Cardiovascular and renal health: Preeclampsia as a risk marker.

BACKGROUND: Cardiovascular (CVD) and chronic kidney disease (CKD) in women have unique risk factors related to hormonal status and obstetric history that must be taken into account. Pregnancy complications, such as preeclampsia (PE), can reveal a subclinical predisposition for the development of future disease that may help identify women who could benefit from early CVD and CKD prevention strategies. MATERIALS AND METHODS: Review of PE and its association with future development of CVD and CKD. RESULTS: Multiple studies have established an association between PE and the development of ischemic heart disease, chronic hypertension, peripheral vascular disease, stroke and CKD. It has not been sufficiently clarified if this relation is a causal one or if it is mediated by common risk factors. Nevertheless, the presence of endothelial dysfunction and thrombotic microangiopathy during pregnancies complicated with PE makes us believe that PE may leave a long-term imprint. Early identification of women who have had a pregnancy complicated by PE becomes a window of opportunity to improve women's health through adequate follow-up and targeted preventive actions. Oxidative stress biomarkers and vascular ultrasound may play a key role in the early detection of this arterial damage. CONCLUSIONS: The implementation of preventive multidisciplinary targeted strategies can help slow down CVD and CKD's natural history in women at risk through lifestyle modifications and adequate blood pressure control. Therefore, we propose a series of recommendations to guide the prediction and prevention of CVD and CKD throughout life of women with a history of PE.

Salud cardiovascular y renal en la mujer: la preeclampsia como marcador de riesgo / Cardiovascular and renal health: Preeclampsia as a risk marker

Antecedentes: La enfermedad cardiovascular (ECV) y renal en la mujer presentan factores de riesgo propios relacionados con el estatus hormonal y los antecedentes obstétricos que deben tenerse en cuenta. Las complicaciones del embarazo, como la preeclampsia (PE), pueden revelar predisposiciones subclínicas a padecer enfermedades futuras que ayuden a identificar a aquellas mujeres que puedan beneficiarse de nuevas oportunidades para la prevención de la ECV y la enfermedad renal crónica. Materiales y métodos: Revisión sobre la PE y su asociación con el desarrollo de ECV y renal futuras. Resultados: Múltiples estudios han establecido una asociación entre PE y el desarrollo de cardiopatía isquémica, hipertensión crónica, enfermedad vascular periférica, accidente cerebrovascular y enfermedad renal. No se ha aclarado suficientemente si esta relación es de causalidad o está mediada por la presencia de factores de riesgo comunes. Sin embargo, la demostración de fenómenos de disfunción endotelial y microangiopatía trombótica en los embarazos que cursan con PE hace suponer que esta puede dejar una impronta a largo plazo. La identificación precoz de las mujeres que han padecido un embarazo complicado con PE es una ventana de oportunidad para mejorar la salud de la mujer, mediante su seguimiento y la adopción de medidas preventivas adecuadas. Los marcadores bioquímicos de daño oxidativo y la ecografía vascular pueden desempeñar un papel clave en la identificación precoz de este daño arterial. Conclusiones: La implantación de estrategias preventivas multidisciplinares y específicas puede ayudar a frenar la historia natural de la ECV y renal en las mujeres de riesgo, a través de la modificación de su estilo de vida y del adecuado control de la tensión arterial. Para ello, proponemos una serie de recomendaciones para guiar el estudio de la predicción y prevención de la ECV tras la PE a lo largo de la vida de la mujer. (AU)

Background: Cardiovascular (CVD) and chronic kidney disease (CKD) in women have unique risk factors related to hormonal status and obstetric history that must be taken into account. Pregnancy complications, such as preeclampsia (PE), can reveal a subclinical predisposition for the development of future disease that may help identify women who could benefit from early CVD and CKD prevention strategies. Materials and methods: Review of PE and its association with future development of CVD and CKD. Results: Multiple studies have established an association between PE and the development of ischemic heart disease, chronic hypertension, peripheral vascular disease, stroke and CKD. It has not been sufficiently clarified if this relation is a causal one or if it is mediated by common risk factors. Nevertheless, the presence of endothelial dysfunction and thrombotic microangiopathy during pregnancies complicated with PE makes us believe that PE may leave a long-term imprint. Early identification of women who have had a pregnancy complicated by PE becomes a window of opportunity to improve women's health through adequate follow-up and targeted preventive actions. Oxidative stress biomarkers and vascular ultrasound may play a key role in the early detection of this arterial damage. Conclusions: The implementation of preventive multidisciplinary targeted strategies can help slow down CVD and CKD's natural history in women at risk through lifestyle modifications and adequate blood pressure control. Therefore, we propose a series of recommendations to guide the prediction and prevention of CVD and CKD throughout life of women with a history of PE. (AU)

