RESUMEN
The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differentiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family transcription-factor-binding motifs in human epidermal CD8+CD103+CD49a+ TRM cells, paralleled by high RUNX2 and RUNX3 protein expression. Sequencing of paired skin and blood samples revealed clonal overlap between epidermal CD8+CD103+CD49a+ TRM cells and circulating memory CD8+CD45RA-CD62L+ T cells. In vitro stimulation of circulating CD8+CD45RA-CD62L+ T cells with IL-15 and TGF-ß induced CD49a expression and cytotoxic transcriptional profiles in a RUNX2- and RUNX3-dependent manner. We therefore identified a reservoir of circulating cells with cytotoxic TRM potential. In melanoma patients, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and improved patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM cells, providing immunosurveillance of infected and malignant cells.
Asunto(s)
Linfocitos T CD8-positivos , Melanoma , Humanos , Linfocitos T CD8-positivos/metabolismo , Integrina alfa1/metabolismo , Integrinas/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Memoria Inmunológica , Antígenos Comunes de Leucocito/metabolismo , Melanoma/metabolismoRESUMEN
Background: Breast augmentation with anatomic implants can achieve a natural look, but over time, implant-related complications can occur. This includes a risk of potential rotation, which can cause a change in breast shape. Reported rates of rotation vary widely (0%-42%). Implant rotation is often detected by physical examination only or as a perioperative finding. Change in breast shape after augmentation requires clinical evaluation. In-office ultrasound allows for detailed assessment of implants for rotation and other complications. Methods: Women with anatomical breast implants seeking follow-up at the International Breast Implant Check Clinic in Stockholm, Sweden, from April 2020 to July 2022 were included in the study. Using a standardized protocol, subjective symptoms were recorded, and a physical examination followed by an ultrasound assessment was performed by a single board-certified plastic surgeon (M.J.) trained in implant assessment via ultrasound. Rotation was defined as an implant rotated past 30 degrees off the breast midline at 6 o'clock. Results: The study included 308 women (mean age 40.1, range 20-78) with bilateral anatomical implants. Overall, 40 women (13.0%) reported a change in breast shape; 35 had one or more implant-related complications, including five with rotation on ultrasound. Of the 308 women, 11 (3.6%) had rotations upon physical examination, and an additional 10 cases were identified using ultrasound. Conclusions: Rotation is a potential complication of anatomical breast implants. However, in this study, change in breast shape was more commonly caused by other implant-related complications. Ultrasound is a valuable tool in evaluating causes of change in breast shape.
RESUMEN
Importance: Multiple-dose antibiotic prophylaxis is widely used to prevent infection after implant-based breast reconstruction despite the lack of high-level evidence regarding its clinical benefit. Objective: To determine whether multiple-dose antibiotic prophylaxis is superior to single-dose antibiotic prophylaxis in preventing surgical site infection (SSI) after implant-based breast reconstruction. Design, Setting, and Participants: This prospective, multicenter, randomized clinical superiority trial was conducted at 7 hospitals (8 departments) in Sweden from April 25, 2013, to October 31, 2018. Eligible participants were women aged 18 years or older who were planned to undergo immediate or delayed implant-based breast reconstruction. Follow-up time was 12 months. Data analysis was performed from May to October 2021. Interventions: Multiple-dose intravenous antibiotic prophylaxis extending over 24 hours following surgery, compared with single-dose intravenous antibiotic. The first-choice drug was cloxacillin (2 g per dose). Clindamycin was used (600 mg per dose) for patients with penicillin allergy. Main Outcomes and Measures: The primary outcome was SSI leading to surgical removal of the implant within 6 months after surgery. Secondary outcomes were the rate of SSIs necessitating readmission and administration of intravenous antibiotics, and clinically suspected SSIs not necessitating readmission but oral antibiotics. Results: A total of 711 women were assessed for eligibility, and 698 were randomized (345 to single-dose and 353 to multiple-dose antibiotics). The median (range) age was 47 (19-78) years for those in the multiple-dose group and 46 (25-76) years for those in the single-dose group. The median (range) body mass index was 23 (18-38) for the single-dose group and 23 (17-37) for the multiple-dose group. Within 6 months of follow-up, 30 patients (4.3%) had their implant removed because of SSI. Readmission for intravenous antibiotics because of SSI occurred in 47 patients (7.0%), and 190 women (27.7%) received oral antibiotics because of clinically suspected SSI. There was no significant difference between the randomization groups for the primary outcome implant removal (odds ratio [OR], 1.26; 95% CI, 0.69-2.65; P = .53), or for the secondary outcomes readmission for intravenous antibiotics (OR, 1.18; 95% CI, 0.65-2.15; P = .58) and prescription of oral antibiotics (OR, 0.72; 95% CI, 0.51-1.02; P = .07). Adverse events associated with antibiotic treatment were more common in the multiple-dose group than in the single-dose group (16.4% [58 patients] vs 10.7% [37 patients]; OR, 1.64; 95% CI, 1.05-2.55; P = .03). Conclusions and Relevance: The findings of this randomized clinical trial suggest that multiple-dose antibiotic prophylaxis is not superior to a single-dose regimen in preventing SSI and implant removal after implant-based breast reconstruction but comes with a higher risk of adverse events associated with antibiotic treatment. Trial Registration: EudraCT 2012-004878-26.
