Virtual Reality Facilitated Exercise Increases Sympathetic Activity and Reduces Pain Perception: A Randomized Crossover Study.

OBJECTIVE: Both virtual reality (VR) and exercise reduce pain while avoiding the risks of traditional pharmacotherapy. The aim of this study was to assess how VR-facilitated exercise modulates sympathetic activity and pain perception. DESIGN: Healthy adult volunteers were randomized by hand dominance and then subjected to a standardized cold pressor test while experiencing a VR application. After a 5-minute washout, participants were crossed-over and repeated the test on their other hand while undergoing a VR-facilitated exercise application. Sympathetic activation, pain sensation, and pain tolerance data were collected identically during both conditions. RESULTS: 110 participants were analyzed. Sympathetic activity increased in both conditions but was higher in the VR-facilitated exercise condition (p < 0.0001). Pain sensation scores were initially higher with VR-facilitated exercise but dropped below the VR-only condition by the end of the intervention (p = 0.0175). There were no differences in pain tolerance between conditions (p = 0.18). CONCLUSION: The decrease in pain perception with VR-facilitated exercise condition compared to VR alone indicates VR-facilitated exercise can be a useful tool for managing pain. Though this effect did not translate into higher pain tolerance, VR-facilitated exercise may be a useful intervention in the setting of physical therapy or for patients with chronic pain.

Diagnosis and Management of Orbital Compartment Syndrome in Burn Patients - a Systematic Review.

Orbital compartment syndrome is a poorly understood complication of acute burns. The purpose of this systematic review is to summarize the literature describing orbital compartment syndrome in burn patients to provide greater detail on risk factors and guide management of this morbid condition. A systematic review of the PubMed, Embase, and Cochrane Library databases was performed in June 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using two validated scoring systems. After removing duplicates, 303 unique articles were reviewed and 8 met inclusion criteria. All publications were retrospective. Most studies considered intraocular pressure >30-40mmHg as diagnostic for orbital compartment syndrome. Sixty unique cases of orbital compartment syndrome were reported. Orbital compartment syndrome occurred most frequently within 24 hours post-burn. The mean total body surface area of burn was 58.7%; the mean 24-hour resuscitation volume was 6.01 cc/kg/%total burn surface area; and 86.5% of cases had periorbital burns. Surgical decompression always started with lateral canthotomy. When pressures were not immediately reduced, cantholysis was performed. Study quality per Median Newcastle Ottawa Scores ranged from 38.9% to 94.4% (median 66.7%). A precise threshold for surgical decompression of OCS remains conflicted; however, IOP>30-40mmHg warrants intervention. Burn surgeons/intensivists should be aware of the risk factors for this vision-threatening complication and act appropriately.

Virtual reality facilitated exercise improves pain perception: A crossover study.

STUDY OBJECTIVE: Both virtual reality (VR) and exercise are recognized for their analgesic and anxiolytic properties. The purpose of this study is to evaluate the ability of VR-facilitated exercise to modulate pain. DESIGN: Within-subject cross-over clinical trial. SETTING: The Stanford Chariot Program conducted this study at Lucile Packard Children's Hospital Stanford (LCPHS). PATIENTS: Healthy participants meeting inclusion criteria were recruited by volunteer solicitation from LCPHS. INTERVENTIONS: Participants were randomized by hand dominance and subjected to a standardized cold pressor test with no VR or exercise. After a 5-min wash-out period, participants repeated the test on their other hand while experiencing a VR-facilitated exercise condition. Pain sensitivity, pain tolerance, and sympathetic activation data were collected during both conditions. MEASUREMENTS: Pain sensitivity was scored 0-10 and collected every 30 s. Pain tolerance was recorded as the duration a participant could endure the painful stimuli. Sympathetic activation was measured by skin conductance response density (SCRD) and recorded in 30 s epochs by a biosensor. In all analyses, data were nested by participant. MAIN RESULTS: Forty-one participants completed both interventions. Pain sensitivity was reduced in the VR-facilitated exercise condition (p < 0.0001). There was no difference in pain tolerance between conditions. While both conditions resulted in an increase in sympathetic activity, SCRD was higher at all time points in the VR-facilitated exercise condition. CONCLUSIONS: The reduction in pain sensitivity indicates VR-facilitated exercise results in improved pain perception. VR-facilitated exercise may be especially useful for patients with chronic pain or other conditions requiring physical therapy, where pain may be exacerbated by exercise.

Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.

OBJECTIVE: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. SUMMARY BACKGROUND DATA: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. METHODS: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. RESULTS: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. CONCLUSION: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.

Use of Local Antibiotic Delivery Systems in Tissue Expander and Implant-Based Breast Reconstruction: A Systematic Review of the Literature.

Background: Periprosthetic infections are a debilitating complication of alloplastic breast reconstruction. Local antibiotic delivery for prophylaxis and infection clearance has been used by other surgical specialties but rarely in breast reconstruction. Because local delivery can maintain high antibiotic concentrations with lower toxicity risk, it may be valuable for infection prophylaxis or salvage in breast reconstruction. Methods: A systematic search of the Embase, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies examining local antibiotic delivery systems for either prophylaxis or salvage of periprosthetic infections were included. Study quality and bias were assessed using the validated MINORS criteria. Results: Of 355 publications reviewed, 8 met the predetermined inclusion criteria; 5 papers investigated local antibiotic delivery for salvage, and 3 investigated infection prophylaxis. Implantable antibiotic delivery devices included polymethylmethacrylate, calcium sulfate, and collagen sponges impregnated with antibiotics. Non-implantable antibiotic delivery methods used irrigation with antibiotic solution into the breast pocket. All studies indicated that local antibiotic delivery was either comparable or superior to conventional methods in both the salvage and prophylaxis settings. Conclusions: Despite varied sample sizes and methodologies, all papers endorsed local antibiotic delivery as a safe, effective method of preventing or treating periprosthetic infections in breast reconstruction.

Use of Antibiotic-impregnated Polymethylmethacrylate (PMMA) Plates for Prevention of Periprosthetic Infection in Breast Reconstruction.

Periprosthetic infections remain a major challenge for breast reconstruction. Local antibiotic delivery systems, such as antibiotic beads and spacers, have been widely used within other surgical fields, but their use within plastic surgery remains scarce. In this study, we demonstrate the use of antibiotic-impregnated polymethylmethacrylate (PMMA) plates for infection prophylaxis in tissue expander (TE)-based breast reconstruction. Methods: A retrospective review of patients who underwent immediate breast reconstruction with prepectoral TEs over the span of 5 years performed by two surgeons was completed, revealing a total of 447 patients. Data pertaining to patient demographics, operative details, and postoperative outcomes were recorded. Fifty patients underwent TE reconstruction with the addition of a PMMA plate (Stryker, Kalamazoo, Michigan) impregnated with tobramycin and vancomycin. Antibiotic plates were removed at the time of TE-to-implant exchange. Patient-matching analysis was performed using the 397 patients without PMMA plates to generate a 50-patient nonintervention cohort for statistical analysis. Results: The intervention cohort (n = 50) and 1:1 patient-matched nonintervention cohort (n = 50) demonstrated no statistically significant differences in patient demographics or operative characteristics other than PMMA plate placement. The rate of operative periprosthetic infection was 4% in the intervention group and 14% in the nonintervention group (P = 0.047). The rate of TE explantation was also reduced in the intervention group (6% versus 18%; P = 0.036). Follow-up averaged 9.1 and 8.9 months for the intervention and nonintervention groups, respectively (P = 0.255). Conclusion: Local antibiotic delivery using antibiotic-impregnated PMMA plates can be safely and effectively used for infection prevention with TE-based breast reconstruction.

