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1.
Am J Med Genet A ; 191(2): 559-563, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36321812

RESUMEN

The Urofacial or Ochoa Syndrome is a very rare congenital disorder that includes vesical bladder dysfunction and a peculiar inverse facial expression, which brings patients to express a sad-crying face while they intend to laugh. Up-to-date treatments have addressed only the urological side of this disease. However, also the impaired facial mimicry has a strong impact on patients' quality of life. We treated a young patient with Botulinum toxin to address this impairment and obtained pleasing results, including a harmonic smile and a very satisfied patient. To the best of our knowledge, this is the first time that the use of Botulinum toxin is reported in literature to address the facial expression component of this disease.


Asunto(s)
Toxinas Botulínicas , Expresión Facial , Humanos , Calidad de Vida , Síndrome
2.
Int J Mol Sci ; 24(18)2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37762247

RESUMEN

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation.


Asunto(s)
Gelatina , Fracción Vascular Estromal , Humanos , Perilipina-2 , Factor A de Crecimiento Endotelial Vascular , Piel , Factor 2 de Crecimiento de Fibroblastos
3.
Dermatology ; 238(5): 851-859, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35086097

RESUMEN

BACKGROUND: Radical excision of debilitating hidradenitis suppurativa lesions is the only curative approach in the advanced stages of the disease. Different concepts for axillary reconstruction do exist, but data on their clinical outcome are scarce. METHODS: This is a retrospective cohort study of two reconstructive methods (posterior arm flap vs. vacuum-assisted closure [VAC] + split-thickness skin graft [STSG]) for axillary defects in patients with severe axillary hidradenitis suppurativa treated at the University Hospital Zurich between 2005 and 2020. RESULTS: A total of 35 patients (mean age 36 ± 10 years, mean BMI 29 ± 5 kg/m2, Hurley stage II-III) with 67 operated axillae were stratified according to their type of reconstruction. Median operation time in the flap group was 144 min (IQR 114-207) (cumulative 181 min [IQR 124-300]) and 50 min (IQR 40-81) in the VAC + STSG group (cumulative 151 min [IQR 94-194], p < 0.01; p = 0.20 [cumulative time]). The cumulative length of stay was 6 ± 3 days in the flap group and 14 ± 7 days in the VAC + STSG group (p < 0.01). Time to complete wound healing was 27 days (IQR 20-49) in the flap group and 62 days (IQR 41-75) in the VAC + STSG group (p < 0.01). Vancouver Scar Scale score was 6 (IQR 4-9) in the flap group and 11 (IQR 9-12) in the VAC + STSG group (p < 0.01). Protective sensory recovery was most satisfactory in the flap group (p < 0.01). Forty-four percent of patients of the VAC + STSG group demonstrated functional impairment of arm abduction. Time to return to work was less in group A with 42 days (IQR 27-57) needed as compared to group B with 48 days (IQR 34-55) needed (p = 0.32). The average cost saving was 25% higher for the flap group than for the VAC + STSG group. CONCLUSION: Despite an increased operation time, axillary reconstruction by the posterior arm flap yields a reduced length of stay, less time to complete wound healing along with restoration of a protective sensibility, and less axillary scarring avoiding functional deficits - eventually allowing earlier return to work.


Asunto(s)
Hidradenitis Supurativa , Procedimientos de Cirugía Plástica , Adulto , Axila/cirugía , Hidradenitis Supurativa/cirugía , Humanos , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Trasplante de Piel , Colgajos Quirúrgicos/cirugía
4.
Proc Natl Acad Sci U S A ; 116(51): 25784-25789, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31792185

RESUMEN

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-ß1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in allograft tissue. TRI-MP also enriched Treg and reduced inflammatory Th1 populations in allograft draining lymph nodes. This local immunotherapy imparted systemic donor-specific tolerance in otherwise immunocompetent rats, as evidenced by acceptance of secondary skin grafts from the hindlimb donor strain and rejection of skin grafts from a third-party donor strain. Ultimately, this therapeutic approach may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.


Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Terapia de Inmunosupresión/métodos , Linfocitos T Reguladores/citología , Tolerancia al Trasplante/fisiología , Alotrasplante Compuesto Vascularizado/métodos , Animales , Citocinas/metabolismo , Sistemas de Liberación de Medicamentos , Inmunosupresores/metabolismo , Ratas
5.
Ann Plast Surg ; 88(3): 271-276, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35130205

RESUMEN

BACKGROUND: Eyelid scarring after severe burn injury of the face is a significant complication endangering vision in addition to the burn scar sequelae. Scar contraction leads to asymmetry and malposition of the eyelid axis, resulting in corneal exposure, eyelid retraction, and incomplete eyelid closure. In consequence, dryness and irritation of the cornea can lead to keratitis, corneal opacity, and vision impairment. In this study, we present our surgical technique for lateral canthopexy in combination with full-thickness skin grafting (FTSGing) in patients with eyelid axis distortion after scar contraction of the periorbital region after severe burn injuries of the face. METHODS: In this retrospective, single-center case study, we present 5 consecutive patients who experienced severe burn injuries to the face between 2014 and 2019. Patients were suffering from ectropion and malposition of the eyelid axis. In all cases, we performed lateral transosseous canthopexy and FTSGing. RESULTS: Improved symmetry and complete eyelid closure were restored in all 5 patients. The following ophthalmological examinations showed resolved corneal erosions, as well as reduction of chemosis and epiphora. Further vision impairment was successfully prohibited. Surgical revision with FTSGing was required in 2 patients because of recurrence of unilateral lower eyelid retraction. CONCLUSIONS: Lateral transosseous canthopexy represents a suitable surgical method to durably correct eyelid malposition, ectropion, and incomplete lid closure in patients with severe scarring of the periorbital region after burns of the face. Early detection of patients at risk and timing of surgical intervention are of great importance.


Asunto(s)
Blefaroplastia , Quemaduras , Ectropión , Quemaduras/complicaciones , Quemaduras/cirugía , Cicatriz/complicaciones , Cicatriz/cirugía , Ectropión/etiología , Ectropión/cirugía , Humanos , Estudios Retrospectivos
6.
J Craniofac Surg ; 33(8): 2631-2637, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35905389

RESUMEN

Major complex cranial defects may be challenging for the reconstructive microsurgeon. Affected patients often present with impaired soft tissues including dura exposure or fistulas. The lacking structural bony support may cause severe neurological issues and in select patients, there is a need for well-vascularized autologous tissue repair. The authors herein elucidate the role of the multiple rib osteomyocutaneous split latissimus dorsi flap for reconstruction of composite skull defects, providing an indication, an exemplary case, operation technique, and literature review. A 40-year-old woman after anaplastic oligodendroglioma resection suffered multiple extrusions and allograft cranioplasty infections. The defect was reconstructed with an osteomyocutaneus split latissimus dorsi flap including costae 3 ribs and a skin island. The included ribs were nourished via the anterior periosteum, while the posterior periosteum was left in place for the protection of the pleura parietalis. A proper amount of craniomedial latissimus dorsi muscle was spared to reduce donor site morbidity. The patient presented after 6 months with stable bony and soft tissue conditions without neurological symptoms, and acceptable donor site morbidity. After failed alloplastic cranioplasties, the free latissimus dorsi flap including vascularized ribs is well suitable for coverage of large compound cranial defects, providing skeletal support, improved contour, and enhanced functional outcome.


