Maternal prepregnancy weight as an independent risk factor for congenital heart defects: systematic review and meta-analysis stratified by cardiac defect subtypes and severity.

OBJECTIVES: To assess and quantify the association between pre-pregnancy maternal overweight and obesity, and the risk of congenital heart defects (CHDs) in offspring. METHODS: This systematic review and meta-analysis included searches of PubMed, Medline, Web of science, and Scopus up to April 20th, 2023. Risk estimates were abstracted or calculated for rising body mass index categories (overweight, obesity, moderate and severe obesity) compared to normal weight (reference). Fixed-effects or random-effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes prior and during pregnancy. Subgroup analyses for specific congenital heart defects were conducted if there were at least two studies with accessible data. The findings were presented in two ways: as groups of defects, categorized using severity and topographic-functional criteria, and as individual defects. The certainty of the evidence for each effect estimate was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: Twenty studies for a total of 4,861,693 patients and 86,136 CHDs cases were included. The risk for CHDs progressively increases from moderate to severe obesity (pooled odds ratio (OR), respectively: 1.15, 95% confidence interval (CI), 1.11-1.20, and 1.39, 95% CI, 1.27-1.53). Sensitivity analysis indicated that this effect persists independently of maternal diabetes status before or during pregnancy. In subgroup analysis, obesity was associated with up to a 1.5-fold increase in the risk of severe CHDs (pooled OR, 1.48; 95% CI, 1.03-2.13). Specifically, severe obesity was found to be associated with an even higher risk, increasing up to 1.8 times for specific CHDs including tetralogy of Fallot (pooled OR, 1.72; 95% CI, 1.38-2.16), pulmonary valve stenosis (pooled OR, 1.79; 95% CI, 1.39-2.30), and atrial septal defects (pooled OR, 1.71; 95% CI, 1.48-1.97). CONCLUSIONS: Maternal weight emerged as a crucial modifiable risk factor for preventing CHDs, particularly the severe forms. Future research is needed to investigate whether weight management prior to pregnancy might serve as a preventive measure against CHDs. Additionally, for pregnant women with obesity, fetal echocardiography ought to be a routine diagnostic procedure. This article is protected by copyright. All rights reserved.

Prenatal diagnosis and postnatal outcome of Type-III vasa previa: systematic review of literature.

OBJECTIVE: Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP. METHODS: A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics. RESULTS: Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation. CONCLUSIONS: The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Autonomic nervous system involvement in autoimmune encephalitis and paraneoplastic neurological syndromes.

In autoimmune neurological diseases, the autonomic nervous system can be the primary target of autoimmunity (e.g. autoimmune autonomic ganglionopathy), or, more frequently, be damaged together with other areas of the nervous system (e.g. Guillain-Barré syndrome). Patients with autoimmune encephalitis and paraneoplastic neurological syndromes (PNS) often develop dysautonomia; however, the frequency and spectrum of autonomic signs and symptoms remain ill defined except for those scenarios in which dysautonomia is a core feature of the disease. Such is the case of Lambert-Eaton myasthenic syndrome, Morvan syndrome or anti-NMDAR encephalitis; in the latter, patients with dysautonomia have been reported to carry a more severe disease and to retain higher disability than those without autonomic dysfunction. Likewise, the presence of autonomic involvement indicates a higher risk of death due to neurological cause in patients with anti-Hu PNS. However, in anti-Hu and other PNS, as well as in the context of immune checkpoint inhibitors' toxicities, the characterization of autonomic involvement is frequently overshadowed by the severity of other neurological symptoms and signs. When evaluated with tests specific for autonomic function, patients with autoimmune encephalitis or PNS usually show a more widespread autonomic involvement than clinically suggested, which may reflect a potential gap of care when it comes to diagnosing dysautonomia. This review aims to revise the autonomic involvement in patients with autoimmune encephalitis and PNS, using for that purpose an antibody-based approach. We also discuss and provide general recommendations for the evaluation and management of dysautonomia in these patients.

Reference ranges of uterine artery pulsatility index from first to third trimester based on serial Doppler measurements: longitudinal cohort study.

