent silicone mesh [Mepitel, Mölnlycke Health Care] and antiseptic gel [polyhexanide/octenidine]) to graft donor sites with (n = 13) or without (n = 15) defocused extracorporeal shock wave therapy (ESWT, 100 impulses/cm(2) at 0.1 mJ/mm(2)) applied once to the donor site, immediately after skin harvest. The randomization sequence was computer generated, and the patients were blinded to treatment allocation. The primary endpoint was time to complete donor site epithelialization and was determined by an independent blinded observer., Results: Statistical tests indicated no unbalanced distribution of subject characteristics across the two study groups. Mean times to complete graft donor site epithelialization for patients who did and did not undergo ESWT were 13.9 +/- 2.0 days and 16.7 +/- 2.0 days, respectively (p = 0.0001)., Conclusions: For centers that apply nonadherent gauze dressings and topical antiseptics to skin graft donor sites, application of a single defocused shock wave treatment immediately after skin graft harvest can significantly accelerate donor site epithelialization., (Copyright 2010 American College of Surgeons. All rights reserved.)

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Background: The current "gold standard" for treatment of chronic fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal is intramedullary screw fixation. Complications with this procedure, however, are not uncommon. Shock wave therapy can be an effective treatment for fracture nonunions. The purpose of this study was to evaluate the safety and efficacy of shock wave therapy as a treatment of these nonunions., Methods: Twenty-three patients with a fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal received high-energy shock wave therapy (2000 to 4000 shocks; energy flux density per pulse, 0.35 mJ/mm(2)), and twenty other patients with the same type of fracture nonunion were treated with intramedullary screw fixation. The numbers of fractures that were healed at three and six months after treatment in each group were determined, and treatment complications were recorded., Results: Twenty of the twenty-three nonunions in the shock wave group and eighteen of the twenty nonunions in the screw fixation group were healed at three months after treatment. One of the three nonunions that had not healed by three months in the shock wave group was healed by six months. There was one complication in the shock wave group (post-treatment petechiae) and eleven complications in the screw-fixation group (one refracture, one case of cellulitis, and nine cases of symptomatic hardware)., Conclusions: Both intramedullary screw fixation and shock wave therapy are effective treatments for fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal. Screw fixation is more often associated with complications that frequently result in additional surgery.

Objectives: Delayed and nonunion of the tibia are not uncommon in orthopaedic practice. Multiple methods of treatment have been developed with variable results. The objective of this study was to define disease-specific and treatment-related factors of prognostic significance in patients undergoing shock wave therapy for tibia nonunion., Design: Retrospective analysis., Patients: One hundred ninety-two patients treated with extracorporeal shock wave therapy (ESWT) at a single referral trauma center, AUVA-Trauma Center Meidling, a large single-referral trauma center located in Vienna, Austria, in an attempt to determine the feasibility and factors associated with the use of ESWT in the treatment for tibia nonunion., Intervention: ESWT coupled with posttreatment immobilization, external fixation, or ESWT alone., Main Outcome Measures: Fracture healing, overall healing percent, and factors associated with ESWT success or failure., Results: At the time of last follow up, 138 of 172 (80.2%) patients have demonstrated complete fracture healing. Mean time from first shock wave therapy to complete healing of the tibia nonunion was 4.8+/-4.0 months. Number of orthopaedic operations (P=0.003), shock wave treatments (P=0.002), and pulses delivered (P=0.04) were significantly associated with complete bone healing. Patients requiring multiple (more than one) shock wave treatments versus a single treatment had a significantly lower likelihood of fracture healing (P=0.003). This may be attributable to the finding that a significantly greater proportion of patients with multiple rather than single ESWT treatments had three or more prior orthopaedic procedures (more than one ESWT, 63.9% versus one ESWT, 23.5%; P<0.001)., Conclusions: ESWT is a feasible treatment modality for tibia nonunion.