Foot Burns and Diabetes: A Systematic Review of Current Clinical Studies and Proposal of a New Treatment Algorithm.

This study aims to systematically identify studies that evaluate lower extremity burn injury in the diabetic population, evaluate their clinical course and patient outcomes, and present a treatment algorithm tailored to diabetic burn patients. Our systematic review of the PubMed and Web of Science databases yielded 429 unique articles. After exclusion and inclusion criteria were applied, 59 articles were selected for evaluation. In diabetic patients, thermal injury was largely a result of decreased awareness and education regarding heat therapies in the context of peripheral neuropathy. All non-case studies found that metrics such as hospital length of stay, ICU admission rates, rates of comorbidity, complication rates, scald injuries, infection rates, and cost of treatment was significantly increased in the diabetic burn population as compared to their nondiabetic counterparts. Where infection was present, microorganisms colonizing diabetic burn wounds were different than those found in the burn wounds of immunocompetent individuals. Operative intervention including split-skin graft, amputation, and debridement were more often utilized in diabetic burn patients. Foot burns in diabetic patients pose unique clinical risks to patients, and as such need to be an alternate treatment protocol to reflect their pathology. Education and training programs are crucial in the prevention of diabetic foot burns to avoid complications, protracted healing, and adverse outcomes. A unique algorithm can guide the unique treatment of this clinical entity.

The Impact of Oncoplastic Reduction on Initiation of Adjuvant Radiation and Need for Reexcision: A Database Evaluation.

INTRODUCTION: Partial breast reconstruction with oncoplastic reduction can provide breast cancer patients with improved aesthetic outcomes after breast conservation therapy. This study evaluates the implications of simultaneous oncoplastic reduction with lumpectomy on complication rates, time to adjuvant radiation therapy, and rates of margin reexcision compared with lumpectomy alone. METHODS: The Clinformatics Data Mart Database is a national deidentified commercial claims data warehouse. From 2003 to 2020, adult female patients were queried to identify patients with a breast cancer diagnosis with International Classification of Disease codes. Among those, current procedural terminology codes were used to identify those who underwent lumpectomy alone versus lumpectomy with oncoplastic reduction. Patient demographics, complications, adjuvant oncologic therapies, and need for reexcision were recorded. Patients not continuously enrolled for at least 6 months before and after the index procedure were excluded. Multivariable regression and χ 2 tests were used for statistical analysis. RESULTS: Of 53,165 patients meeting criteria (mean age, 61.4 ± 11.6 years), 1552 (2.9%) underwent oncoplastic reduction. Diagnoses of most nonsurgical complications (seroma, wound dehiscence, postoperative infection, fat necrosis, tissue necrosis, and nonspecified complications of surgical care) were significantly higher in the oncoplastic reduction group, as were rates of some surgical complications (hematoma, seroma, and tissue debridement). However, undergoing oncoplastic reduction did not impact time to adjuvant radiation ( P = 0.194) and protected against positive margins requiring repeat lumpectomy or completion mastectomy ( P < 0.001). CONCLUSIONS: In patients undergoing breast conservation therapy, simultaneous oncoplastic reduction decreased occurrence of positive margins and did not impact time to adjuvant radiation therapy despite increased rates of surgical and nonsurgical complications.

Grandmaternal exercise improves metabolic health of second-generation offspring.

