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1.
Aesthet Surg J ; 44(3): 329-343, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37562022

RESUMEN

BACKGROUND: The rapidly evolving field of artificial intelligence (AI) holds great potential for plastic surgeons. ChatGPT, a recently released AI large language model (LLM), promises applications across many disciplines, including healthcare. OBJECTIVES: The aim of this article was to provide a primer for plastic surgeons on AI, LLM, and ChatGPT, including an analysis of current demonstrated and proposed clinical applications. METHODS: A systematic review was performed identifying medical and surgical literature on ChatGPT's proposed clinical applications. Variables assessed included applications investigated, command tasks provided, user input information, AI-emulated human skills, output validation, and reported limitations. RESULTS: The analysis included 175 articles reporting on 13 plastic surgery applications and 116 additional clinical applications, categorized by field and purpose. Thirty-four applications within plastic surgery are thus proposed, with relevance to different target audiences, including attending plastic surgeons (n = 17, 50%), trainees/educators (n = 8, 24.0%), researchers/scholars (n = 7, 21%), and patients (n = 2, 6%). The 15 identified limitations of ChatGPT were categorized by training data, algorithm, and ethical considerations. CONCLUSIONS: Widespread use of ChatGPT in plastic surgery will depend on rigorous research of proposed applications to validate performance and address limitations. This systemic review aims to guide research, development, and regulation to safely adopt AI in plastic surgery.


Asunto(s)
Procedimientos de Cirugía Plástica , Cirujanos , Humanos , Inteligencia Artificial , Algoritmos , Lenguaje
2.
Hand (N Y) ; : 15589447231220412, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38159241

RESUMEN

BACKGROUND: Operating rooms (ORs) produce approximately 70% of hospital waste. Greening strategies in the OR aim to reduce the environmental impact of surgery while maintaining patient safety and outcomes. The aim of this study was to strategically reduce waste and cost associated with common ambulatory hand procedures by implementing a 3-stage "green case" plan over a 1-year period in a high-volume tertiary referral hand surgery division. METHODS: A 3-stage greening initiative for hand surgery was designed and implemented in ambulatory open carpal tunnel release (CTR) and trigger finger release (TFR) cases, including: (1) introduction of minor field sterility; (2) implementation of a lean and green minor hand surgery pack and reduced instrument set; and (3) elimination of gown use by surgeons and OR staff. Surgical supply usage and costs were tracked during the study period and compared with control. RESULTS: Each "green case" resulted in savings of $105 compared with the control cases from the preceding year, excluding cost savings associated with reduced waste processing. There was a 64% and 75% reduction in waste and costs after greening, respectively. This equates to a minimum institutional annual savings of $51 000 when used for CTR and TFR. There was no observed increase in surgical site infections or complications after the introduction of greening. CONCLUSION: Greening initiatives can be successfully implemented by surgeons to reduce waste and costs. With targeted greening of CTR and TFR procedures, we significantly reduced waste and decreased costs while maintaining patient safety and outcomes.

3.
Aesthetic Plast Surg ; 47(6): 2351-2359, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37704858

RESUMEN

INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) is becoming increasingly popular, permitting optimal implant positioning on the chest wall, prevention of animation deformity, and reduced patient discomfort. There are, however, concerns related to increased rates of breast implant rippling in pre-pectoral (versus submuscular) IBR, which can prompt a patient to seek revisionary surgery. The aim of this study is to identify factors that can be implemented to reduce implant rippling in the setting of pre-pectoral IBR. METHODS: A literature review was conducted using the PubMed database to determine the rate of rippling in pre-pectoral IBR. Clinical studies in English were included. Further review was then performed to explore technical strategies associated with reduced rates of rippling in pre-pectoral two-stage breast reconstruction. RESULTS: Implant rippling has been reported with a rate varying from 0 to 53.8% in 25 studies of pre-pectoral IBR (including both direct-to-implant and two-stage IBR). The majority of studies reviewed did not demonstrate a significant association between BMI and rippling, suggesting that other factors, likely technical and device-related, contribute to the manifestation of implant rippling. Hence, we explored whether specific technical modifications could be implemented that would reduce the risk of rippling in patients undergoing pre-pectoral IBR. Specifically, we highlight the need for close attention to expansion protocol and pocket dimension, expander fill medium and implant characteristics, and the rationale behind adjunctive procedures to reduce implant rippling. CONCLUSION: Surgical modifications may reduce the incidence of rippling in pre-pectoral breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mamoplastia/efectos adversos , Mamoplastia/métodos , Implantación de Mama/efectos adversos , Implantación de Mama/métodos , Dispositivos de Expansión Tisular , Reoperación/métodos , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
4.
Plast Reconstr Surg Glob Open ; 11(2): e4674, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36798717

