The first clinical validation of whole-genome screening on standard trophectoderm biopsies of preimplantation embryos.

Objective: To validate the performance of our laboratory-developed whole-genome screening assay within clinical preimplantation genetic testing environments. Design: Perform a laboratory-developed whole-genome assay on both cell lines and trophectoderm biopsies, subsequently employing the next-generation sequencing procedure to reach a sequencing depth of 30X. Adhere to the Genome Analysis Toolkit best practices for accuracy, sensitivity, specificity, and precision calculations by comparing samples with references. Our assay was then applied to cell lines and biopsies harboring known pathogenic variants, aiming to ascertain these changes solely from the next-generation sequencing data, independent of parental genome information. Settings: Clinical laboratory. Patients: Coriell cell lines and research embryos with known chromosomal or genetic variants. Research trophectoderm biopsies from a couple that are heterozygous carriers for distinct variants in the same autosomal recessive gene (HOGA1). Intervention: Not applicable. Main Outcome Measures: Accuracy, sensitivity, specificity, and precision were assessed by comparing the samples to their references. For samples with known variants, we calculated our sensitivity to detecting established variants. For the research embryos, noncarrier, carrier, and compound heterozygous states of inherited HOGA1 variants were distinguished independently of parental samples. Results: Amplification of DNA from cell lines and embryos yielded success rates exceeding 99.9% and 98.2%, respectively, although maintaining an accuracy of >99.9% for aneuploidy assessment. The accuracy (99.99%), specificity (99.99%), sensitivity (98.0%), and precision (98.1%) of amplified genome in the bottle (reference NA12878) and embryo biopsies were comparable to results on genomic DNA, including mitochondrial heteroplasmy. Using our assay, we achieved >99.99% sensitivity when examining samples with known chromosomal and genetic variants. This encompassed pathogenic CFTR, BRCA1, and other variants, along with uniparental isodisomies and microdeletions such as DiGeorge syndrome. Our research study identified noncarrier, carrier, and compound heterozygous states within trophectoderm biopsies while simultaneously screening for 1,300 other severe monogenic diseases. Conclusion: To our knowledge, this is the first clinical validation of whole-genome embryo screening. In this study, we demonstrated high accuracy for aneuploidy calls (>99.9%) and genetic variants (99.99%), even in the absence of parental genomes. This assay demonstrates advancements in genomic screening and an extended scope for testing capabilities in the realm of preimplantation genetic testing.

Does aligner refinement have the same efficiency in deep bite correction?: A retrospective study.

BACKGROUND: Refinements are very common in clear aligner treatments. The aim of this study is to assess whether the predictability of deep overbite correction is similar over several refinements using clear aligners (Invisalign, Align Technology, San Jose, Calif) and examine the accuracy of vertical movement and inclination change of individual teeth. METHODS: This retrospective study included 20 deep bite patients (7M and 13F; 32.63 ± 11.88 years old; an initial overbite of 5.09 ± 0.98 mm), consecutively treated from September 2016 and March 2023, who completed at least two sets of aligners, including refinements. The initial, predicted, and achieved models were exported from ClinCheck or OrthoCAD (Cadent Inc, Carlstadt, NJ) and superimposed via best-fit surface-based registration using SlicerCMF (version 4.9.0; cmf.slicer.org). We also examined 15 out of 20 patients who completed treatments. The overbite correction and changes in vertical movement and inclination for individual teeth were measured. Descriptive statistics and a paired t-test or Wilcoxon signed-rank test were performed. P < 0.05 was considered statistically significant. RESULTS: The mean accuracy of overbite correction was 37.63% after 1st set, followed by 11.19%, 6.32%, and 13.80% (2nd-4th sets), respectively. There were statistically significant differences between the predicted and achieved vertical movements and inclination changes for all teeth for the 1st and 2nd sets. For the completed cases, the mean overbite correction was 38.54% compared to the initially planned overbite correction, which is similar to one of the 1st set. Still, the vertical movements and inclination changes of all teeth present statistically significant differences between the initially planned and finally achieved movements except for maxillary lateral incisor torque. CONCLUSIONS: The most overbite correction occurs during the 1st set of aligners, and refinement treatment does not significantly improve the deep bite correction.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.

Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

Safe delivery planning of patients with moyamoya disease in pregnancy: Case series of a single center.

