Comprehensive Evaluation of the BeShape One Device: Assessing Thermal Safety in Noninvasive Body Contouring Using Advanced Techniques.

OBJECTIVES: This study aims to assess the thermal safety profile of the BeShape One Device, a noninvasive, high-intensity, non-focused ultrasound device designed for reducing waist circumference. This device possesses several features that distinguish it from other commercial ultrasound-based fat reduction devices. The study focuses on evaluating temperature-related physiological changes through thermal safety analysis and histopathology in a swine model. MATERIALS AND METHODS: The study utilized three types of applicators-active, demo, and modified-to comprehensively assess the device's impact on various skin layers. Five female Large White X Landrace swine were involved in the study, and the BeShape One Device was applied to designated treatment sites using a specific treatment protocol. The assessment included clinical observations, skin reaction evaluations, gross pathology, histopathological analyses, and advanced temperature measurement techniques, including needle thermocouples, thermal cameras, COMSOL modeling, and CEM43 analysis. RESULTS: Clinical observations indicated the animals' overall well-being throughout the study. Skin reactions, including erythema, edema, bruising, and crust formation, were temporary and resolved over time. Gross pathology revealed no treatment-related pathologies, except for a discoloration related to a tattoo procedure. Histopathological analyses at 30 and 90 days posttreatment demonstrated an absence of heat-related lesions in skin layers. Needle thermocouples and thermal camera measurements supported the device's ability to maintain consistent thermal homogeneity. COMSOL modeling and CEM43 analysis predicted no thermal damage to the skin, confirming the safety of the BeShape One Device. CONCLUSIONS: Under the experimental conditions, the BeShape One Device demonstrated a favorable safety profile. Clinically and histopathologically, no adverse effects were observed. The device's ability to achieve thermal homogeneity in skin layers was validated through advanced temperature measurement techniques. COMSOL modeling and CEM43 analysis further supported the conclusion that the device is safe, making it a promising option for noninvasive body contouring procedures.

Effect of Ultrasound on Thrombus debris during Sonothrombolysis in a Microfluidic device.

Microbubble-mediated sonothrombolysis has been proven to be a non-invasive and efficient method for thrombolysis. Nevertheless, there is a potential risk that the thrombus debris generated during the dissolution of the original thrombus are too large and can lead to hazardous emboli. Using a sonothrombolysis microfluidic platform, we investigated the effects of ultrasound power, thrombolytic agent and microbubble concentration on the size of thrombus debris with the example of microbubble-mediated sonothrombolysis of arterial thrombus. Additionally, we studied the effects of ultrasound power on the size and shape of thrombus debris produced by acute and chronic arterial sonothrombolysis. In acute arterial sonothrombolysis, ultrasound power has significant effect on the size of thrombus debris and steadily increases with the increase of ultrasound power. Conversely, in chronic arterial sonothrombolysis, the size of thrombus debris is minimally affected by ultrasound power. Using the sonothrombolysis microfluidic platform, the relationship between ultrasound power and the safety of sonothrombolysis has been illustrated, and the sonothrombolysis microfluidic platform is demonstrated to be a promising tool for further studies on the process of sonothrombolysis.

Strategies and safety simulations for ultrasonic cervical spinal cord neuromodulation.

Objective. Focused ultrasound spinal cord neuromodulation has been demonstrated in small animals. However, most of the tested neuromodulatory exposures are similar in intensity and exposure duration to the reported small animal threshold for possible spinal cord damage. All efforts must be made to minimize the risk and assure the safety of potential human studies, while maximizing potential treatment efficacy. This requires an understanding of ultrasound propagation and heat deposition within the human spine.Approach. Combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level via two approaches (a) the posterior acoustic window between vertebral posterior arches, and (b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of fifty 0.1 s pulses (pulse repetition frequency: 0.33 Hz, free-field spatial peak pulse-averaged intensity: 10 W cm-2) were simulated for four subjects and for ±10 mm translational and ±10∘rotational source positioning errors.Main results.Target pressures ranged between 20%-70% of free-field spatial peak pressures with the posterior approach, and 20%-100% with the lateral approach. When the posterior source was optimally positioned, peak spine heating values were below 1 ∘C, but source mispositioning resulted in bone heating up to 4 ∘C. Heating with the lateral approach did not exceed 2 ∘C within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately two-fold between subjects. This results in a nearly ten-fold range between subjects in the target pressure achieved per degree of maximum heating.Significance. This study highlights the utility of trans-spine ultrasound simulation software and need for precise source-anatomy positioning to assure the subject-specific safety and efficacy of focused ultrasound spinal cord therapies.