Extracorporeal shock wave therapy (ESWT) influences the differentiation of bone marrow stroma cells towards osteoprogenitors and increases the expression of several growth factors. To assess whether unfocused ESWT might serve as a treatment for osteoporosis, we examined the bone architecture dynamics of ESWT-treated and untreated rat tibiae using in vivo micro-computed tomography (CT) scanning. In addition, the effects of ESWT on fracture healing, using a bilateral fibula osteotomy, were examined. Unilateral unfocused ESWT with 2,000 pulses and an energy flux density of 0.16 mJ/mm(2) was applied to the hind leg of ovariectomized and sham-ovariectomized rats. A single treatment with unfocused ESWT resulted in a higher trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-ovariectomized animals. Three weeks after ESWT, BV/TV was 110% of baseline BV/TV in treated legs versus 101% in untreated contralateral control legs (p = 0.001) and 105% of baseline BV/TV versus 95% at 7 weeks after ESWT (p = 0.0004). In ovariectomized rats, shock wave treatment resulted in a diminished bone loss. At 7 weeks, the BV/TV of the treated legs was 50% of baseline BV/TV, whereas in untreated control legs this was 35% (p = 0.0004). ESWT did not influence acute fracture healing. This study shows that bone microarchitecture can be affected by unfocused shock waves, and indicates that unfocused ESWT might be useful for the treatment of osteopenia and osteoporosis., ((c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objectives: Direct application of low-energy unfocused shock waves induces angiogenesis in ischemic soft tissue. The potential effects of epicardial shock wave therapy applied in direct contact to ischemic myocardium are uncertain., Methods: For induction of ischemic heart failure in a rodent model, a left anterior descending artery ligation was performed in adult Sprague-Dawley rats. After 4 weeks, reoperation with (treatment group, n = 60) or without (control group, n = 60) epicardial shock wave therapy was performed. Low-energy shock waves were applied in direct contact with the infarcted myocardium (300 impulses at 0.38 mJ/m(2)). Additionally, healthy animals (n = 30) with normal myocardium were studied. Angiogenesis, ventricular function upregulation of growth factors, and brain natriuretic peptide levels were analyzed., Results: Histologic analysis revealed significant angiogenesis 6 weeks (treatment group: 8.2 +/- 3.7 vs control group: 2.9 +/- 1.9 vessels per field, P = .016) and 14 weeks (treatment group: 7.1 +/- 3.1 vs control group: 3.2 +/- 1.8 vessels per field, P = .011) after shock wave treatment. In the treatment group ventricular function improved throughout the follow-up period (6 weeks: 37.4% +/- 9% [P < .001] and 14 weeks: 39.5% +/- 9% [P < .001]). No improvement of ventricular function was observed in the control group (6 weeks: 28.6% +/- 5% and 14 weeks: 21.4% +/- 5%). Rat brain natriuretic peptide 45 levels were lower in the treatment group compared with those in the control group 6 and 14 weeks after treatment. Vascular endothelial growth factor, Fms-related tyrosine kinase 1, and placental growth factor levels were upregulated after 24 and 48 hours and 7 days in the treatment group. No effects on healthy myocardium were observed., Conclusion: Direct epicardial low-energy shock wave therapy induces angiogenesis and improves ventricular function in a rodent model of ischemic heart failure.

Background: Wound healing disorders after vein harvesting for coronary artery bypass graft surgery increase morbidity and lower patient satisfaction. Low-energy shock wave therapy (SWT) reportedly improves healing of diabetic and vascular ulcers by overexpression of vascular endothelial growth fractor and downregulation of necrosis factor kappaB. In this study, we investigate whether prophylactic low-energy SWT improves wound healing after vein harvesting for coronary artery bypass graft surgery., Methods: One hundred consecutive patients undergoing coronary artery bypass graft surgery were randomly assigned to either prophylactic low-energy SWT (n = 50) or control (n = 50). Low-energy SWT was applied to the site of vein harvesting after wound closure under sterile conditions using a commercially available SWT system (Dermagold; Tissue Regeneration Technologies, Woodstock, GA). A total of 25 impulses (0.1 mJ/mm(2); 5 Hz) were applied per centimeter wound length. Wound healing was evaluated and quantified using the ASEPSIS score. (ASEPSIS stands for Additional treatment, presence of Serous discharge, Erythema, Purulent exudate, Separation of the deep tissue, Isolation of bacteria, and duration of inpatient Stay). Patient demographics, operative data, and postoperative adverse events were monitored., Results: Patient characteristics and operative data including wound length (SWT 39 +/- 13 cm versus control 37 +/- 11 cm, p = 0.342) were comparable between the two groups. We observed lower ASEPSIS scores indicating improved wound healing in the SWT group (4.4 +/- 5.3) compared with the control group (11.6 +/- 8.3, p = 0.0001). Interestingly, we observed a higher incidence of wound healing disorders necessitating antibiotic treatment in the control group (22%) as compared with the SWT group (4%, p = 0.015). No SWT-associated adverse events were observed in the treatment group., Conclusions: As shown in this prospective randomized study, prophylactic application of low-energy SWT improves wound healing after vein harvesting for coronary artery bypass graft surgery.