Prenatal Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Promising Way to Change the Impact of Cystic Fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is a potentially severe disease. The development of new therapies with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been a great advance in the management of this condition because they improve the function of the faulty CFTR protein rather than palliate its consequences. CFTR modulator therapy improves pancreatic and lung function and, therefore, quality of life, with greater benefits the sooner treatment is started. For this reason, the use of these therapies is being approved for increasingly younger patients. Only two cases of pregnant women taking CFTR modulator therapy with CF fetuses have been reported, suggesting that it could resolve meconium ileus (MI) prenatally and delay/prevent other consequences of CF. CASE PRESENTATION: We report a case of a healthy pregnant patient who underwent CFTR modulator therapy with elexacaftor-tezacaftor-ivacaftor (ETI) in order to treat her fetus with CF (F508del homozygous CFTR mutation) and MI. Ultrasound findings suggestive of MI were observed at 24 weeks. Both parents were tested for CFTR mutations, and both were carriers of the F508del CFTR mutation. The fetus was diagnosed with CF by amniocentesis at 26+2 weeks. Maternal ETI therapy was initiated at 31+1 weeks, and no dilated bowel was observed at 39 weeks. There were no signs of bowel obstruction after birth. Maternal ETI treatment was continued during breastfeeding, with normal liver function. Immunoreactive trypsinogen in the newborn was 58.1 ng/mL, sweat chloride test was 80 mmol/L, and fecal elastase on the second day of life was 58 µg/g. CONCLUSION: Prenatal ETI treatment, as well as during breastfeeding, could solve, prevent, and/or delay CF complications.

Application of a Global Multiparameter Scoring System for the Prenatal Prediction of Coarctation of the Aorta.

To assess prospectively the capability of our previously reported global multiparameter scoring system to predict coarctation of the aorta (CoAo) in fetuses with cardiac asymmetry, we applied and analyzed the performance of our scoring system in predicting postnatal CoAo in fetuses undergoing prenatal echocardiographic assessment because of cardiac asymmetry between 2011 and 2021, and we determined the cut-off points of the score with the best balance between specificity and sensitivity, and of maximum sensitivity and specificity. CoAo was confirmed in 39/179 newborns (21.8%). We found a significantly higher probability of CoAo in fetuses with CoAo than in cases without CoAo (84.2 ± 18.2% vs. 26.0 ± 28.6%, p < 0.001). The AUC of the ROC of the score was 0.93 (95% CI 0.89-0.97). The cut-off value with the best balance between specificity and sensitivity was a predicted risk of ≥53% (sensitivity 92.3% and specificity 80.0%). The cut-off point of maximum sensitivity was ≥35% (sensitivity 100% and specificity 72.9%), and that of maximum specificity was ≥96% (sensitivity 43.6% and specificity 96.4%). In none of the fetuses with a probability of CoAo < 35% was this condition confirmed after birth. This occurred in 102 fetuses in the whole study population (57%) and in 84 of the 111 in whom CoAo was suspected beyond 28 weeks (75.7%). This multiparameter score allows an adequate discrimination between fetuses without CoAo and those with CoAo, reducing the false positive diagnoses in cardiac asymmetry.

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter.

OBJECTIVE: To analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers. METHODS: Retrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis. RESULTS: A total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6-10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14-6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use. CONCLUSIONS: Size ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.

Vaginal metastasis as the initial presentation of leiomyosarcoma: a case report.

BACKGROUND: Uterine leiomyosarcomas are very rare and highly aggressive tumors that have a high rate of recurrence and poor prognosis, even when early diagnosed. Due to their relative rarity, there is limited research on optimal management strategies. CASE PRESENTATION: A 60-year-old woman with a history of an asymptomatic uterine leiomyoma presented in October 2015 with postmenopausal bleeding and a friable vaginal cyst that bled when palpated. A partial cystectomy was performed, and malignant-like cystic and solid components were identified. Histopathology diagnosed an unclassifiable malignant epithelioid tumor. Subsequent imaging studies identified a malignant uterine tumor, a metabolically active vaginal lesion, and two benign leiomyomas. An anterior pelvic exenteration (colpectomy, hysterectomy, bilateral adnexectomy, total cystectomy, and cutaneous ureteroileostomy ad modum Bricker) were performed by laparotomy in March 2016. Examination of the surgical specimens identified a 75 × 75-mm leiomyoma, an 80 × 30-mm infiltrating mesenchymal uterine lesion with vascular invasion and tumor emboli, and a 60 × 30-mm perivascular vaginal tumor. Immunohistochemistry indicated a phenotypic transition from a uterine leiomyosarcoma to a vaginal epithelioid lesion; marker expression changed from the uterine tumor actin+/desmin+/caldesmon+/CD10- phenotype, through the tumor emboli, to an actin-/desmin-/caldesmon-/CD10+ phenotype in the vaginal lesion. A high-grade uterine mesenchymal tumor and vaginal metastasis were diagnosed. Adjuvant chemotherapy with docetaxel, gemcitabine, and doxorubicin commenced in May 2016 and treatment has been well tolerated. CONCLUSIONS: Differentiating leiomyosarcoma from leiomyoma is challenging and few tools other than microscopic evaluation are available. Vaginal compromise in leiomyosarcoma usually results from tumor extension, not hematogenous metastasis. A vaginal metastasis is a very rare initial presentation. We have found only two cases like this described on published literature. The atypical clinical and histological presentation in our case complicated diagnosis and delayed treatment. An early diagnosis and complete surgical clearance gives the best chance of survival, and imaging tools should be applied early in instances of new suspicious malignant lesions.