RESUMEN
BACKGROUND: Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia-reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. METHODS: The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. RESULTS: We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3'-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. CONCLUSIONS: Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.
Asunto(s)
Exosomas , Ferroptosis , Hemo-Oxigenasa 1 , Células Madre Mesenquimatosas , MicroARNs , Animales , Femenino , Ratas , Adenosina/análogos & derivados , Adenosina/metabolismo , Endometrio/metabolismo , Endometrio/lesiones , Endometrio/patología , Exosomas/metabolismo , Ferroptosis/genética , Hemo Oxigenasa (Desciclizante) , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Células Madre Mesenquimatosas/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , MicroARNs/genética , MicroARNs/metabolismo , Ratas Sprague-Dawley , Útero/metabolismo , Útero/lesiones , Útero/patologíaRESUMEN
O parto cesáreo (PC) é o procedimento cirúrgico mais comumente realizado nos Estados Unidos (mais de 1 milhão de cirurgias por ano) e um dos procedimentos mais realizados em todo o mundo.(1) Embora o PC seja um procedimento potencialmente salvador de vidas, quando corretamente indicado, sua frequência aumentou constantemente nas últimas décadas (atualmente 21,1% globalmente, variando de 5%, na África Subsaariana, a 42,8%, na América Latina e no Caribe). Além disso, estudos demonstram tendência continuada de aumento (projeção para 2030: 28,5% globalmente, variando de 7,1%, na África Subsaariana, a 63,4%, no leste da Ásia).(2) República Dominicana, Brasil, Chipre, Egito e Turquia são os líderes mundiais, com taxas de PC variando de 58,1% a 50,8%, respectivamente, o que aponta para uma tendência preocupante de medicalização do parto e indicação excessiva do PC.(2) Outros procedimentos cirúrgicos como dilatação, curetagem, miomectomia e histeroscopia cirúrgica são menos frequentes que o PC. Ainda assim, devido à tendência de maior idade materna, o número de gestantes previamente submetidas a esses procedimentos também tende a aumentar. Esses dados apontam para um número crescente de gestações em úteros manipulados cirurgicamente Gestantes com cicatrizes uterinas prévias correm risco de aumento da morbimortalidade. Complicações como placenta prévia, rotura uterina espontânea, deiscência uterina (com ou sem intrusão placentária), gestação em cicatriz de cesariana (GCC) e distúrbios do espectro do acretismo placentário (EAP) estão associadas a sangramento uterino potencialmente fatal, lesões extrauterinas e parto pré-termo
Asunto(s)
Humanos , Femenino , Embarazo , Placenta Accreta/diagnóstico por imagen , Cesárea/efectos adversos , Útero/lesiones , Cicatriz/complicaciones , Salud Materna , ObstetriciaRESUMEN
Abstract Isthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most patients with this condition are asymptomatic. However, women can present with postmenstrual bleeding, pelvic pain, subfertility, dysmenorrhea, infertility, and scar abscess. Brazil has one of the world s highest cesarean section rates. One of the consequences of the rising rate of CS is the isthmocele, an emerging female health problem. Here we report a case of mucinous cystadenoma arising in a uterine isthmocele, a complication, as far as we could investigate, not yet described in the literature.
