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1.
J Mammary Gland Biol Neoplasia ; 26(3): 235-245, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34228231

RESUMEN

Lipofilling may constitute a technique to assist reconstruction of breasts following prophylactic mastectomy for patients with mutated BRCA1 or BRCA2 genes. However, to date it is not clear whether adipose-derived stromal cells (ADSCs) increase the risk of tumor initiation and progression in this situation. Therefore, the interactions of BRCA1 mutated breast cancer cell lines with normal ADSCs were investigated in the present study. Characteristics of MDA-MB-436 (BRCA1 c.5277 + 1G > A) and HCC1937 (BRCA1 p.Gln1756.Profs*74) were compared to MDA-MB-231 and T47D BRCA1/2 wild-type breast cancer cell lines. ADSCs were cultivated from lipoaspirates of a panel of BRCA1/2- wildtype patients. Interactions of conditioned medium (CM) of these cells with the breast cancer lines were studied using proliferation and migration assays as well as adipokine expression western blot arrays. CM of ADSCs exhibit a dose-dependent stimulation of the proliferation of the breast cancer cell lines. However, of the ADSC preparations tested, only 1 out of 18 samples showed a significant higher stimulation of BRCA1-mutated MDA-MB-436 versus wildtype MDA-MB-231 cells, and all CM revealed lower stimulatory activity for BRCA1-mutated HCC1937 versus wildtype T47D cells. Additionally, migration of breast cancer cells in response to CM of ADSCs proved to be equivalent or slower for BRCA1/2 mutated versus nonmutated cancer cells and, with exception of angiopoietin-like 2, induced expression of adipokines showed no major difference. Effects of media conditioned by normal ADSCs showed largely comparable effects on BRCA1-mutated and wildtype breast cancer cell lines thus advocating lipofilling, preferentially employing allogeneic non-mutated ADSCs.


Asunto(s)
Proteína BRCA1/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/fisiopatología , Células Madre Mesenquimatosas/fisiología , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Medios de Cultivo Condicionados , Femenino , Humanos , Mutación
2.
FASEB J ; 34(3): 3677-3692, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31930613

RESUMEN

Though skin fibroblasts (FB) are the main cell population within the dermis, the different skin FB subsets are not well characterized and the traditional classification into reticular and papillary FBs has little functional relevance. To fill the gap of knowledge on FB diversity in human skin, we performed single-cell RNA sequencing. Investigation of marker genes for the different skin cell subtypes revealed a heterogeneous picture of FBs. When mapping reticular and papillary FB markers, we could not detect cluster specificity, suggesting that these two populations show a higher transcriptional heterogeneity than expected. This finding was further confirmed by in situ hybridization, showing that DPP4 was expressed in both dermal layers. Our analysis identified six FB clusters with distinct transcriptional signatures. Importantly, we could demonstrate that in human skin DPP4+ FBs are the main producers of factors involved in extracellular matrix (ECM) assembly. In conclusion, we provide evidence that hitherto considered FB markers are not ideal to characterize skin FB subpopulations in single-cell sequencing analyses. The identification of DPP4+ FBs as the main ECM-producing cells in human skin will foster the development of anti-fibrotic treatments for the skin and other organs.


Asunto(s)
Fibroblastos/citología , Análisis de Secuencia de ARN/métodos , Piel/citología , Western Blotting , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Humanos , Hibridación in Situ
3.
Int J Mol Sci ; 22(22)2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34830407

