Name: a treatment protocol for achilles tendinopathy with extracorporeal shockwave therapy
Uploaded: 2024-08-02T12:40:00.000+00:00
Duration: 3 min 50 s
Description: Achilles tendinopathy is a common musculoskeletal condition characterized by pain, lower muscle strength, gait abnormality, and reduced quality of life. ...

This protocol was approved by our institution&#39;s human research ethics committee and received informed consent from the subjects. Individuals older than 18 years old, both sexes, with a definite diagnosis of Achilles tendinopathy, were enrolled. Participants who received ankle surgery recently or were diagnosed with any conditions that were contraindications to the treatment were excluded.
1. Patient evaluation
<ol>
	<li>Clinical examination
	<ol>
		<li>Before implementing the protocol, clinically evaluate the patients to rule out other regions that may cause symptoms. Obtain a thorough medical history, including the history of treatments, and rule out any contraindications (e.g., pregnancy, placement over major blood vessels and nerves, presence of pacemakers or other implanted devices, open wounds, joint replacements, epiphysis, blood clotting disorders, active infection, presence of cancerous tissues, impaired mental status of the patient, and/or unwillingness to cooperate).</li>
	</ol>
	</li>
	<li>Physiotherapy examination
	<ol>
		<li>Perform a physical examination to assess the condition being treated through inspection and palpation and evaluate the range of motion (both active and passive) of the ankle.</li>
		<li>Obtain the baseline information of the patient, such as pain and range of motion, using the Victorian Institute of Sports Assessment-Achilles (VISA-A) and/or American Orthopedic Foot and Ankle Society (AOFAS) Hindfoot score as outcome measures5,9,12.</li>
	</ol>
	</li>
</ol>
2. Application technique
NOTE: Before starting the procedure, check whether all the equipment listed in the Table of Materials is available.
<ol>
	<li>Place the patient in a comfortable prone position, with the target area exposed. If the patient is found to have significant tenderness in the calf muscles during the physical examination, expose the lower leg.</li>
	<li>Locate the area that requires treatment after the physical examination and mark these points using a felt tip pen.</li>
	<li>Choose a transmitter based on the desired depth of penetration for the treatment point (Figure 1). Use the conductor R 15 for tendinopathy and D20 (in this study, with energy 0.48 mJ/mm2) for tendinopathy and the trigger point of the deep muscle. Inform the patient that regular sounds made by the transmitters may be heard during treatment.</li>
	<li>Dry the skin thoroughly and apply an adequate amount of gel to the target area as a coupling agent. 
	NOTE: Apply the gel adequately to the treated area and ensure that the shock wave conductors are in contact with the skin surface throughout the treatment.</li>
	<li>As the operator, work in an ergonomic position (Figure 2) to optimize comfort and efficiency. To obtain the best treatment results, ensure good contact between shock wave transducers and the patient&#39;s skin during treatment. 
	NOTE: Do not press the treatment output handle tightly to the affected part; this will not help the treatment.</li>
	<li>Device setup
	<ol>
		<li>Press the Power On/OFF button or touch the liquid crystal display (LCD).</li>
		<li>Inspect parameter options on the display and press the buttons directly on the LCD to make a selection. Adjust the parameters using the up and down buttons.</li>
		<li>Press the Pause or Stop buttons located on the Operator Interface to stop the output. 
		NOTE: Information on the intensity and number of pulses given during the treatments can be obtained from the LCD.</li>
	</ol>
	</li>
	<li>Editing the treatment screen and parameter modification
	<ol>
		<li>Press the edit button and wait for the Edit treatment screen to display. Increase and decrease the parameters on the Edit treatment screen by pressing the up and down buttons as needed during the treatment process based on the patient&#39;s tolerance and response.</li>
		<li>Select the intensity to be used (1.6&#160;Bar in this study). Start at a lower intensity of the therapy, then gradually increase the intensity as high as the patient can tolerate. The recommended intensity range is between 1.4 Bar and 3.0 Bar23.</li>
		<li>Set the frequency of the treatment (10 Hz here). Choose a frequency between 8 Hz and 15 Hz for the treatment24.</li>
		<li>Establish the desired number of shocks to be applied (2,000 in this study); the number of shocks per treatment is 800-3,00023,24.</li>
	</ol>
	</li>
	<li>Begin the treatment by pressing the Start button on the User Interface and activate the handpiece by pressing the trigger button on the handpiece. The unit begins emitting radial pressure wave energy. During the treatment, maintain the contact between the conductor and the skin tissue, and move the handle by drawing a small circle.</li>
	<li>Stopping and pausing therapy
	<ol>
		<li>Stop the therapy by pressing the Stop button on the User Interface.</li>
		<li>Press the Pause button on the User Interface or the trigger button on the handpiece to pause the therapy at any time.</li>
	</ol>
	</li>
	<li>Plan three sessions spaced 1 week apart25.</li>
</ol>
3. Posttreatment protocol
<ol>
	<li>Remove any residual coupling gel from the treated area.</li>
	<li>After treatment, ask the patients to apply ice for no more than 10 min if they feel discomfort. In some cases, patients may suffer intense pain because of an acute resorption process caused by the shock waves.</li>
	<li>To consolidate the therapeutic effect, if necessary, combine ESWT with other physical therapy treatments, such as modalities and exercise. Recommend that the patient do muscle exercise after treatment, especially eccentric exercise23,24.</li>
	<li>Ask the patients to report and look for side effects such as reddening, swelling, pain, hematoma, petechiae, red spots, and skin lesions after previous ESWT; these effects usually appear within a few days after shock wave therapy. Ensure that the symptoms disappear completely before starting treatment.</li>
	<li>If there are no changes in outcome measures, advise the patients to seek a new treatment module or move on to invasive procedures.</li>
</ol>

