Marketing and US Food and Drug Administration Clearance of Artificial Intelligence and Machine Learning Enabled Software in and as Medical Devices: A Systematic Review.

Importance: The marketing of health care devices enabled for use with artificial intelligence (AI) or machine learning (ML) is regulated in the US by the US Food and Drug Administration (FDA), which is responsible for approving and regulating medical devices. Currently, there are no uniform guidelines set by the FDA to regulate AI- or ML-enabled medical devices, and discrepancies between FDA-approved indications for use and device marketing require articulation. Objective: To explore any discrepancy between marketing and 510(k) clearance of AI- or ML-enabled medical devices. Evidence Review: This systematic review was a manually conducted survey of 510(k) approval summaries and accompanying marketing materials of devices approved between November 2021 and March 2022, conducted between March and November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Analysis focused on the prevalence of discrepancies between marketing and certification material for AI/ML enabled medical devices. Findings: A total of 119 FDA 510(k) clearance summaries were analyzed in tandem with their respective marketing materials. The devices were taxonomized into 3 individual categories of adherent, contentious, and discrepant devices. A total of 15 devices (12.61%) were considered discrepant, 8 devices (6.72%) were considered contentious, and 96 devices (84.03%) were consistent between marketing and FDA 510(k) clearance summaries. Most devices were from the radiological approval committees (75 devices [82.35%]), with 62 of these devices (82.67%) adherent, 3 (4.00%) contentious, and 10 (13.33%) discrepant; followed by the cardiovascular device approval committee (23 devices [19.33%]), with 19 of these devices (82.61%) considered adherent, 2 contentious (8.70%) and 2 discrepant (8.70%). The difference between these 3 categories in cardiovascular and radiological devices was statistically significant (P < .001). Conclusions and Relevance: In this systematic review, low adherence rates within committees were observed most often in committees with few AI- or ML-enabled devices. and discrepancies between clearance documentation and marketing material were present in one-fifth of devices surveyed.

Structural, Chemical, and Mechanical Properties of Pressure Garments as a Function of Simulated Use and Repeated Laundering.

Pressure garments are widely employed for management of postburn scarring. Although pressure magnitude has been linked to efficacy, maintenance of uniform pressure delivery is challenging. An understanding of garment fabric properties is needed to optimize pressure delivery for the duration of garment use. To address this issue, compression vests were manufactured using two commonly used fabrics, Powernet or Dri-Tek Tricot, to achieve 10% reduction in circumference for a child-sized mannequin. Applied pressure was tracked on five anatomical sites over 23 hours, before laundering or after one and five laundering cycles. Load relaxation and fatigue of fabrics were tested before laundering or after one and five laundering cycles, and structural analysis via scanning electron microscopy was performed. Prior to laundering, pressure vests fabricated using Powernet or Dri-Tek Tricot generated a maximum pressure on the mannequin of 20 and 23 mm Hg, respectively. With both fabrics, pressure decreased during daily wear. Following five laundering cycles, Dri-Tek Tricot vests delivered a maximum of 7 vs 15 mm Hg pressure for Powernet at the same site. In cyclic tensile and load relaxation tests, exerted force correlated with fabric weave orientation with greatest force measured parallel to a fabric's long axis. The results demonstrate that Powernet exhibited the greatest applied force with the least garment fatigue. Fabric orientation with respect to the primary direction of tension was a critical factor in pressure generation and maintenance. This study suggests that fabrication of garments using Powernet with its long axis parallel to patient's body part circumference may enhance the magnitude and maintenance of pressure delivery.

Effects of early combinatorial treatment of autologous split-thickness skin grafts in red duroc pig model using pulsed dye laser and fractional CO2 laser.

BACKGROUND AND OBJECTIVE: The use of pulsed dye laser (PDL) and fractional CO2 (FX CO2 ) laser therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. While the majority of studies report positive outcomes following PDL or FX CO2 therapy, a number of studies have reported no benefit or worsening of the scar following treatment. The objective of this study was to directly compare the efficacy of PDL, FX CO2 , and PDL + FX CO2 laser therapy in reducing scarring post burn injury and autografting in a standardized animal model. MATERIALS AND METHODS: Eight female red Duroc pigs (FRDP) received 4 standardized, 1 in. x 1 in. third degree burns that were excised and autografted. Wound sites were treated with PDL, FX CO2 , or both at 4, 8, and 12 weeks post grafting. Grafts receiving no laser therapy served as controls. Scar appearance, morphology, size, and erythema were assessed and punch biopsies collected at weeks 4, 8, 12, and 16. At week 16, additional tissue was collected for biomechanical analyses and markers for inflammatory cytokines, extracellular matrix (ECM) proteins, re-epithelialization, pigmentation, and angiogenesis were quantified at all time points using qRT-PCR. RESULTS: Treatment with PDL, FX CO2 , or PDL + FX CO2 resulted in significantly less contraction versus skin graft only controls with no statistically significant difference among laser therapy groups. Scars treated with both PDL and FX CO2 were visually more erythematous than other groups with a significant increase in redness between two and three standard deviations above normal skin redness. Scars treated with FX CO2 were visually smoother and contained significantly fewer wrinkles. In addition, hyperpigmentation was significantly reduced in scars treated with FX CO2 . CONCLUSIONS: The use of fractional carbon dioxide or pulsed dye laser therapy within 1 month of autografting significantly reduced scar contraction versus control, though no statistically significant difference was detected between laser modalities or use of both modalities. Overall, FX CO2 therapy appears to be modestly more effective at reducing erythema, and improving scar texture and biomechanics. The current data adds to prior studies supporting the role of laser therapy in the treatment of burn scars and indicates more study is needed to optimize delivery protocols for maximum efficacy. Lasers Surg. Med. 50:78-87, 2018. © 2017 Wiley Periodicals, Inc.