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebral vascular disease and there is limited clinical experience for pregnant women. Cerebrovascular condition might deteriorated during pregnancy. Management and mode of delivery is challenging for obstetrics specialist. CASE REPORT: Three cases of parturients with moyamoya disease delivered in National Taiwan University Hospital are presented. All were previously diagnosed and one had stroke incidence before current pregnancy course. Two delivered with Cesarean section and one with vaginal delivery, and all delivered at term without maternal or neonatal complication. CONCLUSION: Although delivery method of parturients with MMD has been debating, vaginal delivery may be suitable for certain cases under adequate monitoring and case selection.

Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.

BACKGROUND: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC). METHODS: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared. RESULTS: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity. CONCLUSION: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants.

BACKGROUND: The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. METHODS: We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. RESULTS: Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. CONCLUSION: Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.

Propess versus prostin for induction of labour in term primiparous women.

BACKGROUND: The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between dinoprostone slow-release pessary (Propess) and dinoprostone tablet (Prostin) for labour induction at term in nulliparous women. METHODS: This was a prospective single-blind randomized controlled trial conducted in a tertiary medical centre in Taiwan from September 1, 2020 to February 28, 2021. We recruited nulliparous women at term with a singleton pregnancy, fetus in cephalic presentation, an unfavourable cervix, and the cervical length had been measured by transvaginal sonography three times during labour induction. The main outcomes are duration from induction of labour to vaginal delivery, vaginal delivery rate, maternal and neonatal complication rates. RESULTS: In both groups, Prostin and Propess, 30 pregnant women were enrolled. The Propess group had higher vaginal delivery rate but it did not meet statistically significant difference. The Prostin group had significantly higher rate of adding oxytocin for augmentation (p = 0.0002). No significant difference was observed in either labouring course, maternal or neonatal outcomes. The probability of vaginal delivery was independently related to the cervical length measured by transvaginal sonography 8 h after Prostin or Propess administration as well as neonatal birth weight. CONCLUSION: Both Prostin and Propess can be used as cervical ripening agents with similar efficacy and without significant morbidity. Propess administration was associated with higher vaginal delivery rate and less need to add oxytocin. Intrapartum measurement of cervical length is helpful in predicting successful vaginal delivery.

Predictability of the deep overbite correction using clear aligners.

INTRODUCTION: The objective of this study was to investigate the predictability of overbite correction in patients with deepbite using the clear aligners (Invisalign, Align Technology, San Jose, Calif) and examine the accuracy of vertical movement and inclination change of individual teeth. METHODS: This retrospective study included 24 deepbite patients (10 males and 14 females; aged 32.8 ± 11.9 years; an initial overbite of 5.20 ± 0.95 mm; an average treatment period of 11.04 ± 4.14 months) consecutively treated from September 2016 and completed before August 2021. SmartTrack materials were used for all patients. The initial, predicted, and achieved final models were exported from ClinCheck and superimposed via best-fit surface-based registration using Slicer CMF (version 4.9.0; cmf.slicer.org). The overbite correction, changes in vertical movement, and inclination for individual teeth were measured. Descriptive statistics and a paired t test or Wilcoxon signed-rank test were performed. P <0.05 was considered statistically significant. RESULTS: Mean overbite correction was 33%, with a 1.15 mm improvement after the first set of aligners. All teeth demonstrated statistically significant differences between planned and achieved amounts in vertical movement and inclination change, with the largest difference in maxillary central incisors. Mandibular incisor intrusion and mandibular premolar extrusion had similar accuracies. Regarding inclination change, maxillary central incisors showed the lowest accuracy of 13.3%. CONCLUSIONS: Clear aligner treatment showed an average of 33% overbite correction. Overcorrection and additional refinement treatments are needed in most patients with a deepbite.

Association between statin use and rates of structural and functional loss in glaucoma.

BACKGROUND/AIMS: To evaluate the association between statin use and rates of standard automated perimetry (SAP) and retinal nerve fibre layer (RNFL) change in patients with glaucoma and glaucoma suspects. METHODS: This retrospective cohort study included subjects from the Duke Glaucoma Registry with primary open-angle glaucoma and glaucoma suspects. Subjects were assigned to groups according to history of statin use. Rates of change in SAP mean deviation (MD) and spectral-domain optical coherence tomography (SD OCT) RNFL thickness over time were estimated using linear mixed models and compared in the statin versus control groups. The effect of duration of statin use was also assessed. Patients with glaucoma versus suspects were analysed separately. Analyses were adjusted for potential confounding factors of age, gender, race, intraocular pressure and follow-up time. RESULTS: The study included 10 049 SAP tests and 14 198 SD OCT tests from 3007 eyes (1978 patients) followed for an average of 4.7±2.0 years. Of these, 775 subjects (1179 eyes) had a history of statin use. No difference in rates of change was seen between the statin versus control groups for MD (-0.07±0.16 dB/year vs -0.07±0.15 dB/year; p=0.873, respectively) or RNFL thickness (-0.70±0.60 µm/year vs -0.70±0.61 µm/year; p=0.923, respectively). Multivariable models controlling for potential confounders showed no significant association between duration of statin use and rates of MD or RNFL thickness change. CONCLUSIONS: We did not find a statistically significant association between statin use or duration of statin use and rates of structural and functional change in those with glaucoma or glaucoma suspects.