Using Extracorporeal Shockwave Therapy (ESWT) for Treating Achilles Tendinopathy

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All authors declare no conflicts of interest.

This protocol outlines a standardized treatment protocol for Achilles tendinopathy utilizing radial-ESWT to reduce pain and improve lower extremity function and mobility. It is crucial to closely monitor the patient&#39;s response during treatment to avoid any potential adverse effects. In our study, we observed positive results when we used low-energy ESWT plus eccentric exercise. Table 2 lists the intervention methods and major conclusions of studies on the effectiveness of ESWT for Achilles tendinopathy24,26,27,28,29,30.
Our study showed significant improvements in pain and functional activity after ESWT treatment and did the same results of many studies21,22,23,24,25. In the study conducted by Vahdatpour et al.28, they also showed improvement in outcome measurement of scores of the functional questionnaire such as the American Orthopedic Foot and Ankle Society (AOFAS) questionnaire, except for pain relief, after receiving 4 sessions of ESWT therapy for 4 weeks. The average number of sessions in our study was 2.58, patients received at least 1 session and up to 8 sessions. There was a significant correlation between the number of sessions for shock waves and the degree of pain improvement (p &#60; 0.05).
The effect caused by ESWT in triggering tendon regeneration in people with tendinopathy by stimulating an anti-inflammatory response was confirmed by previous studies that measured interleukins and metalloprotease concentration after ESWT treatment21,22. The effectiveness of ESWT is strongly based on the energy level, number of shocks, and frequency, and these factors need to be carefully taken into account23. Pavone26 and Saxena27 have recommended that it was more beneficial to use a low-energy radial shockwave because of the significant decrease in Roles and Maudsley scores (Figure 3). Therefore, in our protocol, we used the low-energy level (0.48 mJ/mm2). Moreover, except for ESWT treatment, we incorporated eccentric exercise, which has been confirmed to be beneficial by many researchers24,26,30,31,32. As in an RCT conducted by Rompe et al.24, 68 patients were categorized into two groups: one group received a 12 week eccentric exercise program, and the other one received the same exercise protocol combined with three sessions of radial-ESWT treatment (2,000 shocks, 3 bars, 8 Hz, 3 sessions). In the exercise-only group, 56% (19 out of 34 patients) reported complete recovery or substantial improvement, while in the combined approach group, this figure was 82% (28 out of 34 patients) (Figure 4).
In our protocol, after ESWT therapy, we added eccentric training at the end, since ESWT combined with eccentric exercises is beneficial for insertional Achilles tendinopathy27,28. A trial conducted by Rompe et al.24 showed that eccentric loading exercise associated with repetitive ESWT was more effective in pain alleviation and physical function improvement compared to eccentric loading alone for patients with midportion Achilles tendinopathy. In another study26, 40 patients who failed to recover after receiving 3 months of eccentric exercise protocols, were administered four sessions of Focused-ESWT treatment, at 2 week intervals, combined with eccentric exercise training. After the 12 month follow-up, no pain was reported in 65% of patients, and 28% were able to return to their usual activities despite experiencing some residual pain. The combined treatment approach involving ESWT and eccentric exercise was found to be effective for patients who did not observe substantial improvements after solely engaging in eccentric exercises.
The therapeutic effect of ESWT is influenced by many factors, such as the energy level30,33; in our study, we used low-dose shockwaves. Since low-energy ESWT is generally well-tolerated, anesthesia is not recommended due to the mild discomfort during impulse application. A study by Taylor et al.30 reported the risks associated with high doses of ESWT and recommended avoiding its use in patients with refractory Achilles tendon lesions since high-energy ESWT has an adverse effect on tendon recovery and can cause tissue damage. Furthermore, a study conducted by Chao et al.34 showed that lower energy levels with a low number of shocks had a positive stimulating effect, while high energy levels and high shock numbers had notably inhibitory effects.
In this study, patients received at least 1 session and up to 8 sessions; there was a significant correlation between the number of sessions and the degree of pain improvement. However, we lack data on the long-term effect of ESWT treatment, which is a limitation of our study. A study conducted by Vahdatpour et al.28 observed that in the 1 month follow-up, the ESWT group failed to show a significant improvement in outcome measures such as Visual analog scale (VAS) scores or American Orthopedic Foot and Ankle (AOFAS) scores. However, at the 4 month follow-up, there was a notable improvement in outcome measures in the group that received ESWT treatment. This suggests that it takes several weeks for the full effects of ESWT to become apparent. Similarly, Rasmussen et al.35 found there was a significant improvement in the AOFAS score at the 3 month follow-up, except for the VAS score. However, throughout the 3 month duration, the ESWT group consistently exhibited lower VAS scores, compared to the control group. A longer follow-up period might have yielded more accurate results.
There are some limitations of this technique. The first one is that some patients may be initially uncomfortable with the idea of ESWT. Therefore, ramping the intensity serves to acclimate the patient to the pressure of the output. Another limitation is the risk associated with high doses. Many researchers have proved that high-energy ESWT has adverse effects on tendon recovery and can cause tissue damage30,33,34.
In conclusion, ESWT is a promising treatment option for patients with Achilles tendinopathy, but its energy level and application way should be carefully considered to avoid negative effects. Combining ESWT with other therapies, especially with eccentric exercises, may further enhance its effectiveness in improving patient outcomes and pain relief. Carrying out a critical physical assessment before treatment and closely monitoring the patient&#39;s response throughout the treatment process is essential to guarantee safety as well as efficacy.