RESUMEN

Due to its cost-efficiency, high resolution melting (HRM) analysis plays an important role in genotyping of candidate single nucleotide polymorphisms (SNPs). Studies indicate that HRM analysis is not only suitable for genotyping individual SNPs, but also allows genotyping of multiple SNPs in one and the same amplicon, although with limited discrimination power. By targeting the three C>T SNPs rs527559815, rs547832288, and rs16906252, located in the promoter of the O6-methylguanine-DNA methyltransferase (MGMT) gene within a distance of 45 bp, we investigated whether the discrimination power can be increased by coupling HRM analysis with pyrosequencing (PSQ). After optimizing polymerase chain reaction (PCR) conditions, PCR products subjected to HRM analysis could directly be used for PSQ. By analyzing oligodeoxynucleotide controls, representing the 36 theoretically possible variant combinations for diploid human cells (8 triple-homozygous, 12 double-homozygous, 12 double-heterozygous and 4 triple-heterozygous combinations), 34 out of the 36 variant combinations could be genotyped unambiguously by combined analysis of HRM and PSQ data, compared to 22 variant combinations by HRM analysis and 16 variant combinations by PSQ. Our approach was successfully applied to genotype stable cell lines of different origin, primary human tumor cell lines from glioma patients, and breast tissue samples.


Asunto(s)
Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Regiones Promotoras Genéticas/genética , Proteínas Supresoras de Tumor/genética , Mama/metabolismo , Mama/patología , Metilación de ADN/genética , Femenino , Congelación , Genotipo , Glioma/metabolismo , Glioma/patología , Humanos , Polimorfismo de Nucleótido Simple/genética
4.
Microsurgery ; 38(5): 489-497, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29385241

RESUMEN

BACKGROUND: The transverse myocutaneous gracilis (TMG) flap is a widely used alternative to abdominal flaps in autologous breast reconstruction. However, secondary procedures for aesthetic refinement are frequently necessary. Herein, we present our experience with an optimized approach in TMG breast reconstruction to enhance aesthetic outcome and to reduce the need for secondary refinements. METHODS: We retrospectively analyzed 37 immediate or delayed reconstructions with TMG flaps in 34 women, performed between 2009 and 2015. Four patients (5 flaps) constituted the conventional group (non-optimized approach). Thirty patients (32 flaps; modified group) underwent an optimized procedure consisting of modified flap harvesting and shaping techniques and methods utilized to reduce denting after rib resection and to diminish donor site morbidity. RESULTS: Statistically significant fewer secondary procedures (0.6 ± 0.9 versus 4.8 ± 2.2; P < .001) and fewer trips to the OR (0.4 ± 0.7 versus 2.3 ± 1.0 times; P = .001) for aesthetic refinement were needed in the modified group as compared to the conventional group. In the modified group, 4 patients (13.3%) required refinement of the reconstructed breast, 7 patients (23.3%) underwent mastopexy/mammoplasty or lipofilling of the contralateral breast, and 4 patients (13.3%) required refinement of the contralateral thigh. Total flap loss did not occur in any patient. Revision surgery was needed once. CONCLUSIONS: Compared to the conventional group, enhanced aesthetic results with consecutive reduction of secondary refinements could be achieved when using our modified flap harvesting and shaping techniques, as well as our methods for reducing contour deformities after rib resection and for overcoming donor site morbidities.


Asunto(s)
Mamoplastia/métodos , Microcirugia/métodos , Colgajo Miocutáneo/trasplante , Apariencia Física , Recolección de Tejidos y Órganos/métodos , Sitio Donante de Trasplante , Adulto , Cuidados Posteriores , Anastomosis Quirúrgica/normas , Austria , Mama/cirugía , Estudios de Factibilidad , Femenino , Músculo Grácil/trasplante , Hospitales Universitarios , Humanos , Mastectomía/efectos adversos , Mastectomía/rehabilitación , Persona de Mediana Edad , Colgajo Miocutáneo/efectos adversos , Complicaciones Posoperatorias/cirugía , Calidad de Vida , Estudios Retrospectivos , Muslo/cirugía
5.
Ann Plast Surg ; 78(4): 379-385, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27505450

