Prophylactic salpingectomy with delayed oophorectomy as a two-staged alternative for primary prevention of ovarian cancer in BRCA1/2 mutation carriers: women's point of view.

OBJECTIVE: This study aimed to determine BRCA -mutation carrier women's interest and acceptability of participating in a study examining prophylactic salpingectomy with delayed oophorectomy (PSDO) as an alternative to the current recommendation for bilateral salpingo-oophorectomy for risk reduction. METHODS: This is a cross-sectional questionnaire-based study. All women visiting the high-risk clinics for hereditary breast and ovarian cancer in a single tertiary medical center were asked to complete a questionnaire concerning the two-stage approach from October 2018 to December 2019. Before completing the questionnaire, detailed explanation was given by a senior physician regarding the procedure, related background, possible risks, and benefits. RESULTS: The study population included 293 women, of whom 183 (62.4%) were BRCA1 mutation carriers, 97 (33.1%) were BRCA2 mutation carriers, and 13 (4.4%) had unknown familial mutation. Risk-reducing surgery was completed in 160 (55.17%) of the women. First-degree and second-degree family history was reported in 166 (57.24%) and 52 (17.9%) of the women, respectively. Among women surveyed, more than half of the women (n = 66 [51%]) who had yet to undergo risk-reducing surgery reported interest in having PSDO. Similarly, among those who had already received prophylactic surgery, 64 (40%) also considered PSDO to be an acceptable alternative. Multivariate logistic regression analysis found family history of related malignancies to be the only independent factor associated with reduced interest in a study of PSDO (odds ratio, 0.15 [95% confidence interval, 0.29-0.77]; P = 0.02). CONCLUSIONS: Overall, BRCA -mutation carrier women indicated interest in PSDO risk-reducing surgery, taking into consideration the potential additional risk. These findings suggest that a clinical study exploring the equivalence of PSDO as alternative treatment is feasible.

In-utero treatment of prenatal thoracic abnormalities by thoraco-amniotic shunts, short and long term neuro developmental outcome: A single center experience.

BACKGROUND: Severe primary fetal hydrothorax (PFH) and fetal lung lesions (FLL) such as congenital pulmonary airway malformation (CPAM) and Bronchopulmonary sequestration (BPS) are often treated by thoraco-amniotic shunt (TAS). OBJECTIVES: To compare short and long-term outcome of fetuses treated by TAS due to FLL to those treated due to PFH. METHOD: A retrospective analysis was performed for all fetuses treated by TAS, between the years 2004-2015, evaluating the short and long term neurodevelopmental outcome. Long term neurodevelopment was additionally analyzed prospectively by Vineland adaptive behavioral scale (VABS) standardized questionnaires. RESULTS: 38 fetuses were treated by 52 TAS insertions; of which 13 (35%) due to FLL and 25 due to PFH. Perinatal survival was high (87.9%) with 3 neonatal death and one termination of pregnancy (TOP). High survival rate persisted even in cases requiring recurrent shunt insertion (80% survival). There was no significant difference in short or long term outcome including perinatal survival (84% Vs 90%, P = 0.64) and hydrops resolution (91% Vs 63%, p = 0.19). Long term outcome, including rate of neurodevelopmental abnormalities (23.5% Vs 20%) and VABS score (91.3 ± 13.3 Vs 96.4 ± 14.7), were similar for both groups. CONCLUSION: TAS insertion is effective and resulting in high perinatal survival even in cases when sequential insertion is needed. Short and long- term outcome of neonates with FLL treated by TAS are comparable to neonates treated due to PFH.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

Do Serial Sonographic Assessments of Fetuses with Isolated Congenital Diaphragmatic Hernia Help Us Predict Survival?

OBJECTIVE: The aim of this study was to assess the ability of serial prenatal sonographic measurements, and specifically changes in the observed-to-expected lung-to-head ratio (O/E LHR) throughout gestation and to predict survival in congenital diaphragmatic hernia (CDH). METHODS: Retrospective study of CDH fetuses evaluated prenatally and treated postnatally in a single tertiary center, 2008-2020. Sonographic evaluations included side of herniation, liver involvement, and O/E LHR. All data were calculated to assess ability to predict survival. RESULTS: Overall, 94 fetuses were evaluated prenatally and delivered in our medical center. Among them, 75 had isolated CDH and 19 nonisolated. CDH was categorized as left (n = 76; 80.8%), right (n = 16; 17.0%), or bilateral (n = 2; 2.2%). Overall perinatal survival rate was 57% for all live-born infants, 68% in isolated CDH, and 40% in nonisolated (excluding 2 cases that underwent fetoscopic endoluminal tracheal occlusion and did not survive). The O/E LHR was lower in cases with perinatal death compared to survivors. In cases with multiple evaluations, the minimal O/E LHR was the most accurate predictor of survival and need for perinatal extracorporeal membrane oxygenation (ECMO) support. This remained significant when excluding twin pregnancies or when evaluating only isolated left CDH. In addition to disease severity, the side of herniation and liver position was associated with preoperative mortality. CONCLUSION: O/E LHR is associated with perinatal survival. In cases with multiple evaluations, the minimal O/E LHR is the most accurate and significant predictor of perinatal mortality and need for ECMO support.