OBJECTIVE: A major factor in the growing world-wide epidemic of obesity and type 2 diabetes is the increased risk of transmission of metabolic disease from obese mothers to both first (F1) and second (F2) generation offspring. Fortunately, recent pre-clinical studies demonstrate that exercise before and during pregnancy improves F1 metabolic health, providing a potential means to disrupt this cycle of disease. Whether the beneficial effects of maternal exercise can also be transmitted to the F2 generation has not been investigated. METHODS: C57BL/6 female mice were fed a chow or high-fat diet (HFD) and housed in individual cages with or without running wheels for 2 wks before breeding and during gestation. Male F1 offspring were sedentary and chow-fed, and at 8-weeks of age were bred with age-matched females from untreated parents. This resulted in 4 F2 groups based on grandmaternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained. F2 were sedentary and chow-fed and studied up to 52-weeks of age. RESULTS: We find that grandmaternal exercise improves glucose tolerance and decreases fat mass in adult F2 males and females, in the absence of any treatment intervention of the F1 after birth. Grandmaternal exercise also improves F2 liver metabolic function, including favorable effects on gene and miRNA expression, triglyceride concentrations and hepatocyte glucose production. CONCLUSION: Grandmaternal exercise has beneficial effects on the metabolic health of grandoffspring, demonstrating an important means by which exercise during pregnancy could help reduce the worldwide incidence of obesity and type 2 diabetes.

Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High-Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation.

Preclinical studies reveal maternal exercise as a promising intervention to reduce the transmission of multigenerational metabolic dysfunction caused by maternal obesity. The benefits of maternal exercise on offspring health may arise from multiple factors and have recently been shown to involve DNA demethylation of critical hepatic genes leading to enhanced glucose metabolism in offspring. Histone modification is another epigenetic regulator, yet the effects of maternal obesity and exercise on histone methylation in offspring are not known. Here, we find that maternal high-fat diet (HFD; 60% kcal from fat) induced dysregulation of offspring liver glucose metabolism in C57BL/6 mice through a mechanism involving increased reactive oxygen species, WD repeat-containing 82 (WDR82) carbonylation, and inactivation of histone H3 lysine 4 (H3K4) methyltransferase leading to decreased H3K4me3 at the promoters of glucose metabolic genes. Remarkably, the entire signal was restored if the HFD-fed dams had exercised during pregnancy. WDR82 overexpression in hepatoblasts mimicked the effects of maternal exercise on H3K4me3 levels. Placental superoxide dismutase 3 (SOD3), but not antioxidant treatment with N-acetylcysteine was necessary for the regulation of H3K4me3, gene expression, and glucose metabolism. Maternal exercise regulates a multicomponent epigenetic system in the fetal liver resulting in the transmission of the benefits of exercise to offspring.

Reinforced Biologic Mesh Reduces Postoperative Complications Compared to Biologic Mesh after Ventral Hernia Repair.

BACKGROUND: The use of biologic mesh to reinforce the abdominal wall in ventral hernia repair has been proposed as a viable alternative to synthetic mesh, particularly for high-risk patients and in contaminated settings. However, a comparison of clinical outcomes between the currently available biologic mesh types has yet to be performed. METHODS: We performed a retrospective analysis of 141 patients who had undergone ventral hernia repair with biologic mesh, including noncross-linked porcine ADM (NC-PADM) (n = 51), cross-linked porcine ADM (C-PADM) (n = 17), reinforced biologic ovine rumen (RBOR) (n = 36), and bovine ADM (BADM) (n = 37) at the Stanford University Medical Center between 2002 and 2020. Postoperative donor site complications and rates of hernia recurrence were compared between patients with different biologic mesh types. RESULTS: Abdominal complications occurred in 47.1% of patients with NC-PADM, 52.9% of patients with C-PADM, 16.7% of patients with RBOR, and 43.2% of patients with BADM (P = 0.015). Relative risk for overall complications was higher in patients who had received NC-PADM (RR = 2.64, P = 0.0182), C-PADM (RR = 3.19, P = 0.0127), and BADM (RR = 2.11, P = 0.0773) compared with those who had received RBOR. Furthermore, relative risk for hernia recurrence was also higher in all other mesh types compared with RBOR. CONCLUSION: Our data indicate that RBOR decreases abdominal complications and recurrence rates after ventral hernia repair compared with NC-PADM, C-PADM, and BADM.

Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health.

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.

Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue.