Asunto(s)
Mamoplastia , Procedimientos de Cirugía Plástica , Músculos Superficiales de la Espalda , Femenino , Humanos , Adulto , Músculos Superficiales de la Espalda/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/cirugía , Costillas/trasplante , Cráneo/cirugía
7.
Ann Surg ; 274(6): e1179-e1186, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31972652

RESUMEN

OBJECTIVE: The burn victim's inherent state of hyperinflammation frequently camouflages septic events delaying the initiation of targeted intensive care therapy. Accurate biomarkers are urgently needed to support sepsis detection before patients' clinical deterioration. SUMMARY OF BACKGROUND DATA: Evidence on the usefulness of pancreatic stone protein (PSP) as a powerful diagnostic and prognostic marker in critically ill patients has recently accumulated. METHODS: Analysis of biomarker kinetics (PSP, routine markers) was performed on 90 patients admitted to the Zurich Burn Center between May 2015 and October 2018 with burns ≥15% total body surface area with regard to infection and sepsis (Sepsis-3) over a 14-day time course. RESULTS: PSP differentiated between sepsis, infection and sterile inflammation from day 3 onward with an area under the curve of up to 0.89 (P < 0.001), therefore, competing with procalcitonin (area under the curve = 0.86, P < 0.001). Compared to routine inflammatory biomarkers, only PSP demonstrated a significant interaction between time and presence of sepsis - signifying a steeper increase in PSP levels in septic patients as opposed to those exhibiting a nonseptic course (interaction P < 0.001). Event-related analysis demonstrated tripled PSP serum levels within 72 hours and doubled levels within 48 hours before a clinically apparent sepsis. CONCLUSION: PSP is able to differentiate between septic and nonseptic patients during acute burn care. Its steep rise up to 72 hours before clinically overt deterioration has the potential for physicians to timely initiate treatment with reduced mortality and costs.


Asunto(s)
Biomarcadores/sangre , Quemaduras/complicaciones , Litostatina/sangre , Sepsis/sangre , Adulto , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico
8.
Am J Transplant ; 20(5): 1272-1284, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31774619

RESUMEN

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5 mg/kg) for 14 days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10 mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1 × 106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50 mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500 µL ip, POD 1, 5). Banff grade III or 120 days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28 days in CTRL (n = 7), 34 in ASC (n = 6), and 27.5 in ASC-CYP (n = 4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.


Asunto(s)
Tolerancia al Trasplante , Alotrasplante Compuesto Vascularizado , Animales , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Inmunosupresores/uso terapéutico , Ratas , Células del Estroma
9.
J Surg Res ; 254: 175-182, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32450418

RESUMEN

BACKGROUND: Vascularized composite tissue allotransplantation (VCA) opens new possibilities for reconstruction of complex tissue defects, including upper extremity and facial transplantation. The main challenges in VCA transplantation are the side effects of long-term immunosuppression and chronic graft rejection. Translational preclinical animal models are crucial for VCA research to improve clinical outcomes and to study underlying immunologic mechanisms. Herein, we describe a novel, large animal, non-bone-bearing VCA model in inbred, swine leukocyte antigen-typed miniature swine. METHODS: Transplantation of vertical rectus abdominis myocutaneous (VRAM) flaps was performed between fully swine leukocyte antigen-mismatched miniature swine. The flaps were transferred to the posterolateral aspect of the neck of recipients and anastomosed to the common carotid artery and internal jugular vein. Different immunosuppressive drug regimens were used. Clinical graft evaluation was performed daily, and punch biopsies were taken for histology. RESULTS: Ten VRAM transplants were performed. The mean ischemia time was 89.4 min (SD ± 47), mean pedicle length 7.5 cm (SD ± 2), mean venous diameter 2.5 mm (SD ± 0.4), and mean arterial diameter 2.2 mm (SD ± 0.3). Follow-up demonstrated good correlation between clinical appearance and progression of graft rejection confirmed by histologic assessment. Complications were intraoperative cardiac arrest in one recipient and one flap loss due to venous compromise. CONCLUSIONS: VRAM transplantation in miniature swine is an appropriate preclinical VCA model, with the advantage of good clinical and histologic correlation during the course of rejection, as well as easy access to the graft. The availability of inbred, haplotyped animals allows studies across different major histocompatibility complex barriers in a non-bone-bearing VCA.