Resumo Istmocele é a descontinuidade do miométrio no local da cicatriz uterina em paciente com cesariana anterior. A causa da istmocele parece ser multifatorial. Má técnica cirúrgica, baixa localização da incisão, retroflexão uterina, obesidade, tabagismo, cicatrização inadequada de cicatrizes e idade materna são possíveis fatores relacionados. A maioria dos pacientes com esta condição é assintomática. No entanto, as mulheres podem apresentar sangramento pós-menstrual, dor pélvica, subfertilidade, dismenorreia, infertilidade e abscesso cicatricial. O Brasil tem uma das maiores taxas de cesariana do mundo. Uma das consequências da taxa crescente de cesarianas é a istmocele, um problema emergente de saúde feminina. Aqui relatamos um caso de cistoadenoma mucinoso originado em uma istmocele uterina, uma complicação ainda não descrita, até onde pudemos investigar.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Útero/lesiones , Cistoadenoma MucinosoRESUMEN
Objective: The effectiveness of tissue engineering materials combining porcine small intestine submucosa (SIS) and umbilical cord mesenchymal stem cells (UC-MSCs) on uterine injury in female rat after full-thickness uterine resection was evaluated as a basis for clinical treatment of postoperative uterine injury. Methods: After complex culture with SIS and UC-MSCs, cell adhesion, growth, and proliferation were assessed. Before the implantation, a surgical procedure of bilateral full-thickness uterine resection (0.5-2.0 cm long and 0.3 cm wide) was performed to obtain the rat uterine injury model, while the sham-operated rats were used as controls. Hematoxylin-eosin (H&E) staining results and fertility of female rats in each group were assessed to determine the critical resection length of the full-thickness uterine resection. Then SIS or UC-MSCs-SIS were implanted into the female rats from the uterine injury group, followed by assessments of H&E staining, the expression of ki67, α-SMA, and leukemia inhibitory factor (LIF), and fertility to determine the effectiveness of SIS and UC-MSCs-SIS on uterine injury in female rat. Results: At 24, 48, and 72 h, the cells grew progressively on the SIS material. In the 1.5 cm and 2.0 cm groups, the pregnancy rate, proportion of the uterus supporting live embryo growth, number of live embryos, and proportion of live embryos were all significantly less than those in the 0.5 cm and sham-operated groups. In the 2.0 cm group, there was little tissue regeneration at the center of the injury and not conducive to subsequent assessment. The UC-MSCs-SIS and SIS groups were better on morphological development, cell proliferation, LIF expression, and fertility than the control group. Conclusions: UC-MSCs show good adhesion, growth, and proliferation on the SIS scaffold material. The optimal resection length in full-thickness uterine resection on female rat is 1.5 cm. UC-MSCs-SIS is the effective treatment for repairing a injury after the full-thickness resection of the uterus in this research. Impact Statement The acquired severe uterus injury is a serious condition, which prone to uterine adhesions. Postoperative endometrial repairment and prevention of intrauterine adhesion recurrence are two major clinical challenges. Fortunately, the development of tissue engineering technology makes repairing a uterine injury possible. There are two main contributions from this study. First, due to ethical requirements, it is difficult to assess the repairing effect on uterus by invasive experiments in a clinical practice. Therefore, we constructed a full-thickness uterine injury rat model, which allows us to assess the repairing effect of treatments after severe uterine injuries in vivo. Second, it explored the effect of using a combination of and umbilical cord mesenchymal stem cells and small intestine submucosa materials on improving uterine repairments, providing a potential possibility for a future clinical practice.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Femenino , Embarazo , Ratas , Endometrio/metabolismo , Porcinos , Cordón Umbilical , Útero/lesiones , Útero/metabolismoRESUMEN
Uterine factor infertility is increasingly common in modern society and has severely affected human life and health. However, the existing biomaterial scaffold-mediated systems remain limited in efficient uterus recovery, leading to low pregnancy rate and live births. Here, reconstructable uterus-derived materials (RUMs) are demonstrated by combining uterus-derived extracellular matrix and seeded chorionic villi mesenchymal stem cells for uterus recovery, achieving highly efficient live births in rats with severe uterine injury. The RUMs can be designed into different states (such as, liquid RUMs and solid RUMs) and shapes (such as, cuboid, triangular-prism, and cube) in terms of requirements. The RUMs can effectively prevent intrauterine adhesion, and promote endometrial regeneration and muscle collagen reconstruction, as well as, accelerate wound healing by constructing a physical barrier and secreting cytokines, allowing efficient uterus recovery. The injured uterus nearly achieves complete recovery after treating with the RUMs and has normal pregnancies for supporting fetal development and live births, similar to the normal rats. The study provides a regenerative medicine therapeutics for uterine factor infertility.