Background: Nonhealing wounds are a major, functionally-limiting medical problem impairing quality of life for millions of people each year. Various studies report complete wound epithelialization of 48 to 56% over 30 to 65 d with different treatment modalities including ultrasound, topical rPDGF-BB, and composite acellular matrix. This is in contrast to comparison control patients treated with standard wound care, demonstrating complete epithelialization rates of 25 to 39%. Extracorporeal shock wave therapy (ESWT) may accelerate and improve wound repair. This study assesses the feasibility and safety of ESWT for acute and chronic soft-tissue wounds., Study Design: Two hundred and eight patients with complicated, nonhealing, acute and chronic soft-tissue wounds were prospectively enrolled onto this trial between August 2004 and June 2006. Treatment consisted of debridement, outpatient ESWT [100 to 1000 shocks/cm(2) at 0.1 mJ/mm(2), according to wound size, every 1 to 2 wk over mean three treatments], and moist dressings., Results: Thirty-two (15.4%) patients dropped out of the study following first ESWT and were analyzed on an intent-to-treat basis as incomplete healing. Of 208 patients enrolled, 156 (75%) had 100% wound epithelialization. During mean follow-up period of 44 d, there was no treatment-related toxicity, infection, or deterioration of any ESWT-treated wound. Intent-to-treat multivariate analysis identified age (P = 0.01), wound size < or =10 cm(2) (P = 0.01; OR = 0.36; 95% CI, 0.16 to 0.80), and duration < or =1 mo (P < 0.001; OR = 0.25; 95% CI, 0.11 to 0.55) as independent predictors of complete healing., Conclusions: The ESWT strategy is feasible and well tolerated by patients with acute and chronic soft tissue wounds. Shock wave therapy is being evaluated in a Phase III trial for acute traumatic wounds.

Extracorporeal shock wave therapy has been used increasingly in musculoskeletal disorders although its biologic mechanisms are not understood completely. The current study evaluated the effects of extracorporeal shock wave therapy on human osteoblastlike cells by using an electrohydraulic shock wave generator and comparing three energy levels. (Group A, 14 kV and 0.15 mJ/mm2; Group B, 21 kV and 0.31 mJ/mm2; Group C, 28 kV and 0.40 mJ/mm2; Control Group, no energy) and two total impulses (500, 1000) for each level. At the end of treatment, a reduction by approximately 76% was observed in Group C cell number versus basal value when compared with the other groups. Viability, biochemical activity, and gene expression of cultured cells were evaluated 24 and 48 hours after treatment. The viability test showed a decrease in Group C viability of approximately 54% at both culture times as compared with the other groups. Significant increases in nitric oxide, osteocalcin, and transforming growth factor-beta1 production ranging from 10% to 35% were found in Group A. All treated groups had lower C-terminal procollagen Type I values than the Control Group, but important increases were observed between 24 and 48 hours in all groups except Group C. This particular finding reveals that osteoblast differentiation in Group A is enhanced strongly during the first 24 hours after exposure leading after another 24 hours to an increase in C-terminal procollagen Type I production and consequently in bone matrix deposition. The current study showed that one of the most important aspects to be considered is not the total number of impulses used, but the energy level of the shock waves, therefore confirming that extracorporeal shock wave therapy has a dose-dependent initial destructive effect on cells when the selected energy is higher than 21 kV.