Multivariable prediction models for fetal macrosomia and large for gestational age: A systematic review.

BACKGROUND: The identification of large for gestational age (LGA) and macrosomic fetuses is essential for counselling and managing these pregnancies. OBJECTIVES: To systematically review the literature for multivariable prediction models for LGA and macrosomia, assessing the performance, quality and applicability of the included model in clinical practice. SEARCH STRATEGY: MEDLINE, EMBASE and Cochrane Library were searched until June 2022. SELECTION CRITERIA: We included observational and experimental studies reporting the development and/or validation of any multivariable prediction model for fetal macrosomia and/or LGA. We excluded studies that used a single variable or did not evaluate model performance. DATA COLLECTION AND ANALYSIS: Data were extracted using the Checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies checklist. The model performance measures discrimination, calibration and validation were extracted. The quality and completion of reporting within each study was assessed by its adherence to the TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) checklist. The risk of bias and applicability were measured using PROBAST (Prediction model Risk Of Bias Assessment Tool). MAIN RESULTS: A total of 8442 citations were identified, with 58 included in the analysis: 32/58 (55.2%) developed, 21/58 (36.2%) developed and internally validated and 2/58 (3.4%) developed and externally validated a model. Only three studies externally validated pre-existing models. Macrosomia and LGA were differentially defined by many studies. In total, 111 multivariable prediction models were developed using 112 different variables. Model discrimination was wide ranging area under the receiver operating characteristics curve (AUROC 0.56-0.96) and few studies reported calibration (11/58, 19.0%). Only 5/58 (8.6%) studies had a low risk of bias. CONCLUSIONS: There are currently no multivariable prediction models for macrosomia/LGA that are ready for clinical implementation.

Routine use of cell salvage during cesarean section: A practice evaluation.

INTRODUCTION: Intraoperative cell salvage is a well-documented alternative to donor blood transfusion given the scarcity of donor blood pools and the incumbent risk of allogenic blood transfusion. Its use in obstetrics has been limited by concern over fetal alloimmunization due to the risk of fetomaternal hemorrhage. However, there are a paucity of studies reporting on outcome. The aim of this study was to report on a four-year experience of routine use of intraoperative cell salvage and the impact on subsequent pregnancy outcomes. MATERIAL AND METHODS: This was a tertiary center retrospective service evaluation cohort study and included all women undergoing cesarean section between December 2014 and November 2018 in a tertiary obstetric unit, identifying women who had reinfusion of intraoperative cell salvage. Data regarding index pregnancy as well as subsequent pregnancies at the hospital were extracted from hospital electronic records. Subsequent pregnancy outcome and maternal antibody status in that pregnancy were collected up until November 2022. RESULTS: During the study period, 6656 cesarean sections were performed, with 436 (6.6%) receiving reinfusion of salvaged blood. The mean volume of reinfused blood was 396 mL. A total of 49 (0.7%) women received donor blood transfusion. Of those who received reinfusion of salvaged blood, 79 (18.1%) women had subsequent pregnancies over the eight-year follow-up period. There was one case (0.23%) of fetal cell alloimmunization demonstrated by the presence of anti-D antibodies on the subsequent pregnancy booking bloods. CONCLUSIONS: Routine intraoperative cell salvage may be used to reduce the need for blood transfusion during cesarean section. The risk of fetal cell alloimmunization in a future pregnancy following reinfusion of intraoperative cell salvage is one in 436. Given an apparent small risk of fetal cell alloimmunization, further work is required to establish the safety profile of intraoperative cell salvage in pregnancy.

Functional characterisation of a novel ovarian cancer cell line, NUOC-1.

BACKGROUND: Cell lines provide a powerful model to study cancer and here we describe a new spontaneously immortalised epithelial ovarian cancer cell line (NUOC-1) derived from the ascites collected at a time of primary debulking surgery for a mixed endometrioid / clear cell / High Grade Serous (HGS) histology. RESULTS: This spontaneously immortalised cell line was found to maintain morphology and epithelial markers throughout long-term culture. NUOC-1 cells grow as an adherent monolayer with a doubling time of 58 hours. The cells are TP53 wildtype, positive for PTEN, HER2 and HER3 expression but negative for oestrogen, progesterone and androgen receptor expression. NUOC-1 cells are competent in homologous recombination and non-homologous end joining, but base excision repair defective. Karyotype analysis demonstrated a complex tetraploid karyotype. SNP array analysis of parent and derived subpopulations (NUOC-1-A1 and NUOC-1-A2) cells demonstrated heterogeneous cell populations with numerous copy number alterations and a pro-amplification phenotype. The characteristics of this new cell line lends it to be an excellent model for investigation of a number of the identified targets. MATERIALS AND METHODS: The cell line has been characterised for growth, drug sensitivity, expression of common ovarian markers and mutations, clonogenic potential and ability to form xenografts in SCID mice. Copy number changes and clonal evolution were assessed by SNP arrays.

Phosphatase and Tensin Homolog Is a Potential Target for Ovarian Cancer Sensitization to Cytotoxic Agents.

OBJECTIVES: The phosphatase and tensin homolog (PTEN) tumor suppressor protein has been found to be inactivated or mutated in various human malignancies and to play a role in cisplatin and poly(ADP-ribose) polymerase inhibitor sensitivity. In this study, we assessed the association of PTEN loss with homologous recombination (HR) deficiency and increased chemosensitivity. MATERIALS AND METHODS: The PTEN knockdown models were created using MISSION shRNA lentiviral transduction particles in cell lines derived from normal ovarian surface epithelium and a mixed endometrioid/clear-cell carcinoma. Sensitivity to common therapeutics was assessed using sulforhodamine B assay. Twenty-eight unselected primary epithelial ovarian cancer cultures derived from ascitic fluid collected at the time of surgery and matched genomic DNA were assessed for PTEN mutations using polymerase chain reaction amplification and Sanger sequencing and for mRNA expression using quantitative reverse transcription-polymerase chain reaction; HR was determined using γH2AX/RAD51 assay. The Cancer Genome Atlas data were analyzed using cBioPortal. RESULTS: In the carcinoma cell line, the PTEN knockdown enhanced sensitivity to cisplatin, rucaparib, doxorubicin, camptothecin, paclitaxel, and irradiation. In the primary ovarian cancer cultures, 2 point mutations were found (1105T>TG, 25L>L in 6 cultures and 1508G>GA, 159R>R in 4 cultures). The PTEN mRNA expression varied over 40-fold between the cultures, but did not correlate with HR status or in vitro sensitivity to cisplatin or rucaparib. The Cancer Genome Atlas data showed a rate of 8% alteration in PTEN and a trend toward improved survival in PTEN-mutated cases. CONCLUSIONS: These data indicate that although PTEN mutations in ovarian cancer are rare, PTEN inhibition results in therapeutic sensitization. Therefore, PTEN may be an important therapeutic target, in at least some cancers.