Asunto(s)
Rechazo de Injerto/patología , Recto del Abdomen/trasplante , Animales , Recto del Abdomen/patología , Porcinos , Porcinos Enanos , Trasplante Heterotópico , Trasplante Homólogo
10.
World J Surg ; 44(9): 3000-3009, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32451625

RESUMEN

BACKGROUND: Altered levels of pro-inflammatory markers secondary to trauma or surgery present a major problem to physicians in being prone to interfere with the clinical identification of infectious events. METHODS: Patients admitted to Zurich Burn Center between May 2015 and October 2018 with burns ≥10% total body surface area (TBSA) and without infection. Longitudinal analysis of the time course of PSP and routine inflammatory biomarkers [procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC)] over two days after (a) trauma with initial debridement and (b) subsequent burn surgeries was performed. The influence of TBSA, abbreviated burn severity index (ABSI), age and length of operation was investigated using a linear mixed effect regression model. RESULTS: Sixty-six patients (15 female) were included with a mean age of 45.5 ± 18.3 years, median TBSA of 22% (IQR 17) and mean ABSI score 6.8 ± 2.7. PSP was the only biomarker that showed no association with any of the baseline characteristics. Additionally, PSP serum levels did not change over time neither after the burn trauma (p = 0.832) nor after secondary procedures (p = 0.113), while PCT levels increased significantly after the trauma (p < 0.001). Similarly, CRP serum levels were elevated significantly after both trauma and surgery (p < 0.001), whereas WBC values demonstrated a significant decline after the trauma (p < 0.001). CONCLUSION: Established biomarkers (WBC, CRP and PCT) demonstrate decisive alterations after tissue destruction caused by burn injuries and subsequent surgical interventions. The robustness of PSP serum levels toward these inflammatory insults is a quality criterion for an upcoming sepsis biomarker.


Asunto(s)
Quemaduras/cirugía , Litostatina/sangre , Adulto , Anciano , Biomarcadores/sangre , Superficie Corporal , Quemaduras/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/sangre , Índices de Gravedad del Trauma
11.
J Vasc Res ; 56(4): 163-180, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31266018

RESUMEN

Vascularized composite allotransplantation (VCA) has emerged as a useful reconstructive option for patients suffering from major tissue defects and functional deficits. While the technical feasibility has been optimized and more than 130 VCAs have been performed during the last two decades, hurdles such as acute and chronic allograft rejection, graft deterioration, and eventual functional impairment need to be addressed. Recently, chronic graft rejection and progressive failure have been linked to vascular alterations observed in the allografts. Graft vasculopathy (GV) may play a pivotal role in long-term graft deterioration. The understanding of the underlying pathophysiological processes and their initial triggers is of utmost importance in the prevention, attenuation, and therapy of GV. While there are reports on the etiology and development of GV in solid organ transplantation, there are limited data with respect to chronic rejection and GV in the realm of VCA. Nevertheless, recent reports from long-term VCA recipients suggest that GV could truly jeopardize allografts in the follow-up evaluation. Chronic rejection and GV include different entities and might have different pathways in distinct organs. Herein, we reviewed the current literature on vascular changes during both acute and chronic allograft rejection, with a focus on their clinical and translational significance for VCA.


Asunto(s)
Aloinjertos Compuestos/irrigación sanguínea , Rechazo de Injerto/etiología , Alotrasplante Compuesto Vascularizado/efectos adversos , Enfermedad Aguda , Animales , Enfermedad Crónica , Aloinjertos Compuestos/inmunología , Trasplante Facial/efectos adversos , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Trasplante de Mano/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
12.
Aesthet Surg J ; 37(4): 474-482, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28364525

