Objective Custom prescription helmets for plagiocephaly may be a significant financial burden for families, especially when not covered by insurance. This study aims to identify factors that influence the success of crowdsourcing campaigns for this therapy.Design GoFundMe campaigns were collected by searching terms such as "plagiocephaly" and "baby helmet." Two reviewers analyzed each campaign for variables, including demographic data, story elements, and photo characteristics. Univariate logistic regression was used to determine each variable's impact on success, defined as attaining >= 75% of a campaign goal and significance of p <= 0.05.Results Campaign data from 2011 to 2022 were analyzed. Initial search yielded 1464 campaigns; among these 413 met final inclusion criteria. On average, campaigns raised $2005 (range: $0-$7799) and requested $3151 (range: $160-$30,000). In total, 228 (54%) achieved success, 167 (40%) met their goal, and 35 (8%) raised no funds. A total of $828,256 was raised from the requested $1,301,317. The average reported age was six months (range: 2-17 m). Significant factors associated with success were military affiliation, providing multiple images, including a quoted cost, providing campaign updates, indicating a sense of urgency, diagnosis of torticollis, and mentioning possible complications without treatment. Raising additional funds for therapy, multiple helmets, and unrelated medical costs negatively impacted success. Racial disparities were observed between campaigns. Additionally, regional differences were noted between campaigns.Conclusions Crowdsourcing can be a successful endeavor for some families experiencing financial hardships from helmet therapy. This study highlights current gaps within healthcare coverage for helmet treatment and identifies various factors influencing crowdfunding campaigns.
Background:To date, there is little guidance regarding current adjuvant therapies for primary surgical repair of cleft lip. There are studies on the effect of botulinum toxin type A, revision fat grafting, silicone gel and sheeting, intense pulsed light, and carbon dioxide lasers to ameliorate contracture and hypertrophic scar formation, but a comprehensive review of these options is lacking. The aim of this scoping review is to examine adjuvant techniques and therapies that modulate scar outcomes for primary cleft lip repair outcomes in the perioperative period. Methods: PROSPERO, PubMed/MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrial.gov were searched for studies that evaluated adjuvant therapies for primary cleft lip repair. Results: The initial search resulted in 688 studies, with 48 studies including relevant key terms in the title and abstract screening. After the full-text screening, 11 studies were included in the final scoping review. These included 3 studies about use of botulinum toxin injection, 2 studies about fat grafting, 2 studies about nasal stents, and 4 studies about various topical treatments. In the Jadad quality index evaluation and MINORS assessment of the methodological quality of the included papers, there was a strong level of agreement among the 2 raters respectively (weighted κ = 1, κ = 0.817, both P-value < .0001). Conclusion: From this scoping review, adjuvant therapies such as utilizing botulinum toxin and immediate fat grafting intraoperatively and nasal stents and topical treatments including antibiotic ointment, lidocaine, hydrogen peroxide, and silicone gels postoperatively are worthwhile to consider as a combination of adjuvant treatments to prevent adverse scar formation in patients undergoing primary cleft lip repair. The most robust evidence lies with botulinum toxin use.
BACKGROUND:Adverse airway events (AAEs) are rare but devastating complications following palatoplasty. The purpose of this study is to evaluate patient risk factors for their effect on these complications. We hypothesize that prolonged operative time and the presence of multiple medical comorbidities are risk factors for AAEs. DESIGN:Retrospective cohort study. SETTING:Participant hospitals in the Pediatric American College of Surgeons National Surgical Quality Improvement Program year 2016-2019. PATIENTS:Cases of palatoplasty in children under 3 years of age. OUTCOMES:Adverse airway events including postoperative reintubation or any requirement of postoperative mechanical ventilation. RESULTS:A total of 6668 patients met inclusion criteria. The median operative time was 126 min (IQR 82). AAEs were identified in 107 (1.6%) patients. The incidence of risk factors was found to increase with age and AAEs were more prevalent in younger and older patients. Although patients in the older age groups had significantly higher burden of comorbidities, differences in age were not independently associated with AAEs. Following multivariable logistic regressions, operative times greater than 2 h, ASA class ≥3, >3 medical comorbidities, and black race were found to be significant independent risk factors. CONCLUSIONS:In this large, retrospective database study in palatoplasty, increased operative time, ASA classification ≥3, multiple comorbidities, and black race were independently associated with AAEs.
