Skin Pigmentation Affects ViOptix T.Ox Performance in Variably Pigmented Preclinical Model of Flap Ischemia and Congestion.

Background: Free flap monitoring is more difficult in patients with dark skin because ischemia and congestion can be masked by pigmentation. For this reason, adjunct methods such as cutaneous near-infrared spectroscopy are of elevated importance in patients with highly pigmented skin. The purpose of this experiment is to determine if ViOpitx T.Ox performance is affected by cutaneous pigmentation. Methods: Swine with naturally occurring areas of nonpigmented and pigmented skin were used. Pigmentation of each animal was assessed using spectrophotometry and histopathology. During normoxemia, tissue oxygenation (StO2) measurements were taken of nonpigmented and pigmented skin using the T.Ox device. A bicolor pedicled rectus abdominis myocutaneous flap was raised, and T.Ox probe was adhered to adjacent areas of opposite coloration on the same flap. StO2 was measured continuously during reversible episodes of flap ischemia and congestion (n = 4 swine, n = 6 flaps). Results: There was not a significant difference between baseline StO2 values of nonpigmented (49% ± 7.9%) and pigmented skin (47% ± 6.2%). The absolute change in StO2 was significantly larger during both ischemia (6%) and congestion (16%) in nonpigmented skin compared with adjacent pigmented skin. Conclusions: T.Ox detects flap ischemia and congestion in both highly pigmented and nonpigmented skin. However, surgeons need to be aware that StO2 changes related to complete flap ischemia or congestion may be much more subtle than what is seen in nonpigmented skin. This study establishes a novel internally controlled porcine model that isolates the impact of skin pigmentation when assessing cutaneous devices measuring tissue oxygenation.

Trimodal wireless intramuscular device detects muscle pressure, flow, and oxygenation changes in porcine model of lower extremity compartment syndrome.

PURPOSE: Compartment syndrome remains difficult to diagnose early in its clinical course. Pressure transducer catheters have been used to directly measure intracompartmental pressure (ICP), but this method is unreliable, with a false positive rate of 35%. We have previously used intramuscular near infrared spectroscopy to detect changes in tissue oxygen saturation (StO2) in response to increasing ICP using a novel implantable probe. However, measuring StO2 may not be sufficient to identify CS in the clinical setting. The pathophysiology of CS consists of increased ICP, leading to decreased tissue perfusion, and resulting in reduced tissue oxygenation. More clinically useful information may come from the integration of multiple data streams to aid in the diagnosis of CS. In this study, we present a novel, intramuscular probe capable of simultaneous measurement of ICP, StO2, and microvascular blood flow in a porcine model of ACS. METHODS: Proof of concept for this device is demonstrated in a porcine lower extremity balloon compression model of ACS. Pressure was maintained for 20 min (short-term) or 3 h (long-term) before the balloon volume was removed. RESULTS: In both short- and long-term experiments, as ICP increased with increasing balloon volume, the novel multimodal sensor simultaneously and reliably detected pressure elevation and corresponding reversible reductions in microvascular flow rate and tissue oxygenation. CONCLUSION: This novel trimodal device simultaneously measured the elevated ICP, decreased perfusion, and tissue ischemia of evolving ACS, substantiating our basic understanding of CS pathophysiology.

Assessing an Online Patient Decision Aid about Upper Extremity Reconstructive Surgery for Cervical Spinal Cord Injury: Pilot Testing Knowledge, Decisional Conflict, and Acceptability.