Asunto(s)
Clindamicina , Mamoplastia , Antibacterianos/uso terapéutico , Cloxacilina , Femenino , Humanos , Masculino , Mamoplastia/efectos adversos , Estudios Prospectivos , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
The purpose of this retrospective study was to evaluate the cutaneous somatosensory function and patients' subjective experience after bilateral prophylactic mastectomy and immediate reconstruction with implants. Twenty-four patients treated during an eight-year period were included. Somatosensory examination was made at least two years after the latest surgery to study perception thresholds to touch, warmth, cold, and heat pain, using quantitative techniques. Patients also completed a questionnaire about subjective sensitivity. Sixteen women who had had no previous breast surgery were used as a control group. Most patients reported decreased sensitivity in the breasts, which was confirmed by the results from the quantitative somatosensory examination. The results also showed that the ability to experience sexual feelings in the breast is usually lost after this type of operation, and as many as 14 patients reported spontaneous or stimulus-evoked discomfort in the breasts.
Asunto(s)
Implantación de Mama , Neoplasias de la Mama/prevención & control , Mama/cirugía , Mastectomía Simple , Piel/inervación , Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios , Sensación Térmica , Tacto , Resultado del TratamientoRESUMEN
The demand for risk-reducing mastectomy (RRM) to avoid breast cancer has increased over the last several years, and knowledge of the outcome after this prophylactic surgical procedure is important. The primary aim of this study was to prospectively compare breast sensibility before and after RRM in a consecutive series of women. The study also investigated whether the nipples were less numb if the nipple areola complexes (NACs) were spared compared with regrafted nipple tips. Forty-six women who selected bilateral RRM with immediate reconstruction using implants at the Karolinska University Hospital, Solna, Stockholm, Sweden, were included in the study. The median patient age at the time of surgery was 39 years (range 26-58). All patients were evaluated preoperatively and at least 2 years postoperatively (median 29 months). Tactile, thermal and nociceptive cutaneous sensibilities were studied with quantitative techniques. The patients at the postoperative evaluation completed a questionnaire about subjective feelings in both breasts. The results showed that breast sensibility is significantly impaired after RRM. Additionally, the ability to experience sexual sensations in the breast is often lost. An NAC-sparing surgery did not result in better nipple sensibility.
Asunto(s)
Neoplasias de la Mama/prevención & control , Mama/fisiopatología , Mama/cirugía , Mamoplastia/efectos adversos , Mastectomía/efectos adversos , Adulto , Femenino , Humanos , Hipoestesia/etiología , Persona de Mediana Edad , Nocicepción , Estudios Prospectivos , Encuestas y Cuestionarios , Sensación Térmica , Factores de Tiempo , TactoRESUMEN
BACKGROUND: Mastectomy due to breast cancer is associated with chronic pain and a negative impact on sexuality. The purposes of the study were to analyze the prevalence of pain and discomfort in the breasts, impact on sexuality, quality of life, and feelings of regret after bilateral prophylactic mastectomy and immediate reconstruction with implants. METHODS: Fifty-nine women operated 2004-2006 were included. A questionnaire was sent out two years after the procedure. Complications and re-operations were recorded. RESULTS: Mean follow-up time was 29 months. 93% of patients answered the questionnaire. 69% reported pain and 71% discomfort in the breasts. Lost or much reduced sexual sensations were reported by 85% and enjoyment of sex was negatively impacted for 75% of patients. Quality of life was not affected and feelings of regret were almost non-existent. CONCLUSIONS: It is important to inform women approaching this prophylactic procedure about the risk of having unwanted secondary effects.
