Fostering inclusivity in research engagement for underrepresented populations in Parkinson's disease: The FIRE-UP PD study.

BACKGROUND: Members of vulnerable populations are underrepresented in Parkinson's disease (PD) research. A complex web of research barriers perpetuates this gap. Community-based research methods are one approach to addressing this issue. The present PD study was designed to examine the effectiveness of community-based interventions to overcome barriers and increase research participation among underrepresented groups (URGs). METHODS: Eight study sites across the US were selected and paired based on proposed interventions with specific URGs. Surveys assessed knowledge and attitudes toward PD research. Finally, researchers examined whether the present study affected recruitment to Fox Insight, an online PD research study also recruiting at each site. RESULTS: In total, 474 participants were recruited. At post-intervention for the FIRE-UP PD Study, recruitment increased significantly in intervention compared to control sites among Black and African American non-Hispanic/Latino populations (p = 0.003), White Hispanic/Latino (p = 0.003) populations, and Not Listed Hispanic/Latino populations (p < 0.001) as well as those with an educational attainment of a high school diploma/General Education Diploma (GED) (p = 0.009), and an income <$20,000 (p = 0.005) or between $20,000-$34,999 (p < 0.001). Study surveys measuring changes in awareness and attitudes toward PD research had mixed results. In Fox Insight, 181 participants were passively recruited with a shift toward more diverse participant demographics. CONCLUSION: Research participation demographics reflective of the general population are critical to PD investigation and treatment. The FIRE-UP PD Study showed the effectiveness of localized community engagement strategies in increasing URG recruitment to PD research. Therefore, further PD research employing community-based methods to improve diverse participant recruitment is needed.

Do Surgical Smoke Evacuators Increase the Risk of Hearing Loss for Operative Personnel During Routine Adenotonsillectomy Surgery?

INTRODUCTION: Aerosol mitigation equipment implemented due to COVID-19 has increased noise levels in the operating room (OR) during otolaryngological procedures. Intraoperative sound levels may potentially place personnel at risk for occupational hearing loss. This study hypothesized that cumulative intraoperative noise exposures with aerosol mitigation equipment exceed recommended occupational noise exposure levels. METHODS: Sound levels generated by the surgical smoke evacuator (SSE) during adenotonsillectomy were measured using a sound level meter and compared to surgery without SSE. RESULTS: Thirteen adenotonsillectomy surgeries were recorded. Mean sound levels with the SSE were greater than the control (72 ± 3 A-weighted decibels (dBA) vs. 68 ± 2 dBA; p=0.015). Maximum noise levels during surgery with SSE reached 82 ± 3 dBA. CONCLUSION: Surgeons performing adenotonsillectomy with aerosol mitigation equipment are exposed to significant noise levels. Intraoperative sound levels exceeded international standards for work requiring concentration. Innovation is needed to reduce cumulative OR noise exposures.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

High Prevalence of Obstructive Sleep-Disordered Breathing in Pediatric Patients With Turner Syndrome.

OBJECTIVE: Girls with Turner syndrome (TS) often have features that have been associated with obstructive sleep-disordered breathing (oSDB). However, little is known about oSDB in TS. Herein, we aimed to characterize oSDB in young patients with TS and identify associated risk factors. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Tertiary care pediatric hospital. METHODS: We reviewed medical records for patients diagnosed with TS seen at our institution between October 1, 2007 and December 31, 2019 with the first outpatient visit before age 6 years. The prevalence of oSDB was compared to the general pediatric population with 1-sample binomial proportion tests. Clinical characteristics were compared between those diagnosed with oSDB and those without oSDB, and risk factors for oSDB were identified. RESULTS: Of 151 patients with TS, 73 (48%) were diagnosed with oSDB which is 4-fold higher than the general pediatric population (12%, P < 0.0001). In the multivariable model, adenoid, tonsillar, and inferior turbinate hypertrophy, birthweight, failure to thrive, and older age at the last clinic visit were all associated with increased odds for oSDB. CONCLUSION: Young children with TS have a high prevalence of oSDB and thus should be screened for oSDB. Polysomnography should be performed in those with associated risk factors and symptoms oSDB. Treatment of oSDB is imperative as individuals with TS are already at increased risk of behavioral problems, neurocognitive deficits, and growth impairment that may be worsened with oSDB.

Effect of Perioperative Antithrombotics on Postoperative Transfusion and Hematoma in Head and Neck Free Flaps.

Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects. Study Design: Retrospective cohort study. Setting: Departments of Otolaryngology-Head and Neck Surgery at the University of Alabama at Birmingham, the University of Colorado, and the University of California Irvine. Methods: A multi-institutional, retrospective review on microvascular reconstruction of the head and neck between August 2013 to July 2021. Perioperative antithrombotic data were collected to examine predictors of postoperative transfusion and hematoma. Results: A total of 843 free flaps were performed. Preoperative hemoglobin, hematocrit, operative time, and flap type were positive predictors of postoperative transfusion in both bivariate (P < .0001) and multivariate analyses (P < .0001). However, neither anticoagulation nor antiplatelet therapy were predictive of postoperative transfusion rates and hematoma formation. Conclusion: Antithrombotic regimens do not increase the risk of postoperative transfusion or hematoma in head and neck microvascular reconstruction. Based on this limited data, perioperative antithrombotic regimens can be considered in patients who may otherwise be at risk for these postoperative complications.

Selective targeting of IL2Rßγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.

The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rßγ on PD-1-expressing cells. Selectively targeting the intermediate-affinity IL-2Rßγ can be leveraged to induce anti-tumor immune responses in effector T cells and natural killer (NK) cells while limiting the negative regulation of IL-2Rα activation on Tregs. Using radiation therapy (RT) in combination with PD1-IL2v improves local tumor control and survival, and controls metastatic spread in orthotopic HNSCC tumor models. PD1-IL2v drives systemic activation and expansion of circulating and tumor-infiltrating cytotoxic T cells and NK cells while limiting Treg-mediated immunosuppression. These data show that PD1-L2v induces durable systemic tumor control in HNSCC.

Simultaneous targeting of PD-1 and IL-2Rßγ with radiation therapy inhibits pancreatic cancer growth and metastasis.

In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rß and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8+ T cell subsets with a transcriptionally and metabolically active phenotype and preferential activation of antigen-specific CD8+ T cells. In combination with single-dose RT, PD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8+ T cells, T cell stemness, tumor-specific memory immune response, natural killer (NK) cell activation, and decreased Tregs. These data show that PD1-IL2v leads to profound local and distant response in PDAC.

Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision.

OBJECTIVE: To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision. STUDY DESIGN: A retrospective review of all patients with microvascular free tissue transfer to the head and neck between August 2013 and July 2021. SETTING: Otolaryngology-Head and Neck Surgery Departments at University of Alabama at Birmingham, University of Colorado, and University of California Irvine. METHODS: Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA) and vasopressor use, and leech therapy were collected plus microvascular free flap outcomes. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed. RESULTS: A total of 843 microvascular free flaps were included. The overall rate of flap failure was 4.0% (n = 34). The overall rate of pedicle anastomosis revision (artery, vein, or both) was 5.0% (n = 42) with a failure rate of 47.6% (n = 20) after revision. Anastomotic revision significantly increased the risk of flap failure (odds ratio [OR] 52.68, 95% confidence interval [CI] [23.90, 121.1], p < .0001) especially when both the artery and vein were revised (OR 9.425, 95% CI [2.117, 52.33], p = .005). Free flap failure after the anastomotic revision was not affected by postoperative antiplatelet therapy, postoperative prophylactic anticoagulation, intraoperative heparin bolus, tPA, and therapeutic anticoagulation regardless of which vessels were revised and if a thrombus was identified. CONCLUSION: In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.

Promising Implants in Rhinoplasty.

Many dilemmas in rhinoplasty tempt surgeons to use exogenous materials. We have long looked toward implants to decrease operative time, to achieve a more reliable result, or when there is a paucity of autologous material. More than ever, the innovative and highly lucrative field of nasal implantology is developing technologically advanced products. This article looks at some popular nasal implant choices with a look toward what might be on the horizon.

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors.

In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.

Exploring feedback-controlled versus open-circuit electrochemical lipolysis in ex vivo and in vivo porcine fat: A feasibility study.