RESUMEN

Distraction osteogenesis (DO) is used for skeletal defects; however, up to 50% of cases exhibit complications. Previous mouse models of long bone DO have been anecdotally hampered by postoperative complications, expense, and availability. To improve clinical techniques, cost-effective, reliable animal models are needed. Our focus was to develop a new mouse tibial distractor, hypothesized to result in successful, complication-free DO. Methods: A lightweight tibial distractor was developed using CAD and 3D printing. The device was fixed to the tibia of C57Bl/6J mice prior to osteotomy. Postoperatively, mice underwent 5 days latency, 10 days distraction (0.15 mm every 12 hours), and 28 days consolidation. Bone regeneration was examined on postoperative day 43 using micro-computed tomography (µCT) and Movat's modified pentachrome staining on histology (mineralized volume fraction and pixels, respectively). Costs were recorded. We compared cohorts of 11 mice undergoing sham, DO, or acute lengthening (distractor acutely lengthened 3.0 mm). Results: The histological bone regenerate was significantly increased in DO (1,879,257 ± 155,415 pixels) compared to acute lengthening (32847 ± 1589 pixels) (P < 0.0001). The mineralized volume fraction (bone/total tissue volume) of the regenerate was significantly increased in DO (0.9 ± 0.1) compared to acute lengthening (0.7 ± 0.1) (P < 0.001). There was no significant difference in bone regenerate between DO and sham. The distractor was relatively low cost ($11), with no complications. Conclusions: Histology and µCT analysis confirmed that the proposed tibial DO model resulted in successful bone formation. Our model is cost-effective and reproducible, enabling implementation in genetically dissectible transgenic mice.

5.
Sci Rep ; 13(1): 2097, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747028

RESUMEN

Mandibular distraction osteogenesis (DO) is mediated by skeletal stem cells (SSCs) in mice, which enact bone regeneration via neural crest re-activation. As peripheral nerves are essential to progenitor function during development and in response to injury, we questioned if denervation impairs mandibular DO. C57Bl6 mice were divided into two groups: DO with a segmental defect in the inferior alveolar nerve (IAN) at the time of mandibular osteotomy ("DO Den") and DO with IAN intact ("DO Inn"). DO Den demonstrated significantly reduced histological and radiological osteogenesis relative to DO Inn. Denervation preceding DO results in reduced SSC amplification and osteogenic potential in mice. Single cell RNA sequencing analysis revealed that there was a predominance of innervated SSCs in clusters dominated by pathways related to bone formation. A rare human patient specimen was also analyzed and suggested that histological, radiological, and transcriptional alterations seen in mouse DO may be conserved in the setting of denervated human mandible distraction. Fibromodulin (FMOD) transcriptional and protein expression were reduced in denervated relative to innervated mouse and human mandible regenerate. Finally, when exogenous FMOD was added to DO-Den and DO-Inn SSCs undergoing in vitro osteogenic differentiation, the osteogenic potential of DO-Den SSCs was increased in comparison to control untreated DO-Den SSCs, modeling the superior osteogenic potential of DO-Inn SSCs.