The Achilles tendon is one of the most robust tendons in the body, yet it is highly susceptible to injuries. Tendons play a crucial role in enabling joint motion and stability by transmitting tensile loads produced by muscles onto bones1. Tendinopathy&#160;is a concept describing chronic tendon degeneration and deconditioning, also called tendinitis2. However, the exact cause of Achilles Tendinopathy2 remains unclear. It is believed to result from a combination of factors, including overuse stresses, impaired blood flow, and lack of flexibility2. One of the major contributors to the development of Achilles tendon injuries is the excessive load force applied during intense activities such as running, without allowing sufficient time for proper tendon repair1. This continuous stress on the tendon can lead to the gradual accumulation of microtraumas and ultimately result in injury progression3. This highlights the importance of proper management, rest, and adequate rehabilitation periods in preventing such injuries and maintaining the health of the Achilles tendon. The diagnosis of Achilles tendinopathy relies mainly on a comprehensive patient history and clinical examination4. A typical symptom is the occurrence of morning stiffness or limited range of motion after prolonged inactivity, accompanied by gradually increasing pain during physical activity2. Athletes often go through pain at the beginning and end of the training, with a period of decreased discomfort in between. However, since the condition worsens, even slight exertion can lead to the onset of pain, greatly affecting daily activities. In severe cases, individuals may even experience pain while at rest5.
The management of Achilles tendinopathy primarily involves conservative approaches, even though approximately 25%-29% of patients may eventually require surgery for the condition5. Cardoso et al.6 summarized an overview of the current treatment of Achilles tendinopathy, including medications, exercise, corticosteroid injections, platelet-rich plasma injections, manual therapy, and modalities. Among these treatments, the most widely recommended is exercise, which targets the injured tendons, especially mechanical loading exercises; eccentric exercise has been considered a better intervention. Even though it has been proven useful to decrease pain and improve function in the short term, a significant portion of patients have not responded to this strategy in a long-term study7, and some patients seek other treatments.
In recent years, extracorporeal shockwave therapy (ESWT) has demonstrated beneficial effects on musculoskeletal disorders and has become an effective treatment for tendinopathy8,9. There is now increasing evidence supporting the effectiveness of ESWT for lower extremity tendinopathy10 and upper extremity tendinopathy11. Originally used in urology for kidney stone treatment, ESWT has found therapeutic application in a wide range of medical and musculoskeletal conditions, making it a major innovation in the field of regenerative medicine12. There are two types of ESWT: focused shock waves and radial pressure waves13,14; the main difference between them is their physical characteristics. As a result, they stimulate diverse regenerative biological reactions in musculoskeletal tissue, activating proteins that play a role in chondroprotection15, vessel regeneration16,17, reducing inflammatory18, anti-apoptosis19, immunomodulation20, neurophysiological mechanisms, and pain relief11. ESWT also triggers the initiation of the healing processes, which facilitates the proliferation, differentiation, and migration of diverse cell types such as mesenchymal stem cells, endothelial cells, fibroblasts, and tendon cells. Additionally, it promotes the synthesis of collagen21. Furthermore, ESWT has been found to induce several tendon-specific responses that facilitate the healing progress22.
Although radial-ESWT is considered effective in Achilles tendinopathy treatment, there are various reports on the technique of radial ESWT without any consensus on the parameters. In this paper, we present a detailed treatment protocol for treating Achilles Tendinopathy using ESWT.