Asunto(s)
Nacimiento Vivo , Células Madre Mesenquimatosas , Animales , Colágeno , Endometrio , Femenino , Embarazo , Ratas , Útero/lesionesRESUMEN
Bone mesenchymal stem cells (BMSCs) have been used for the treatment of acute uterine injury (AUI)-induced intrauterine adhesion (IUA) via interacting with the endothelial progenitor cells (EPCs), and BMSCs-derived exosomes (BMSCs-exo) may be the key regulators for this process. However, the underlying mechanisms have not been studied. Based on the existed literatures, lipopolysaccharide (LPS) was used to induce AUI in mice models and EPCs to mimic the realistic pathogenesis of IUA in vivo and in vitro. Our data suggested that LPS induced apoptotic and pyroptotic cell death in mice uterine horn tissues and EPCs, and the clinical data supported that increased levels of pro-inflammatory cytokines IL-18 and IL-1ß were also observed in IUA patients' serum samples, and silencing of NLRP3 rescued cell viability in LPS-treated EPCs. Next, the LPS-treated EPCs were respectively co-cultured with BMSCs in the Transwell system and BMSCs-exo, and the results hinted that both BMSCs and BMSCs-exo reversed the promoting effects of LPS treatment-induced cell death in EPCs. Then, we screened out miR-223-3p, as the upstream regulator for NLRP3, was enriched in BMSCs-exo, and BMSCs-exo inactivated NLRP3-mediated cell pyroptosis in EPCs via delivering miR-223-3p. Interestingly, upregulation of miR-223-3p attenuated LPS-induced cell death in EPCs. Collectively, we concluded that BMSCs-exo upregulated miR-223-3p to degrade NLRP3 in EPCs, which further reversed the cytotoxic effects of LPS treatment on EPCs to ameliorate LPS-induced AUI.
Asunto(s)
Células Progenitoras Endoteliales/metabolismo , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/metabolismo , Útero/lesiones , Útero/patología , Animales , Apoptosis , Secuencia de Bases , Supervivencia Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Silenciador del Gen , Humanos , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Ratones Endogámicos BALB C , Sustancias Protectoras/metabolismo , Piroptosis , Regulación hacia Arriba/genéticaRESUMEN
To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor É (ER-É), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-É expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.
Asunto(s)
Genotipo , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/patogenicidad , Hepatitis E/complicaciones , Útero/lesiones , Útero/virología , Aborto Espontáneo , Animales , Modelos Animales de Enfermedad , Femenino , Anticuerpos Antihepatitis/inmunología , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Masculino , Ratones , Ratones Endogámicos BALB C , Embarazo , Resultado del Embarazo , Anomalías Urogenitales/virología , Útero/anomalías , Útero/patología , Esparcimiento de VirusRESUMEN
Obstetric anal sphincter injury (OASI) is strongly associated with a major negative impact on women's health. Due to the consequences of an undiagnosed and therefore unrepaired OASI, it is essential to prevent or at least diagnose OASI at childbirth. We need to promote training of professionals to improve OASI screening at childbirth. High-risk situations such as operative delivery must be identified and preventive strategies such as the choice of a less traumatic instrument (vacuum) and mediolateral episiotomy should be considered. For a woman with OASI and/or symptoms, postnatal consultation with a specialist on pelvic floor disorders is essential to correctly orient her toward an adequate care pathway and to eventually identify occult or underestimated OASI. More data are required on therapeutic approaches for symptomatic women, primarily including physical therapy, sacral neuromodulation, delayed sphincter repair and palliative devices.