Asunto(s)
Osteogénesis por Distracción , Osteogénesis , Humanos , Animales , Ratones , Osteogénesis/genética , Ratones Endogámicos C57BL , Mandíbula/fisiología , Regeneración Ósea , Desnervación , Fibromodulina
6.
Plast Reconstr Surg ; 151(2): 200e-206e, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36332003

RESUMEN

BACKGROUND: Several clinical studies have reported autologous breast reconstruction (ABR) to be associated with a higher postoperative complication rate; however, few have investigated the impact of reconstructive modality on complication severity. This study examines the impact of reconstructive modality on complication severity in a matched cohort of patients who underwent ABR versus implant-based breast reconstruction (IBR). METHODS: A retrospective study of patients who underwent nipple-sparing mastectomy with immediate reconstruction was performed. Propensity score matching ensured adequate matching of patients who underwent ABR and staged prepectoral IBR, respectively. Patient demographics, breast measurements, and postoperative outcomes (including the incidence and severity of complications) were analyzed. Multivariable logistic regression analysis was performed. P < 0.05 was considered significant. RESULTS: One hundred twenty-eight patients (214 breast reconstructions) were included for analysis (ABR, n = 64; IBR, n = 64). No difference in overall complication rate was noted ( P = 0.61). However, a significant association of IBR with major complications was noted ( P = 0.02). In contrast, minor complications were significantly more frequent following ABR ( P = 0.04). CONCLUSIONS: Although the reconstructive modality did not appear to have an effect on the overall complication rate, it did significantly affect the severity of postoperative complications, with major and minor complications being associated with IBR and ABR, respectively. These findings are relevant to patient-centered decision-making, as they provide further granularity regarding postoperative complications and address the issue of complication severity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Estudios Retrospectivos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Mamoplastia/efectos adversos , Implantes de Mama/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
7.
J Hand Surg Glob Online ; 4(4): 201-207, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35880155

RESUMEN

Purpose: Peripheral nerve injury (PNI) is a known adverse event following upper-limb surgery performed under brachial plexus regional anesthesia (RA). When PNI is noted after surgery, patients and providers often have questions about which factors might have contributed to this complication. This systematic review evaluates the literature on hand and shoulder surgeries performed under ultrasound-guided, plexus RA to identify factors potentially associated with PNI, including the surgery location and block type. We hypothesized that shoulder surgery might be associated with an increased risk of PNI compared to hand surgery. Methods: A systematic review of the relevant literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only prospective studies on the use of ultrasound-guided, preoperative, brachial plexus RA for hand or shoulder surgery on adult patients were included. Study groups were categorized according to surgery location and block type and compared across a number of factors via univariate and multivariate analyses. Results: A total of 3,037 abstracts were screened; 192 full-text articles were independently reviewed by 2 of the authors; and 53 studies were included in the systematic review analysis. Following hand surgery, PNI was reported at an average rate of 1.35% ± 3.21% across 836 subjects in 40 study groups; after shoulder surgery, the average rate was 0.50% ± 1.57% across 3,383 subjects in 15 study groups. There was no statistically significant correlation between the incidence of PNI and surgery location (P =.70) or any of the most common approaches for brachial plexus anesthesia in the multivariate analysis. Conclusions: This systematic review of over 50 articles on upper-limb surgery performed under RA shows no association between the incidence of PNI and the location of surgery or type of brachial plexus block. Type of study/level of evidence: Diagnostic II.