OBJECTIVE: To provide gestational-age (GA)-specific reference ranges for mean uterine artery (UtA) pulsatility index (PI) based on longitudinal data assessment throughout pregnancy. METHODS: This was a prospective longitudinal cohort study of singleton low-risk pregnancies with adequate health and nutritional status at the time of enrolment and without fetal anomaly, receiving prenatal care between January 2018 and July 2021 at the Maternal Fetal Medicine Unit of IRCCS San Raffaele Scientific Institute, Milan, Italy. Women were recruited at ≤ 12 + 6 weeks' gestation and underwent serial standardized ultrasound monitoring, including UtA-PI measurement, by experienced certified operators until delivery. Association of UtA-PI with GA was modeled with fractional polynomial regression. Equations for mean ± SD of the estimated curves were calculated, as well as GA-specific reference charts of centiles for UtA-PI from 10 + 0 to 39 + 0 gestational weeks. RESULTS: We included 476 healthy, low-risk pregnant women and a total of 2045 ultrasound scans (median, 4 (range, 3-9) per patient) were available for analysis. Mean UtA-PI was 1.84 ± 0.55, 1.07 ± 0.38 and 0.78 ± 0.23 in the first, second and third trimesters of pregnancy, respectively. Goodness-of-fit assessment revealed that second-degree smoothing was the most accurate fractional polynomial for describing the course of UtA-PI throughout gestation; therefore, it was modeled in a multilevel framework for the construction of UtA-PI curves. We observed a rapid and substantial decrease in mean UtA-PI before 16 weeks, with subsequent smoother decrement of the slope and more stable values from 20 until 39 weeks. The 3rd , 5th , 10th , 25th , 50th , 75th , 90th , 95th and 97th centiles according to GA for UtA-PI are provided, as well as equations to allow calculation of any value as a centile. CONCLUSIONS: UtA-PI shows a progressive non-linear decrease throughout pregnancy. The new reference ranges for GA-specific mean UtA-PI constructed using rigorous methodology may have a better performance compared with previous models for screening for placenta-associated diseases in the early stages of pregnancy and for evaluating the potential risk for pregnancy-induced hypertension and/or small-for-gestational age later in pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neurological adverse events of immune checkpoint inhibitors: An update of clinical presentations, diagnosis, and management.

The use of immune checkpoint inhibitors (ICIs) has represented a major advance in cancer treatment. By enhancing endogenous immune responses to destroy cancer cells, ICIs can cause immune-related adverse events (irAEs), with possible involvement of any organ system. IrAEs are frequent, particularly those involving the skin or the endocrine system, and usually completely reversible after temporary immunosuppression, while neurological irAEs (n-irAEs) are relatively rare, often severe, and they carry a considerable risk of mortality and long-term disability. They usually affect the peripheral nervous system, mainly manifesting as myositis, polyradiculoneuropathy, or cranial neuropathy, and, less frequently, involve the central nervous system, causing encephalitis, meningitis, or myelitis. Although somehow reminiscent of the disorders that neurologists are familiar to deal with in their daily practice, n-irAEs are characterized by distinctive features from their idiopathic counterparts; for instance, myositis may have a predominant oculo-bulbar involvement reminiscent of myasthenia gravis and frequently associates with myocarditis; peripheral neuropathy, although often resembling Guillain-Barré syndrome, usually responds to corticosteroids. Remarkably, several associations between the neurological phenotype and the type of ICIs or the type of cancer have emerged in the last few years, and the growing administration of ICIs in patients with neuroendocrine cancers has led to an increased number of reports of paraneoplastic neurological syndromes (triggered or worsened by ICIs). This review aims to update current knowledge regarding the clinical presentation of n-irAEs. We also discuss the essential parts of the diagnostic approach, and we provide general recommendations for the management of these disorders.

Advances in treatments of patients with classical and emergent neurological toxicities of anticancer agents.