Comparing the Safety and Effectiveness of Microfocused Ultrasound: Standard vs Targeted Tissue Protocol in Lifting and Tightening the Lower Face and Upper Neck.

BACKGROUND: Micro-focused ultrasound with visualization (MFU-V) delivers energy to specific soft tissue layers beneath the epidermis with the ability to lift and tighten the lower face and neck.  Objective: To determine the efficacy of microfocused ultrasound with visualization (MFU-V) using a standard treatment line protocol versus a customized treatment line protocol based on the patient's unique anatomy targeting the superficial muscular aponeurotic system and fibrous septae for lifting and tightening of the lower face and neck. METHODS: This was a single-center, prospective, randomized, investigator-blinded clinical trial. 51 subjects were randomized to receive a single treatment of MFU-V targeting the lower face and neck using either a standard or custom treatment protocol.   Results: Subjects in both standard and custom treatment groups noted a greater than one-point improvement in jawline laxity. Three-dimensional photography measurements also demonstrated lifting of the lower face and neck in both treatment groups. CONCLUSION: Custom and standard treatment MFU-V protocols produce a safe and effective treatment for tightening and lifting the lower face and neck. Custom treatment protocols aid in maximizing results for patients with variations in the anatomy of the lower face and neck.  J Drugs Dermatol. 2024;23(4):7647.     doi:10.36849/JDD.7647.

Safety and efficacy of clot-dissolving therapies for submassive pulmonary embolism: A network meta-analysis of randomized controlled trials.

BACKGROUND: Acute pulmonary embolism (PE) is a serious condition that needs quick and effective treatment. Anticoagulation therapy is the usual care for most PE patients but may not work well for higher-risk ones. Thrombolysis breaks the clot and improves blood flow. It can be given systemically or locally. Ultrasound-assisted catheter-directed thrombolysis (USAT) is a new technique that boosts clot-busting drugs. This network meta-analysis compares death, bleeding, and benefits of four treatments in acute submassive PE. METHODS: We comprehensively searched relevant databases up to July 2023 for RCTs. The outcomes encompassed all-cause mortality, major and minor bleeding, PE recurrence, and hospital stay duration. Bayesian network meta-analysis computed odds ratios (OR) and 95 % CI estimates. RESULTS: In this network meta-analysis of 23 RCTs involving 2521 PE patients, we found that SCDT had the most favorable performance for mortality, as it had the lowest odds ratio (OR) among the four interventions (OR 5.41e-42; 95 % CI, 5.68e-97, 1.37e-07). USAT had the worst performance for major bleeding, as it had the highest OR among the four interventions (OR 4.73e+04; 95 % CI, 1.65, 9.16e+13). SCDT also had the best performance for minor bleeding, as it had the lowest OR among the four interventions (OR 5.68e-11; 95 % CI, 4.97e-25, 0.386). CONCLUSION: Our meta-analysis suggests that SCDT is the most effective treatment intervention in improving the risks of All-cause mortality and bleeding. Thrombolytic therapy helps in improving endpoints including the risk of PE recurrence and the duration of hospital stay.

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis.

BACKGROUND: Transcranial Pulse Stimulation (TPS) has been recently introduced as a novel ultrasound neuromodulation therapy with the potential to stimulate the human brain in a focal and targeted manner. Here, we present a first retrospective analysis of TPS as an add-on therapy for Parkinson's disease (PD), focusing on feasibility, safety, and clinical effects. We also discuss the placebo response in non-invasive brain stimulation studies as an important context. METHODS: This retrospective clinical data analysis included 20 PD patients who received ten sessions of TPS intervention focused on the individual motor network. Safety evaluations were conducted throughout the intervention period. We analyzed changes in motor symptoms before and after TPS treatment using Unified Parkinson's Disease Rating Scale part III (UPDRS-III). RESULTS: We found significant improvement in UPDRS-III scores after treatment compared to baseline (pre-TPS: 16.70 ± 8.85, post-TPS: 12.95 ± 8.55; p < 0.001; Cohen's d = 1.38). Adverse events monitoring revealed no major side effects. CONCLUSION: These preliminary findings suggest that TPS can further improve motor symptoms in PD patients already on optimized standard therapy. Findings have to be evaluated in context with the current literature on placebo effects.