Objective Utilizing biological scaffolds for cartilage tissue engineering is a promising tool for improving auricular reconstruction. Decellularized auricular scaffolds provide a means of regenerating cartilage for in vivo implantation, but identifying the ideal regenerative mix remains challenging. Methods Human cadaver auricular cartilage was decellularized and recellularized with either auricular chondrocytes alone, auricular chondrocytes with adipose-derived stem cells, or both cells with platelet-rich plasma. Confirmation of decellularization and recellularization was done by hematoxylin and eosin staining. Extracellular matrix preservation and production were determined by Masson's trichrome, Alcian blue, and Verhoeff-van Gieson staining. Collagen II assessments were made using immunohistochemistry. Results Decellularization of cadaver auricular cartilage was confirmed by the absence of cells, reduction in glycosaminoglycans, and the preservation of collagen and elastin. Recellularization was more efficient when chondrocytes were seeded with adipose-derived stem cells, which was enhanced by adding platelet-rich plasma. Coculture with platelet-rich plasma yielded better total collagen (56% increase) and glycosaminoglycan (47% increase) induction. Moreover, when platelet-rich plasma was added, collagen II induction was significantly increased (42%; P < 0.05). Conclusion We identified a regenerative protocol that included auricular chondrocytes, adipose-derived stem cells, and platelet-rich plasma, which stimulated chondrogenesis on decellularized auricular cartilage. This finding provides a model to explore cartilage formation and the potential for improving auricular and cartilage-based reconstruction.
INTRODUCTION: Adipose-derived stem cell (ADSC) secretomes have been demonstrated to have potential therapeutic applications in various conditions, including wound healing, tissue repair, and autoimmune diseases. The ADSC secretome includes a variety of proteins, growth factors, and a wide range of signaling molecules, which should be further analyzed to pave the way for the development of novel ADSC-based therapies. Prior secretome analyses have been limited to select individual donors, so it is not clear whether there is variability amongst donors. Because ADSC-based therapies would entail autologous grafting, the aim of our investigation was therefore to determine whether the secretome therapeutic benefits are consistent from donor to donor. METHODS: Lipoaspirate was obtained from 9 healthy donors undergoing elective liposuction at the Department of Plastic Surgery, University of California, Irvine. The lipoaspirate underwent a cellular isolation protocol and was passaged to obtain a pure population of ADSC’s. After culturing to confluency, secretome samples were collected and sent to Eve Technologies, Inc (AB, Canada) for interrogation. The secretome report was subsequently decoded followed by classification of proteins into 3 categories: low, mid, and high secretion. This partitioned data was then imported into REACTOME and STRING for visualization and interpretation of implicated pathways and protein-protein interactions, respectively. An algorithm was then utilized to identify significant pathways and interactions present across combinations of all 3 secretion categories. RESULTS: 23 genes and associated proteins with a low coefficient of variation were identified across all donors. A REACTOME and STRING analysis of all combined data demonstrated 152 implicated cellular pathways. After analyzing the partitioned data and evaluating for overlap between all secretion levels, 37 significant pathways were identified. The pathways were then classified according to their contributions to general biological processes. Pathways involving signaling and regulation of IL-4, IL-13, and IL-17 were associated with immunomodulation. The secretomes also contained proteins contributing to the regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis. Lastly, Insulin-Like Growth Factor Binding Proteins (IGFB) involved in the regulation of IGF were identified. CONCLUSION: Our investigation demonstrates that ADSC secretomes contain key factors that are consistently present across donors. The identified factors have been implicated in various immunomodulatory and angiogenic processes, in addition to the regulation of IGF transport and uptake through IGF binding proteins. These findings suggest that autologous grafting in patients may reliably provide consistent therapeutic advantages for wound healing, scar modulation, and autoimmune processes.
Purpose Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into ad-ipocytes in vitro and alters their contractile nature in vivo.Methods Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry.Results Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treat-ments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not.Conclusions Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion.Clinical relevance The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture. (J Hand Surg Am. 2023;48(9):914e922. Copyright (c) 2023 by the American Society for Surgery of the Hand. All rights reserved.)