RESUMEN

Background: Cosmetic surgery tourism characterizes a phenomenon of people traveling abroad for aesthetic surgery treatment. Problems arise when patients return with complications or need of follow-up care. Objectives: To investigate the complications of cosmetic surgery tourism treated at our hospital as well as to analyze arising costs for the health system. Methods: Between 2010 and 2014, we retrospectively included all patients presenting with complications arising from cosmetic surgery abroad. We reviewed medical records for patients' characteristics including performed operations, complications, and treatment. Associated cost expenditure and Diagnose Related Groups (DRG)-related reimbursement were analyzed. Results: In total 109 patients were identified. All patients were female with a mean age of 38.5 ± 11.3 years. Most procedures were performed in South America (43%) and Southeast (29.4%) or central Europe (24.8%), respectively. Favored procedures were breast augmentation (39.4%), abdominoplasty (11%), and breast reduction (7.3%). Median time between the initial procedure abroad and presentation was 15 days (interquartile range [IQR], 9) for early, 81.5 days (IQR, 69.5) for midterm, and 4.9 years (IQR, 9.4) for late complications. Main complications were infections (25.7%), wound breakdown (19.3%), and pain/discomfort (14.7%). The majority of patients (63.3%) were treated conservatively; 34.8% became inpatients with a mean hospital stay of 5.2 ± 3.8 days. Overall DRG-related reimbursement premiums approximately covered the total costs. Conclusions: Despite warnings regarding associated risks, cosmetic surgery tourism has become increasingly popular. Efficient patients' referral to secondary/tertiary care centers with standardized evaluation and treatment can limit arising costs without imposing a too large burden on the social healthcare system. Level of Evidence: 4.


Asunto(s)
Atención a la Salud/economía , Costos de la Atención en Salud/estadística & datos numéricos , Tiempo de Internación/economía , Turismo Médico , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/economía , Adolescente , Adulto , Femenino , Humanos , Reembolso de Seguro de Salud/economía , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/economía , Derivación y Consulta/economía , Estudios Retrospectivos , Centros de Atención Secundaria/normas , Suiza , Centros de Atención Terciaria/normas , Adulto Joven
13.
Curr Opin Organ Transplant ; 20(6): 608-14, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26536421

RESUMEN

PURPOSE OF REVIEW: Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS: Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY: Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Alotrasplante Compuesto Vascularizado , Animales , Rechazo de Injerto/inmunología , Humanos , Tolerancia Inmunológica , Trasplante Homólogo
14.
Cytotherapy ; 16(10): 1345-60, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24972742

RESUMEN

BACKGROUND AIMS: Stem cells participate in vascular regeneration following critical ischemia. However, their angiogenic and remodeling properties, as well as their role in ischemia-related endothelial leukocyte activation, need to be further elucidated. Herein, we investigated the effect of bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a critically ischemic murine skin flap model. METHODS: Groups received either 1 × 10(5), 5 × 10(5), or 1 × 10(6) BM-MSCs or cell-free conditioned medium (CM). Controls received sodium chloride. Intravital fluorescence microscopy was performed for morphological and quantitative assessment of micro-hemodynamic parameters over 12 days. RESULTS: Tortuosity and diameter of conduit-arterioles were pronounced in the MSC groups (P < 0.01), whereas vasodilation was shifted to the end arteriolar level in the CM group (P < 0.01). These effects were accompanied by angiopoietin-2 expression. Functional capillary density and red blood cell velocity were enhanced in all treatment groups (P < 0.01). Although a significant reduction of rolling and sticking leukocytes was observed in the MSC groups with a reduction of diameter in postcapillary venules (P < 0.01), animals receiving CM exhibited a leukocyte-endothelium interaction similar to controls. This correlated with leukocyte common antigen expression in tissue sections (P < 0.01) and p38 mitogen-activated protein kinase expression from tissue samples. Cytokine analysis from BM-MSC culture medium revealed a 50% reduction of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-12, tumor necrosis factor-α, interferon-γ) and chemokines (keratinocyte chemoattractant, granulocyte colony-stimulating factor) under hypoxic conditions. DISCUSSION: We demonstrated positive effects of BM-MSCs on vascular regeneration and modulation of endothelial leukocyte adhesion in critical ischemic skin. The improvements after MSC application were dose-dependent and superior to the use of CM alone.