<table><tbody><tr><td>ESWT device</td><td>Chattanooga</td><td>&amp;nbsp;Intelect RPW 2074-INT</td><td>incorporate touch screen technology to ensure a high degree of simplicity. The easy-to-use menu-drive user interface guarantees reliable selection of all necessary parameters for treatment set-up as well as during patient treatment.</td></tr><tr><td>Gel</td><td>KeppLer</td><td>KL-250 type II</td><td>In order to obtain the best treatment results, it is necessary to ensure good contact between shock wave transducers and the patient&#039;s skin during treatment.&amp;nbsp;</td></tr><tr><td>Handpiece</td><td>Chattanooga</td><td>D-ACTOR Apllicator</td><td>The handle of the therapeutic apparatus can be used with a variety of transmitters, each of which is specially designed to achieve optimal efficacy.</td></tr><tr><td>Mark pen</td><td>general</td><td></td><td></td></tr><tr><td>Tissue</td><td>general</td><td></td><td></td></tr><tr><td>transmitters</td><td>Chattanooga</td><td>R15,D20</td><td>Each type of transmitter has its own unique therapeutic effect and scope of application.In our study, we use R15 and D20.</td></tr></tbody></table>

a treatment protocol for achilles tendinopathy with extracorporeal shockwave therapy

Achilles tendinopathy is a common musculoskeletal condition characterized by pain, lower muscle strength, gait abnormality, and reduced quality of life. There are two categories of Achilles tendinopathy: insertional Achilles tendinopathy and mid-portion Achilles tendinopathy. Currently, mechanical loading programs are considered the standard of care for the population with Achilles tendinopathy.
Extracorporeal shockwave therapy (ESWT) is considered a secondary conservative treatment for tendinopathy as it is effective and safe. It can be used either as a monotherapy or as part of a multimodal treatment plan. ESWT has been extensively studied in orthopedics, where it was shown to intensify fracture healing and successfully treat overuse conditions of tendons and fascia. It is believed that shockwaves have both mechanical and cellular effects that ultimately result in the repair of damaged tendinous tissue and improved function of the Achilles tendon. However, there is a lack of consistency in the literature surrounding the effectiveness, especially the protocols. Therefore, we enrolled 36 patients with a diagnosis of Achilles tendinopathy, using radial ESWT (0.48 mJ/mm2, 2,000 shockwaves, 10 Hz, 1.6&#160;bars, 2 sessions once a week). Freedom from pain was experienced by 16.7% of these participants, and there was a significant decrease in pain in all of them.