8.
J Plast Reconstr Aesthet Surg ; 75(9): 3060-3067, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35768293

RESUMEN

BACKGROUND: Textured tissue expanders (TTEs) were introduced to limit migration and reduce capsular contracture, which were inherent to smooth tissue expanders (STEs). Previous reports suggest that textured devices have increased rates of bacterial contamination and biofilm formation in comparison with smooth devices. Recently, the relative increased association of anaplastic large cell lymphoma (ALCL) with textured versus smooth devices has led to increased adoption of smooth devices. The aim of our study is to evaluate the post-operative surgical site infection (SSI) rates of STEs versus TTEs. METHODS: A retrospective case series was conducted at a single academic teaching hospital from April 2016 to December 2019. The primary outcome variable was the development of a post-operative SSI. RESULTS: One hundred seventy-seven breasts underwent reconstruction with TTEs and 109 breasts underwent reconstruction with STE. In total, 54 SSIs were recorded (n = 34 TTE; n = 20 STE), with the majority of infections occurring within the first 30 post-operative days (TTE 65%, STE 70%). There was no statistically significant difference in overall post-operative infection rates between TTE and STE groups when broken down into the following time points: <30 day, 30-60 days, and >90 days (p = 0.924). There was no statistically significant difference between infection type (superficial vs. deep, p = 0.932), infection management (medical, surgical, or both, p = 0.409) or salvage results (p = 0.078) seen in STE versus TTE cohort. On multivariate analysis, seroma history was associated with SSI development (OR 3.18, p = 0.041). CONCLUSION: There was no significant difference in the rate of post-operative SSI following breast reconstruction with STE relative to TTE.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Implantes de Mama/efectos adversos , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia/métodos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Dispositivos de Expansión Tisular
9.
Plast Reconstr Surg ; 150(1): 28-36, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35499585

RESUMEN

BACKGROUND: Traditionally, saline is used for intraoperative/postoperative expansion in two-stage alloplastic breast reconstruction. Recently, intraoperative expansion with air has been proposed, to reduce pressure on the mastectomy skin flap in the immediate postoperative setting. The authors examined whether the intraoperative tissue expansion medium (i.e., air versus saline) affected postmastectomy complications in two-stage prepectoral reconstruction. METHODS: This was a retrospective cohort study of 87 patients (144 breasts) undergoing prepectoral breast reconstruction at the authors' institution. Patient data were abstracted from medical records. Stepwise, multivariable-adjusted logistic regression using robust variances was used to identify predictors of postmastectomy complications. Statistical and power analyses were completed. RESULTS: Of the 87 study patients, 29 (33.3 percent) received intraoperative saline fill and 58 (66.7 percent) received air fill. Demographic/clinical data were well-matched between cohorts. Median follow-up was 165 days, and average patient age was 46.7 years. Initial tissue expander fill volumes were similar between study cohorts ( p = 0.2). The crude association between air versus saline fill on overall complication rates suggested that air-filled tissue expanders may be protective (OR = 0.4; p = 0.03), and the suggested protective effect was maintained with borderline significance even after potential confounders (i.e., American Society of Anesthesiologists class III or higher, body mass index, diabetes, mastectomy specimen weight, smoking status) were added to the model (OR = 0.4; p = 0.05). In addition, fewer complications requiring salvage reoperation were observed with air-filled tissue expanders (adjusted OR = 0.3; p = 0.02). CONCLUSIONS: The medium used for immediate intraoperative tissue expansion impacted postmastectomy outcomes in patients undergoing two-stage prepectoral breast reconstruction. The results demonstrated that air-filled tissue expanders were associated with fewer postoperative complications/salvage reoperations relative to saline-filled tissue expanders. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Implantes de Mama/efectos adversos , Neoplasias de la Mama/etiología , Femenino , Humanos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Mastectomía/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Solución Salina , Expansión de Tejido/métodos , Dispositivos de Expansión Tisular/efectos adversos
10.
Sci Transl Med ; 14(645): eabj9152, 2022 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-35584231

RESUMEN

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.


Asunto(s)
Quemaduras , Contractura , Animales , Quemaduras/patología , Cicatriz/patología , Contractura/patología , Mecanotransducción Celular , Piel/patología , Trasplante de Piel/métodos , Porcinos
11.
Plast Reconstr Surg ; 149(2): 316-322, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35077404