Recent studies demonstrate that adaptations to white adipose tissue (WAT) are important components of the beneficial effects of exercise training on metabolic health. Exercise training favorably alters the phenotype of subcutaneous inguinal WAT (iWAT) in male mice, including decreasing fat mass, improving mitochondrial function, inducing beiging, and stimulating the secretion of adipokines. In this study, we find that despite performing more voluntary wheel running compared with males, these adaptations do not occur in the iWAT of female mice. Consistent with sex-specific adaptations, we report that mRNA expression of androgen receptor coactivators is upregulated in iWAT from trained male mice and that testosterone treatment of primary adipocytes derived from the iWAT of male, but not female mice, phenocopies exercise-induced metabolic adaptations. Sex specificity also occurs in the secretome profile, as we identify cysteine-rich secretory protein 1 (Crisp1) as a novel adipokine that is only secreted from male iWAT in response to exercise. Crisp1 expression is upregulated by testosterone and functions to increase glucose and fatty acid uptake. Our finding that adaptations to iWAT with exercise training are dramatically greater in male mice has potential clinical implications for understanding the different metabolic response to exercise training in males and females and demonstrates the importance of investigating both sexes in studies of adipose tissue biology.

Effects of maternal and paternal exercise on offspring metabolism.

Maternal and paternal obesity and type 2 diabetes are recognized risk factors for the development of metabolic dysfunction in offspring, even when the offspring follow a healthful lifestyle. Multiple studies have demonstrated that regular physical activity in mothers and fathers has striking beneficial effects on offspring health, including preventing the development of metabolic disease in rodent offspring as they age. Here, we review the benefits of maternal and paternal exercise in combating the development of metabolic dysfunction in adult offspring, focusing on offspring glucose homeostasis and adaptations to metabolic tissues. We discuss recent findings regarding the roles of the placenta and sperm in mediating the effects of parental exercise on offspring metabolic health, as well as the mechanisms hypothesized to underlie these beneficial changes. Given the worldwide epidemics of obesity and type 2 diabetes, if these findings translate to humans, regular exercise during the reproductive years might limit the vicious cycles in which increased metabolic risk propagates across generations.

Low intensity pulsed ultrasound (LIPUS) maintains osteogenic potency by the increased expression and stability of Nanog through spleen tyrosine kinase (Syk) activation.

Mesenchymal stem cells (MSCs) are a powerful tool for cell-based, clinical therapies like bone regeneration. Therapeutic use of cell transplantation requires many cells, however, the expansion process needed to produce large quantities of cells reduces the differentiation potential of MSCs. Here, we examined the protective effects of low intensity pulsed ultrasound (LIPUS) on the maintenance of osteogenic potency. Primary osteoblastic cells were serially passaged between 2 and 12 times with daily LIPUS treatment. We found that LIPUS stimulation maintains osteogenic differentiation capacity in serially passaged cells, as characterized by improved matrix mineralization and Osteocalcin mRNA expression. Decreased expression of Nanog, Sox2, and Msx2, and increased expression of Pparg2 from serial passaging was recovered in LIPUS-stimulated cells. We found that LIPUS stimulation not only increased but also sustained expression of Nanog in primary osteoblasts and ST2 cells, a mouse mesenchymal stromal cell line. Nanog overexpression in serially passaged cells mimicked the recuperative effects of LIPUS on osteogenic potency, highlighting the important role of Nanog in LIPUS stimulation. Additionally, we found that spleen tyrosine kinase (Syk) is an important signaling molecule to induce Nanog expression in LIPUS-stimulated cells. Syk activation was regulated by both Rho-associated kinase 1 (ROCK1) and extracellular ATP in a paracrine manner. Interestingly, the LIPUS-induced increase in Nanog mRNA expression was regulated by ATP-P2X4-Syk Y323 activation, while the improvement of Nanog protein stability was controlled by the ROCK1-Syk Y525/526 pathway. Taken together, these results indicate that LIPUS stimulation recovers and maintains the osteogenic potency of serially passaged cells through a Syk-Nanog axis.