The neurotoxicity associated to the anticancer treatments has received a growing body of interest in the recent years. The development of innovating therapies over the last 20years has led to the emergence of new toxicities. Their diagnosis and management can be challenging in the clinical practice and further research is warranted to improve the understanding of their pathogenic mechanisms. Conventional treatments as radiation therapy and chemotherapy are associated to well-known and under exploration emerging central nervous system (CNS) and peripheral nervous system (PNS) toxicities. The identification of the risk factors and a better understanding of their pathogeny through a "bench to bedside and back again" approach, are the first steps towards the development of toxicity mitigation strategies. New imaging techniques and biological explorations are invaluable for their diagnosis. Immunotherapies have changed the cancer treatment paradigm from tumor cell centered to immune modulation towards an efficient anticancer immune response. The use of the immune checkpoints inhibitors (ICI) and CAR-T cells (chimeric antigen receptor) lead to an increase in the incidence of immune-mediated toxicities and new challenges in the neurological patient's management. The neurological ICI related adverse events (n-irAE) are rare but potentially severe and may present with both CNS and PNS involvement. The most frequent and well characterized, from a clinical and biological standpoint, are the PNS phenotypes: myositis and polyradiculoneuropathy, but the knowledge on CNS phenotypes and their treatments is expanding. The n-irAE management requires a good balance between dampening the autoimmune toxicity without impairing the anticancer immunity. The adoptive cell therapies as CAR-T cells, a promising anticancer strategy, trigger cellular activation and massive production of proinflammatory cytokines inducing frequent and sometime severe toxicity known as cytokine release syndrome and immune effector cell-associated neurologic syndrome. Their management requires a close partnership between oncologist-hematologists, neurologists, and intensivists. The oncological patient's management requires a multidisciplinary clinical team (oncologist, neurologist and paramedical) as well as a research team leading towards a better understanding and a better management of the neurological toxicities.

Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology.

OBJECTIVE: To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT). METHODS: This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ2 test and conversion of prenatal to postnatal centiles. RESULTS: A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10th centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90th centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10th centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90th centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3rd centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90th -97th centile and > 97th centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Family Needs After Traumatic Brain Injury: A VA TBI Model Systems Study.

OBJECTIVE: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) who sustained a traumatic brain injury (TBI) and to identify predictors of the unmet family caregiver needs. SETTING: Five Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs). PARTICIPANTS: Family caregivers of SMVs enrolled in the VA PRC TBI Model Systems (TBIMS) national database who were within their first 5 years post-TBI ( n = 427). DESIGN: Observational study. MAIN OUTCOME MEASURE: The Family Needs Questionnaire-Revised (FNQ-R) was completed by each SMV's designated caregiver. ANALYSES: Descriptive analyses were conducted on the FNQ-R responses at the item, domain, and total score levels. Unadjusted univariable and adjusted multivariable regression models were fitted to identify predictors of total unmet needs and unmet family need domains. RESULTS: FNQ-R item-level and domain-level descriptive results indicated that health information was the most frequently met need domain. In contrast, emotional and instrumental support domains were the least often met. On average, family caregivers reported that 59.2% of the 37 FNQ-R needs were met at the time of the follow-up assessment. Regression models indicated that both the number of SMV-perceived environmental barriers and whether the SMV received mental health treatment within the past year predicted the number of unmet FNQ-R needs. SMV-reported environmental barriers predicted increased unmet needs in all 6 family caregiver domains, and SMV mental health treatment in the past year predicted more unmet family caregiver emotional support, community support, and professional support needs. CONCLUSIONS: The current findings can be used to inform policy and programming for VA and Department of Defense to proactively address the specific needs of families and caregivers experienced in the first 5 years post-TBI.

Giga-voxel multidimensional fluorescence imaging combining single-pixel detection and data fusion.

Time-resolved fluorescence imaging is a key tool in biomedical applications, as it allows to non-invasively obtain functional and structural information. However, the big amount of collected data introduces challenges in both acquisition speed and processing needs. Here, we introduce a novel technique that allows to acquire a giga-voxel 4D hypercube in a fast manner while measuring only 0.03% of the dataset. The system combines two single-pixel cameras and a conventional 2D array detector working in parallel. Data fusion techniques are introduced to combine the individual 2D and 3D projections acquired by each sensor in the final high-resolution 4D hypercube, which can be used to identify different fluorophore species by their spectral and temporal signatures.

High dose brachytherapy with non sealed 188Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results.

