Therapeutic Options for Migraines in the Microsurgical Patient: A Scoping Review.

BACKGROUND: There exists an increasing array of treatments proposed to prevent, alleviate, and abort symptoms of a migraine; however, for patients who undergo reconstructive microsurgery, caution must be taken to preserve vascular integrity. This study is the first-to-date scoping review of vascular and bleeding risk of current migraine therapies, with the purpose of identifying potential therapeutic agents for postoperative migraine management appropriate for microsurgical patients. METHODS: Currently available migraine therapeutics were compiled from UpToDate and the American Academy of Family Physicians. A PubMed literature review was performed for each therapeutic's effect on bleeding or vascular involvement. Data were compiled into tables of abortive, symptom-controlling and prophylactic, and non-pharmacologic treatments. Expert microsurgeons reviewed the data to provide recommendations for optimized patient care. RESULTS: Triptans and other ergot derivatives demonstrated strong evidence of vasoconstriction and were greatly advised against for immediate post-microsurgical use. Novel pharmaceutical therapies like Lasmiditan and CGRP antagonists have no literature indicating potential for vasoconstriction or hematoma and remain an investigational option for abortive medical treatment. For symptom control, acetaminophen appears the safest option, with clinical judgment and further research needed for use of NSAIDs. Alternative treatment techniques may include migraine prophylaxis with botulinum toxin injection or nutraceutical treatment via magnesium supplementation or Coenzyme Q10 administration, minimizing the need for additional medication in the postoperative setting. CONCLUSIONS: Patients undergoing reconstructive microsurgery have a unique medical profile limiting the therapeutic options available to treat migraines. This review provides preliminary evidence to be considered as a guide for prescribing therapeutics for migraine in the postoperative setting.

Evaluation of Health Literacy in Plastic Surgery Using a Crowdsourced Patient Survey.

Little is known about the levels of health literacy (HL) among plastic and reconstructive surgery (PRS) patients compared with the general population. This study aimed to characterize HL levels in patients interested in plastic surgery and identify potential risk factors associated with inadequate levels of HL among this population. Methods: Amazon's Mechanical Turk was used to distribute a survey. The Chew's Brief Health Literacy Screener was used to evaluate the level of HL. The cohort was divided into two groups: non-PRS and PRS groups. Four subgroups were created: cosmetic, noncosmetic, reconstructive, and nonreconstructive groups. A multivariable logistic regression model was constructed to assess associations between levels of HL and sociodemographic characteristics. Results: A total of 510 responses were analyzed in this study. Of those, 34% of participants belong to the PRS group and 66% to the non-PRS group. Inadequate levels of HL were evidenced in 52% and 50% of the participants in the non-PRS and PRS groups, respectively (P = 0.780). No difference in HL levels was found in the noncosmetic versus cosmetic groups (P = 0.783). A statistically significant difference in HL levels was evidenced between nonreconstructive versus reconstructive groups after holding other sociodemographic factors constant (0.29, OR; 95% CI, 0.15-0.58; P < 0.001). Conclusions: Inadequate levels of HL were present in almost half of the cohort, which highlights the importance of adequately assessing HL levels in all patients. It is of utmost importance to evaluate HL in clinical practice using evidence-based criteria to better inform and educate patients interested in plastic surgery.

Misconceptions, Myths, and Mystery: A Cross-sectional Survey Study on Public Knowledge and Values of Microsurgery.

BACKGROUND: Microsurgery is a foundational plastic surgery principle. However, public unawareness of microsurgery and its associated rigorous training in the United States may contribute to current misconceptions and undervaluing of plastic and reconstructive surgeons. This study aims to characterize public knowledge of microsurgery. METHODS: A cross-sectional survey was conducted from August to September 2021 using Amazon Mechanical Turk to assess baseline public knowledge of microsurgery. A multivariable logistic regression model was constructed to evaluate the association between baseline knowledge and demographic characteristics. Significance was set to a p < 0.05. RESULTS: A total of 516 responses were analyzed. The mean age was 36.7 years (standard deviation, 16.04 years; white, 84%; non-Hispanic, 70%). Of those surveyed, 52% agreed that general surgeons perform microsurgery, while only 28% agreed that plastic and reconstructive surgeons perform microsurgery. When asked if head and neck reconstruction, breast reconstruction, and finger replantation required microsurgery, only 28, 41, and 41% of respondents agreed, respectively. When controlled for sociodemographic factors, Hispanics had significantly more odds to mistake that head and neck reconstruction did not require microsurgery (odds ratio [OR] 95% CI 0.49; 0.30-0.80; p = 0.004) and less odds to consider plastic and reconstructive surgeons for reconstruction (OR 0.51; 95% CI 0.32-0.84; p = 0.008). Females had 1.63 more odds of considering plastic and reconstructive surgeons for reconstruction (95% CI 1.09-2.43; p = 0.017). Low-educated participants had significantly more odds to consider general surgeons as those who performed reconstructive microsurgery (OR 8.70; 95% CI 1.09-69.40; p = 0.041). CONCLUSION: Misconceptions of microsurgery as a foundational principle of plastic surgery persist and correlate with undervaluing the specialty. Knowledge differs by ethnicity, level of education, and gender. Therefore, patient counseling should use culturally appropriate elements to demystify microsurgery, build value, and better inform risks and benefits.