The Effect of IFT80 Deficiency in Osteocytes on Orthodontic Loading-Induced and Physiologic Bone Remodeling: In Vivo Study.

Osteocytes are the main mechanosensory cells during orthodontic and physiologic bone remodeling. However, the question of how osteocytes transmit mechanical stimuli to biological responses remains largely unanswered. Intraflagellar transport (IFT) proteins are important for the formation and function of cilia, which are proposed to be mechanical sensors in osteocytes. In particular, IFT80 is highly expressed in mouse skulls and essential for ciliogenesis. This study aims to investigate the short- and long-term effects of IFT80 deletion in osteocytes on orthodontic bone remodeling and physiological bone remodeling in response to masticatory force. We examined 10-week-old experimental DMP1 CRE+.IFT80f/f and littermate control DMP1 CRE-.IFT80f/f mice. After 5 and 12 days of orthodontic force loading, the orthodontic tooth movement distance and bone parameters were evaluated using microCT. Osteoclast formation was assessed using TRAP-stained paraffin sections. The expression of sclerostin and RANKL was examined using immunofluorescence stain. We found that the deletion of IFT80 in osteocytes did not significantly impact either orthodontic or physiologic bone remodeling, as demonstrated by similar OTM distances, osteoclast numbers, bone volume fractions (bone volume/total volume), bone mineral densities, and the expressions of sclerostin and RANKL. Our findings suggest that there are other possible mechanosensory systems in osteocytes and anatomic limitations to cilia deflection in osteocytes in vivo.

Prediction of clinical outcomes in women with placenta accreta spectrum using machine learning models: an international multicenter study.

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.

The Prenatal Diagnosis and Clinical Outcomes of Fetuses With 15q11.2 Copy Number Variants: A Case Series of 36 Patients.

Prenatal genetic counseling of fetuses diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1-BP2 region is difficult due to limited information and controversial opinion on prognosis. In total, we collected the data of 36 pregnant women who underwent prenatal microarray analysis from 2010 to 2017 and were assessed at National Taiwan University Hospital. Comparison of the maternal characteristics, prenatal ultrasound findings, and postnatal outcomes among the different cases involving the 15q11.2 BP1-BP2 region were presented. Out of the 36 fetuses diagnosed with CNVs involving the BP1-BP2 region, five were diagnosed with microduplications and 31 with microdeletions. Among the participants, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its low pathogenicity. In our study, the prenatal abnormal ultrasound findings were recorded in 12 participants and were associated with 15q11.2 deletions. No obvious developmental delay or neurological disorders were detected in early childhood.

Glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated to be 3.5%. With the growing number and proportion of older persons in the population, it is projected that 111.8 million people will have glaucoma in 2040. Currently available treatments cannot reverse glaucomatous damage to the visual system; however, early diagnosis and treatment can prevent progression of the disease. In most cases, glaucoma is a chronic condition that requires lifelong management. This article reviews the pathophysiology, classification, clinical manifestations, diagnosis, and management of glaucoma.

The "rail sign": an ultrasound finding in placenta accreta spectrum indicating deep villous invasion and adverse outcomes.