RESUMEN

BACKGROUND: Management of the nipple-areola complex is an important issue in primary breast reconstruction. When nipple-sparing mastectomy is not suitable, alternatives are immediate nipple-areola complex replantation and delayed reconstruction. The aim of this study was to examine whether patients benefit more from nipple-areola complex preservation by immediate replantation or delayed nipple-areola complex reconstruction. METHODS: Postoperative results and patient satisfaction after 54 primary breast reconstructions with immediate nipple-areola complex replantation or delayed nipple-areola complex reconstruction were retrospectively evaluated. RESULTS: The nipple-areola complex was replanted immediately in 37 cases and reconstructed later with nipple sharing and full-thickness skin grafting in 17 cases. Compared with immediate replantation, delayed reconstruction resulted in significantly better postoperative nipple projection (P = 0.01*, Mann-Whitney U test), greater similarity of color and projection with the contralateral side and greater patient satisfaction (Breast-Q). Complete loss of projection occurred in 4 of the 37 replanted nipple-areola complexes. No complete nipple-areola complex necrosis or tumor recurrence was observed in any patient. CONCLUSIONS: Immediate nipple-areola complex replantation is a safe and reliable procedure for selected patients with contraindications for nipple-sparing mastectomy who have a strong desire to maintain their own nipple-areola complexes, or in bilateral cases. However, drawbacks of this procedure include loss of projection and depigmentation. Delayed reconstruction with nipple sharing and full-thickness skin grafting is a good alternative, especially in unilateral cases; it leads to better postoperative results and greater patient satisfaction, but it involves a nipple-areola complex-free period.


Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía Subcutánea/métodos , Pezones/cirugía , Cicatrización de Heridas/fisiología , Adulto , Austria , Neoplasias de la Mama/patología , Estudios de Cohortes , Estética , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Cuidados Posoperatorios/métodos , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Resultado del Tratamiento
6.
Support Care Cancer ; 23(6): 1741-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25433440

RESUMEN

PURPOSE: In a longitudinal observation, extravasation of antitumoural compounds and the efficacy of its structured interdisciplinary management were assessed in a routine setting. METHODS: One hundred sixty-nine patients with extravasation of cytotoxics were managed according to a prospective approach documenting the extravasated compound, localisation, duration until full symptom resolution and sequelae. Surgery was implemented in the case of failure of conservative measures. RESULTS: In 155 (91.7 %) out of 169 patients, conservative management was successful (surgical intervention, 14 patients). Extravasations of anthracyclines (N = 44), platinum compounds (N = 41), vinca alkaloids (N = 20) and taxanes (N = 19) were often associated with erythema, oedema and pain. The median period until full resolution of symptoms differed among the administered cytotoxics (anthracyclines, 55 days; taxanes and vinca alkaloids, 27 days; platinum compounds, 14 days) with statistical significance between the vesicants. Histologically, surgically resected specimens showed extensive necrotic areas with inflammatory infiltrates at the periphery of the removed lesions. CONCLUSIONS: In a routine setting, the standardised management of cytotoxic extravasations by an interdisciplinary task force resulted in a satisfactory outcome. When surgical intervention was indicated, complete remission of the lesions within a median of 14 days reduced the delay in the administration of further chemotherapy to a minimum. The proposed approach is therefore considered as suitable to manage extravasations in cancer chemotherapy in a large number of subjects and to ensure patient adherence to cytotoxic treatment.


Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Extravasación de Materiales Terapéuticos y Diagnósticos/epidemiología , Extravasación de Materiales Terapéuticos y Diagnósticos/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Dioxoles/uso terapéutico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Taxoides/efectos adversos , Taxoides/uso terapéutico , Tetrahidroisoquinolinas/uso terapéutico , Trabectedina , Resultado del Tratamiento , Alcaloides de la Vinca/efectos adversos , Alcaloides de la Vinca/uso terapéutico , Adulto Joven
7.
Cells ; 12(11)2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37296582

RESUMEN

The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5-intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5-intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon-intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Metilación de ADN/genética , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Empalme Alternativo/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
8.
World J Surg ; 36(9): 2230-6, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22552500