RESUMEN

BACKGROUND: Nipple-sparing mastectomy is associated with greater patient satisfaction than non-nipple-sparing approaches. Although various nipple-sparing mastectomy incisions have been described, the authors hypothesized that incision location would impact the rate and location of ischemic complications to the mastectomy skin flap. METHODS: A prospectively maintained database was queried to identify patients who underwent nipple-sparing mastectomy with immediate microsurgical reconstruction with a minimum postoperative follow-up of 12 months. The impact of incision location on postoperative ischemic complications was investigated. Major complications were defined as those that required reexploration in the operating room or inpatient management; minor complications were amenable to outpatient management. Multivariable logistic and linear regression were performed to investigate risk factors for postoperative complications following breast reconstruction. RESULTS: Eighty-seven patients met inclusion criteria. The following nipple-sparing mastectomy incisions were used: radial with a periareolar extension (39 percent), inframammary fold (31 percent), vertical with a periareolar extension (22 percent), vertical (6 percent), and radial (2 percent). Seven patients (8 percent) had major complications, whereas twenty-six patients (29.9 percent) developed minor postoperative complications. Inframammary fold incisions were associated with significantly greater rates of mastectomy skin flap necrosis (p = 0.002), whereas periareolar incisions were associated with significantly greater rates of postoperative nipple-areola complex necrosis (p = 0.04). CONCLUSIONS: The authors report a significant association between incision location and ischemic complications to the breast skin envelope in microsurgical breast reconstruction. The authors observed a significant association of inframammary fold and periareolar incisions with mastectomy skin flap and nipple-areola complex necrosis, respectively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Asunto(s)
Neoplasias de la Mama/cirugía , Isquemia/etiología , Mamoplastia/efectos adversos , Mamoplastia/métodos , Mastectomía Subcutánea , Microcirugia , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Colgajos Quirúrgicos , Adulto Joven
12.
Adv Wound Care (New Rochelle) ; 11(10): 548-559, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34074152

RESUMEN

Significance: By 2030, there will be >4 million radiation-treated cancer survivors living in the United States. Irradiation triggers inflammation, fibroblast activation, and extracellular matrix deposition in addition to reactive oxygen species generation, leading to a chronic inflammatory response. Radiation-induced fibrosis (RIF) is a progressive pathology resulting in skin pigmentation, reduced elasticity, ulceration and dermal thickening, cosmetic deformity, pain, and the need for reconstructive surgery. Recent Advances: Deferoxamine (DFO) is a U.S. Food and Drug Administration (FDA)-approved iron chelator for blood dyscrasia management, which has been found to be proangiogenic, to decrease free radical formation, and reduce cell death. DFO has shown great promise in the treatment and prophylaxis of RIF in preclinical studies. Critical Issues: Systemic DFO has a short half-life and is cumbersome to deliver to patients intravenously. Transdermal DFO delivery is complicated by its high atomic mass and hydrophilicity, preventing stratum corneum penetration. A transdermal drug delivery system was developed to address these challenges, in addition to a strategy for topical administration. Future Directions: DFO has great potential to translate from bench to bedside. An important step in translation of DFO for RIF prophylaxis is to ensure that DFO treatment does not affect the efficacy of radiation therapy. Furthermore, after an initial plethora of studies reporting DFO treatment by intravenous and subcutaneous routes, a significant advantage of recent studies is the success of transdermal and topical delivery. Given the strong foundation of basic scientific research supporting the use of DFO treatment on RIF, clinicians will be closely following the results of the ongoing human studies.


Asunto(s)
Quelantes , Deferoxamina , Administración Cutánea , Administración Tópica , Deferoxamina/farmacología , Deferoxamina/uso terapéutico , Fibrosis , Humanos
13.
Nat Commun ; 12(1): 5256, 2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34489407

RESUMEN

Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.


Asunto(s)
Indoles/farmacología , Mecanotransducción Celular/fisiología , Piel/lesiones , Sulfonamidas/farmacología , Cicatrización de Heridas/fisiología , Animales , Diferenciación Celular , Células Cultivadas , Colágeno/metabolismo , Femenino , Fibroblastos , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Quinasa 1 de Adhesión Focal/metabolismo , Regeneración Tisular Dirigida , Humanos , Indoles/sangre , Mecanotransducción Celular/efectos de los fármacos , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Piel/efectos de los fármacos , Piel/patología , Fenómenos Fisiológicos de la Piel , Estrés Mecánico , Sulfonamidas/sangre , Porcinos , Cicatrización de Heridas/efectos de los fármacos
14.
Nature ; 597(7875): 256-262, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34381212