Background. While nerve and tendon transfer surgery can restore upper extremity function and independence after midcervical spinal cord injury, few individuals (∼14%) undergo surgery. There is limited information regarding these complex and time-sensitive treatment options. Patient decision aids (PtDAs) convey complex health information and help individuals make informed, preference-consistent choices. The purpose of this study is to evaluate a newly created PtDA for people with spinal cord injury who are considering options to optimize upper extremity function. Methods. The PtDA was developed by our multidisciplinary group based on clinical evidence and the Ottawa Decision Support Framework. A prospective pilot study enrolled adults with midcervical spinal cord injury to evaluate the PtDA. Participants completed surveys about knowledge and decisional conflict before and after viewing the PtDA. Acceptability measures and suggestions for further improvement were also solicited. Results. Forty-two individuals were enrolled and completed study procedures. Participants had a 20% increase in knowledge after using the PtDA (P < 0.001). The number of participants experiencing decisional conflict decreased after viewing the PtDA (33 v. 18, P = 0.001). Acceptability was high. To improve the PtDA, participants suggested adding details about specific surgeries and outcomes. Limitations. Due to the COVID-19 pandemic, we used an entirely virtual study methodology and recruited participants from national networks and organizations. Most participants were older than the general population with a new spinal cord injury and may have different injury causes than typical surgical candidates. Conclusions. A de novo PtDA improved knowledge of treatment options and reduced decisional conflict about reconstructive surgery among people with cervical spinal cord injury. Future work should explore PtDA use for improving knowledge and decisional conflict in the nonresearch, clinical setting. Highlights: People with cervical spinal cord injury prioritize gaining upper extremity function after injury, but few individuals receive information about treatment options.A newly created patient decision aid (PtDA) provides information about recovery after spinal cord injury and the role of traditional tendon and newer nerve transfer surgery to improve upper extremity upper extremity function.The PtDA improved knowledge and decreased decisional conflict in this pilot study.Future work should focus on studying dissemination and implementation of the ptDA into clinical practice.

Point-of-Care Tissue Oxygenation Assessment with SnapshotNIR for Alloplastic and Autologous Breast Reconstruction.

In breast reconstruction, mastectomy and free flaps are susceptible to vascular compromise and tissue necrosis. The SnapshotNIR device (Kent Imaging, Calgary, AB, Canada) utilizes near-infrared spectroscopy to measure tissue oxygen saturation (StO2) and hemoglobin concentration. Here, we report on the use of this device for StO2 monitoring among patients receiving alloplastic or autologous breast reconstruction. Methods: Patients receiving immediate alloplastic reconstruction after mastectomy or autologous reconstruction were enrolled. Preoperative, intraoperative, and postoperative images were taken of the flaps. StO2 and hemoglobin were measured at the following locations: superior and inferior breast, free flap skin paddle (when applicable), and un-operated control skin. Linear mixed effects model for repeated measurements was used to model measurements to estimate the area effect difference across time, time effect difference across area, and pairwise comparisons between two areas at each time point. Results: Thirty-two breasts underwent alloplastic reconstruction; 38 breasts underwent autologous reconstruction. No enrollees developed skin necrosis. StO2 was highest after mastectomy and closure in alloplastic reconstructions. StO2 was observed to decline at follow-up in autologous reconstructions. Mean preoperative StO2 was highest in breasts that had previously undergone mastectomy and alloplastic reconstruction. Conclusions: The SnapshotNIR device detected normal spatial and temporal differences in tissue oxygenation over the operative course of alloplastic and autologous breast reconstruction. A multi-institutional, prospective clinical trial is needed to determine the sensitivity and specificity of this device for detecting skin flap necrosis.

Compound Effect of Hypoalbuminemia and Obesity on Complications after Autologous Breast Reconstruction.