RESUMEN

BACKGROUND: Treating large and extensive pilonidal sinus disease is a challenging task. Long-term reports on flaps suitable for coverage of large, wide, local-excision defects are sparse. We prospectively evaluated data with a minimum 1-year follow-up of the use of a single-sided, innervated, superior gluteal artery perforator flap. METHODS: Twenty-one patients (1 woman, 20 men) with a median age of 26 years (min - max = 18 - 46) were included in the study period from September 2005 to April 2010. We recorded flap size, major and minor complications, hospital length of stay, impairment in activities of daily living, pain, aesthetic outcomes, and sensibility in the gluteal region (PSSD, pressure-specified sensory device) at 6 and 12 months postoperatively. RESULTS: The mean defect size (±SD) was 13.0 ± 1.9 × 8.6 ± 1.3 × 5.5 ± 1.2 cm (height × width × depth), and median length of hospital stay was 9 days (range = 7-11). Only two patients developed minor wound-healing complications. Visual analog pain scales significantly improved, with no pain detectable at 12 months postoperatively (p < 0.0001). The aesthetic appearance of the results was good in the majority of patients (61.9-85.7 %). PSSD showed gradual normalization, with retained sensibility in the flap area over 12 months postoperatively (p = 0.0232). During the median 36-month (range = 20-60) follow-up, we have not observed any recurrence in the operated area. CONCLUSIONS: The innervated superior gluteal artery perforator flap is a useful technique for covering large and recurrent pilonidal sinus defects following wide local excision and represents an excellent tool in the surgical armamentarium for achieving long-lasting outcomes in this young group of patients.


Asunto(s)
Colgajo Perforante/irrigación sanguínea , Seno Pilonidal/cirugía , Procedimientos de Cirugía Plástica/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Colgajo Perforante/inervación , Resultado del Tratamiento , Adulto Joven
9.
Int J Surg ; 104: 106694, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35662621

RESUMEN

INTRODUCTION: Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients undergoing oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking. METHODS: Patients diagnosed with BIRADS IV-VI lesion were eligible if resection of ≥10% of the breast volume was planned. Patients were allowed to decide whether they wanted to undergo CBC or oncoplastic breast conservation (OBC). Patients who underwent mastectomy and immediate breast reconstruction (IBR) were also included for comparison. The primary endpoint was breast self-esteem using the Breast Image Scale (BIS) at 12 months, secondary endpoints were perioperative morbidity and QoL using the BREAST-Q questionnaire. RESULTS: From 2011 to 2016, 205 patients were included in the study. 116 patients (56.6%) received CBC, 46 (22.4%) OBC and 43 (21%) MIBR. Women in the OBC group were more likely to have tumors ≥ 2 cm than those in the CBC group (34.7% vs. 17.5%, respectively). Women who underwent MIBR were more likely to have tumors > 5 cm than those in the CBC and OBC groups (23% vs 1% and 10%, respectively). The BIS and BREAST-Q improved in each group after 12 months but did not differ significantly between groups at any time point. Surgical complications (seroma, bleeding, infection, necrosis) were numerically more likely in the OBC and MIBR groups. CONCLUSION: OBC and the MIBR allow for resection of larger tumors with a similar quality of life as CBC.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamoplastia , Mastectomía/métodos , Estudios Prospectivos , Calidad de Vida , Estudios Retrospectivos
10.
Matrix Biol ; 108: 55-76, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35278628

RESUMEN

Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells show a unique, pro-fibrotic phenotype. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. This study suggests the contribution of a Schwann cell - macrophage cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.


Asunto(s)
Cicatriz Hipertrófica , Queloide , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/terapia , Matriz Extracelular/patología , Humanos , Queloide/patología , Células de Schwann/patología , Cicatrización de Heridas
11.
Anesth Analg ; 113(1): 199-201, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21525181

RESUMEN

The combined effects of anesthesia, motor blockade, and chemically induced sympathectomy after brachial plexus blockade can have a beneficial impact, when applied in selected, isolated diseased states of the upper limb. With the aim of using the prolonged effects of brachial plexus blockade for a future therapeutic application, we demonstrated a dependable methodology of venous blood gas monitoring and confirmed an improved oxygen balance of the blocked versus nonblocked upper extremity in a controlled, prospective study in healthy patients undergoing elective hand surgery.