OBJECTIVES: Minimally invasive fat sculpting techniques are becoming more widespread with the development of office-based devices and therapies. Electrochemical lipolysis (ECLL) is a needle-based technology that uses direct current (DC) to electrolyze tissue water creating acid and base in situ. In turn, fat is saponified and adipocyte cell membrane lysis occurs. The electrolysis of water can be accomplished using a simple open-loop circuit (V-ECLL) or by incorporating a feedback control circuit using a potentiostat (P-ECLL). A potentiostat utilizes an operational amplifier with negative feedback to allow users to precisely control voltage at specific electrodes. To date, the variation between the two approaches has not been studied. The aim of this study was to assess current and charge transfer variation and lipolytic effect created by the two approaches in an in vivo porcine model. METHODS: Charge transfer measurements from ex vivo V-ECLL and P-ECLL treated porcine skin and fat were recorded at -1 V P-ECLL, -2 V P-ECLL, -3 V P-ECLL, and -5 V V-ECLL each for 5 min to guide dosimetry parameters for in vivo studies. In follow-up in vivo studies, a sedated female Yorkshire pig was treated with both V-ECLL and P-ECLL across the dorsal surface over a range of dosimetry parameters, including -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL, and 5 V V-ECLL each treated for 5 min. Serial biopsies were performed at baseline before treatment, 1, 2, 7, 14, and 28 days after treatment. Tissue was examined using fluorescence microscopy and histology to compare the effects of the two ECLL approaches. RESULTS: Both V-ECLL and P-ECLL treatments induced in-vivo fat necrosis evident by adipocyte membrane lysis, adipocyte denuclearization, and an acute inflammatory response across a 28-day longitudinal study. However, -1.5 V P-ECLL produced a smaller spatial necrotic effect compared to 5 V V-ECLL. In addition, 5 V V-ECLL produced a comparable necrotic effect to that of -2.5 V and -3.5 V P-ECLL. CONCLUSIONS: V-ECLL and P-ECLL at the aforementioned dosimetry parameters both achieved fat necrosis by adipocyte membrane lysis and denuclearization. The -2.5 V and -3.5 V P-ECLL treatments created spatially similar fat necrotic effects when compared to the 5 V V-ECLL treatment. Quantitatively, total charge transfer between dosimetry parameters suggests that -2.5 V P-ECLL and 5 V V-ECLL produce comparable electrochemical reactions. Such findings suggest that a low-voltage closed-loop potentiostat-based system is capable of inducing fat necrosis to a similar extent compared to that of a higher voltage direct current system.

Multimodality Management of EBV-Associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare cancer of the nasopharyngeal mucosa with a specific geographic predisposition. NPC is often associated with Epstein-Barr Virus (EBV) infection and as a result contains many characteristic biomarkers. Treatment of locally-contained NPC is generally achieved through use of radiotherapy (RT), as part of a multimodality treatment regimen. Induction chemotherapy followed by concurrent RT and platinum-based chemotherapy regimen has emerged as the definitive treatment of choice for locoregionally-advanced NPC. Recently, immunotherapy is finding a role in the treatment of recurrent or metastatic NPC. Immune checkpoint blockade therapies targeted against the programmed death-1 (PD-1) receptor have demonstrated efficacy in early phase clinical trials, with ongoing phase III trials in effect. Biomarkers for treatment efficacy remain an ongoing area of investigation, with important prognostic implications on the horizon.

Electrochemical treatment of ex vivo human abdominal skin and potential use in scar management: A pilot study.

INTRODUCTION: Scar treatments aim to address pathologic collagen deposition; however, they can be expensive or difficult to control. Electrochemical therapy (ECT) offers a simple alternative treatment. The purpose of this study is to examine the acid-base and histological changes in ex vivo human abdominal skin following ECT. METHODS: Forty-two ex vivo human panniculus tissue sections collected from six individuals were tumesced with normal saline. ECT was performed by inserting two platinum needle electrodes connected to a DC power supply into each specimen. Voltage was varied (3-6 V) and applied for 5 minutes. Each specimen was sectioned across both electrode insertion sites and immediately stained with pH sensitive dye. The width of dye color change for each dosimetry pair was calculated. Hematoxylin and eosin staining was used to evaluate samples. RESULTS AND DISCUSSION: ECT caused a spatially localised and dose-dependent increased area of acidic and basic pH around the anode and cathode, respectively. A significantly greater mean width of pH change was generated at the cathode compared to the anode in all treatment groups. Histological evaluation displayed broad condensation and hyalinisation of dermal collagen. CONCLUSION: ECT triggered dermal pH alterations and changed the underlying structural framework of the specimen. This technology may serve as a low-cost, minimally invasive local soft-tissue remodeling technique with potential application in scar management. LEVEL OF EVIDENCE: 5. LAY SUMMARY: Electrochemical therapy is a novel treatment that causes spatially selective dermal injury in areas of interest. This study measures the effects of electrochemical therapy when applied to abdominal skin. Electrochemical therapy appears to have beneficial effects by causing a highly localised reduction in collagen content or local softening of tissue, which is consistent with other studies on scar therapies, including chemexfoliation, radiofrequency technologies, and lasers. However, electrochemical therapy can be performed at a fraction of the costs of these aforementioned modalities.

Electrochemical Therapy of In Vivo Rabbit Cutaneous Tissue.