Asunto(s)
Células de la Médula Ósea/fisiología , Capilares/fisiología , Endotelio/fisiología , Isquemia , Leucocitos/fisiología , Células Madre Mesenquimatosas/fisiología , Regeneración/fisiología , Piel/irrigación sanguínea , Animales , Capilares/patología , Comunicación Celular , Células Cultivadas , Endotelio/metabolismo , Femenino , Isquemia/patología , Isquemia/fisiopatología , Leucocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Piel/inmunología
15.
J Clin Med ; 13(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38673668

RESUMEN

Background: Nowadays, multimodal cancer therapy results in very high survival rates of early-stage breast cancer and microsurgical flap-based breast reconstruction has become safe and reliable, with gradually increasing demand because of its durable and aesthetically pleasing results. This study aimed to explore the impact of different flap shaping and inset techniques on patient-reported outcome measures (PROMs) with regard to the aesthetic result in abdominal flap-based breast reconstruction. Methods: A systematic review was performed screening Pubmed, Cochrane Library and Web of Science for original articles reporting flap inset strategies, concomitantly providing PROMs on the aesthetic result. Results: Of 319 studies identified, six met the inclusion criteria. The studies described different flap rotation options according to the patient's morphology, different inset planes, and avoidance of the monitoring skin paddle, and suggested that a higher flap-to-mastectomy mass ratio was associated with better aesthetic results. In two comparative studies, according to the PROMs (BREAST-Q, Likert scale) and independent observer judgement, both higher patient satisfaction and superior aesthetic results were observed with the newly described techniques. Conclusions: Emphasis on the aesthetic outcome in terms of breast shape and symmetry, providing an individualized approach of flap inset, considering the contralateral breast's shape and volume, results in higher satisfaction scores.

16.
J Surg Res ; 184(2): 1205-13, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23651811

RESUMEN

BACKGROUND: Botulinum toxin (BTX) A and B are commonly used for aesthetic indications and in neuromuscular disorders. New concepts seek to prove efficacy of BTX for critical tissue perfusion. Our aim was to evaluate BTX A and B in a mouse model of critical flap ischemia for preoperative and intraoperative application. METHODS: BTX A and B were applied on the vascular pedicle of an axial pattern flap in mice preoperatively or intraoperatively. Blood flow, tissue oxygenation, tissue metabolism, flap necrosis rate, apoptosis assay, and RhoA and eNOS expression were endpoints. RESULTS: Blood-flow measurements 1 d after the flap operation revealed a significant reduction to 53% in the control group, while flow was maintained or increased in all BTX groups (103%-129%). Over 5 d all BTX groups showed significant increase in blood flow to 166-187% (P < 0.01). Microdialysis revealed an increase of glucose and reduced lactate/pyruvate ratio and glycerol levels in the flap tissue of all BTX groups. This resulted in significantly improved tissue survival in all BTX groups compared with the control group (62% ± 10%; all P < 0.01): BTX A preconditioning (84% ± 5%), BTX A application intraoperatively (88% ± 4%), BTX B preconditioning (91% ± 4%), and intraoperative BTX B treatment (92% ± 5%). This was confirmed by TUNEL assay. Immunofluorescence demonstrated RhoA and eNOS expression in BTX groups. All BTX applications were similarly effective, despite pharmacologic dissimilarities and different timing. CONCLUSIONS: In conclusion, we were able to show on a vascular, tissue, cell, and molecular level that BTX injection to the feeding arteries supports flap survival through ameliorated blood flow and oxygen delivery.