Immersion Ultrasound Therapy in Combination with Manual Therapy in the Treatment of Ischemic Digital Ulcers in Systemic Sclerosis.

Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods: We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results: In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 ± 11.0 vs. 19.05 ± 8.83; p < 0.05), pain (NRS: 5.55 ± 1.2 vs. 2.9 ± 1.09; p < 0.05), and PSST score (24.4 ± 4.0 vs. 16.2 ± 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 ± 9.72 vs. 22.7 ± 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 ± 1.09 vs. 4.5 ± 1.07; p < 0.05) and in the PSST scale (16.2 ± 2.36 vs. 20.4 ± 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions: Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma.

Patient satisfaction of microfocused ultrasound treatments on the face and neck laxity: A narrative review.

BACKGROUND: Microfocused ultrasound with visualization (MFU-V) delivers focused ultrasound energy to heat tissue and has emerged as a fast and effective noninvasive method for treating skin laxity. After obtaining approval in 2009 by the Food and Drug Administration, satisfactory feedback was recorded using several scoring systems for MFU-V treatment for facial and neck laxity. AIM: To evaluate the efficacy and satisfaction rates of MFU-V for facial and neck laxity treatment by providing a basis for developing a validated scoring system for MFU-V treatment. METHOD: A constrictive survey was carried out by selecting relevant publications on MFU-V treatment of facial and neck laxity using PubMed, Medline, and Embase electronic databases from January 2017 to March 2022. RESULTS: Of the 11 original articles used in this review, the majority of the scoring methods used were the subjective global aesthetic improvement scale and the 5-point scale rating global aesthetic improvement in appearance. Around half of the patients were described as much improved or very much improved on days 30 and 90, while most returned to baseline on Day 360. Most of the adverse events reported were mild bruising, redness, and pain. None of the patients reported serious adverse events. A burn occurred in one case because of improper application of the probe. CONCLUSION: The MFU-V provides excellent and promising responses for treating facial and neck laxity. A few mild events were observed, such as erythema, pain, edema, and injection-site induration, all of which resolved within approximately 2-3 days.

A Systematic Review of the Efficacy of Microfocused Ultrasound for Facial Skin Tightening.

Objective: to systematically review the efficacy of microfocused ultrasound (MFU) for facial skin tightening. Methods: A systematic search was performed (Pubmed, Embase) to assess the efficacy of single MFU treatments for facial skin tightening. Eligible studies included randomised controlled trials, controlled trials, cohort studies and case series (n ≥ 10). Objective and subjective outcomes were assessed. Results: A total of 693 studies were identified of which 16 studies were eligible. All the studies involved female patients. MFU is capable of tightening the skin, as observed in studies measuring the results of brow lifts (0.47−1.7 mm) and submental lifts (measured as a 26−45 mm2 reduction in the submental area on lateral photographs). Data from the Global Aesthetic Improvement Scale (GAIS) were pooled, and the day 90 pooled subjective investigator reported scores (IGAIS) (n = 337) showed that 92% of the patients demonstrated an improvement in skin tightening and/or in wrinkle reduction which continued up to one year. Longer-term follow-up data are not available. The patient-reported pooled scores (SGAIS) (n = 81) showed that the skin improvements were mild and continued to increase from 42% (90 days) to 53% (360 days) post-treatment. The MFU treatment was moderately painful and caused transient erythema with or without oedema. Other adverse effects were rare (2%), including dysesthesia (numbness or hypersensitivity), bruising and stinging, mandibular burns, striations and contact dermatitis. Various device settings, treatment protocols and energies were applied. Excessive skin laxity and a BMI > 30 were posed as relative contraindications for MFU treatment because positive results declined with an increase in laxity and BMI. Conclusions: MFU treatment is effective in tightening female patients' mildly to moderately lax facial skin. Future studies should focus on objective treatment outcomes, optimising treatment regimens and male patients.