Asunto(s)
Canal Anal/lesiones , Episiotomía/efectos adversos , Útero/lesiones , Adulto , Canal Anal/cirugía , Episiotomía/métodos , Femenino , Humanos , Complicaciones del Trabajo de Parto , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Útero/cirugíaRESUMEN
BACKGROUND: A uterine manipulator cannot be used to elevate the ovary in benign ovarian surgery during pregnancy. This report describes our method of elevation of the ovary using a metreurynter with the success rate of the procedure and a comparison of surgical results and pregnancy outcomes between the successful and unsuccessful cases. METHODS: Between August 2003 and February 2020, 11 pregnant patients with a tumor found sunk in the Cul-de-sac underwent laparoscopic cystectomy for a benign ovarian cyst with a metreurynter. The surgical results, success and failure of the elevation by a metreurynter, pregnancy outcomes, and fetal status at delivery were evaluated. RESULTS: Elevation of ovarian tumors with a metreurynter was successful in nine cases. However, it was unsuccessful in the remaining two cases wherein the ovary was lifted with forceps while the uterus was in a compressed state. The operative time was also longer in these cases. The pregnancy prognosis, however, was good for both, successful and unsuccessful cases. CONCLUSIONS: The metreurynter is an inexpensive and practical obstetric device, and its optimal use allows the performance of a procedure with minimal burden on a pregnant uterus. Therefore, we recommend the appropriate use of this method to enable effective laparoscopic cystectomy of ovarian tumors during pregnancy.
Asunto(s)
Fondo de Saco Recto-Uterino/cirugía , Complicaciones Intraoperatorias , Laparoscopía , Quistes Ováricos , Ovariectomía , Complicaciones del Embarazo , Instrumentos Quirúrgicos , Adulto , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Laparoscopía/efectos adversos , Laparoscopía/instrumentación , Laparoscopía/métodos , Elevación/efectos adversos , Tempo Operativo , Quistes Ováricos/patología , Quistes Ováricos/cirugía , Ovariectomía/efectos adversos , Ovariectomía/métodos , Neumoperitoneo Artificial/métodos , Embarazo , Complicaciones del Embarazo/patología , Complicaciones del Embarazo/cirugía , Resultado del Embarazo , Instrumentos Quirúrgicos/efectos adversos , Instrumentos Quirúrgicos/clasificación , Útero/lesionesRESUMEN
BACKGROUND: Motor vehicle crashes (MVCs) are a leading cause of death in pregnant women. Even after minor trauma, there is risk of fetal complications. The purpose of this study was to compare injuries and outcomes in pregnant with matched nonpregnant women after MVC and evaluate the incidence and type of pregnancy-related complications. METHODS: Retrospective study at a Level I trauma center included pregnant MVC patients, admitted 2009 to 2019. Pregnant patients were matched for age, seatbelt use, and airbag deployment with nonpregnant women (1:3). Gestation-related complications included uterine contractions, vaginal bleeding, emergency delivery, and fetal loss. RESULTS: During the study period, there were 6,930 MVC female admissions. One hundred forty-five (2%) were pregnant, matched with 387 nonpregnant. The seat belt use (71% in nonpregnant vs. 73% in pregnant, p = 0.495) and airbag deployment (10% vs. 6%, p = 0.098) were similar in both groups. Nonpregnant women had higher Injury Severity Score (4 vs. 1, p < 0.0001) and abdominal Abbreviated Injury Scale (2 vs. 1, p < 0.001), but a smaller proportion sustained abdominal injury (18% vs. 53%, p < 0.0001). Mortality (1% vs. 0.7%, p = 0.722), need for emergency operation (6% vs. 3%, p = 0.295) or angiointervention (0.3% vs. 0%, p = 0.540), ventilator days (3 vs. 8, p = 0.907), and intensive care unit (4 vs. 4, p = 0.502) and hospital length of stay (2 vs. 2, p = 0.122) were all similar. Overall, 13 (11.1%) patients developed gestation-related complications, most commonly uterine contractions (6.3%), need for emergency delivery (3.5%), and vaginal bleeding (1.4%). CONCLUSION: Most pregnant patients hospitalized for MVC suffered minor injuries. Pregnant women had lower Injury Severity Score and abdominal Abbreviated Injury Scale than matched nonpregnant women. However, there was still a considerable incidence of gestation-related complications. It is imperative that pregnant patients be closely monitored even after minor trauma. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.