A retrospective study of patients with Achilles tendinopathy was performed on individuals older than 18 years old, with a definite diagnosis of Achilles tendinopathy. Exclusion criteria were recent ankle surgery or any condition that is a contraindication of ESWT.
This study included 36 participants. diagnosis with Achilles tendinopathy, 18 females and 18 males. Of these patients, their average age was 43.7 years, ranging between 18 and 64 years. All the patients complained of pain; 11 out of 36 patients had reduced range of motion (Table 1).
The treatment protocol was applied to all participants. In our study, the minimum number of sessions was one, and the maximum was eight. For these participants, a significant decrease in pain was achieved, and 4 of them were even pain-free after treatment, although all of them complained of pain at the beginning. Only 4 of them had impairment of ankle range of motion at the end. They got a significant improvement in the VISA-A Scale, which increased from 50.3 to 90.5.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66010/66010fig01.jpg" /> 
Figure 1: Illustrations of six different transmitters and their specifications. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66010/66010fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66010/66010fig02.jpg" /> 
Figure 2: Applicator positioning. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66010/66010fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66010/66010fig03.jpg" /> 
Figure 3: Changes in Roles and Maudsley scores before and after low-energy ESWT. The Roles and Maudsley scale allows the patient to subjectively describe their pain, with a score ranging from 0 to 4 points from excellent to poor. Abbreviation: ESWT = extracorporeal shockwave therapy. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66010/66010fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/66010/66010fig04.jpg" /> 
Figure 4: Changes in primary outcome measures before and after the 4 month follow-up. (A) The Victorian Institute of Sport Assessment-Achilles Scale used to evaluate the clinical severity of patients with chronic Achilles tendinopathy, had a maximum score of 100. (B) The Likert scale, used for general assessment, was scored by the patient on a 6 point scale (1 = completely recovered, 2 = much improved, 3 = somewhat improved, 4 = hardly improved, 5 = not improved, 6 = worse). (C) Numeric Rating Scale used to assess pain severity when patients with Achilles tendinopathy load, using a 0-10 scale. The control group received a 12 week eccentric exercise program, and the treated group received the same exercise protocol combined with three sessions of radial-ESWT treatment. Abbreviations: ESWT = extracorporeal shockwave therapy; VISA-A = Victorian Institute of Sport Assessment-Achilles; NRS = Numeric Rating Scale. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66010/66010fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td colspan="3">Demographic characteristics</td>
		</tr>
		<tr>
			<td>Age</td>
			<td colspan="2">43.7(18-64)</td>
		</tr>
		<tr>
			<td rowspan="2">Gender</td>
			<td>Male</td>
			<td>18(50%)</td>
		</tr>
		<tr>
			<td>Female</td>
			<td>18(50%)</td>
		</tr>
		<tr>
			<td>Number of sessions</td>
			<td colspan="2">2.58(1-8)</td>
		</tr>
		<tr>
			<td rowspan="2">Visual&#160;Analogue&#160;Scale(VAS)</td>
			<td>Before</td>
			<td>4.06(3-5)</td>
		</tr>
		<tr>
			<td>After</td>
			<td>1.28(0-3)</td>
		</tr>
		<tr>
			<td rowspan="2">Stiffness</td>
			<td>Before</td>
			<td>11(30.5%)</td>
		</tr>
		<tr>
			<td>After</td>
			<td>4(11.1%)</td>
		</tr>
		<tr>
			<td>Complications</td>
			<td colspan="2">10(27.8)</td>
		</tr>
	</tbody>
</table>
Table 1: Demographic characteristics. Visual Analogue Scale used Numerical rating scales with 0-10 scores; a higher score indicates greater pain intensity. Abbreviation: VAS = Visual Analogue Scale.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Authors</td>
			<td>N. partici-pants</td>
			<td>Follow-up (months)</td>
			<td colspan="2">Treatment</td>
			<td colspan="3">Parameters</td>
			<td colspan="2">outcome&#160; measures (pain)</td>
			<td colspan="2">Functional improvement</td>
		</tr>
		<tr>
			<td>Rompe et al. 24</td>
			<td>68</td>
			<td>4</td>
			<td colspan="2">eccentric loading vs eccentric loading + low-energy ESWT</td>
			<td colspan="3">radial ESWT, 2000 shocks, 3 Bar</td>
			<td colspan="2">VAS 
			&#8211;13.5 (&#8211;22.5 to 5.5) ( P = .0016)</td>
			<td colspan="2">Likert scale 
			0.8 (0.08 to 1.5), P = .035</td>
		</tr>
		<tr>
			<td>Pavone et al.26</td>
			<td>40</td>
			<td>12</td>
			<td colspan="2">ESWT + eccentric exercises</td>
			<td colspan="3">Low-energy radial ESWT, 4 sessions, 800 shocks, 4 Hz</td>
			<td colspan="2">VAS 
			&#8722;5.8 &#177; 1.2 SD (P &#60; 0.001)</td>
			<td colspan="2">AOFAS 
			+19.8 &#177;5.0 SD (P &#60; 0.001)</td>
		</tr>
		<tr>
			<td>Saxena et al.27</td>
			<td>60</td>
			<td>12</td>
			<td colspan="2">ESWT</td>
			<td colspan="3">&#160;low-intensity 2500 shocks, at 2.4 Bar ranging, 11 to 13 Hz</td>
			<td colspan="2">/</td>
			<td colspan="2">Roles-Maudsley 
			1.44 &#177; 0.87 SD (P &#60; 0.001)</td>
		</tr>
		<tr>
			<td>Vahdatpour et al.28</td>
			<td>43</td>
			<td>4</td>
			<td colspan="2">ESWT vs Sham SWT</td>
			<td colspan="3">1500 shocks, focused shockwaves (0.25&#8211;0.4 mJ/mm2, 2.3 Hz); 3000 shocks, radial shockwaves (1.8&#8211;2.6 mJ/mm2, 2.21 Hz).</td>
			<td colspan="2">VAS. &#8722;3.70&#177;2.27 (p&#60;0.001)</td>
			<td colspan="2">AOFAS 
			20.90&#177;13.51, p&#60;0.001</td>
		</tr>
		<tr>
			<td>Wheeler et al.29</td>
			<td>39</td>
			<td>6</td>
			<td colspan="2">ESWT</td>
			<td colspan="3">10 Hz and 2000 shocks</td>
			<td colspan="2">painDETECT questionnaire. 
			&#8722;4.8 (NAT) and &#8722;3.9 (IAT) (P &#60; 0.01)</td>
			<td colspan="2">VISA-A 
			23% (0% to 43%)(IAT) and 11% (7% to 22%)(NAT)</td>
		</tr>
		<tr>
			<td>Taylor et al.30</td>
			<td>54</td>
			<td>24</td>
			<td colspan="2">ESWT</td>
			<td colspan="3">Low-energy radial ESWT,&#160; 2000 shots, 10 Hz, 1.5&#8211;2.5 bar</td>
			<td colspan="2">VAS 
			&#8722;4.8 (NAT) and &#8722;3.9 (IAT) (P &#60; 0.01)</td>
			<td colspan="2">VISA-A 
			+66 points (P &#60; 0.001)</td>
		</tr>
	</tbody>
</table>
Table 2: Case series and primary outcome measures after treatment. Abbreviations: SWT = shockwave therapy; ESWT = extracorporeal SWT; VAS = Visual Analogue Scale; NAT = Non-insertional Achilles tendinopathy; IAT = Insertional Achilles tendinopathy; VISA-A = Victorian Institute of Sport Assessment-Achilles; NRS = Numeric Rating Scale; AOFAS = American Orthopedic Foot and Ankle Society.