BACKGROUND: Ultrasound has demonstrated a high accuracy in the prenatal diagnosis of placenta accreta spectrum. However, it is not known whether ultrasound findings can pinpoint the depths of villous invasion, recommend surgical strategies, and predict clinical outcomes. OBJECTIVE: We described an ultrasound descriptor for the placenta accreta spectrum and investigated whether it can predict the severity of villous invasion and clinical outcomes. STUDY DESIGN: The patients with placenta accreta spectrum in this retrospective cross-sectional study were diagnosed and managed in our hospital from 2002 to 2017. The placenta, with overlying myometrium and bladder, was mapped with color Doppler sonography while the patient's bladder was full. A "rail sign" was defined as 2 parallel neovascularizations depicted by color Doppler sonography over the uterovesical junction and bladder mucosa, with interconnecting bridging vessels perpendicular to both. The patients received serial ultrasound examinations and surgery at our hospital. An unpaired t test and Pearson chi-square test compared the pathology subtypes, surgical strategies, and clinical outcomes in patients with or without a rail sign. RESULTS: We enrolled 133 consecutive cases of placenta accreta spectrum confirmed either by surgical inspection or pathology examination. Patients with a rail sign had a significantly higher risk of an abnormally invasive placenta (placenta increta or placenta percreta) than those patients without a rail sign (83.3% [60 of 72] vs 27.9% [17 of 61]; odds ratio, 12.94; P<.001). In addition, patients with a rail sign had a higher probability of perioperative approaches, including preoperative vascular control (58.3% [42 of 72] vs 21.3% [13 of 61]; odds ratio, 5.17; P<.001) and uterine artery embolization (34.7% [25 of 72] vs 11.5% [7 of 61]; odds ratio, 4.1; P=.0002]. Furthermore, patients with a rail sign carried a higher risk of adverse clinical outcomes than patients without a rail sign, such as blood transfusion (80.6% [58 of 72] vs 36.1% [22 of 61]; odds ratio, 7.34; P<.001], admission to the intensive care unit (33.3% [24 of 72] vs 16.4% [10 of 61]; odds ratio, 2.55; P=.026), hysterectomy (75% [54 of 72] vs 24.6% [15 of 61]; odds ratio, 9.2; P<.001), and bladder invasion (16.7% [12 of 72] vs 4.9% [3 of 61]; odds ratio, 3.86; P=.033). Notably, the negative predictive value of bladder invasion was 95.1%, indicating a high confidence to reject bladder invasion while the rail sign was negative. When the rail sign was used as a screening test, the positive likelihood ratio of predicting deep villous invasion was 3.64 and correlated with an increased probability of 20% to 25%. Patients with a rail sign also had a greater blood loss (2944±2748 mL vs 1530±1895 mL; P<.001) and a longer hospital stay (11.9±10.9 days vs 8.6±7.1 days; P=.036) than patients without a rail sign. CONCLUSION: A "rail sign" depicted by color Doppler sonography correlates with deeper villous invasion, additional perioperative approaches, and more adverse outcomes.

Uncontrolled before-after study adding carbetocin in addition to oxytocin decreases blood loss for cesarean section in twin pregnancies.

PURPOSE: To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies. METHODS: This is a retrospective uncontrolled before-after study done in a tertiary center in Taiwan, 2010-2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated. RESULTS: After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: -0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (-40.33 mL, 95%CI: -80.32∼ -0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15). CONCLUSION: The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH.

Prediction of success of uterus-preserving management in women with placenta accreta spectrum (CON-PAS score): A multicenter international study.

OBJECTIVE: To create a model for prediction of success of uterine-preserving procedures in women with placenta accreta spectrum (PAS). METHODS: PAS-ID is a multicenter study that included 11 centers from 9 countries. Women with PAS, who were managed between January 1, 2010 and December 31, 2019, were retrospectively included. Data were split into model development and validation cohorts, and a prediction model was created using logistic regression. Main outcome was success of uterine preservation. RESULTS: Out of 797 women with PAS, 587 were eligible. Uterus-preserving procedures were successful in 469 patients (79.9%). Number of previous cesarean sections (CS) was inversely associated with management success (adjusted odds ratio [aOR] 0.02, 95% confidence interval [CI] 0.001-3.63 with five previous CS). Other variables were complete placental invasion (aOR 0.14, 95% CI 0.05-0.43), type of CS incision (aOR 0.04, 95% CI 0.01-0.25 for classical incision), compression sutures (aOR 2.48, 95% CI 1.00-6.16), accreta type (aOR 3.76, 95% CI 1.13-12.53), incising away from placenta (aOR 5.09, 95% CI 1.52-16.97), and uterine resection (aOR 102.57, 95% CI 3.97-2652.74). CONCLUSION: The present study provides a prediction model for success of uterine preservation, which may assist preoperative and intraoperative decisions, and promote incorporation of uterine preservation procedures in comprehensive PAS protocols.

Monocyte Subsets With High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8.

Osteoclasts (OCs) are bone-resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type (WT) mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C- monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of preestablished transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of interferon regulatory factor 8 (IRF8), a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8-deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation. © 2020 American Society for Bone and Mineral Research (ASBMR).