BACKGROUND AND AIM: High dose brachytherapy using a non sealed 188Re-resin (Rhenium-SCT®, Oncobeta® GmbH, Munich, Germany) is a treatment option for non-melanoma skin cancer (NMSC). The aim of this prospective study was to assess the efficacy and the safety of a single application of Rhenium-SCT® in NMSC. MATERIALS AND METHOD: Fifty consecutive patients (15F, 35 M, range of age 56-97, mean 81) showing 60 histologically proven NMSCs were enrolled and treated with the Rhenium-SCT® between October 2017 and January 2020. Lesions were located on the face, ears, nose or scalp (n = 46), extremities (n = 9), and trunk (n = 5). Mean surface areas were 7.0 cm2 (1-36 cm2), mean thickness invasion was 1.1 mm (0.2-2.5 mm), and mean treatment time was 79 min (21-85 min). Superficial, mean, and target absorbed dose were 185 Gy, 63 Gy, and 31 Gy respectively. Patients were followed-up at 14, 30, 60, 90, and 180 days posttreatment, when dermoscopy and biopsy were performed. Mean follow-up was 20 months (range 3-33 months). Early skin toxicity was classified according to Common Terminology Criteria for Adverse Events (CTCAE). Cosmetic results were evaluated after at least 12 months according to Radiation Therapy Oncology Group (RTOG) scale. RESULTS: At 6 months follow-up, histology and dermoscopy were available for 54/60 lesions, of which 53/54 (98%) completely responded. One patient showed a 1-cm2 residual lesion that was subsequently surgically excised. Twelve months after treatment, 41/41 evaluable lesions were free from relapse. Twenty four months after treatment, 23/24 evaluable lesions were free of relapse. In 56/60 lesions early side effects, resolving within 32 days were classified as grades 1-2 (CTCAE). In the remaining 4/60 lesions, these findings were classified as grade 3 (CTCAE) and lasted up to 8-12 weeks but all resolved within 90 days. After at least 12 months (12-33 months), cosmetic results were excellent (30 lesions) or good (11 lesions). CONCLUSION: High dose brachytherapy with Rhenium-SCT® is a noninvasive, reasonably safe, easy to perform, effective and well-tolerated approach to treat NMSCs, and it seems to be a useful alternative option when surgery or radiation therapy are difficult to perform or not recommended. In our population 98% of the treated lesions resolved completely after a single application and only one relapsed after 2 years. Larger patients' population and longer follow-up are needed to confirm these preliminary data and to find the optimal dose to administer in order to achieve complete response without significant side effects.

Enhanced diffuse optical tomographic reconstruction using concurrent ultrasound information.

Multimodal imaging is an active branch of research as it has the potential to improve common medical imaging techniques. Diffuse optical tomography (DOT) is an example of a low resolution, functional imaging modality that typically has very low resolution due to the ill-posedness of its underlying inverse problem. Combining the functional information of DOT with a high resolution structural imaging modality has been studied widely. In particular, the combination of DOT with ultrasound (US) could serve as a useful tool for clinicians for the formulation of accurate diagnosis of breast lesions. In this paper, we propose a novel method for US-guided DOT reconstruction using a portable time-domain measurement system. B-mode US imaging is used to retrieve morphological information on the probed tissues by means of a semi-automatical segmentation procedure based on active contour fitting. A two-dimensional to three-dimensional extrapolation procedure, based on the concept of distance transform, is then applied to generate a three-dimensional edge-weighting prior for the regularization of DOT. The reconstruction procedure has been tested on experimental data obtained on specifically designed dual-modality silicon phantoms. Results show a substantial quantification improvement upon the application of the implemented technique. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Prospective longitudinal cohort study of uterine arteries Doppler in singleton pregnancies obtained by IVF/ICSI with oocyte donation or natural conception.