Asunto(s)
Neoplasias de la Mama/prevención & control , Mastectomía/efectos adversos , Mastectomía/psicología , Dolor/epidemiología , Calidad de Vida/psicología , Sexualidad/psicología , Adulto , Anciano , Mama/cirugía , Neoplasias de la Mama/genética , Enfermedad Crónica , Emociones , Femenino , Humanos , Modelos Logísticos , Mamoplastia/efectos adversos , Mamoplastia/psicología , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: The demand for bilateral mastectomy and immediate breast reconstruction has increased in recent years, primarily due to the development of genetic testing. The aim of this study was to evaluate if there was a difference between anatomically shaped and round permanent expandable implants in one-stage bilateral breast reconstruction after bilateral prophylactic mastectomy. METHODS: The anatomically shaped permanent expander implant McGhan Style 150 (Inamed, Santa Barbara, Calif.) was compared with the round permanent expander implant Siltex Becker 25 (Mentor, Santa Barbara, Calif.). Thirty-six women who opted for bilateral prophylactic mastectomy and immediate reconstruction with implants from 2004 to 2006 were included and randomly assigned to each group [18 women (36 breasts) per group]. Time to follow-up was a minimum of 2 years after the bilateral prophylactic mastectomy. Implant-related complications, breast symmetry, aesthetic outcome, and patient satisfaction were evaluated. Aesthetic outcome was evaluated by an expert panel that also tried to recognize if the breasts were reconstructed with anatomically shaped or round implants. Patient satisfaction was evaluated by a questionnaire. RESULTS: Average time to follow-up was 30 months (range, 24 to 49 months). There was no statistical difference between the two implant groups in terms of complications, breast symmetry, or outcome scores from the expert panel and patient assessment. The expert panel guessed the right implant shape in 42 percent of the anatomically shaped implants and 66 percent of the round implants. CONCLUSION: In immediate one-stage breast reconstruction after bilateral prophylactic skin-sparing mastectomy, anatomically shaped and round permanent expander implants had comparable complication rates, aesthetic outcomes, and patient satisfaction after 2 years of follow-up.
Asunto(s)
Implantes de Mama , Mamoplastia , Satisfacción del Paciente , Adulto , Implantes de Mama/efectos adversos , Neoplasias de la Mama/prevención & control , Estética , Femenino , Humanos , Mastectomía , Persona de Mediana EdadRESUMEN
UNLABELLED: Previous studies regarding body image after bilateral prophylactic mastectomy with breast reconstruction have reported a risk of reduced satisfaction with body image and adverse effects on sexual life. The aim of this retrospective study was to find areas for future surgical improvements to optimize patient satisfaction with the aesthetic result after bilateral prophylactic mastectomy and immediate breast reconstruction with implants. Nipple-areola complexes were reconstructed. Twenty-four consecutive and standardized operated women were included. The follow-up time was an average of 5.4 (range: 2.4-10.2) years. The outcome in terms of breast symmetry, size, and firmness were measured with objective and subjective methods, and results were compared to those from a control group of 24 women. Patient satisfaction was evaluated with a questionnaire. Main findings were that the overall aesthetic result was regarded as good in both objective and subjective evaluations and that breast symmetry in patients was as common as in the control group, but reconstructed breasts were firmer. Twenty of 24 patients thought that the aesthetic result exceeded their expectations, and 22/24 would recommend this kind of breast reconstruction to another woman. In contrast with the predictions of plastic surgeons, patients were most dissatisfied with the nipple-areola reconstruction. CONCLUSIONS: The overall aesthetic result after bilateral prophylactic mastectomy and immediate breast reconstruction with implants was good and symmetrical. Patient satisfaction with nipple-areola reconstruction was only moderate. The results emphasize the importance of a preoperative discussion with the patient regarding whether to keep or reconstruct the nipple-areola complex while planning a prophylactic mastectomy.