Asunto(s)
Accidentes de Tránsito/mortalidad , Airbags , Vehículos a Motor , Complicaciones del Embarazo/etiología , Cinturones de Seguridad , Escala Resumida de Traumatismos , Traumatismos Abdominales/epidemiología , Adulto , California/epidemiología , Parto Obstétrico/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Embarazo , Complicaciones del Embarazo/mortalidad , Estudios Retrospectivos , Centros Traumatológicos , Útero/lesiones , Adulto JovenRESUMEN
<b>Background and Objective:</b> Female infertility and reproductive problems have increased worldwide. Medical treatment of such conditions has high costs with various side effects. Alternative medicine, essentially herbal plants, has been projecting to improve female infertility and reproductive health. This study was aimed to evaluate the efficacy of single or combined administration of matcha and ashwagandha teas against H<sub>2</sub>O<sub>2</sub>-induced Utero-ovarian oxidative injury and cell death in female rats. <b>Materials and Methods:</b> Fifty adult female rats were used. Ten rats were kept healthy while in others Utero-ovarian oxidative injury was induced by drinking 1% H<sub>2</sub>O<sub>2</sub> water <i>ad libitum</i>. Injured rats were divided into 4 groups (10 rats/each), one group set as injured control and the other 3 groups the doses of supplemented teas were 200 mg kg<sup></sup><sup>1</sup> b.wt. and 100 mg kg<sup></sup><sup>1</sup> b.wt. from each or both teas, respectively. <b>Results:</b> The results displayed that both teas contain active components including flavonoids, polyphenols and possess antioxidant activity. Drinking 1% H<sub>2</sub>O<sub>2</sub> water significantly (p<u><</u>0.01)decreased the estrous cycle time, body, ovary and uterus weights, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone and estrogen (E2) levels, uterine and ovarian superoxide dismutase (SOD) activity and reduced glutathione (GSH) level while caused a substantial increase (p<u><</u>0.01) in uterine and ovarian malondialdehyde (MDA) level, DNA fragmentation percent, caspase-3 (Casp-3), 8-hydroxydeoxyguanosine (8-OHdG), tumour necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) levels as well as cyclooxygenase-2 (COX-2) activity. Moreover, microscopic observations of uterine and ovarian tissues were consistent with the biochemical results. <b>Conclusion:</b> Oral administration of tested teas improved and ameliorated all the biochemical and microscopic observations by restricting cellular DNA damage and protecting uterine and ovarian tissues from oxidative injury and cell death. The best improvement was observed in the matcha administered group.
Asunto(s)
Camellia sinensis/metabolismo , Útero/efectos de los fármacos , Withania/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Ovario/efectos de los fármacos , Ovario/lesiones , Ratas , Resultado del Tratamiento , Útero/lesionesRESUMEN
INTRODUCTION: Uterus transplantation is a complex surgical procedure. Uterine ischemia/reperfusion (IR) damage occurring in this process may cause loss of function in the uterus. Cell damage must be prevented for a healthy uterine function and successful transplantation. Cannabinoids, with their increasing clinical use, are substances with strong anti-inflammatory and antioxidative effects and have a role in immune system regulation. However, their efficacy in uterine IR damage is still unknown. This study provides information on the potential applications cannabinoids agonist JWH-133 in uterine IR damage and, hence, in the transplant process. METHODS: Rats were divided into 4 groups (n = 8), performed uterine IR, and treated 2 groups with JWH-133. After anesthesia, ischemia was applied for 1 h to the uterus while reperfusion was applied for 3 h. After the experiment, malondialdehyde (MDA) levels and phosphorylated nuclear factor-kappa B (p-NF-κB) expression were examined in the tissue samples. Also, cell damage was evaluated by histopathological imaging and TUNEL staining. RESULTS: In the uterine IR group, NF-κB expression and MDA levels were detected at high levels. Histopathological examinations and TUNEL staining revealed extensive cell damage. On the other hand, in groups treated with JWH-133, dose-dependent NF-κB expression and MDA levels decreased (p < 0.05). Depending on the dose, the rate of surviving cells increased in TUNEL staining results. CONCLUSION: The results showed that JWH-133 was effective in reducing uterine IR damage. Cannabinoids may be a new alternative that may be used in the transplantation process in the future.