Technique of Abdominal Wall Tissue Expansion for the Treatment of Massive Complicated Ventral Hernias.

Abdominal wall tissue expansion is a unique technique that seeks to augment and expand both the fascial and subcutaneous tissues/skin layers to achieve durable closure of otherwise challenging ventral hernias. In addition to allowing primary fascial closure in a majority of cases, this technique enables reduced tension on the closure, potentially decreasing the recurrence rate. This article describes the senior author's surgical technique for abdominal wall tissue expansion in massive complicated ventral hernias. The plastic surgeon is at a unique advantage to assist with the repair of massive complicated ventral hernias given their comfort with complex tissue handling and expandable devices. This specialized technique thus provides an opportunity for plastic surgeons to serve as expert co-surgeons with general surgery colleagues to help achieve superior outcomes in patients with these challenging hernias.

Sustainable Cleft Care: A Comprehensive Model Based on the Global Smile Foundation Experience.

INTRODUCTION: Clefts of the lip and palate are leading congenital facial anomalies. Underserved patients with these facial differences lack access to medical care, surgical expertise, prenatal care, or psychological support. Moreover, the disease results in significant economic strains on patients and their families. While surgical outreach programs have attempted to fill this void, significant challenges facing international comprehensive cleft care persist. OBJECTIVE: Propose a path toward international sustainable cleft care based on the Global Smile Foundation experience. RESULTS: International sustainable comprehensive cleft care can be achieved by regulating surgical outreach programs. Regulation of these missions would ensure standardized care and encourage stakeholders to cooperate and adequately allocate funding and resources. Capacity building can be achieved through "diagonal" cleft care delivery models, multidisciplinary workshops, fellowship programs, research and quality assurance, as well as leveraging emerging technologies such as Augmented Reality. CONCLUSION: International comprehensive cleft care requires continuous collaborative efforts between visiting and local teams as well as international and national organizations. Standardizing and regulating current practices as well as promoting capacity building initiatives can contribute to sustainable cleft care.

Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

PURPOSE: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. EXPERIMENTAL DESIGN: Our models of HER2+ breast cancer exhibit molecular signatures that are reflective of advanced human HER2+ breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers. Using these, we vaccinated against the oncogenic HER2Δ16 isoform, a nondriver tumor-associated gene (GFP), and specific neoepitopes. We further tested the effect of vaccination or anti-PD-1, alone and in combination. RESULTS: We found that only vaccination targeting HER2Δ16, a driver of oncogenicity and HER2-therapeutic resistance, could elicit significant antitumor responses, while vaccines targeting a nondriver tumor-specific antigen or tumor neoepitopes did not. Vaccine-induced HER2-specific CD8+ T cells were essential for responses, which were more effective early in tumor development. Long-term tumor control of advanced cancers occurred only when HER2Δ16 vaccination was combined with αPD-1. Single-cell RNA sequencing of tumor-infiltrating T cells revealed that while vaccination expanded CD8 T cells, only the combination of vaccine with αPD-1 induced functional gene expression signatures in those CD8 T cells. Furthermore, we show that expanded clones are HER2-reactive, conclusively demonstrating the efficacy of this vaccination strategy in targeting HER2. CONCLUSIONS: Combining oncogenic driver targeted vaccines with selective ICB offers a rational paradigm for precision immunotherapy, which we are clinically evaluating in a phase II trial (NCT03632941).

Preclinical Optimization of a Shelf-Ready, Injectable, Human-Derived, Decellularized Allograft Adipose Matrix.

IMPACT STATEMENT: Trauma, disease, surgery, or congentital defects can cause soft tissue losses in patients, leading to disfigurement, functional impairment, and a low quality of life. In the lack of available effective methods to reconstruct these defects, acellular adipose matrices could provide a novel therapeutic solution to such challenge.