PURPOSE: Advances in microtia reconstruction, including ear scaffolding and prosthesis, have a high failure rate due to the avascular nature of cartilage, loss of structure, and immunogenic reaction to foreign material.1 Improvements in bioengineered materials and scaffolding have started to tackle these issues, but there is a noticeable gap in the microtia and auricular cartilage literature. Little testing has been performed on the biomechanical characteristics of microtia cartilage and how it compares to phenotypically normal auricular cartilage.2-4 Thus, we characterized the biomechanical properties of distinct sections of microtia cartilage relative to anatomical regions of normal adult auricular cartilage. We hypothesized that the biomechanical properties of microtia cartilage would be uniform throughout and not different from the healthy adult auricular cartilage. METHOD: Healthy adult and juvenile microtia ear cartilage, initially stored at -80°C, were thawed at 4°C overnight and dissected at room temperature. For the adult normal cartilage, 3mm punch biopsies were taken from the concha, helix, anti-helix, tragus, anti-tragus, and scapha. For the microtia ears, 4mm punch biopsies were taken from the superior, middle, and inferior regions as topographical regions could be not appreciated. Creep indentation testing was performed to determine the compressive stiffness of the specimens. Using an automated system, an indenter tip (0.5mm for adult, 1mm for microtia) was applied to samples under various appropriate weights to achieve 10 - 15% strain within the tissue. A semi-analytical, semi-numerical, linear biphasic model and finite element analysis were used to obtain the aggregate modulus and shear modulus from the experimental data. Tensile properties were also measured. After samples were trimmed to forma dog-bone shape, they underwent uniaxial tensile strain at 1% gauge length per second until sample failure. Force data were normalized to sample cross-sectional area to generate a stress-strain curve from which tensile Young’s modulus and ultimate tensile strength were obtained. The data was analyzed by using one-way ANOVA. RESULTS: Our study found that the tensile and compression properties of the superior, middle, inferior regions of microtia tissue were not statistically different from each other (p > 0.05 for all measures). When comparing the tensile Young’s modulus (5.26 MPa vs. 5.81 MPa), ultimate tensile strength (3.99 MPa vs. 3.46 MPa), aggregate modulus (154.2 kPa vs. 172.0 kPa), and shear modulus (80.6 kPa vs. 85.5 kPa) of the microtia ear to those of the adult ear, respectively, the upper portion of a healthy adult ear, including the helix and concha, was not significantly different than the microtia tissue. In contrast, the permeability of the microtia tissue (7.8 vs. 36.1 1015*m4/N.s) was significantly different than all regions of a healthy adult ear (p < 0.05). CONCLUSION: These results have added to our understanding of microtia tissue and elucidated a possible relationship with specific regions of the healthy adult ear. We plan to combine biomechanical data with biochemical and histological data to form a more complete understanding of microtia tissue and normal auricular cartilage. REFERENCES: 1. Bly RA, Bhrany AD, Murakami CS, Sie KC. Microtia Reconstruction. Facial Plast Surg Clin North Am. 2016;24(4):577-591. doi:10.1016/j.fsc.2016.06.011 2. Huwe LW, Brown WE, Hu JC, Athanasiou KA. Characterization of costal cartilage and its suitability as a cell source for articular cartilage tissue engineering. J Tissue Eng Regen Med. 2018 May;12(5):1163-1176. doi: 10.1002/term.2630. Epub 2018 Jan 21. PMID: 29286211; PMCID: PMC5948132. 3. Zopf DA, Flanagan CL, Nasser HB, et al. Biomechanical evaluation of human and porcine auricular cartilage. Laryngoscope. 2015 Aug;125(8):E262-8. doi: 10.1002/lary.25040. Epub 2015 Apr 17. PMID: 25891012; PMCID: PMC4512857. 4. Griffin MF, O’Toole G, Sabbagh W, Szarko M, Butler PE. Comparison of the compressive mechanical properties of auricular and costal cartilage from patients with microtia. J Biomech. 2020 Apr 16;103:109688. doi: 10.1016/j.jbiomech.2020.109688. Epub 2020 Feb 25. PMID: 32145904.