Younger age is a significant factor for poorer adherence in fracture patients who received low-intensity pulsed ultrasound: A retrospective study.

BACKGROUND: The factors for poor adherence to therapy in patients with postoperative fracture who are treated with low-intensity pulsed ultrasound remain unknown. Therefore, we designed a retrospective cohort study to determine the various factors for poorer adherence to therapy in patients with postoperative fracture who were treated with low-intensity pulsed ultrasound therapy. METHODS: We retrospectively analyzed the data of postoperative patients who underwent low-intensity pulsed ultrasound after fracture surgery from January 2010 to May 2019. The patients were categorized into two groups as follows: group G, including those with a good adherence rate (>72%), and group P, including those with a poor adherence rate (<72%). Factors, such as age, sex, how the rental cost of low-intensity pulsed ultrasound was paid (by the patients themselves or by the insurance company), living (alone or with someone), insurance claim item (fractures within 3 weeks after osteosynthesis or delayed or non-union fractures), low-intensity pulsed ultrasound device-type (earlier- or next-generation), duration of low-intensity pulsed ultrasound use, fracture site (upper or lower limb), frequency of hospital visits (regular or irregular), and employment status (employed/unemployed) were compared between groups G and P. RESULTS: In total, 96 patients (74 and 22 patients in groups G and P, respectively) who underwent low-intensity pulsed ultrasound were included in the study. Univariate analysis revealed that younger patients (P < 0.001) and patients who did not regularly visit the hospital (P = 0.024) were more likely to have poorer adherence to therapy. Multiple logistic regression analysis revealed that age was the only independent, pertinent factor for poorer adherence to therapy (odds ratio, 8.570; 95% confidence interval, 2.770-26.50; P < 0.001), with a cutoff value of 41 years. CONCLUSIONS: Younger age is a significant factor for poorer adherence in patients undergoing low-intensity pulsed ultrasound therapy.

Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models.

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.

Improving Voice Outcomes After Thyroid Surgery - Review of Safety Parameters for Using Energy-Based Devices Near the Recurrent Laryngeal Nerve.

Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery.

Ultrasonic agitation reduces the time of calcium hydroxide antimicrobial effect and enhances its penetrability.

OBJECTIVES: The objective of the present work was to evaluate the ultrasonic agitation, time and vehicle (propylene glycol or distilled water) on the antimicrobial potential and penetrability of calcium hydroxide pastes on infected dentin by means of Confocal Laser Scanning Microscopy (CLSM) and microbiological culture (MC). MATERIALS AND METHODS: Dentin specimens were infected with Enterococcus faecalis using a new contamination protocol of 5 days. The specimens were divided into eight groups and dressed with the pastes for 7 or 15 days: G1) calcium hydroxide (CH) + propylene glycol (prop)/7 days (d), G2) CH + prop/7d + ultrasonic agitation (U), G3) CH + distilled water (dw)/7d, G4) CH + dw/7d + U, G5) CH + prop/15d, G6) CH + prop/15d + U, G7) CH + dw/15d, G8) CH + dw/15d + U. The ultrasonic activation was made for 1 min in both directions with a plain point insert. After medications removal, the images obtained by CLSM showed the viable (green) and dead (red) bacteria with Live and Dead dye. By the MC, the dentinal wall debris obtained by burs were collected for colony counts. For the penetration test, the Rodamine B dye was added to the CH pastes and analyzed by CLSM. RESULTS: The 7 and 15-days CH + prop+U pastes performed better antimicrobial efficacy, followed by the CH + dw+U/15d paste. CONCLUSIONS: All pastes demonstrated better penetration and antimicrobial activity against E. faecalis when agitated with ultrasound, even in periods of up to seven days. The propylene glycol vehicle showed better results. CLINICAL RELEVANCE: Agitation of the dressing that remains for less time inside the root canal can optimize the decontamination of endodontic treatment.