Author Spotlight: Effectiveness of Extracorporeal Shockwave Therapy in Achilles Tendinopathy Treatment

Achilles tendinopathy is a common musculoskeletal condition for which loading programs are currently the standard of care. However, the treatment protocols vary. We therefore propose a protocol for Achilles tendinopathy treatment using extracorporeal shockwave therapy.

A Treatment Protocol for Achilles Tendinopathy with Extracorporeal Shockwave Therapy

Achilles tendinopathy is a common musculoskeletal condition characterized by pain, lower muscle strength, gait abnormality, and reduced quality of life. ...

a-treatment-protocol-for-achilles-tendinopathy-with-extracorporeal

Nanyang Technological University

Research

JoVE Journal

Medicine

954 Views.  The First affiliated Hospital of Zhejiang University, College of Medicine. Achilles tendinopathy is a common musculoskeletal condition for which loading programs are currently the standard of care. However, the treatment protocols vary. We therefore propose a protocol for Achilles tendinopathy treatment using extracorporeal shockwave therapy.

Video: Author Spotlight: Effectiveness of Extracorporeal Shockwave Therapy in Achilles Tendinopathy Treatment

Collection Protocol for Human Pancreas

This dissection and sampling procedure was developed for the Network for Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation of pancreas recovered from cadaveric organ donors. The pancreas is divided into 3 main regions (head, body, tail) followed by serial transverse sections throughout the medial to lateral axis. Alternating sections are used for fixed paraffin and fresh frozen blocks and remnant samples are minced for snap frozen sample preparations, either with or without RNAse inhibitors, for DNA, RNA, or protein isolation. The overall goal of the pancreas dissection procedure is to sample the entire pancreas while maintaining anatomical orientation.
Endocrine cell heterogeneity in terms of islet composition, size, and numbers is reported for human islets compared to rodent islets 1. The majority of human islets from the pancreas head, body and tail regions are composed of insulin-containing &beta;-cells followed by lower proportions of glucagon-containing &alpha;-cells and somatostatin-containing &delta;-cells. Pancreatic polypeptide-containing PP cells and ghrelin-containing epsilon cells are also present but in small numbers. In contrast, the uncinate region contains islets that are primarily composed of pancreatic polypeptide-containing PP cells 2. These regional islet variations arise from developmental differences. The pancreas develops from the ventral and dorsal pancreatic buds in the foregut and after rotation of the stomach and duodenum, the ventral lobe moves and fuses with the dorsal 3. The ventral lobe forms the posterior portion of the head including the uncinate process while the dorsal lobe gives rise to the rest of the organ. Regional pancreatic variation is also reported with the tail region having higher islet density compared to other regions and the dorsal lobe-derived components undergoing selective atrophy in type 1 diabetes4,5.
Additional organs and tissues are often recovered from the organ donors and include pancreatic lymph nodes, spleen and non-pancreatic lymph nodes. These samples are recovered with similar formats as for the pancreas with the addition of isolation of cryopreserved cells. When the proximal duodenum is included with the pancreas, duodenal mucosa may be collected for paraffin and frozen blocks and minced snap frozen preparations.

This video demonstrates a dissection procedure for processing human pancreas into multiple storage formats. Anatomical orientation is maintained throughout the pancreatic regions to allow definition of regional islet composition and density.

This dissection and sampling procedure was developed for the Network for Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation ...