STUDY QUESTION: Do uterine arteries Doppler studies show different pulsatility index (UtA-PI) measurements in IVF/ICSI pregnancies with oocyte donation (OD) as compared to natural conceptions? SUMMARY ANSWER: In IVF/ICSI pregnancies with OD, UtA-PI is reduced by an average of about 40% as compared to pregnancies with natural conception. WHAT IS KNOWN ALREADY: OD pregnancies present worse pregnancy outcomes as compared to natural conception, particularly for increased incidence of pre-eclampsia (PE). Recent evidence shows that IVF/ICSI pregnancies with frozen blastocyst transfer also present higher prevalence of PE and 15% lower UtA-PI as compared to pregnancies after fresh blastocyst transfers. STUDY DESIGN, SIZE, DURATION: Prospective, longitudinal matched cohort study performed in the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, between 2013 and 2018. The analysis is based on 584 Doppler observations collected from 296 women with different method of conception (OD n = 122; natural conception n = 174). PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI viable singleton pregnancies with OD and natural conception control pregnancies matched for BMI and smoking, performing repeated UtA-PI measurements at 11-34 weeks. Miscarriages, abnormalities, twins, significant maternal diseases and other types of ARTs were excluded. Log mean left-right UtA-PI was used for analysis with linear mixed model (LMM) and correction for significant confounders. Pregnancy outcome was also analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Participants after OD were older and more frequently nulliparous (mean age: OD 43.4, 95% CI from 42.3 to 44.6; natural conception 35.1, 95% CI from 34.5 to 35.7; P-value < 0.001; nulliparous: OD 96.6%; natural conception 56.2%; P-value < 0.001). Mean pulsatility index was lower in OD (UtA-PI: natural conception 1.22; 95% CI from 1.11 to 1.28; OD 1.04; 95% CI from 0.96 to 1.12; P-value < 0.001). A significant effect of parity, gestational age (GA) modeled with a cubic polynomial and BMI was described in the LMM. The mean Log UtA-PI was on average 37% lower in OD as compared to natural conception pregnancies at LMM (P-value < 0.001). We also found a significant interaction between longitudinal UtA-PI Doppler and GA. Therefore, at 11 weeks' gestation the Log UtA-PI was 42% lower and, at 34 weeks, the differences reduced to 32%. GA at delivery and birth weight were statistically lower in OD group; however, birthweight centile was not statistically different. Preeclampsia was 11-fold more common in the OD group (0.6% and 6.6%, P-value = 0.003). No other significant difference in pregnancy outcome was shown in the study groups (gestational diabetes mellitus, small or large for GA). LIMITATIONS, REASONS FOR CAUTION: It was not possible to properly match for maternal age and to blind the assessment given the major differences between cohorts; however, we did not find significant within-groups effects related to maternal age. Future research is needed to reassess outcomes and correct them for maternal characteristics (e.g. cardiovascular function). WIDER IMPLICATIONS OF THE FINDINGS: This finding reproduces our previous discovery of lower UtA-PI in frozen as compared to fresh blastocyst transfer. The vast majority of OD is obtained by the use of cryopreservation. We speculate that increased uterine perfusion may be the physiological response to compensate dysfunctions both in the mother and in the placenta. STUDY FUNDING/COMPETING INTEREST(S): This is a non-funded study. The authors do not declare competing interest. TRIAL REGISTRATION NUMBER: N/A.

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

OBJECTIVE: To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. DESIGN: Multicentre retrospective cohort analysis. SETTING: Four Italian hospitals. POPULATION: Unselected nulliparous women at 11-13 weeks of gestation from January 2014 through to January 2018. METHODS: Model performance was evaluated based on discrimination and calibration. MAIN OUTCOME MEASURES: Delivery before 37 weeks of gestation with a diagnosis of pre-eclampsia. RESULTS: Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P = 0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P = 0.007). CONCLUSIONS: In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. TWEETABLE ABSTRACT: Simple risk score predicts preterm pre-eclampsia in Italy.

Uterine artery Doppler in singleton pregnancies conceived after in-vitro fertilization or intracytoplasmic sperm injection with fresh vs frozen blastocyst transfer: longitudinal cohort study.

OBJECTIVE: Pregnancies conceived by frozen blastocyst transfer (FBT) have higher gestational age and weight at birth as compared to those derived by fresh blastocyst transfer. The aim of this study was to evaluate uterine artery pulsatility index (UtA-PI) in pregnancies conceived by in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques using fresh vs cryopreserved blastocysts. METHODS: This was a prospective longitudinal study of viable singleton IVF/ICSI pregnancies conceived after FBT or fresh blastocyst transfer, that underwent serial ultrasound assessment at San Raffaele Hospital, Milan, Italy at 7-37 gestational weeks. We excluded pregnancies conceived using other assisted reproductive techniques such as egg donation, twin gestation, pregnancy with abnormality and those resulting in miscarriage. Pregnant women underwent ultrasound assessment at 7-10, 11-14, 18-25 and 26-37 weeks' gestation. Mean UtA-PI was measured using Doppler ultrasound according to The Fetal Medicine Foundation criteria. Pregnancy outcomes were recorded. The primary outcome was mean UtA-PI measurement and secondary outcomes were gestational age at birth, birth weight and fetal and maternal complications, including small-for-gestational age (SGA), pre-eclampsia and large-for-gestational age. UtA-PI values were made Gaussian after log10 transformation. Analysis of repeated measures using a multilevel linear mixed model (fixed effects and random effects) was performed. The possible effect of other covariates on UtA-PI Doppler values, including body mass index, SGA and pre-eclampsia, was also evaluated. RESULTS: A total of 367 IVF/ICSI cycles, comprising 164 with fresh blastocyst transfer and 203 with FBT, were included and a total of 625 observations (median, 2.5 (range, 1-4)) were collected and analyzed. The FBT group had on average 14% lower UtA-PI compared with the fresh-blastocyst-transfer group. In pregnancies with SGA fetuses, UtA-PI was 18% higher compared to pregnancies without, irrespective of the study group. Pregnancies that underwent fresh blastocyst transfer had significantly lower birth-weight centile (43.4 ± 23.3 vs 50.0 ± 23.1; P = 0.007) and a higher rate of SGA (7.9% vs 2.0%; P = 0.008) compared to those that underwent FBT. No significant differences were found between the two groups with respect to gestational age at birth and rates of preterm birth, pre-eclampsia, gestational diabetes mellitus and large-for-gestational age. CONCLUSION: UtA-PI and the proportion of SGA are lower in IVF/ICSI pregnancies conceived after FBT as compared to fresh blastocyst transfer. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