BACKGROUND: Obesity is among the risk factors identified that impair postoperative wound healing. Recently, malnutrition and sarcopenia have also been found to correlate with poor surgical outcomes; however, the effect of malnutrition in the setting of obesity is understudied, particularly in reconstructive surgery. The authors examine the American College of Surgeons National Surgery Quality Improvement Program database to determine the impact of obesity plus hypoalbuminemia on complications after autologous breast reconstruction. METHODS: Autologous breast reconstruction procedures (pedicled and free flaps) were collected from the 2009 to 2019 National Surgery Quality Improvement Program databases by CPT codes ( n = 23,690). Patients without height, weight, or preoperative serum albumin data ( n = 12,825) were excluded. Demographics and postoperative outcomes were compared in patients with obesity (body mass index >30 kg/m 2 ) and malnutrition (albumin <3.5 g/dL). Propensity score-matched cohorts with and without malnutrition were also compared. RESULTS: A total of 10,865 procedures were included in analysis; 4565 involved patients with obesity (42%). Obesity was associated with increased length of stay, reoperations, wound complications, and medical complications (all P < 0.001). Among patients with obesity, 198 had malnutrition (4.3%). The combination of obesity and malnutrition was associated with a higher rate of wound complications (16%) over obesity alone (9.2%) or malnutrition alone (9.2%, both P < 0.05). This difference is recapitulated in propensity score-matched analysis. CONCLUSION: Hypoalbuminemia, a marker of malnutrition, is underappreciated in obese patients and is associated with worse surgical outcomes after autologous breast reconstruction compared with obesity alone. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Percutaneously introduced wireless intramuscular near-infrared spectroscopy device detects muscle oxygenation changes in porcine model of lower extremity compartment syndrome.

Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool. Under ideal conditions, NIRS directly measures the oxygenation of intracompartmental muscle (StO2 ), thereby obviating the challenges of interpreting equivocal clinical examination or ICP data. Despite these potential advantages, existing NIRS sensors are plagued by technical difficulties that limit clinical utility. Most of these limitations relate to their transcutaneous design that makes them susceptible to both interference from intervening skin/subcutaneous tissue, underlying hematoma, and instability of the skin-sensor interface. Here, we present a flexible, wireless, Bluetooth-enabled, percutaneously introducible intramuscular NIRS device that directly and continuously measures the StO2 of intracompartmental muscle. Proof of concept for this device is demonstrated in a swine lower extremity balloon compression model of acute CS, wherein we simultaneously track muscle oxygenation, ICP, and compartment perfusion pressure (PP). The observed StO2 decreased with increasing ICP and decreasing PP and then recovered following pressure reduction. The mean change in StO2 as the PP was decreased from baseline to 30 mmHg was -7.6%. The mean difference between baseline and nadir StO2 was -17.4%. Cross-correlations (absolute value) describing the correspondence between StO2 and ICP were >0.73. This novel intramuscular NIRS device identifies decreased muscle perfusion in the setting of evolving CS.

Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.

BACKGROUND: Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO2) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO2 measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy. METHODS: The intratissue microvascular flow-sensing device includes a resistive heater, 4 thermistors, a small battery, and a Bluetooth chip, which allows connection to a smart device. Convection of applied heat is measured and mathematically transformed into a measurement of blood flow velocity. This was tested alongside Vioptix T.Ox in a porcine rectus abdominis myocutaneous flap model of arterial and venous occlusion. After flap elevation, the thermal device was deployed intramuscularly, and the cutaneous T.Ox device was applied. Acland clamps were alternately applied to the flap artery and veins to achieve 15 minutes periods of flap ischemia and congestion with a 15 minutes intervening recovery period. In total, five devices were tested in three flaps in three separate pigs over 16 vaso-occlusive events. RESULTS: Flow measurements were responsive to both ischemia and congestion, and returned to baseline during recovery periods. Flow measurements corresponded closely with measured StO2. Cross-correlation at zero lag showed agreement between these two sensing modalities. Two novel devices tested simultaneously on the same flap showed only minor variations in flow measurements. CONCLUSION: This novel probe is capable of detecting changes in tissue microcirculatory blood flow. This device performed well in a swine model of flap ischemia and congestion, and shows promise as a potentially useful clinical tool. Future studies will investigate performance in fasciocutaneous flaps and characterize longevity of the device over a period of several days.

Wireless implantable optical probe for continuous monitoring of oxygen saturation in flaps and organ grafts.