PURPOSE: Adverse airway events (AAEs), defined as postoperative intubation or reintubation are an uncommon but devastating complication following palatoplasty. We hypothesize that prolonged OR time and presence of medical comorbidities are risk factors for AAEs. METHODS: Patients who underwent palatoplasty between 2016 and 2019, under 3 years of age, were identified from the Pediatric American College of Surgeons National Surgical Quality Improvement Program. Demographics, medical comorbidities, and outcomes were collected. Risk factors were assessed using univariate and multivariate analyses. RESULTS: A total of 6,668 patients met inclusion criteria. The median OR time was 126 minutes. AAEs were identified in 107 (1.6%) patients. After multivariable logistic regression, risks factors associated with AAEs included: greater than 2 hours OR time or presence of pulmonary, cardiac, neurological, and gastrointestinal comorbidities. Although patients in the older age group had significantly higher incidence of comorbidities, it did not lead to significantly higher odds of AAEs. CONCLUSION: AAEs are associated with increased OR time and noted in patients with multiple comorbidities. These patients may require greater postoperative monitoring.
PURPOSE: Bioengineering advances have been made in the field of auricular reconstruction, but many challenges still exist due to the lack of compatible biomaterials, the unique characteristics of cartilage, and its avascular nature. Decellularized tissue has gained popularity as a biomaterial scaffold for repopulating human cells.1 While decellularizing human auricular cartilage has been performed and proven in many bioengineering material studies, our protocol was developed with the goal of maintaining the optimal cell structure and integrity for recellularization. Many current protocols focus on complete decellularization, but not preservation of the components and structure of the cartilage itself, including the maintenance of glycosaminoglycans (GAGS).2-5 Other studies, however, have shown very time-intensive or expensive methods to ensure structural integrity of the cartilage. Therefore, we hypothesize that the optimization of auricular cartilage decellularization will be beneficial in the clinical setting as human decellularized tissue will become more commonly used in reconstructive procedures, such as the treatment of microtia. METHOD: Human adult auricular cadaver cartilage was obtained. The skin and perichondrium were removed to create a uniform structure. After an initial dry 12-hour freeze, the specimen was thawed at room temperature. The sample was then placed in phosphate-buffered solution (PBS) at -20°C and subsequently washed in deionized water. For the decellularization, the cartilage was agitated with 4% sodium deoxycholate at room temperature and washed with PBS. Next, the sample was placed in 2% deoxyribonuclease followed by 0.25% trypsin at room temperature. This process was repeated for 14 cycles in total. Trypsin was only utilized for the initial 4 cycles. The tissue was analyzed histologically to show complete decellularization and preservation of the cartilaginous structure. The overall structure and cellular content were assessed by hematoxylin and eosin (HE) staining. Alcian blue staining was performed to assess the presence of GAGs, Masson’s Trichrome for collagen fibers, and Verhoeff Van Geison’s stain for elastic fibers. RESULTS: Our histological data showed complete decellularization when analyzed with HE staining with preservation of the cartilaginous structure when analyzed with Masson’s Trichrome. There were preserved extracellular matrix (ECM) components with well-defined structures that were comparable to those seen prior to decellularization. CONCLUSION: Decellularization was successful with the new protocol. These new changes are significant in that our protocol utilizes inexpensive resources to process a human auricular ear with optimal preservation of structural integrity. Compared to current protocols, trypsin was optimized to ensure proper decellularization without interrupting surrounding ECM and removal of GAGs. The updated protocol will allow us to utilize a structure closer to the native scaffold. The next step is to recellularize the decellularized scaffold to create a structure for clinical use. REFERENCES: 1. Schwarz S, Koerber L, Elsaesser AF, et al. Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications. Tissue Eng Part A. 2012 Nov;18(21-22):2195-209. doi: 10.1089/ten.TEA.2011.0705. Epub 2012 Jul 20. PMID: 22690787. 2. Al-Qurayshi Z, Wafa EI, Rossi Meyer MK, Owen S, Salem AK. Tissue Engineering the Pinna: Comparison and Characterization of Human Decellularized Auricular Biological Scaffolds. ACS Appl Bio Mater. 2021 Sep 20;4(9):7234-7242. doi: 10.1021/acsabm.1c00766. Epub 2021 Aug 31. PMID: 34568774; PMCID: PMC8456428. 3. Gilpin A, Yang Y. Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications. Biomed Res Int. 2017;2017:9831534. doi:10.1155/2017/9831534 Rahman S, Griffin M, Naik A, Szarko M, Butler PEM. 4. Optimising the decellularization of human elastic cartilage with trypsin for future use in ear reconstruction. Sci Rep. 2018 Feb 15;8(1):3097. doi: 10.1038/s41598-018-20592-x. PMID: 29449572; PMCID: PMC5814427. Utomo L, Pleumeekers MM, Nimeskern L, et al. 5. Preparation and characterization of a decellularized cartilage scaffold for ear cartilage reconstruction. Biomed Mater. 2015 Jan 13;10(1):015010. doi: 10.1088/1748-6041/10/1/015010. PMID: 25586138.