Tightening and Reduction of Unwanted Submental Fat Using Triple-Layer High-Intensity Focused Ultrasound: Clinical and 3-Dimensional Imaging Analysis.

BACKGROUND: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence of their use. OBJECTIVE: The authors sought to evaluate the safety and efficacy of a novel triple-layer high-intensity focused ultrasound (HIFU) regimen for SMF reduction. METHODS: Forty Korean subjects with moderate/severe SMF were evaluated after receiving a session of triple-layer HIFU treatments (using 3.0-, 4.5-, and 6.0-mm focusing transducers). The objective evaluation based on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and patients' satisfaction based on the 7-point Subject Self-Rating Scale (SSRS) were determined 8 weeks after treatment. Three-dimensional image analysis was also performed. RESULTS: At the follow-up visit, the proportion of treatment responders defined as subjects with ≥1-point improvement in CR-SMFRS was 62.5%, and the proportion of patients satisfied with appearance of their face and chin (score ≥4 on the SSRS) was 67.5% of the total patients. The results of 3-dimensional analysis were consistent with clinical observations. Only mild and transient side effects were observed for some patients with no serious adverse effects. CONCLUSION: The triple-layer HIFU regimen including the novel 6.0-mm transducer has benefits for tightening and rejuvenation of the area with unwanted SMF, showing reasonable safety profiles.

Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep.

Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.

Efficacy and Safety of High-Intensity, High-Frequency, Parallel Ultrasound Beams for Fine Lines and Wrinkles.

BACKGROUND: Ultrasound energy has been used for cutaneous rejuvenation, including treatment of fine lines and wrinkles. Ultrasound waves of high intensity can induce thermal injury in the dermis, which causes tissue coagulation and remodeling. OBJECTIVE: To examine the safety and utility of a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams to improve fine lines and wrinkles of the face and neck. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated the utility of this novel ultrasound device to improve fine lines and wrinkles. Sixty subjects were enrolled for single treatment to the face and neck. RESULTS: Fifty-eight subjects completed the study. The mean age was 58 years, and 87.9% were women. Fitzpatrick skin Types I to VI were represented. Assessments compared 12-week follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 78% of subjects. There was significant improvement of 1 to 3 Fitzpatrick Wrinkle and Elastosis Scale units in 86% of subjects. For investigator global improvement scores, 88% of subjects had improvement. Overall, 72% of subjects noted improvement, and the majority were satisfied. There were no device-related adverse events. CONCLUSION: Treatment with a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams safely improved the clinical appearance of fine lines and wrinkles of the face and neck.

Microbubbles and Ultrasound Accelerated Thrombolysis for Peripheral Arterial Occlusions: The Outcomes of a Single Arm Phase II Trial.

OBJECTIVE: Acute peripheral arterial occlusions can be treated by catheter directed thrombolysis (CDT). However, CDT is time consuming and accompanied by the risk of bleeding complications. The addition of contrast enhanced ultrasound and microbubbles could improve thrombus susceptibility to thrombolytic agents and potentially shorten treatment time with a lowered risk of bleeding complications. This article reports the outcomes of the safety and feasibility of this novel technique. METHODS: In this single arm phase II trial, 20 patients with acute lower limb ischaemia received CDT combined with an intravenous infusion of microbubbles and locally applied ultrasound during the first hour of standard intra-arterial thrombolytic therapy. The primary endpoint was safety, i.e., occurrence of serious adverse events (haemorrhagic complications and/or amputation) and death within one year. Secondary endpoints included angiographic and clinical success, thrombolysis duration, additional interventions, conversion, and quality of life. RESULTS: The study included 20 patients (16 men; median age 68.0 years; range, 50.0 - 83.0; and 40% native artery and 60% bypass graft). In all patients, the use of microbubble contrast enhanced sonothrombolysis could be applied successfully. There were no serious adverse events related to the experimental treatment. Duplex examination showed flow distal from the occlusion after 23.1 hours (range 3.1 - 46.5) with a median thrombolysis time of 47.5 hours (range 6.0 - 81.0). The short term ABI and pain scores significantly improved; however, no changes were observed before or after thrombolysis in the microcirculation. Overall mortality and amputation rates were both 2% within one year. The one year patency rate was 55%. CONCLUSION: Treatment of patients with acute peripheral arterial occlusions with contrast enhanced sonothrombolysis is feasible and safe to perform in patients. Further research is necessary to investigate the superiority of this new treatment over standard treatment.