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O2-sensing probes, and fluorine magnetic resonance imaging methods are limited by their intermittent measurements, requirements for skilled personnel, indirect interfaces, and/or their tethered connections. This paper reports a wireless, miniaturized, minimally invasive near-infrared spectroscopic system designed for uninterrupted monitoring of local-tissue oxygenation. A bioresorbable barbed structure anchors the probe stably at implantation sites for a time period matched to the clinical need, with the ability for facile removal afterward. The probe connects to a skin-interfaced electronic module for wireless access to essential physiological parameters, including local tissue oxygenation, pulse oxygenation, and heart rate. In vitro tests and in vivo studies in porcine flap and kidney models demonstrate the ability of the system to continuously measure oxygenation with high accuracy and sensitivity.

Implantable, wireless, self-fixing thermal sensors for continuous measurements of microvascular blood flow in flaps and organ grafts.

Vascular pedicle thrombosis after free flap transfer or solid organ transplantation surgeries can lead to flap necrosis, organ loss requiring re-transplantation, or even death. Although implantable flow sensors can provide early warning of malperfusion and facilitate operative salvage, measurements performed with existing technologies often depend on extrinsic conditions such as mounting methods and environmental fluctuations. Furthermore, the mechanisms for fixing such probes to vascular or skeletal structures may disrupt the normal blood flow or cause unnecessary tissue damage. Requirements for wired connections to benchtop readout systems also increase costs, complicate clinical care and constrain movements of the patient. Here, we report a wireless, miniaturized flow sensing system that exploits sub-millimeter scale, multi-nodal thermal probes, with biodegradable barbs that secure the probes to the surrounding tissues in a manner that facilitates removal after a period of use. These smartphone-readable devices, together with experimentally validated analytical models of the thermal transport physics, enable reliable, accurate flow sensing in ways that are largely immune to variations in temperature and mechanical perturbations. In vivo demonstrations of this technology in porcine myocutaneous flap and kidney malperfusion models highlight the essential capabilities in microsurgical and transplantation-related biomedical application scenarios.

National Outcomes of Prophylactic Lymphovenous Bypass during Axillary Lymph Node Dissection.

BACKGROUND: Breast cancer treatment, including axillary lymph node excision, radiation, and chemotherapy, can cause upper extremity lymphedema, increasing morbidity and health care costs. Institutions increasingly perform prophylactic lymphovenous bypass (LVB) at the time of axillary lymph node dissection (ALND) to reduce the risk of lymphedema but reports of complications are lacking. We examine records from the American College of Surgeons (ACS) National Surgery Quality Improvement Program (NSQIP) database to examine the safety of these procedures. METHODS: Procedures involving ALND from 2013 to 2019 were extracted from the NSQIP database. Patients who simultaneously underwent procedures with the Current Procedural Terminology (CPT) codes 38999 (other procedures of the lymphatic system), 35201 (repair of blood vessel), or 38308 (lymphangiotomy) formed the prophylactic LVB group. Patients in the LVB and non-LVB groups were compared for differences in demographics and 30-day postoperative complications including unplanned reoperation, deep vein thrombosis (DVT), wound dehiscence, and surgical site infection. Subgroup analysis was performed, controlling for extent of breast surgery and reconstruction. Multivariate logistic regression was performed to identify predictors of reoperation. RESULTS: The ALND without LVB group contained 45,057 patients, and the ALND with LVB group contained 255 (0.6%). Overall, the LVB group was associated with increased operative time (288 vs. 147 minutes, p < 0.001) and length of stay (1.7 vs. 1.3 days, p < 0.001). In patients with concurrent mastectomy without immediate reconstruction, the LVB group had a higher rate of DVTs (3.0 vs. 0.2%, p = 0.009). Reoperation, wound infection, and dehiscence rates did not differ across subgroups. Multivariate logistic regression showed that LVB was not a predictor of reoperations. CONCLUSION: Prophylactic LVB at time of ALND is a generally safe and well-tolerated procedure and is not associated with increased reoperations or wound complications. Although only four patients in the LVB group had DVTs, this was a significantly higher rate than in the non-LVB group and warrants further investigation.