Asunto(s)
Agonistas de Receptores de Cannabinoides/farmacología , Cannabinoides/farmacología , Sustancias Protectoras/farmacología , Receptor Cannabinoide CB2/agonistas , Daño por Reperfusión/prevención & control , Útero/lesiones , Animales , Apoptosis/efectos de los fármacos , Agonistas de Receptores de Cannabinoides/administración & dosificación , Cannabinoides/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Etiquetado Corte-Fin in Situ , Inyecciones Intraperitoneales , Malondialdehído/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Sustancias Protectoras/administración & dosificación , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Útero/efectos de los fármacos , Útero/metabolismo , Útero/patologíaRESUMEN
BACKGROUND: Ureteral injury is a feared complication in colorectal surgery that has been increasing over the past decade. Some have attributed this to an increased adoption of minimally invasive surgery (MIS), but the literature is hardly conclusive. In this study we aim to further assess the overall trend of ureteral injuries in colorectal surgery, and investigate propensity adjusted contributions from open and MIS to include robotic-assisted surgery. METHODS: This is a retrospective analysis of colorectal surgeries from 2006 to 2016 using the Nationwide Inpatient Sample (NIS) database. Multivariable logistic regression was performed to identify predisposing and protective factors. Demographics, hospital factors, and case-mix differences for open and MIS were accounted for via propensity analysis. The NIS coding structure changed in 2015, which could introduce a potential source of incongruity in complication rates over time. As a result, all statistical analyses included only the first nine years of data, or were conducted before and after the change for comparison. RESULTS: Of 514,162 colorectal surgeries identified there were 1598 ureteral injuries (0.31%). Ureteral injuries were found to be increasing through 2015 (2.3/1000 vs 3.3/1000; p < 0.001) and through the coding transition to 2016 (4.8/1000; p < 0.001). This trend was entirely accounted for by injuries made during open surgery, with decreasing injury rates for MIS over time. Adjusted odds ratio (OR) for ureteral injury with all MIS vs. open cases was 0.81 (95% CI 0.70-0.93, p = 0.003) and for robotic-assisted surgery alone versus open cases was 0.50 (95% CI 0.33-0.77, p = 0.001). CONCLUSIONS: The incidence rate of ureteral injuries during open colorectal surgery is increasing over time, but have been stable or decreasing for MIS cases. These findings hold even after using propensity score analysis. More research is needed to further delineate the impact of MIS and robotic-assisted surgery on ureteral injuries.
Asunto(s)
Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Útero , Femenino , Humanos , Laparoscopía/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Útero/lesionesRESUMEN
BACKGROUND: Traumatic separation of the cervix from the uterine corpus is rare. We describe a case in which this injury was identified and surgically repaired at initial presentation to preserve fertility. CASE: An 18-year-old woman presented with a pelvic crush injury after a motor vehicle accident. Imaging revealed pelvic fractures and bladder rupture. Complete transection of the uterine corpus at the level of the internal os was identified at laparotomy. The gynecology service was consulted and circumferentially reattached the corpus to the cervix. CONCLUSION: Uterine integrity should be confirmed in female patients with pelvic crush injuries who undergo exploratory laparotomy given the unknown extent of intra-abdominal trauma. Immediate surgical correction of uterine transection at the time of injury with restoration of the genital outflow tract is feasible and may allow preservation of fertility.