Noninvasive Flap Preconditioning by Foam-Mediated External Suction Improves the Survival of Fasciocutaneous Axial-Pattern Flaps in a Type 2 Diabetic Murine Model.

BACKGROUND: Advances in reconstructive surgery are leading to an increased number of flaps at risk for ischemic necrosis, because of either intrinsic (e.g., larger flap size) or extrinsic (e.g., diabetes) factors. Methods to preoperatively improve flap vascularity and limit postoperative ischemia are lacking. Noninvasive suction, using either a macrodeformational silicone cup interface (external volume expansion) or a microdeformational polyurethane foam interface (foam-mediated external volume expansion), has been shown to induce angiogenesis in tissues. The authors investigated whether the preoperative use of external volume expansion/foam-mediated external volume expansion improves flap survival in an obesity-induced diabetic animal model. METHODS: Db/Db mice underwent either mechanical stimulation with suction for 5 days using either external volume expansion or foam-mediated external volume expansion, or received no stimulation (n = 8 per group). Five days after the last stimulation, a critical-size, axial-pattern, fasciocutaneous flap was raised in all animals. Postoperatively, flap survival was monitored with digital imaging for 10 days. After this period, flaps were harvested to assess tissue survival, angiogenesis, and inflammation, using histology and polymerase chain reaction. RESULTS: Foam-mediated external volume expansion preconditioning significantly increased the viable flap area (28 percent), viable flap volume (27 percent), and flap capillary density (36 percent) in comparison to controls; vascular endothelial growth factor was also up-regulated (>300 percent). In contrast, external volume expansion resulted in a severe inflammatory response and increased flap necrosis. CONCLUSIONS: Foam-mediated external volume expansion improves flap survival in obese diabetic mice. This procedure may allow for improved clinical rates of flap survival in high-risk patients.

Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery.

In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.

Skin Substitutes and Bioscaffolds: Temporary and Permanent Coverage.

Advancements in surgical wound treatment have led to skin substitutes and bioscaffolds as temporary and permanent coverage for burn wounds. Skin substitutes are used to improve wound coverage and restore the functional and aesthetic qualities of skin, and help to prevent wound infection and maintain a moist wound healing environment. Although allografts are preferred when autografts are not possible, high costs and limited availability have led to the use of xenografts and the development of skin substitutes and bioscaffolds. Despite constant evolution in the development of these skin substitutes and bioscaffolds, no single product stands out as the gold standard.

Hyperspectral Imaging Provides Early Prediction of Random Axial Flap Necrosis in a Preclinical Model.

BACKGROUND: Necrosis remains a significant complication in cutaneous flap procedures. Monitoring, and ideally prediction, of vascular compromise in the early postoperative period may allow surgeons to limit the impact of complications by prompt intervention. Hyperspectral imaging could be a reliable, effective, and noninvasive method for predicting flap survival postoperatively. In this preclinical study, the authors demonstrate that hyperspectral imaging is able to correlate early skin perfusion changes and ultimate flap survival in a preclinical model. METHODS: Thirty-one hairless, immunocompetent, adult male mice were used. Random pattern dorsal skin flaps were elevated and sutured back into place with a silicone barrier. Hyperspectral imaging and digital images were obtained 30 minutes, 24 hours, or 72 hours after flap elevation and before sacrifice on postoperative day 7. RESULTS: Areas of high deoxygenated hemoglobin change (124; 95 percent CI, 118 to 129) seen at 30 minutes after surgery were associated with greater than 50 percent flap necrosis at postoperative day 7. Areas demarcated by high deoxygenated hemoglobin at 30 minutes postoperatively had a statistically significant correlation with areas of macroscopic necrosis on postoperative day 7. Analysis of images obtained at 24 and 72 hours did not show similar changes. CONCLUSIONS: These findings suggest that early changes in deoxygenated hemoglobin seen with hyperspectral imaging may predict the region and extent of flap necrosis. Further clinical studies are needed to determine whether hyperspectral imaging is applicable to the clinical setting.

Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model.

BACKGROUND: Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. METHODS: Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis. RESULTS: Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at -25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes. CONCLUSION: Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.

Injectable Shape-Memorizing Three-Dimensional Hyaluronic Acid Cryogels for Skin Sculpting and Soft Tissue Reconstruction.