OBJECTIVES: To examine the acid-base and histological changes in in vivo rabbit cutaneous tissue after electrochemical therapy. STUDY DESIGN: In vivo rabbit tissue study. METHODS: The shaved skin on the backs of female Oryctolagus cuniculi were assigned to treatments with or without tumescence with normal saline. Two platinum-needle electrodes were inserted into each treatment area and connected to a direct current (DC) power supply. Voltage (3-5 V) was varied and applied for 5 minutes. The wound-healing process was monitored via digital photography and ultrasonography until euthanasia at day 29. Treatment areas were biopsied, and specimens were sectioned through a sagittal midline across both electrode insertion sites. Samples were then evaluated utilizing light microscopy (hematoxylin and eosin, Masson's Trichrome, and Picrosirius red). RESULTS: Treatment sites developed mild inflammation that dissipated at lower voltages or became scabs at higher voltages. Ultrasonography demonstrated acoustic shadowing with spatial spread that increased with increasing voltage application. The 4- and 5-V sites treated with saline had localized areas of increased tissue density at day 29. Although specimens treated with 3 V did not look significantly different from control tissue, 4- and 5-V samples with and without saline tumescence had finer, less-organized collagen fibers and increased presence of fibrocytes and inflammatory infiltrates. CONCLUSIONS: Electrochemical therapy caused localized injury to in vivo rabbit cutaneous tissue, prompting regenerative wound repair. With future development, this technology may offer precise, low-cost rejuvenation to restore the functionality and appearance of dermal scars and keloids. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2196-E2203, 2021.

Electrosurgery Turbinate Reduction Revisited: Can Comparable Volumetric Heating be Achieved Without Feedback Control?

BACKGROUND AND OBJECTIVES: Temperature-controlled radiofrequency inferior turbinate ablation (TCRFA) uses a feedback system to control thermal injury and achieve precise volumetric heating to induce specific scar formation. However, it requires costly single-use proprietary consumables. Comparable volumetric tissue heating may be achieved for a fraction of the cost by adjusting the power settings on traditional monopolar electrosurgery devices that use low-cost needle tips. This pre-clinical study aims to determine the optimized power parameters to achieve electrosurgical coagulum volume similar to that of TCRFA. STUDY DESIGN/MATERIALS AND METHODS: An electrosurgery submucosal diathermy (SMD) system (cut mode, 4-32 W, 5-120 seconds) and a temperature-controlled radiofrequency ablation system (standard clinical parameters for treating inferior turbinate hypertrophy) were used to coagulate egg white and chicken breast. Coagulum major and minor axis were measured, and lesion volume was approximated as prolate spheroid. RESULTS: No significant difference in volume was found between the temperature-controlled system and the electrosurgery system at 8 W for 30 seconds, 8 W for 60 seconds, 16 W for 30 seconds, 32 W for 5 seconds, and 32 W for 15 seconds. The time to achieve equivalent lesion size was significantly less in the SMD system when compared to the temperature-controlled system (P < 0.05). CONCLUSION: Electrosurgery handpieces may achieve similar lesion volume effects as the temperature feedback-controlled, single-use handpieces when set to the optimized parameters. SMD handpieces are significantly more cost and time effective than proprietary devices, and they are easily used in the office. SMD devices may be a more affordable alternative to temperature-controlled systems with comparable lesion volume effect and may be valuable for office-based therapy. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Electrochemical degradation and saponification of porcine adipose tissue.

Body contouring achieved via subcutaneous adipose tissue reduction has notably advanced over the past century, from suction assisted lipectomy to techniques with reduced degrees of invasiveness including laser, radiofrequency, high frequency focused ultrasound, cryolipolysis, and drug-based injection approaches. These costly techniques have focused on damaging adipocyte cell membranes, hydrolyzing triglycerides (TGs), or inducing apoptosis. Here, we present a simple, low-cost technique, termed electrochemical lipolysis (ECLL). During ECLL, saline is injected into the subcutaneous adipose tissue, followed by insertion of needle electrodes and application of an electrical potential. Electrolysis of saline creates localized pH gradients that drive adipocyte death and saponification of TGs. Using pH mapping, various optical imaging techniques, and biochemical assays, we demonstrate the ability of ECLL to induce acid and base injury, cell death, and the saponification of triglycerides in ex vivo porcine adipose tissue. We define ECLL's potential role as a minimally-invasive, ultra-low-cost technology for reducing and contouring adipose tissue, and present ECLL as a potential new application of an emerging electrochemical redox based treatment modality.