Asunto(s)
Lesiones por Aplastamiento/cirugía , Laparotomía/métodos , Procedimientos de Cirugía Plástica/métodos , Útero/lesiones , Útero/cirugía , Accidentes de Tránsito , Adolescente , Lesiones por Aplastamiento/etiología , Femenino , Humanos , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Rotura , Vejiga Urinaria/lesiones , Vejiga Urinaria/cirugíaRESUMEN
Uterine surgical scarring is an increasing risk factor for adverse pregnant consequences that threaten fetal-maternal health. The detailed molecular features of scar implantation remain largely unknown. We aim to study the pathologic features of uterine surgical scarring and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scarring with a uterine incision penetrating the myometrium to endometrium to examine the pathologic changes and transcriptome profiles of uterine scarring at various postsurgery (PS) time points, as well as features of the feto-maternal interface during scar implantation. We found that uterine surgical scar recovery was consistently poor at PS3 until PS90, as shown by a reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocyte infiltration. Transcriptome annotation indicated significant chronic inflammation at the scarring site. At the peri-implantation and postimplantation stages, abnormal expression of various steroid-responsive genes at the scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure, and disorientation of the implanted embryo, restricted stromal cell proliferation, and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including overinvasion of trophoblast cells into the decidua and insufficient fetal blood vessel branching in the labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are the pivotal molecular basis for adverse pregnancy consequences of scar implantation.
Asunto(s)
Cicatriz/complicaciones , Endometrio/efectos de los fármacos , Hormonas Esteroides Gonadales/farmacología , Complicaciones del Embarazo/etiología , Útero/lesiones , Animales , Cicatriz/genética , Cicatriz/metabolismo , Cicatriz/patología , Decidua/efectos de los fármacos , Decidua/metabolismo , Decidua/patología , Modelos Animales de Enfermedad , Implantación del Embrión/efectos de los fármacos , Implantación del Embrión/fisiología , Endometrio/lesiones , Endometrio/patología , Endometrio/fisiología , Femenino , Ratones , Embarazo , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/patología , Complicaciones del Embarazo/fisiopatología , Embarazo Ectópico/etiología , Embarazo Ectópico/genética , Embarazo Ectópico/metabolismo , Embarazo Ectópico/patología , Herida Quirúrgica/complicaciones , Herida Quirúrgica/genética , Herida Quirúrgica/metabolismo , Herida Quirúrgica/patología , Enfermedades Uterinas/etiología , Enfermedades Uterinas/fisiopatología , Útero/efectos de los fármacos , Útero/patología , Útero/fisiologíaRESUMEN
OBJECTIVE: This study aims to compare two techniques (External pop-out versus classic technique) for delivery of the fetal head during elective cesarean section (CS).The potential clinical predictors associated with unintended uterine incision extension during fetal head delivery among women delivered by elective CS were also assessed. METHODS: A randomized clinical trial conducted at a tertiary University hospital between February 2017 and January 2019. Participants were randomly assigned to the classic head delivery technique (group I) or external Pop-out (EPO) technique (group II). The primary outcome was the incidence of unintended uterine incision extension during elective CS. A logistic regression model was utilized to examine the association between patient's characteristics and the occurrence of unintended uterine incision extension. RESULTS: Participants in both groups (455 women in each group) had similar demographic characteristics. The EPO group had a significantly lower incidence of uterine incision extension than the classic group (p = 0.006). The operative time was significantly shorter in the EPO group (p = 0.000), which was also significantly easier than the classic technique (p = 0.001). The high body mass index (p = 0.004), previous delivery by CS (p = 0.010), high birth weight (p = 0.001) and the classic technique for head delivery (p = 0.002) were significant predictors for uterine incision tears. CONCLUSIONS: EPO technique is an easy technique for fetal head delivery during elective CS with a lower risk of uterine incision extension and shorter operative time.