Background: RealSelf is an online community that hosts an expansive number of online reviews for cosmetic and reconstructive plastic surgery procedures. The purpose of this study is to analyze patient satisfaction with breast reconstruction procedures from RealSelf to determine factors contributing to a positive or negative patient experience. Methods: The breast reconstruction category from RealSelf.com was analyzed using a web crawler-based application built from Python and Selenium. Reviews were collected from May 2009 to November 2021. Information including RealSelf’s inherent “worth it” ranking system, review text, the number of submitted photographs, and the number of readers who found the review helpful was captured. The content of the review was then independently reviewed by the authors and was categorized with key factors that determined positive or negative reviews. Results: A total of 3451 breast reconstruction reviews were collected. After the authors analyzed each review, 3225 (94.33%) were identified as positive reviews. The most common factors associated with positive reviews were physician demeanor (n = 2600, 31.7%), aesthetic outcome (n = 1955, 23.8%), or staff (n = 1543, 18.8%), while negative reviews were associated with unfavorable aesthetic outcome (n = 94, 28.9%), physician demeanor (n = 82, 25.2%), or postoperative complications (n = 75, 23.1%). Conclusions: Although there are surveys that analyze patient satisfaction for breast reconstruction, there has not been a study that analyzed a large online review database. Predominating factors in both positive and negative reviews were physician demeanor and aesthetic outcome.
Chronic invasive fungal sinusitis (CIFS) is an invasive fungal infection that can occur in immunocompetent individuals and is typically caused by Aspergillus species. Although many reported cases are unable to identify an etiology for the infection, certain risk factors such as chronic intranasal cocaine use can make patients susceptible to CIFS. This case report describes a unique case of CIFS secondary to Curvularia species in an immunocompetent patient with intranasal drug use.
Microglia mediate chronic neuroinflammation following central nervous system (CNS) disease or injury, and in doing so, damage the local brain environment by impairing recovery and contributing to disease processes. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R) and can be eliminated via administration of CSF1R inhibitors. Resolving chronic neuroinflammation represents a universal goal for CNS disorders, but long-term microglial elimination may not be amenable to clinical use. Notably, withdrawal of CSF1R inhibitors stimulates new microglia to fully repopulate the CNS, affording an opportunity to renew this cellular compartment. To that end, we have explored the effects of acute microglial elimination, followed by microglial repopulation, in a mouse model of extensive neuronal loss. Neuronal loss leads to a prolonged neuroinflammatory response, characterized by the presence of swollen microglia expressing CD68 and CD45, as well as elevated levels of cytokines, chemokines, complement, and other inflammatory signals. These collective responses are largely resolved by microglial repopulation. Furthermore, microglial repopulation promotes functional recovery in mice, with elevated plus maze performance matching that of uninjured mice, despite the loss of 80% of hippocampal neurons. Analyses of synaptic surrogates revealed increases in PSD95 and synaptophysin puncta with microglial repopulation, suggesting that these cells sculpt and regulate the synaptic landscape. Thus, our results show that short-term microglial elimination followed by repopulation may represent a clinically feasible and novel approach to resolve neuroinflammatory events and promote brain recovery.