Incorporating patient centered benefits as endpoints in randomized trials of maintenance therapies in advanced ovarian cancer: A position paper from the GCIG symptom benefit committee.

BACKGROUND: Quality of life and patient reported outcome measures (PROMs) are important secondary endpoints and incorporated in most contemporary clinical trials. There have been deficiencies in their assessment and reporting in ovarian cancer clinical trials, particularly in trials of maintenance treatment where they are of particular importance. The Gynecologic Cancer InterGroup (GCIG) symptom benefit committee (SBC) recently convened a brainstorming meeting with representation from all collaborative groups to address questions of how to best incorporate PROMs into trials of maintenance therapies to support the primary endpoint which is usually progression free survival (PFS). These recommendations should harmonize the collection, analysis and reporting of PROM's across future GCIG trials. METHODS: Through literature review, trials analysis and input from international experts, the SBC identified four relevant topics to address with respect to promoting the role of PROMs to support the PFS endpoint in clinical trials of maintenance treatment for OC. RESULTS: The GCIG SBC unanimously accepted the importance of integrating PROM's in future maintenance trials and developed four guiding principles to be considered early in trial design. These include 1) adherence to SPIRIT-PRO guidelines, 2) harmonization of selection, collection and reporting of PROM's; 3) combining Health Related Quality of Life (HRQL) measures with clinical endpoints and 4) common approaches to dealing with incomplete HRQL data. CONCLUSIONS: Close attention to incorporating HRQL and PROM's is critical to interpret the results of ovarian cancer clinical trials of maintenance therapies. There should be a consistent approach to assessing and reporting patient centered benefits across all GCIG trials to enable cross trial comparisons which can be used to inform practice.

The pre-gestational triglycerides and high-density lipoprotein cholesterol ratio is associated with adverse perinatal outcomes: A retrospective cohort analysis.

OBJECTIVE: To investigate associations between pre-gestational dyslipidemia, expressed as the ratio between triglycerides (TG) and high-density lipoprotein cholesterol (HDL), and adverse maternal and neonatal outcomes. METHODS: A retrospective cohort analysis included women with TG and HDL measurements available up to 52 weeks before conception who delivered a singleton, non-anomalous infant. The study population was stratified according to a TG/HDL ratio cutoff of 3. Primary maternal outcomes included gestational diabetes or hypertensive disorders of pregnancy and neonatal outcomes after delivery before 37 weeks. RESULTS: Among 5226 women included, 4446 (85.1%) had TG/HDL <3 and 780 (14.9%) ≥3. TG/HDL ratio ≥3 vs <3 was associated with higher rates of gestational diabetes (13.1% vs 5.2%, P<0.0001) and hypertensive disorders of pregnancy (5.3% vs 2.2%, P<0.0001). Larger babies (3229.7 ± 520.7 g vs 3181.7 ± 504.4 g, P=0.015) with higher birth weight percentile (59.0 ± 26.4 vs 55.1 ± 26.6, P<0.0001) and increased rates of large-for-gestational-age (14.5% vs 10.8%, P=0.007) and macrosomia (5.6% vs 3.9%, P=0.026) were found. In multivariate analysis, TG/HDL ≥3 remained an independent risk-factor for gestational diabetes (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.02-2.39) and pre-eclampsia (aOR 3.02, 95% CI 1.82-5.01). CONCLUSIONS: An increase in adverse pregnancy outcomes was reported, mainly gestational diabetes and pre-eclampsia, when TG/HDL ratio up to 1 year before pregnancy was ≥3.

Personalized charts for the fetal corpus callosum length.

Objective: To personally customize the antenatal ultrasound charts for the fetal corpus callosum (CC) length. Methods: A retrospective analysis of fetal neuro-sonography scans. Cases were grouped as normal neuro-sonographic evaluation (normal) or as high risk and suspected brain anomaly (abnormal). The normal group was subcategorized according to Cignini's CC length charts. Data of fetuses with a CC length between the 5th-95th percentile served for creating new charts, describing the ratio of the CC length to the major biometric parameters as a function of gestational age (GA). Results: A total of 410 measurements were included. Of them 255 were normal and 155 abnormal. The CC length/estimated fetal weight (EFW) ratio had the strongest linear association with GA (R2 = 0.929). Applying charts using this ratio to the normal group, significantly increased the percent of CC length measurements defined as normal from 84.7 to 94.5% (p < .001). Conversely, applying these charts to the abnormal group nonsignificantly decreased the number of measurement defined as normal from 89 to 83.2% (p = .137) Conclusions: The CC length/EFW ratio is strongly and linearly associated with GA. Using this personalized ratio may improve the diagnostic accuracy of CC evaluation by adjusting the CC length to the fetus natural proportions.