The biophysical effects of localized electrochemical therapy on porcine skin.

BACKGROUND: Minimally-invasive methods to treat scars address a common pathway of altering collagen structure, leading to collagen remodeling. OBJECTIVE: In this study, we employed in situ redox chemistry to create focal pH gradients in skin, altering dermal collagen, in a process we refer to as electrochemical therapy (ECT). The effects of ECT to induce biochemical and structural changes in ex vivo porcine skin were examined. METHODS: During ECT, two platinum electrodes were inserted into fresh porcine skin, and following saline injection, an electrical potential was applied. pH mapping, high frequency ultrasonography, and two photon excitation microscopy and second harmonic generation (SHG) microscopy were used to evaluate treatment effects. Findings were correlated with histology. RESULTS: Following ECT, pH mapping depicted acid and base production at anode and cathode sites respectively, with increasing voltage and application time. Gas formation during ECT was observed with ultrasonography. Anode sites showed significant loss of SHG signal, while cathode sites showed disorganized collagen structure with fewer fibrils emitting an attainable signal. Histologically, collagen denaturation at both sites was confirmed. CONCLUSION: We demonstrated the production of in situ acid and base in skin occurring via ECT. The effects chemically and precisely alter collagen structure through denaturation, giving insight on the potential of ECT as a simple, low-cost, and minimally-invasive means to remodel skin and treat scars.

Electrochemolipolysis of Human Adipose Tissue.

Importance: Body fat contouring procedures have increasingly grown in popularity over the years. As such, there is a need for inexpensive, minimally invasive, and simple fat reduction/contouring technique. Objective: To examine the acid-base and histological changes in ex vivo human adipose tissue after electrochemolipolysis (ECL). Design, Setting, and Participants: Panniculus tissue specimens obtained after abdominoplasty procedures were tumesced with normal saline. Two platinum needle electrodes were inserted into each sample and connected to a DC power supply. Voltage (3-6 V) was varied and applied for 5 min. Specimens were sectioned through a sagittal midline across both electrode insertion sites and immediately stained with pH-sensitive dye. A numerical algorithm was used to calculate the area of the dye color change for each dosimetry pair. Samples were also evaluated utilizing light microscopy (hematoxylin and eosin). An ex vivo human adipose tissue model was used for evaluating the effects of ECL. Results: Acidic and basic pH was appreciated surrounding the anode and cathode insertion sites, respectively. The effect was spatially localized and dose dependent. Statistical analysis of these data showed no significant difference between the mean area of the pH disturbance generated at the anode compared with the cathode at 3 V for 5 min (6.04 mm2 vs. 2.95 mm2, p = 0.40, 95% CI -4.8 to 11). A significantly greater area of pH disruption was generated at the cathode versus the anode in groups 4 V for 5 min (14.7 mm2 vs. 5.00 mm2, p = 0.032, 95% CI 0.93-19), 5 V for 5 min (15.5 mm2 vs. 6.72 mm2, p = 0.019, 95% CI 1.6-16), and 6 V for 5 min (22.5 mm2 vs. 10.0 mm2, p = 0.047, 95% CI 0.22-25). Acute structural changes in adipocytes were observed in all specimens. Vascular damage with adjacent adipocyte necrosis was prominent at the cathode site in group 6 V for 5 min. Conclusions and Relevance: ECL at the studied dosimetry parameters induced acid and base changes in human adipose tissue, suggesting its potential use in nonsurgical fat reduction as an ultralow cost alternative to current lipolytic devices and pharmaceuticals. Level of Evidence: NA.

The use of optical coherence tomography and convolutional neural networks to distinguish normal and abnormal oral mucosa.

Incomplete surgical resection of head and neck squamous cell carcinoma (HNSCC) is the most common cause of local HNSCC recurrence. Currently, surgeons rely on preoperative imaging, direct visualization, palpation and frozen section to determine the extent of tissue resection. It has been demonstrated that optical coherence tomography (OCT), a minimally invasive, nonionizing near infrared mesoscopic imaging modality can resolve subsurface differences between normal and abnormal head and neck mucosa. Previous work has utilized two-dimensional OCT imaging which is limited to the evaluation of small regions of interest generated frame by frame. OCT technology is capable of performing rapid volumetric imaging, but the capacity and expertise to analyze this massive amount of image data is lacking. In this study, we evaluate the ability of a retrained convolutional neural network to classify three-dimensional OCT images of head and neck mucosa to differentiate normal and abnormal tissues with sensitivity and specificity of 100% and 70%, respectively. This method has the potential to serve as a real-time analytic tool in the assessment of surgical margins.