Shock Wave Application to Cell Cultures

Shock waves nowadays are well known for their regenerative effects. Basic research findings showed that shock waves do cause a biological stimulus to target cells or tissue without any subsequent damage. Therefore, in vitro experiments are of increasing interest. Various methods of applying shock waves onto cell cultures have been described. In general, all existing models focus on how to best apply shock waves onto cells.
However, this question remains: What happens to the waves after passing the cell culture? The difference of the acoustic impedance of the cell culture medium and the ambient air is that high, that more than 99% of shock waves get reflected! We therefore developed a model that mainly consists of a Plexiglas built container that allows the waves to propagate in water after passing the cell culture. This avoids cavitation effects as well as reflection of the waves that would otherwise disturb upcoming ones. With this model we are able to mimic in vivo conditions and thereby gain more and more knowledge about how the physical stimulus of shock waves gets translated into a biological cell signal (&#8220;mechanotransduction&#34;).

Shock waves nowadays are well known for their regenerative effects. Therefore in vitro experiments are of increasing interest. We therefore developed a model for in vitro shock wave trials (IVSWT) that enables us to mimic in vivo conditions thereby avoiding distracting physical effects.

Shock waves nowadays are well known for their regenerative effects. Basic research findings showed that shock waves do cause a biological stimulus to ...

Bioengineering

Protocols for Assessing Radiofrequency Interactions with Gold Nanoparticles and Biological Systems for Non-invasive Hyperthermia Cancer Therapy

Cancer therapies which are less toxic and invasive than their existing counterparts are highly desirable. The use of RF electric-fields that penetrate deep into the body, causing minimal toxicity, are currently being studied as a viable means of non-invasive cancer therapy. It is envisioned that the interactions of RF energy with internalized nanoparticles (NPs) can liberate heat which can then cause overheating (hyperthermia) of the cell, ultimately ending in cell necrosis.
In the case of non-biological systems, we present detailed protocols relating to quantifying the heat liberated by highly-concentrated NP colloids. For biological systems, in the case of in vitro experiments, we describe the techniques and conditions which must be adhered to in order to effectively expose cancer cells to RF energy without bulk media heating artifacts significantly obscuring the data. Finally, we give a detailed methodology for in vivo mouse models with ectopic hepatic cancer tumors.

We describe the protocols used to investigate the interactions of 13.56 MHz radiofrequency (RF) electric-fields with gold nanoparticle colloids in both non-biological and biological systems (in vitro/vivo). These interactions are being investigated for applications in cancer therapy.

Cancer therapies  which are less toxic and invasive than their existing counterparts are highly  desirable. The use of RF electric-fields that penetrate ...

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill1.
Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone2. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab6. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis7. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial26. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians&#8217; choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm10.
There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

A novel methodology that is employed for the treatment of recurrent glioblastomas is described. This treatment approach employs the application of alternating electric tumor treating fields (TTFields), known as TTF Therapy in combination with bevacizumab, a targeted agent that is currently FDA approved as monotherapy.

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA ...

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

In this manuscript, we describe percutaneous isolated hepatic perfusion with simultaneous chemofiltration as treatment for unresectable liver metastases. This procedure is performed under general anaesthesia in the angiosuite by an experienced team, consisting of an interventional radiologist, a clinical perfusionist and anaesthesiologist.

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn ...

Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for acute as well as end-stage lung diseases. With the increase in clinical demand and prolonged use of ECMO, procedural optimization and prevention of multi-organ damage are of critical importance. The aim of this protocol is to present a detailed technique of veno-venous ECMO in a non-intubated, spontaneously breathing mouse. This protocol demonstrates the technical design of the ECMO and surgical steps. This murine ECMO model will facilitate the study of pathophysiology related to ECMO (e.g., inflammation,bleeding and thromboembolic events). Due to the abundance of genetically modified mice, the molecular mechanisms involved in ECMO-related complications can also be dissected.

Here we present a protocol describing the technique of veno-venous extracorporeal membrane oxygenation (ECMO) in a non-intubated, spontaneously breathing mouse. This murine model of ECMO can be effectively implemented in experimental studies of acute and end-stage lung diseases.

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for ...

Virtual Prism Adaptation Therapy: Protocol for Validation in Healthy Adults

Hemispatial neglect is a common impairment after stroke. It is associated with poor functional and social outcomes. Therefore, an adequate intervention is imperative for the successful management of hemispatial neglect. However, the clinical use of various interventions is limited in real clinical practice. Prism adaptation therapy is one of the most evidence-based rehabilitation modalities to treat hemispatial neglect. To overcome any possible shortcoming that may occur with prism therapy, we developed a new system using immersive virtual reality and depth-sensing camera to create a virtual prism adaptation therapy (VPAT). To validate the VPAT system, we designed an experimental protocol investigating the behavioral errors and changes in cortical activation via the VPAT system. Cortical activation was measured by functional near infrared spectroscopy (fNIRS). The experiment consisted of four phases. All four included clicking, pointing or rest applied to right-handed healthy people. Clicking versus pointing was used for investigating the cortical region related with the gross motor task, and pointing with VPAT versus pointing without VPAT was used for investigating the cortical region associated with visuospatial perception. The preliminary results from four healthy participants showed that pointing errors by the VPAT system was similar to the conventional prism adaptation therapy. Further analysis with more participants and fNIRS data, as well as a study in patients with stroke may be required.