Asunto(s)
Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Piel/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguínea , Supervivencia Tisular/fisiología , Animales , Apoptosis/fisiología , Femenino , Hemodinámica/fisiología , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Óxido Nítrico Sintasa de Tipo III/fisiología , Piel/patología , Proteína de Unión al GTP rhoA/fisiología
17.
J Clin Med ; 12(16)2023 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-37629315

RESUMEN

BACKGROUND: The face is commonly affected in thermal injuries, with a demand for proper recognition and the correct choice of treatment to guarantee optimal aesthetic and functional outcomes. It is highly vascularized and often heals conservatively, highlighting the particular relevance of conservative treatment modalities, many of which require daily re-applications or dressing changes, which can be painful and tedious for both the patient and the healthcare providers. Motivated by encouraging results of a novel temporary nanofibrous epidermal layer, we herein present a case series of this technology in a case series of patients suffering from facial burns and treated in our Burn Center. PATIENTS AND METHODS: Patients with superficial partial-thickness facial burns and mixed pattern burns, which were treated with SpinCare™, an electrospun nanofibrous temporary epidermal layer, between 2019 and 2021, at our institution were analyzed retrospectively. The Manchester scar scale (MSS) and numeric rating scale (NRS) were used for scar, pain, and outcome evaluation at different time points by five independent board-certified plastic surgeons with profound experience in burn surgery. RESULTS: Ten patients (m = 9; f = 1) were treated and evaluated retrospectively. The mean age was 38.8 ± years (SD ± 17.85). The mean healing time was 6.4 days (SD ± 1.56). The mean follow-up was 16.4 months (SD ± 11.33). The mean MSS score was 5.06 (SD ± 1.31), and the mean NRS Score for pain was significantly reduced from initially 7 to 0.875 upon application (mean (pre-application) 7 ± 0.7 and (application) 0.875 ± 1.26; p ≤ 0.0001). Patients reported a NRS score of 10 in terms of functional and cosmetic outcomes at their final follow-up appointment. No adverse effects were observed. CONCLUSIONS: The application of a nanofibrous temporary epidermal layer such as SpinCare™ represents a relatively easy-to-use, well-tolerated, and effective alternative for the treatment of partial-thickness facial burns.

18.
Burns ; 49(5): 1103-1112, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36031494

RESUMEN

BACKGROUND: Electrical injuries follow a specific pathophysiology and may progressively damage both skin and deeper tissues, frequently ending in amputations. Type and timing of soft tissue reconstruction after electrical burns is crucial for proper outcome. The aim of this study was to assess surgical management and outcome of patients with electrical injuries treated at the Zurich Burn Center over the last 15 years, with emphasis on risk factors for amputation and reconstructive strategy. METHODS: Patient charts were reviewed retrospectively to identify cases admitted at the Zurich Burns Center (2005-2019). Patient characteristics and surgical management, with a special focus on amputations, reconstruction and outcome were analyzed and risk factors for amputation were assessed. RESULTS: Eighty-nine patients were identified and a total of 522 operations were performed. Escharotomy and fasciotomies were performed in 40.5% and 24.7% of cases, respectively, mainly at admission. The total amputation rate was 13.5% (23 amputations, 12 patients). Development of compartment syndrome, rhabdomyolysis, high myoglobin and CK blood levels, kidney failure, sepsis and respiratory complications during the course were related to higher risk of amputation (p < 0.001). Sixty-six flap-based reconstructions were performed (25% cases): 49 loco-regional flaps, 3 distant pedicled flaps, 14 free flaps. Two flaps were lost (flap failure rate 14%). Both flap losses occurred in cases of early reconstruction (within 5-21 days). CONCLUSIONS: Electrical injuries are still cause of elevated morbidity and mortality, with high amputation rate. Predictors for amputation can support physicians in the surgical care and decision-making. Reconstruction remains challenging in this type of injury: the surgical management with early decompression, serial necrectomies and delayed early reconstruction remains the procedure of choice at our unit.