The objective assessment of the effects on cognition functioning among military personnel exposed to hypobaric-hypoxia: A pilot fMRI study.

OBJECTIVE: To identify regions of the brain affected during cognitive working memory during tasks to assess attention, planning and decision making among military aviation personnel who have chronic intermittent exposure to high altitude environment. METHOD: A case-control study was conducted in the Universiti Putra Malaysia among eight military personnel, four of whom had chronic intermittent exposure to high altitude training. They were divided into two groups, chronic intermittent exposure group (CE) (n=4) and a control group (n=4). They underwent a task-based functional magnetic resonance imaging (fMRI) that utilised spatial working memory task to objectively evaluate the neural activation in response to the Tower of London paradigm. Each correct answer was given a score of one and the maximum achievable score was 100%. RESULTS: A consecutive dichotomised group of CE (4/8) and control (4/8) of age-matched military aviation personnel with a mean age of 37.23±5.52 years; showed significant activation in the right middle frontal gyrus (MFG). This in turn was positively correlated with response accuracy. A significant difference in the response accuracy was noted among both the groups at p<0.05. CONCLUSION: At the minimum results of power analysis of this preliminary fMRI study, our group of aviation personnel who had chronic intermittent exposure to hypobaric hypoxic environment, did not have any significant decrease in cognitive function namely attention, decision-making and problem solving compared to controls during a working memory task.

The FT/FD-dependent initiation of flowering under long-day conditions in the day-neutral species Nicotiana tabacum originates from the facultative short-day ancestor Nicotiana tomentosiformis.

Photoperiod is an important external stimulus governing the precise timing of the floral transition in plants. Members of the FLOWERING LOCUS T (FT)-like clade of phosphatidylethanolamine-binding proteins induce this developmental process in numerous species by forming regulatory protein complexes with FD-like bZIP transcription factors. We identified several thus far unknown FT-like and FD-like genes in the genus Nicotiana and found that, even in the day-neutral species Nicotiana tabacum, floral initiation requires the photoperiod-dependent expression of several FT-like genes. Furthermore, floral promotion under long-day (LD) and short-day (SD) conditions is mediated by an FT-like protein (NtFT5) that originates from the genome of the paternal, facultative SD ancestor Nicotiana tomentosiformis. In contrast, its ortholog of the maternal LD ancestor Nicotiana sylvestris is not present in the genome of N. tabacum cv. SR1. Expression profiling in N. tabacum and its ancestors confirmed the relevance of these FT and FD orthologs in the context of polyploidization. We also found that floral inhibition by tobacco FT-like proteins is not restricted to SD conditions, highlighting the coincident expression of tobacco FT-like genes encoding floral activators and floral inhibitors. Multicolor bimolecular fluorescence complementation analysis revealed the preferential formation of FT/FD complexes that promote rather than inhibit flowering, which in concert with the regulation of NtFT and NtFD expression could explain how floral promotion overcomes floral repression during the floral transition in tobacco.

Novel time-resolved camera based on compressed sensing.

Time-resolved cameras with high temporal resolution (down to ps) enable a huge set of novel applications ranging from biomedicine and environmental science to material and device characterization. In this work, we propose, and experimentally validate, a novel detection scheme for time-resolved imaging based on a compressed sampling approach. The proposed scheme unifies into a single element all the required operations, i.e. space modulation, space integration and time-resolved detection, paving the way to dramatic cost reduction, performance improvement and ease of use.

Multivariable evaluation of maternal hemodynamic profile in pregnancy complicated by fetal growth restriction: prospective study.

OBJECTIVE: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension). METHODS: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors. RESULTS: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters. CONCLUSION: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.