Asunto(s)
Cesárea/métodos , Feto , Cabeza/embriología , Adulto , Peso al Nacer , Índice de Masa Corporal , Cesárea/efectos adversos , Cesárea Repetida , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Humanos , Laceraciones/prevención & control , Embarazo , Herida Quirúrgica/prevención & control , Resultado del Tratamiento , Útero/lesionesRESUMEN
INTRODUCTION: To date, there are few reports describing the management of traumatic gynecologic injuries leaving physicians with little guidance. OBJECTIVE: Describe the injury patterns and the preferred management of these injuries. METHODS: A retrospective cohort study was performed using the National Trauma Data Bank (NTDB) from years 2011 to 2013. Female patients age 16 years and older with internal gynecologic injuries were identified based on diagnosis codes. Demographics, associated diagnoses and procedure codes were compiled for the cohort. RESULTS: 313 patients met inclusion criteria. The mechanism of injury was blunt in 236 (75%) patients, penetrating in 68 (21%), and other in 9 (4%). The mean Injury Severity Score was 16.6 ± 14.6. Mean age was 34 ± 21 years old. 226 (74.8%) patients had an ovarian and/or fallopian tube injury, 71 (25.2%) had a uterine injury, 8 (3%) had both, and 8 (3%) had injury to the ovarian or uterine vessels only. Of the 226 patients with ovarian and/or fallopian tube injury, 11(5%) underwent repair and 10 (4%) underwent salpingo-oophorectomy. Of the 71 uterine injuries, 15 (21%) underwent repair and 5 (7%) required a hysterectomy. CONCLUSIONS: Most traumatic internal gynecologic injuries result from blunt mechanism. Currently, these injuries are largely managed non-operatively. When surgery was performed, ovarian and uterine repair was more common than salpingo-oophorectomy and hysterectomy. Prospective large-scale studies are needed to establish a standard of treatment for the management of gynecologic trauma and to assess both short and long term outcomes and fertility rates.
Asunto(s)
Genitales Femeninos/lesiones , Heridas y Lesiones/terapia , Adolescente , Adulto , Estudios de Cohortes , Trompas Uterinas/lesiones , Femenino , Humanos , Histerectomía , Puntaje de Gravedad del Traumatismo , Persona de Mediana Edad , Ovario/irrigación sanguínea , Ovario/lesiones , Sistema de Registros , Estudios Retrospectivos , Salpingooforectomía , Útero/irrigación sanguínea , Útero/lesiones , Heridas no Penetrantes/terapia , Heridas Penetrantes/terapia , Adulto JovenRESUMEN
Treatment for cancer has the potential to significantly diminish fertility and, further, to negatively impact the obstetrical outcomes of pregnancies that do occur. Cancer survivors have decreased rates of fertility and increased rates of pregnancy complications, such as preterm birth and low birth weight, after exposure to chemotherapy. To date, research on the impact of chemotherapy and radiotherapy on fertility and pregnancy outcomes has focused largely on the gonadotoxic effect of cancer treatments on ovaries, while the uterus and endometrium have not been extensively studied. It is intuitive, however, that decreased fertility and poorer obstetrical outcomes may be substantially mediated through injury to a highly mitotic tissue like the endometrium, which is also central to embryo implantation and utero-placental exchange. Pregnancy complications in cancer survivors might be due to compromised blood supply to the endometrium and myometrium affecting placentation or altered remodeling of the pregnant uterus secondary to radiation fibrosis. Alterations in endometrial receptivity at the molecular level could affect pregnancy implantation and early pregnancy loss, but later complications also can occur. This review focuses on understanding the unintended effects of chemotherapy and radiotherapy on uterine function in female cancer survivors and the impact on pregnancy, and summarizes mechanisms to protect and treat the uterus before and after cancer chemotherapy and radiotherapy.
Asunto(s)
Preservación de la Fertilidad , Infertilidad Femenina/terapia , Neoplasias/complicaciones , Útero/lesiones , Endometrio/patología , Femenino , Humanos , Infertilidad Femenina/inducido químicamente , Infertilidad Femenina/patología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ovario/patología , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/patología , Útero/efectos de los fármacos , Útero/patologíaRESUMEN
Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E2-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E2-HP hydrogel on the recovery of IUA. Our results showed that E2-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E2-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E2-HP hydrogel can effectively transfer E2 into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.