Intramuscular Near-Infrared Spectroscopy for Muscle Flap Monitoring in a Porcine Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Agent-based model provides insight into the mechanisms behind failed regeneration following volumetric muscle loss injury.

Skeletal muscle possesses a remarkable capacity for repair and regeneration following a variety of injuries. When successful, this highly orchestrated regenerative process requires the contribution of several muscle resident cell populations including satellite stem cells (SSCs), fibroblasts, macrophages and vascular cells. However, volumetric muscle loss injuries (VML) involve simultaneous destruction of multiple tissue components (e.g., as a result of battlefield injuries or vehicular accidents) and are so extensive that they exceed the intrinsic capability for scarless wound healing and result in permanent cosmetic and functional deficits. In this scenario, the regenerative process fails and is dominated by an unproductive inflammatory response and accompanying fibrosis. The failure of current regenerative therapeutics to completely restore functional muscle tissue is not surprising considering the incomplete understanding of the cellular mechanisms that drive the regeneration response in the setting of VML injury. To begin to address this profound knowledge gap, we developed an agent-based model to predict the tissue remodeling response following surgical creation of a VML injury. Once the model was able to recapitulate key aspects of the tissue remodeling response in the absence of repair, we validated the model by simulating the tissue remodeling response to VML injury following implantation of either a decellularized extracellular matrix scaffold or a minced muscle graft. The model suggested that the SSC microenvironment and absence of pro-differentiation SSC signals were the most important aspects of failed muscle regeneration in VML injuries. The major implication of this work is that agent-based models may provide a much-needed predictive tool to optimize the design of new therapies, and thereby, accelerate the clinical translation of regenerative therapeutics for VML injuries.

A coupled framework of in situ and in silico analysis reveals the role of lateral force transmission in force production in volumetric muscle loss injuries.

Volumetric muscle loss injuries (VML) are challenging to treat because of the variability in wound location. Regenerative medicine offers promising alternative treatments, but there is little understanding of the correlation between magnitude of VML injuries and corresponding functional deficits that must be addressed. There is a need for a tool that can elucidate the relationship between VML injury and force loss, as well as the impact on specific mechanisms responsible for force production. The purpose of this study was to develop a novel coupled framework of in situ and in silico methods to more precisely understand the relationship between injury location and force production deficits. We created a three-dimensional finite-element model of the pennate latissimus dorsi (LD) muscle in the rat and validated the model experimentally. We found that the model's prediction (2.6 N/g Model I, 2.1 N/g Model V) compared favorably to in situ testing of isometric force generation of the injured rat LD muscle (2.8 ±â€¯0.3 N/g Experimental I, 2.0 ±â€¯0.2 N/g Experimental V). Further model analysis revealed that the contribution from lateral and longitudinal force transmission to the total force varied with injury location and led to a greater understanding of the mechanisms responsible for VML-related force deficits. In the future, the coupled computational and experimental framework can be used to inform development of preclinical VML injury models that better recapitulate the spectrum of VML injuries observed in affected patients, and the mechanistic insight can accelerate the creation of improved regenerative therapeutics for VML injuries.

Decellularized extracellular matrix microparticles seeded with bone marrow mesenchymal stromal cells for the treatment of full-thickness cutaneous wounds.

Extracellular matrix materials mechanically dissociated into submillimeter particles have a larger surface area than sheet materials and enhanced cellular attachment. Decellularized porcine mesothelial extracellular matrix microparticles were seeded with bone marrow-derived mesenchymal stromal cells and cultured in a rotating bioreactor. The mesenchymal stromal cells attached and grew to confluency on the microparticles. The cell-seeded microparticles were then encapsulated in varying concentrations of fibrin glue, and the cells migrated rapidly off the microparticles. The combination of microparticles and mesenchymal stromal cells was then applied to a splinted full-thickness cutaneous in vivo wound model. There was evidence of increased cell infiltration and collagen deposition in mesenchymal stromal cells-treated wounds. Cell-seeded microparticles have potential as a cell delivery and paracrine therapy in impaired healing environments.