This experimental protocol demonstrates the use of virtual prism adaptation therapy (VPAT) in healthy adults and the association between VPAT and functional near infrared spectroscopy to determine the effect of VPAT on cortical activation. Results suggest that VPAT may be feasible and could induce similar behavioral adaptation as conventional prism adaptation therapy.

Hemispatial neglect is a common impairment after stroke. It is associated with poor functional and social outcomes. Therefore, an adequate intervention is ...

A Standardized Murine Model of Extracorporeal Shockwave Therapy Induced Soft Tissue Regeneration

Shockwave therapy (SWT) shows promising regenerative effects in several different tissues. However, the underlying molecular mechanisms are poorly understood. Angiogenesis, a process of new blood vessel formation is a leading driver of regeneration in softer tissues as well as a recently discovered effect of SWT. How the mechanical stimulus of SWT induces angiogenesis and regeneration and which pathways are involved is not fully understood. To further improve the clinical use of SWT and gain valuable information about how mechanical stimulation can affect tissue and tissue regeneration, a standardized model of SWT is needed. We, hereby, describe a standardized, easy to implement murine model of shockwave therapy induced regeneration, utilizing the hind-limb ischemia model.

This article describes a standardized murine model of tissue regeneration via shockwave treatment.

Shockwave therapy (SWT) shows promising regenerative effects in several different tissues. However, the underlying molecular mechanisms are poorly ...

Treatment Protocol for Rotator Cuff Calcific Tendinitis Using a Single-Crystal Piezoelectric Focused Shock Wave Source

Focused shock waves have emerged as a highly effective noninvasive therapeutic option for the treatment of calcific tendinitis of the shoulder. There are three types of focused shock wave generators: electrohydraulic, electromagnetic, and piezoelectric. According to our literature search, there are no reports of results with the use of single-crystal piezoelectric generators in calcific tendinitis of the shoulder. In a consecutive retrospective series of 23 patients with G&#228;rtner type I and II calcifications of the rotator cuff, we performed three applications of high-energy piezoelectric focused waves (4,000 pulses per session with a frequency of 6 Hz). At the final follow-up (average of 14 months), 82.6% of the cases showed complete resorption of the calcification in radiographic controls. In 8.7% of the cases, partial disappearance of the calcification was achieved, and in the remaining 8.7% there were no significant changes. Single-crystal piezoelectric generators have a success rate comparable to those already reported with electrohydraulic and electromagnetic devices.

Calcific tendinitis of the shoulder is a relatively common condition with numerous treatment options. Here, we discuss the indications of focused shock waves generated by a single-crystal piezoelectric device, describe a treatment protocol, and present the preliminary results.

Focused shock waves have emerged as a highly effective noninvasive therapeutic option for the treatment of calcific tendinitis of the shoulder. There are ...

Exosome Isolation after in vitro Shock Wave Therapy

Shock wave therapy is routinely applied in orthopedic indications including tendinopathies such as lateral epicondylitis (tennis elbow) and Achilles tendinitis (heel spurs) as well as non-healing wounds and bones. Despite different pathologies, the combination of an angiogenic and an anti-inflammatory effect of shock wave therapy leads to regeneration in soft tissue and bones. In over 30 years of clinical application, no side effects were observed. Furthermore, basic research even revealed regenerative effects on ischemic myocardium.
In a previous work we could show that the mechanical stimulus of cultured cells is translated via an exosome release into a biological response. However, the exact mechanism remains to be elucidated. Mechanical coupling is crucial when applying shock wave therapy as even small air bubbles can absorb shock waves. The previously described water bath method is a valid method to guarantee adequate and reproducible shock wave application in vitro.
We were able to develop a feasible and replicable protocol to isolate exosomes from cultured cells after shock wave application. Thereby we demonstrate a possibility to study underlying mechanisms of mechanotransduction as well as the regenerative and angiogenic potential of shock wave released exosomes.

Exosomes are released upon in vitro application of shockwaves. Here, we describe how to apply shockwaves on cultured endothelial cells and subsequently isolate exosomes for further investigation.

Shock wave therapy is routinely applied in orthopedic indications including tendinopathies such as lateral epicondylitis (tennis elbow) and Achilles ...