RESUMEN

Loss of skeletal integrity during ageing and disease is associated with an imbalance in the opposing actions of osteoblasts and osteoclasts1. Here we show that intrinsic ageing of skeletal stem cells (SSCs)2 in mice alters signalling in the bone marrow niche and skews the differentiation of bone and blood lineages, leading to fragile bones that regenerate poorly. Functionally, aged SSCs have a decreased bone- and cartilage-forming potential but produce more stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell RNA-sequencing studies link the functional loss to a diminished transcriptomic diversity of SSCs in aged mice, which thereby contributes to the transformation of the bone marrow niche. Exposure to a youthful circulation through heterochronic parabiosis or systemic reconstitution with young haematopoietic stem cells did not reverse the diminished osteochondrogenic activity of aged SSCs, or improve bone mass or skeletal healing parameters in aged mice. Conversely, the aged SSC lineage promoted osteoclastic activity and myeloid skewing by haematopoietic stem and progenitor cells, suggesting that the ageing of SSCs is a driver of haematopoietic ageing. Deficient bone regeneration in aged mice could only be returned to youthful levels by applying a combinatorial treatment of BMP2 and a CSF1 antagonist locally to fractures, which reactivated aged SSCs and simultaneously ablated the inflammatory, pro-osteoclastic milieu. Our findings provide mechanistic insights into the complex, multifactorial mechanisms that underlie skeletal ageing and offer prospects for rejuvenating the aged skeletal system.


Asunto(s)
Envejecimiento/patología , Huesos/patología , Senescencia Celular , Inflamación/patología , Nicho de Células Madre , Células Madre/patología , Animales , Proteína Morfogenética Ósea 2/metabolismo , Regeneración Ósea , Linaje de la Célula , Femenino , Curación de Fractura , Hematopoyesis , Factor Estimulante de Colonias de Macrófagos/metabolismo , Masculino , Ratones , Células Mieloides/citología , Osteoclastos/citología , Rejuvenecimiento
15.
Nat Commun ; 12(1): 4640, 2021 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-34330896

RESUMEN

Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cells derived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. Crossing Axin2LacZ/+ mouse, endowing enhanced Wnt activation, to a Twist1+/- mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy in Twist1+/- mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.


Asunto(s)
Suturas Craneales/metabolismo , Craneosinostosis/genética , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica/métodos , Células Madre/metabolismo , Animales , Proteína Axina/genética , Proteína Axina/metabolismo , Diferenciación Celular/genética , Proliferación Celular/genética , Células Cultivadas , Suturas Craneales/citología , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Sistema Musculoesquelético/citología , Sistema Musculoesquelético/metabolismo , Células Madre/citología , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo , Vía de Señalización Wnt/genética , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo
16.
Ann Plast Surg ; 86(5S Suppl 3): S414-S417, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33833172

RESUMEN

INTRODUCTION: Radiation therapy is a known risk factor for capsular contracture formation after implant-based breast reconstruction. Although autologous fat grafting (AFG) has been shown to reverse radiation-induced tissue fibrosis, its use as a prophylactic agent against capsular contraction has not been assessed in the clinical setting. In the setting of 2-stage implant-based reconstruction and postmastectomy radiation therapy, we explored the effect AFG has on the prevalence of capsular contracture. MATERIALS AND METHODS: A retrospective chart review of patients who underwent immediate tissue expander (TE) placement followed by postmastectomy radiation therapy and secondary implant-based reconstruction at our institution between January 2012 and December 2019 was performed. Patients were divided into 2 cohorts based on whether or not AFG was performed at the time of secondary reconstruction. The primary outcome of interest was the occurrence of capsular contracture after TE exchange. RESULTS: Overall 57 patients (57 breasts) were included, 33 of whom received AFG at the time of TE exchange. All but 1 patient underwent submuscular implant placement, and the mean follow-up was 1.96 years. There was no significant difference in the prevalence of medical comorbidities between the study groups.Capsular contracture occurred in 24 patients (42.1%). Seventeen of these patients had undergone AFG at the time of TE exchange (17/33 patients, 51.5%), and 7 of these patients had not (7/24 patients, 29.2%). Most of the capsular contracture cases were Baker grades III or IV (14 patients, 58.3%), and 50% of patients with capsular contracture of any grade ultimately required operative intervention. Multivariate logistic regression analysis demonstrated that AFG did not significantly influence the occurrence or severity of capsular contracture, or did not impact the need for operative intervention in this patient population. CONCLUSIONS: Implant-based reconstruction of the irradiated breast is associated with high postoperative capsular contracture rates. Although AFG has shown promise in reversing radiation-induced dermal fibrosis, no protective effect on the development of capsular contracture after stage 2 reconstruction was observed in this study population. Further investigation in the form of randomized, prospective studies is needed to better assess the utility of AFG in preventing capsular contracture in irradiated patients.


Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Contractura , Mamoplastia , Tejido Adiposo , Implantación de Mama/efectos adversos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Contractura/epidemiología , Contractura/etiología , Contractura/prevención & control , Humanos , Contractura Capsular en Implantes/epidemiología , Contractura Capsular en Implantes/etiología , Contractura Capsular en Implantes/prevención & control , Mastectomía , Estudios Prospectivos , Radioterapia Adyuvante , Estudios Retrospectivos
17.
J Plast Reconstr Aesthet Surg ; 74(7): 1503-1507, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33341386

RESUMEN

Breast reconstruction often renders the chest skin and nipple areolar complex (NAC) insensate. We propose a new technique of preserving the intercostal nerves during mastectomy and using them to reinnervate the NAC following mastectomy and immediate autologous tissue reconstruction. The technique involves preservation of the lateral intercostal nerves during mastectomy, dissection of the lateral intercostal nerves to length, coaptation of the intercostal nerves to a nerve graft which is then tunneled through the free flap and the distal nerve graft is then coapted to the nerve stumps at the base of the NAC. We performed a retrospective analysis of 14 breasts, which underwent nipple reinnervation during immediate autologous breast reconstruction. Mean age was 49 years (range: 32-61 years). Sensory outcomes, as tested with Semmes-Weinstein monofilaments, were compared to a cohort of breasts that underwent nipple sparing mastectomy without neurotization. Compared to control patients, there was no statistically significant difference (p = 0.0969) in sensation between pre-operative and post-operative nipple sensation at final follow-up. This proof-of-concept study suggests that immediate re-innervation of the NAC in the setting of immediate breast reconstruction enhances recovery of the NAC sensation.


Asunto(s)
Neoplasias de la Mama/cirugía , Nervios Intercostales , Mamoplastia/métodos , Pezones/inervación , Pezones/cirugía , Adolescente , Adulto , Femenino , Colgajos Tisulares Libres/inervación , Humanos , Mastectomía , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Retrospectivos
19.
J Hand Surg Glob Online ; 2(3): 166-170, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-35415493

RESUMEN

Neonatal compartment syndrome is a rare condition. Early diagnosis and timely surgical intervention are paramount to optimize outcome. Time to fasciotomy is the most important prognostic factor. The purposes of this study were to describe a case presentation of neonatal compartment syndrome associated with a compound birth presentation and to perform a literature review. In this case, the neonate's fingers were noted to be present on maternal cervical examination 24 hours before delivery. The patient then was noted to have a sentinel skin lesion. A diagnosis of neonatal compartment syndrome was suspected, and she underwent urgent fasciotomy. Literature review identified a total of 60 patients from 26 studies. Most patients were managed operatively. All patients presented with a sentinel skin lesion, emphasizing the importance of this clinical sign in diagnosis. Manometry is not routinely performed and no standards are available for acceptable pressure gradients.

20.
Front Dent Med ; 12020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35664558

RESUMEN

Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace "like with like." With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation in vivo can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level in vivo without prior in vitro culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated in situ with broad potential applications in craniofacial tissue engineering.

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