Asunto(s)
Bloqueo Nervioso Autónomo/métodos , Plexo Braquial/metabolismo , Monitoreo Intraoperatorio/métodos , Consumo de Oxígeno/fisiología , Adulto , Anciano , Análisis de los Gases de la Sangre/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
12.
Wien Klin Wochenschr ; 133(5-6): 202-208, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33128100

RESUMEN

BACKGROUND: The face is affected in more than 50% of patients with extensive burn trauma. Effective treatment is of importance to avoid hypertrophic scarring, functional impairment and social stigmatization. MATERIAL AND METHODS: All patients treated with Acticoat7™ due to superficial and deep partial thickness burns of the face between 2008 and 2017 at the intensive care unit (ICU) for burn trauma at the Department for Plastic and Reconstructive Surgery of the Medical University of Vienna were retrospectively analyzed. Patients were evaluated for the number of required dressing changes until complete re-epithelialization, bacterial colonization, potential complications and the need for primary and secondary surgery. RESULTS: A total of 100 patients were analyzed. It took a median dressing change rate of 1 (range 0-5) in the superficial partial thickness and 3 (range 1-11) in the deep partial thickness group. Conservative treatment of deep partial thickness wounds was possible in 79% and 17% of these patients required secondary scar revision. Although bacterial colonization of the wounds frequently occurred, wound infections were rarely observed. CONCLUSION: Acticoat7™ is a valuable dressing for treating superficial and deep partial thickness burn wounds of the face in an intensive care unit setting. It enables extended time intervals between dressing changes without an increased risk for complications.


Asunto(s)
Quemaduras , Cicatrización de Heridas , Vendajes , Quemaduras/terapia , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
13.
Clin Case Rep ; 9(5): e04094, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34084506

RESUMEN

Extraosseous osteoblastoma of the breast, a rare disease, was diagnosed in a prepubertal girl. After tumor excision, the patient recovered well and an optimal cosmetic result was achieved. Interdisciplinary discussions about the case are essential.

14.
Cancer Chemother Pharmacol ; 88(2): 203-209, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33907881

RESUMEN

PURPOSE: As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose-toxicity relation. METHODS: From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject). RESULTS: After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17 µg per 100 mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3 weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2 weeks, when therapy was resumed in all patients with reasonable time delay. CONCLUSION: Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/farmacocinética , Epirrubicina/efectos adversos , Epirrubicina/farmacocinética , Distribución Tisular/fisiología , Anciano , Antraciclinas/efectos adversos , Antraciclinas/farmacocinética , Antraciclinas/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Citocinas/metabolismo , Doxorrubicina/efectos adversos , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Necrosis/inducido químicamente , Necrosis/metabolismo , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/metabolismo , Colgajos Quirúrgicos/patología , Cicatrización de Heridas/efectos de los fármacos
15.
Sci Rep ; 11(1): 10035, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976374

RESUMEN

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI - 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155-170] min for chloroprocaine versus 380 [209-450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile.Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria-BASG).


Asunto(s)
Anestésicos Locales/administración & dosificación , Bloqueo Nervioso , Procaína/análogos & derivados , Ropivacaína/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Axila , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procaína/administración & dosificación , Estudios Prospectivos , Ultrasonografía Intervencional , Adulto Joven
16.
Nat Commun ; 12(1): 6242, 2021 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-34716325

RESUMEN

Despite recent advances in understanding skin scarring, mechanisms triggering hypertrophic scar formation are still poorly understood. In the present study, we investigate mature human hypertrophic scars and developing scars in mice at single cell resolution. Compared to normal skin, we find significant differences in gene expression in most cell types present in scar tissue. Fibroblasts show the most prominent alterations in gene expression, displaying a distinct fibrotic signature. By comparing genes upregulated in murine fibroblasts during scar development with genes highly expressed in mature human hypertrophic scars, we identify a group of serine proteases, tentatively involved in scar formation. Two of them, dipeptidyl-peptidase 4 (DPP4) and urokinase (PLAU), are further analyzed in functional assays, revealing a role in TGFß1-mediated myofibroblast differentiation and over-production of components of the extracellular matrix in vitro. Topical treatment with inhibitors of DPP4 and PLAU during scar formation in vivo shows anti-fibrotic activity and improvement of scar quality, most prominently after application of the PLAU inhibitor BC-11. In this study, we delineate the genetic landscape of hypertrophic scars and present insights into mechanisms involved in hypertrophic scar formation. Our data suggest the use of serine protease inhibitors for the treatment of skin fibrosis.


