RESUMO
Background: For patients using peritoneal dialysis (PD), the peritoneal membrane can develop fibrosis and angiogenesis, leading to ultrafiltration failure, chronic hypervolemia and increased risk of technique failure and mortality. Matrix metalloproteinases (MMPs), and specifically the gelatinases (MMP2 and MMP9), may be involved in peritoneal membrane injury. Methods: From stable PD patients, mesothelial cells were assayed for MMP gene expression. MMP9 was overexpressed in mouse peritoneum by adenovirus, and MMP9 -/- mice were subjected to transforming growth factor ß (TGF-ß)-induced peritoneal fibrosis. Results: MMP9 mRNA expression correlated with peritoneal membrane solute transport properties. Overexpression of MMP9 in the mouse peritoneum induced submesothelial thickening and angiogenesis. MMP9 induced mesothelial cell transition to a myofibroblast phenotype measured by increased alpha smooth muscle actin and decreased E-cadherin expression. Angiogenesis was markedly reduced in MMP9 -/- mice treated with an adenovirus expressing active TGF-ß compared with wild-type mice. TGF-ß-mediated E-cadherin cleavage was MMP9 dependent, and E-cadherin cleavage led to ß-catenin-mediated signaling. A ß-catenin inhibitor blocked the angiogenic response induced by AdMMP9. Conclusions: Our data suggest that MMP9 is involved in peritoneal membrane injury possibly through cleavage of E-cadherin and induction of ß-catenin signaling. MMP9 is a potential biomarker for peritoneal membrane injury and is a therapeutic target to protect the peritoneal membrane in PD patients.
Assuntos
Caderinas/metabolismo , Soluções para Hemodiálise/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/etiologia , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , beta Catenina/metabolismo , Animais , Transporte Biológico , Caderinas/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , beta Catenina/genéticaRESUMO
BACKGROUND: As survivorship for breast cancer continues to improve, emphasis of care falls upon improving patients' quality of life. Understanding physical and mental health in the preoperative period is needed to aid surgical decision making and improve patient experience. METHODS: Consecutive patients awaiting total mastectomy (TM), TM with immediate breast reconstruction (IBR) and breast conserving surgery (BCS) were prospectively recruited. Scores for PHQ-9, GAD-7, Breast-Q, EQ5D(5L), PEG were collected preoperatively. Association was measured with multivariate analyses. RESULTS: 477 participants (374 BSC, 46 âTM, 84 IBR) were included. Younger patients and those choosing IBR reported worse depression and anxiety symptoms. Clinical tumor features did not affect patient reported outcomes. Higher Breast-Q scores were seen with BCS and lower scores with TM. CONCLUSIONS: Patients scheduled for IBR and younger patients reported worse symptoms of depression and anxiety, regardless of clinical features. This will help with surgical decision making and identify patients in need for additional perioperative supports.
Assuntos
Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Neoplasias da Mama/cirurgia , Mastectomia/psicologia , Qualidade de Vida , Depressão/epidemiologia , Depressão/etiologia , Ansiedade/epidemiologia , Ansiedade/etiologiaRESUMO
As rates of total mastectomy rise, the relationships between surgery modality with domains of health-related quality of life is not well understood. This study reports differences in depression, anxiety, pain, and health status among a cohort of women scheduled to receive total mastectomy or breast-conserving surgery. Patient-reported outcomes measured preoperative differences between patients receiving total mastectomy or breast-conserving surgery in a cross-sectional design. Regression analyses was used to model health outcomes and adjust for patient demographics on patient measures. Participants scheduled for total mastectomy were more likely to report more severe symptoms of depression and anxiety. This association was non-significant after adjusting for demographic differences. Younger participants were more likely to be scheduled for total mastectomy. Age was negatively associated with symptoms of depression and anxiety. Screening patients for mental health symptoms may be particularly important among younger patients who were more likely to report depression and anxiety before their surgery and were more likely to receive total mastectomy.
Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Mastectomia/psicologia , Neoplasias da Mama/complicações , Mastectomia Segmentar/psicologia , Qualidade de Vida/psicologia , Estudos TransversaisRESUMO
High DNA fragmentation index (DFI) may be associated with poor outcome after IVF. Our aim was to determine whether DFI impacts blastocyst quality or clinical outcome. This retrospective study included 134 couples who underwent 177 IVF-ICSI and pre-implantation genetic screening (PGS) cycles during January 1st, 2014-March 31st, 2016 and had documented previous DFI. Group 1 (DFI>30%) encompassed 25 couples who underwent 36 cycles; Group 2 (DFI 15-30%) included 45 couples and 57 cycles; group 3 (DFI<15%) included 64 couples and 83 cycles. Male partners within group 1 were older (45.1 compared to 40.6 and 38.3 years, respectively, p<0.05), had higher BMI (32.4 compared to 26.6 and 25.8 respectively, p<0.05) and lower sperm count and motility (46*106/ml and 35.5%, respectively) compared to groups 2 (61.8*106/ml and 46.6%, respectively) and 3 (75.8*106/ml and 55.1%, respectively, p<0.05). Female parameters including ovarian reserve and response and embryo development were similar. Total numbers of biopsied blastocysts were 116, 175 and 259 in groups 1, 2 and 3, respectively. PGS for 24 chromosomes revealed comparable euploidy rate of 46-50.4%, with a similar morphological classification. No significant differences were found regarding pregnancy rates or pregnancy loss. It seems that DFI doesn't correlate with blastocyst aneuploidy or morphological grading.