Asunto(s)
Quemaduras por Electricidad , Quemaduras , Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Humanos , Estudios Retrospectivos , Quemaduras/complicaciones , Quemaduras por Electricidad/complicaciones , Complicaciones Posoperatorias/etiología , Amputación Quirúrgica , Resultado del Tratamiento
19.
Plast Reconstr Surg Glob Open ; 11(6): e5024, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37334393

RESUMEN

Osteoradionecrosis (ORN) manifested as symptomatic nonunion between primary free flap and native mandible after primary bony reconstruction of the mandible is an entity not included in current conventional ORN staging guidelines. This article reports on and proposes early management of this debilitating condition using a chimeric scapular tip free flap (STFF). Methods: A retrospective review was performed examining cases with bony nonunion at the junction of primary free fibula flap (FFF) and native mandible at a single center over a 10-year duration, which required a second free bone flap. Details of each case (patient demographics, oncological details, primary surgery, presentation, and secondary surgery) were documented and analyzed. Outcomes of the treatment were assessed. Results: Four patients (two men and two women; age range, 42-73 years) out of a total of 46 primary FFF were identified. All patients presented with symptoms of low-grade ORN and radiological signs of nonunion. All cases were reconstructed with chimeric STFF. The duration of follow-up ranged from 5 to 20 months. All patients reported resolution of symptoms and radiological evidence of union. Two of four patients subsequently received osseointegrated dental implants. Conclusions: Institutional rate of nonunion after primary FFF requiring a second free bone flap is 8.7%. All the patients of this cohort presented with a similar clinical entity easily discounted as an infected nonunion postosseous flap reconstruction. There is no ORN grading system that currently guides the management of this cohort. Good outcomes are possible with early surgical intervention with a chimeric STFF.

20.
Microvasc Res ; 83(2): 249-56, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22080047

RESUMEN

Angiogenesis and arteriogenesis are regenerative vascular mechanisms dedicated to cope with critical ischemia after the interruption of the anatomical axial blood supply. The aim of the present study was to visualize, quantify and monitor the orchestration of these mechanisms and their microhemodynamic efficacy. A murine skin flap model was used that allowed for repetitive investigation of identical vascular structures by intravital microscopy. In the conduit arterioles, diameter and relative length increased to 133 ± 20% and 260 ± 80% over 7 days, respectively (both P<0.01), which reduced vascular resistance in this segment to 82 ± 35%. After 1 week, a peak in accumulation of activated leukocytes could be observed in the postcapillary venules (P<0.01) without relevant hemodynamic changes. Thereafter, the arteriolar remodeling was replaced by angiogenesis. Functional capillary density was increased to 141 ± 10% (P<0.01) and capillary diameter to 123 ± 6% (P<0.01) after 14 days. Both mechanisms of vascular regeneration were associated with increases in the capillary perfusion index, to 194 ± 42% (P<0.05) after 7 days and 366 ± 21% after 14 days (P>0.01). Immunohistochemical analysis revealed a correlation of arteriogenesis with eNOS upregulation and of angiogenesis with VEGF upregulation in the corresponding vessels. In conclusion, arteriogenesis was the initial regenerative mechanism leading to arteriolar remodeling, reduction in vascular resistance, and increase in capillary perfusion over the first 7 days. Thereafter, capillary perfusion was improved by angiogenesis in terms of an increase in functional capillary density.


Asunto(s)
Procedimientos Quirúrgicos Dermatologicos , Hemodinámica , Isquemia/fisiopatología , Microcirculación , Neovascularización Fisiológica , Piel/irrigación sanguínea , Colgajos Quirúrgicos/efectos adversos , Animales , Arteriolas/metabolismo , Arteriolas/fisiopatología , Capilares/metabolismo , Capilares/fisiopatología , Circulación Colateral , Enfermedad Crítica , Modelos Animales de Enfermedad , Isquemia/metabolismo , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III/metabolismo , Recuperación de la Función , Flujo Sanguíneo Regional , Factores de Tiempo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Resistencia Vascular , Vasodilatación , Vénulas/fisiopatología
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