Asunto(s)
Cicatriz/patología , Dipeptidil Peptidasa 4/genética , Proteínas de la Membrana/genética , Animales , Diferenciación Celular/efectos de los fármacos , Cicatriz/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Femenino , Expresión Génica , Humanos , Proteínas de la Membrana/metabolismo , Ratones Endogámicos BALB C , Miofibroblastos/efectos de los fármacos , Miofibroblastos/fisiología , Análisis de la Célula Individual , Fosfato de Sitagliptina/farmacología , Factor de Crecimiento Transformador beta1/farmacología
17.
J Sex Med ; 7(6): 2130-2138, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20233279

RESUMEN

INTRODUCTION: Sex reassignment surgery is an important step for transsexuals, since it is known to help the patients to live more easily in their gender role and to significantly increase quality of life. AIMS: To critically evaluate our experience with the combined procedure of hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy for female-to-male (FtM) transsexual patients. METHODS: Thirty-two FtM transsexuals who underwent hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in one single operative setting. MAIN OUTCOME MEASURES: Operating time and complications, both intra-and postoperatively. RESULTS: Patients were 30.0 ± 5.8 years of age, with a body mass index of 24.8 ± 3.5 kg/m(2). The majority of patients underwent hysterectomy and bilateral salpingo-oophorectomy by laparoscopy (31/32, 96.9%). The median operating time was 222.5 minutes (inter-quartile range [IQR] 190-270 minutes). The median postoperative stay was eight days (IQR, 7-9 days). Postoperative adverse events were found in five patients (15.6%), including breast hematomas as the most frequent complication (4/32, 12.5%). In one patient (1/32; 3.1%), conversion from laparoscopy to laparotomy was necessary, which was considered an adverse event. None of our patients required reoperation or readmission to the hospital. CONCLUSION: Combined hysterectomy/salpingo-oophorectomy, and bilateral mastectomy in a single operating session seems a safe, feasible, and valuable procedure for FtM transsexuals.


Asunto(s)
Histerectomía , Mastectomía , Ovariectomía , Complicaciones Posoperatorias/etiología , Salpingectomía , Cirugía de Reasignación de Sexo , Transexualidad/cirugía , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía , Grupo de Atención al Paciente , Adulto Joven
18.
Handchir Mikrochir Plast Chir ; 52(2): 107-115, 2020 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-32259857

RESUMEN

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease, which affects areas of the body that bear apocrine glands. In extensive cases, a combination of surgical and antibiotic treatment is often needed. Studies are available on the effects of clindamycin, also in combination with rifampicin, or tetracyclines. However, there are few precise recommendations for the perioperative application of antibiotic agents. PATIENTS/MATERIAL AND METHODS: An anonymous survey was conducted to determine the current status quo of perioperative antibiotic treatment. Physicians and surgeons were surveyed who worked at a department for plastic surgery, general surgery or dermatology in the German-speaking area. The questionnaire itself was created with Limesurvey© and was sent out to qualified departments, with the help from federal ministries of health. The responses were statistically analysed with IBM® SPSS® version 23. RESULTS: In most cases, the antibiotic treatment started before surgical intervention. Bacterial swabs were the most important factor in the selection of antibiotic agents. Most of theparticipants adjusted the treatment to the microbiological results, regardless of the chosen moment of application. Clindamycin was the most often used topical and systemic agent. The combination with rifampicin was most common. Adalimumab was the most commonly used antibody against tumor necrosis factor-alpha (TNF-α). In nearly half of the cases, antibodies were combined with antibiotics, and then the duration of treatment was usually longer. The extent of the disease was the most important factor for the necessity of surgical interventions. The wide excision of the whole affected area with subsequent healing by secondary intention was the surgical method of choice in all but one area. CONCLUSION: This study has shown that there are significant differences in the treatment between disciplines and countries. On the one hand, the disease severity, on the other hand, individual experience and preferences affect the treatment. Depending on the discipline that determined the therapy, some treatments are provided more rarely or not at all. Revised and up-to-date guidelines embodying all relevant disciplines would be desirable for a standardised therapy.