Scar formation following excisional and burn injuries in a red Duroc pig model.

Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn-induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome. Standardized, full-thickness thermal wounds were created on the dorsum of female, red Duroc pigs. Wounds for the dermatome model were created using two different total dermatome settings: ∼1.5 mm and ≥ 1.9 mm. Results from analysis over 150 days showed that burn wounds healed at much slower rate and contracted more significantly than dermatome wounds of both settings. The burn scars were hairless, had mixed pigmentation, and displayed fourfold and twofold greater excess erythema values, respectively, compared with ∼1.5 mm and ≥ 1.9 mm deep dermatome injuries. Burn scars were less elastic, less pliable, and weaker than scars resulting from excisional injuries. Decorin and versican gene expression levels were elevated in the burn group at day 150 compared with both dermatome groups. In addition, transforming growth factor-beta 1 was significantly up-regulated in the burn group vs. the ∼1.5 mm deep dermatome group at all time points, and expression remained significantly elevated vs. both dermatome groups at day 150. Compared with scars from dermatome wounds, the burn scar model described here demonstrates greater similarity to human hypertrophic scar. Thus, this burn scar model may provide an improved platform for studying the pathophysiology of burn-related hypertrophic scarring, investigating current anti-scar therapies, and development of new strategies with greater clinical benefit.

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation.

Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial (n = 5) and transfemoral (n = 5) amputation were compared to able-limb controls (n = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probe-based approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.

Elevated vacuum suspension preserves residual-limb skin health in people with lower-limb amputation: Randomized clinical trial.

A growing number of clinical trials and case reports support qualitative claims that use of an elevated vacuum suspension (EVS) prosthesis improves residual-limb health on the basis of self-reported questionnaires, clinical outcomes scales, and wound closure studies. Here, we report first efforts to quantitatively assess residual-limb circulation in response to EVS. Residual-limb skin health and perfusion of people with lower-limb amputation (N = 10) were assessed during a randomized crossover study comparing EVS with nonelevated vacuum suspension (control) over a 32 wk period using noninvasive probes (transepidermal water loss, laser speckle imaging, transcutaneous oxygen measurement) and functional hyperspectral imaging approaches. Regardless of the suspension system, prosthesis donning decreased perfusion in the residual limb under resting conditions. After 16 wk of use, EVS improved residual-limb oxygenation during treadmill walking. Likewise, prosthesis-induced reactive hyperemia was attenuated with EVS following 16 wk of use. Skin barrier function was preserved with EVS but disrupted after control socket use. Taken together, outcomes suggest chronic EVS use improves perfusion and preserves skin barrier function in people with lower-limb amputation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; "Evaluation of limb health associated with a prosthetic vacuum socket system": NCT01839123; https://clinicaltrials.gov/ct2/show/NCT01839123?term=NCT01839123&rank=1.

Burn Scar Biomechanics after Pressure Garment Therapy.

BACKGROUND: The current standard of care for the prevention and treatment of scarring after burn injury is pressure garment therapy. Although this therapy has been used clinically for many years, controversy remains regarding its efficacy. The authors evaluated the efficacy of pressure garment therapy in a female red Duroc pig burn model in which wound depth could be tightly controlled. METHODS: Full-thickness burn wounds were generated on female red Duroc pigs. At day 28 after burn, pressure garment therapy was applied to half the wounds (10 mmHg), with control wounds covered with garments that exerted no compression. Scar area, perfusion, hardness, and elasticity were quantified at days 0, 28, 42, 56, and 72 using computerized planimetry, laser Doppler, and torsional ballistometry. Scar morphology was assessed at days 28, 56, and 76 using histology, immunohistochemistry, and transmission electron microscopy. RESULTS: Pressure garment therapy significantly hindered scar contraction, with control scars contracting to 64.6 percent + 13.9 percent original area at day 72, whereas pressure garment therapy scars contracted to 82.7 percent + 17.9 percent original area. Pressure garments significantly reduced skin hardness and increased skin strength by 1.3 times. No difference in perfusion or blood vessel density was observed. The average collagen fiber diameter was greater in control burns than in pressure garment therapy. CONCLUSIONS: Pressure garment therapy was effective at reducing scar contraction and improving biomechanics compared with control scars. These results confirm the efficacy of pressure garments and highlight the need to further investigate the role of pressure magnitude and the time of therapy application to enhance efficacy for optimal biomechanics and patient mobility.

High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.