INTRODUCTION: Hyaluronic acid (HA)-based fillers are used for various cosmetic procedures. However, due to filler migration and degradation, reinjections of the fillers are often required. Methacrylated HA (MA-HA) can be made into injectable shape-memorizing fillers (three-dimensional [3D] MA-HA) aimed to address these issues. In this study, shape retention, firmness, and biocompatibility of 3D MA-HA injected subcutaneously in mice were evaluated. MATERIALS AND METHODS: Fifteen mice, each receiving two subcutaneous injections in their back, were divided into four groups receiving HA, MA-HA, 3D MA-HA, or saline, respectively. Digital imaging, scanning electron microscope (SEM) and in vivo imaging system (IVIS), durometry, and histology were utilized to evaluate in vitro/vivo degradation and migration, material firmness, and the angiogenic (CD31) and immunogenic (CD45) response of the host tissue toward the injected materials. RESULTS: Digital imaging, SEM, and IVIS revealed that 3D MA-HA fillers maintained their predetermined shape for at least 30 days in vitro and in vivo. Little volume effects were noted in the saline and other control groups. There were no differences in skin firmness between the groups or over time. Histology showed intact skin architecture in all groups. Three-dimensional MA-HA maintained its macroporous structure with significant angiogenesis at the 3D MA-HA/skin interfaces and throughout the 3D MA-HA. There was no significant inflammatory response to any of the injected materials. CONCLUSION: 3D MA-HA showed remarkable tissue compatibility, compliance, and shape predictability, as well as retention, and thus might be suitable for various skin sculpting and soft tissue reconstruction purposes.

Cortical bone invasion in non-transfusion-dependent thalassemia: tumefactive extramedullary hematopoiesis reviewed.

OBJECTIVE OF THE STUDY: To assess the prevalence of cortical bone invasion (CBI) with secondary extramedullary hematopoiesis (EMH) in patients with non-transfusion-dependent thalassemia (NTDT), to determine its predilection sites on thoracic and abdominal imaging, to determine whether there is an association between various clinical and hematological parameters, and to evaluate its various findings mainly on magnetic resonance imaging (MRI), in addition to computed tomography (CT) scans. MATERIALS AND METHODS: This is a retrospective cohort study of 57 patients with NTDT imaged by CT or MRI. Both clinical and laboratory data were gathered. An imaging scoring system was used to describe the appearance of CBI by MRI. RESULTS: Twenty-seven patients (47.4 %) were found to have CBI and EMH with the most common location being the thoracic spine. Splenectomy and lower hemoglobin level were found to be independent risk factors for its development. Most lesions were homogenous (70 %), had predominant red marrow signal (67 %), and well-defined margins (89 %). CONCLUSION: CBI and secondary tumefactive EMH are common findings in patients with NTDT, with distinct imaging and clinical characteristics. An increased risk was seen in patients with splenectomy and lower hemoglobin. The imaging scoring system described is helpful in diagnosing and describing this entity, hence precluding unnecessary biopsies.

Venous thromboembolism and preoperative steroid use: analysis of the NSQIP database to evaluate risk in surgical patients.

BACKGROUND: Despite several prophylactic strategies, postoperative venous thromboembolism (VTE) remains a major cause of morbidity and mortality. Therefore, the search for modifiable preoperative risk factors is crucial. Few reports have explored this issue but the direct relationship between preoperative steroid use and postoperative VTE in surgical patients remains unexplored. METHODS: We used The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database in our study. After analyzing patient characteristics, we used multivariate logistic regression to assess the crude and adjusted effect of steroids on VTE, our primary outcome. RESULTS: Data was obtained for 1,921,901 patients, 58,667 of whom were on glucocorticoids for at least 30days preoperatively. VTE was higher in patients on steroids with an adjusted odds ratio of 1.54, 95% confidence interval (CI) 1.45-1.64. The adjusted odds ratio for the secondary outcomes: mortality, urinary tract occurrences, wound occurrences, sepsis, cardiac and respiratory adverse events were 1.42 (CI 1.35-1.49), 1.40 (CI 1.30-1.50), 1.58 (CI 1.51-1.66), 1.51 (CI 1.42-1.60), 1.19 (CI 1.11-1.29) and 1.302 (CI 1.301-1.303) respectively. CONCLUSIONS: Our results suggest that surgical patients with prolonged preoperative glucocorticoid intake are at a higher risk of developing postoperative VTE as well as other secondary outcomes including: all-cause mortality, urinary tract occurrences, sepsis, wound occurrences, cardiac and respiratory adverse events. These are important findings since preoperative glucocorticoid use is a modifiable factor.

Priapism, an emerging complication in ß-thalassemia intermedia patients.

The increase in survival rate of ß-thalassemia (ß-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in ß-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with ß-thal intermedia (ß-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.