Asunto(s)
Hidradenitis Supurativa/cirugía , Antibacterianos/uso terapéutico , Enfermedad Crónica , Humanos , Encuestas y Cuestionarios , Factor de Necrosis Tumoral alfa
19.
Burns ; 46(1): 136-142, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31420263

RESUMEN

INTRODUCTION: Air-fluidized therapy (AFT) has long been used in the treatment of severe burns. In patients with extensive burns involving the posterior trunk, we aim to keep affected posterior areas dry and to postpone their treatment, initially applying available split-thickness skin grafts in functionally more important regions. We retrospectively assessed the impact of AFT on the survival of patients treated in the burn intensive care unit (ICU) of the Medical University of Vienna, Austria, between 2003 and 2016. METHODS: This retrospective single-center study included patients aged ≥18 years with burned total body surface area (TBSA) ≥20% and IIb-III° thermal injuries on the posterior trunk who received AFT. Survival rates were compared with those predicted by the abbreviated burn severity index (ABSI). Demographic, clinical, and surgical data were analyzed. RESULTS: Seventy-five of 110 patients with posterior trunk burns received AFT. Their survival rate exceeded that predicted by the ABSI score (mean ABSI, 10.0 ± 2.0; 73.3% (95% CI: 62-83%) survival rate vs. 20-40% predicted; p < 0.0001); no such difference was observed in the non-AFT group (mean, 8.8 ± 1.9; 65.7% (95% CI: 48-81%) survival rate vs. 50-70% predicted). Patients receiving AFT had significantly greater TBSA (median, 50% (35-60) vs. 30% (25-45) and longer ICU stays (median, 63 (36-92) vs. 18 (9-52) days; both p < 0.0001). Fifty-one (68.0%) patients in the AFT group and 26 (74.3%) patients in the non-AFT group underwent posterior trunk surgery (p = 0.66) a median of 16 (10-26) and 5 (2.5-9.5) days, respectively, after admission (p < 0.0001). CONCLUSIONS: Patients receiving AFT had significantly better survival than predicted by ABSI score in contrast to patients not receiving AFT although burn injuries in this group were more severe (greater TBSA, higher ABSI). As intensive care was similar in these groups aside from AFT, the better survival could be attributed to this additional therapy.


Asunto(s)
Traumatismos de la Espalda/terapia , Lechos , Quemaduras/terapia , Diseño de Equipo , Repitelización , Tasa de Supervivencia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Traumatismos de la Espalda/patología , Superficie Corporal , Unidades de Quemados , Quemaduras/patología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Piel , Índices de Gravedad del Trauma , Adulto Joven
20.
J Clin Med ; 9(7)2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32668782

RESUMEN

Breast cancer is among the most commonly diagnosed cancers in the world, affecting one in eight women in their lifetimes. The disease places a substantial burden on healthcare systems in developed countries and often requires surgical correction. In spite of this, much of the breast cancer pathophysiology remains unknown, allowing for the cancer to develop to later stages prior to detection. Many women undergo reduction mammaplasties (RM) to adjust breast size, with over 500,000 operations being performed annually. Tissue samples from such procedures have drawn interest recently, with studies attempting to garner a better understanding of breast cancer's development. A number of samples have revealed nascent cancer developments that were previously undetected and unexpected. Investigating these so-called "occult" findings of cancer in otherwise healthy patients may provide further insight regarding risk factors and countermeasures. Here, we detail occult findings of cancer in reduction mammaplasty samples provided from a cohort of over 5000 patients from 16 different institutions in Europe. Although the majority of our resected breast tissue specimens were benign, our findings indicate that there is a continued need for histopathological examination. As a result, our study suggests that preoperative imaging should be routinely performed in patients scheduled for RM, especially those with risk factors of breast cancer, to identify and enable a primary oncologic approach.

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