Ultrasonic Bone Scalpel (USBS) Does Not Reduce Blood Loss During Posterior Spinal Fusion (PSF) in Patients with Adolescent Idiopathic Scoliosis (AIS): Randomized Clinical Trial.

STUDY DESIGN: Randomized Clinical Trial. OBJECTIVE: The aim of this study was to compare the efficacy of USBS with standard-of-care surgical instruments during posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS) by evaluating the difference in estimated blood loss per level fused (EBL/level). SUMMARY OF BACKGROUND DATA: PSF surgery for AIS is often associated with high blood loss. Use of an ultrasonic bone scalpel (USBS) has been proposed to reduce blood loss during scoliosis surgery. METHODS: This was a single-blinded (patient-blinded), randomized, controlled superiority trial. We randomized 66 patients with AIS undergoing PSF to the control group (osteotome) or the experimental group (USBS). The primary outcome was intraoperative EBL/level obtained from red blood cell salvage reports. One-year follow-up was available for 57 of 62 (92%) of patients. RESULTS: EBL/level averaged 35 and 39 mL/level in the experimental and control groups, respectively [adjusted mean difference USBS - osteotome -8 mL/level, 95% CI: -16.4 to 0.3 mL/level, P = 0.0575]. There was no difference in curve correction [adjusted mean difference: -1.7%, 95% CI: -7.0 to 3.6%, P = 0.5321] or operative time [adjusted mean difference: -3.55 minutes, 95% CI: -22.45 to 15.46 min, P = 0.7089] between groups. Complications requiring change in routine postoperative care were noted in eight patients: two occurred in patients assigned to the experimental group and six occurred in patients assigned to the control group. CONCLUSION: There was no clinically significant difference in total blood loss, EBL/level, or complications between the two groups. In contrast to reports from other centers, at our high-volume spine center, USBS did not lead to reduced blood loss during PSF for AIS. These results may not be generalizable to centers with longer baseline operative times or higher baseline average blood loss during PSF for AIS.Level of Evidence: 1.

Application of low-intensity pulsed therapeutic ultrasound on mesenchymal precursors does not affect their cell properties.

Ultrasound is considered a safe and non-invasive tool in regenerative medicine and has been used in the clinic for more than twenty years for applications in bone healing after the approval of the Exogen device, also known as low-intensity pulsed ultrasound (LIPUS). Beyond its effects on bone health, LIPUS has also been investigated for wound healing of soft tissues, with positive results for various cell processes including cell proliferation, migration and angiogenesis. As LIPUS has the potential to treat chronic skin wounds, we sought to evaluate the effects produced by a conventional therapeutic ultrasound device at low intensities (also considered LIPUS) on the migration capacity of mouse and human skin mesenchymal precursors (s-MPs). Cells were stimulated for 3 days (20 minutes per day) using a traditional ultrasound device with the following parameters: 100 mW/cm2 with 20% duty cycle and frequency of 3 MHz. At the parameters used, ultrasound failed to affect s-MP proliferation, with no evident changes in morphology or cell groupings, and no changes at the cytoskeletal level. Further, the migration and invasion ability of s-MPs were unaffected by the ultrasound protocol, and no major changes were detected in the gene/protein expression of ROCK1, integrin ß1, laminin ß1, type I collagen and transforming growth factor ß1. Finally, RNA-seq analysis revealed that only 10 genes were differentially expressed after ultrasound stimulation. Among them, 5 encode for small nuclear RNAs and 2 encode for proteins belonging to the nuclear pore complex. Considering the results overall, while the viability of s-MPs was not affected by ultrasound stimulation and no changes were detected in proliferation/migration, RNA-seq analysis would suggest that s-MPs do respond to ultrasound. The use of 100 mW/cm2 intensity or conventional therapeutic ultrasound devices might not be optimal for the stimulation the properties of cell populations. Future studies should investigate the potential application of ultrasound using variations of the tested parameters.