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The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field., (© 2024. Springer Nature Limited.)

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R 2 D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) affects both grey and white matter (WM), but considerably more is known about the former. Interestingly, WM disruption has been consistently observed and thoroughly described using imaging modalities, particularly MRI which has shown WM functional disconnections between the hippocampus and other brain regions during AD pathogenesis when early neurodegeneration and synapse loss are also evident. Nonetheless, high-resolution structural and functional analyses of WM during AD pathogenesis remain scarce. Given the importance of the myelinated axons in the WM for conveying information across brain regions, such studies will provide valuable information on the cellular drivers and consequences of WM disruption that contribute to the characteristic cognitive decline of AD. Here, we employed a multi-scale approach to investigate hippocampal WM disruption during AD pathogenesis and determine whether hippocampal WM changes accompany the well-documented grey matter losses. Our data indicate that ultrastructural myelin disruption is elevated in the alveus in human AD cases and increases with age in 5xFAD mice. Unreliable action potential propagation and changes to sodium channel expression at the node of Ranvier co-emerged with this deterioration. These findings provide important insight to the neurobiological substrates and functional consequences of decreased WM integrity and are consistent with the notion that hippocampal disconnection contributes to cognitive changes in AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Advances in technology have correlated with expanding prenatal genetic testing options for pregnant people. Leading medical organizations recommend cell-free DNA as the most sensitive screening test for trisomies 13, 18, and 21, as well as for fetal sex chromosome aneuploidies. The commercially available testing options go beyond these recommended tests, and prenatal care professionals should be familiar with the tests that their patients may choose despite being beyond the scope of current medical recommendations. This article explains updates in cell-free DNA technology and clinical considerations for prenatal care professionals, recognizing that this is a rapidly changing field of science and health care., (© 2024 by the American College of Nurse‐Midwives.)

(1) The Russian invasion of Ukraine forced many people to leave their country and seek asylum in various European countries, with serious consequences from a health perspective. In this context, we describe the health measures undertaken by AcToVax4NAM Consortium Countries (Cyprus-Germany-Greece-Italy-Malta-Poland-Romania-Spain) to prevent Vaccine-Preventable Disease (VPD) outbreaks in the context of mass movements of populations that resulted from the crisis in Ukraine. (2) We collected information on the vaccinations offered to Ukrainians in the Consortium Countries. (3) All these countries have provided Temporary Protection (TP) status to refugees from Ukraine and have followed the recommendations of European and International Agencies to offer them vaccinations according to the National Immunisation Programmes. The COVID-19 vaccination is offered in all countries with regard to the general population. Most countries provide information on TP and access to health/vaccination services in the Ukrainian language. (4) The information collected shows a common effort to ensure the adequate planning of health and vaccination services for refugees from Ukraine and, very often, to include them in the national vaccination offer. It is important that this initial response towards people who have fled Ukraine will be continued following the emergency but, more importantly, that it serves as a best practice towards all migrants and refugees entering the EU.

Background: Pregnancy is a high-risk time for patients with Marfan syndrome or Loeys-Dietz syndrome because of the risk for cardiovascular complications, including the risk for aortic dissection. Little is known about the differences in obstetrical and cardiac outcomes based on delivery hospital setting (academic or academic-affiliated vs community medical centers)., Objective: This study aimed to evaluate the obstetrical and cardiac outcomes of patients with Marfan syndrome or Loeys-Dietz syndrome based on delivery hospital setting., Study Design: This was a secondary analysis of a retrospective, observational cohort study of singleton pregnancies among patients with a diagnosis of Marfan syndrome or Loeys-Dietz syndrome from 1990 to 2016. Patients were identified through the Marfan Foundation, the Loeys-Dietz Syndrome Foundation, or the Cardiovascular Connective Tissue Clinic at Johns Hopkins Hospital. Data were obtained via self-reported obstetrical history and verified by review of medical records. Nonparametric analyses were performed using Fisher's exact tests and Wilcoxon rank-sum tests., Results: A total of 273 deliveries among patients with Marfan syndrome or Loeys-Dietz syndrome were included in this analysis (Table 1). More patients who had a known diagnosis before delivery of either Marfan syndrome or Loeys-Dietz syndrome delivered at an academic hospital as opposed to a community hospital (78.6% vs 59.9%; P=.001). Patients with Marfan syndrome or Loeys-Dietz syndrome who delivered at academic centers were more likely to have an operative vaginal delivery than those who delivered at community centers (23.7% vs 8.6%; P=.002). When the indications for cesarean delivery were assessed, connective tissue disease was the primary indication for the mode of delivery at community centers when compared with academic centers (55.6% vs 43.5%; P=.02). There were higher rates of cesarean delivery for arrest of labor and/or malpresentation at community hospitals than at academic centers (23.6% vs 5.3%; P=.01). There were no differences between groups in terms of the method of anesthesia used for delivery. Among those with a known diagnosis of Marfan syndrome or Loeys-Dietz syndrome before delivery, there were increased operative vaginal delivery rates at academic hospitals than at community hospitals (27.2% vs 15.1%; P=.03) (Table 2). More patients with an aortic root measuring ≥4 cm before or after pregnancy delivered at academic centers as opposed to community centers (33.0% vs 10.2%; P=.01), but there were no significant differences in the median size of the aortic root during pregnancy or during the postpartum assessment between delivery locations. Cardiovascular complications were rare; 8 patients who delivered at academic centers and 7 patients who delivered at community centers had an aortic dissection either in pregnancy or the postpartum period (P=.79)., Conclusion: Patients with Marfan syndrome or Loeys-Dietz syndrome and more severe aortic phenotypes were more likely to deliver at academic hospitals. Those who delivered at academic hospitals had higher rates of operative vaginal delivery. Despite lower frequencies of aortic root diameter >4.0 cm, those who delivered at community hospitals had higher rates of cesarean delivery for the indication of Marfan syndrome or Loeys-Dietz syndrome. Optimal delivery management of these patients requires further prospective research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts., Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression., Results: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2., Conclusions: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification., (Copyright © 2024 by the American Society of Nephrology.)

The study's aim was to determine the prevalence of depression and anxiety in children with Beckwith-Wiedemann syndrome (BWS) and their effects on social relationships and family acceptance. The Pediatric Symptom Checklist-35 items (PSC-35), Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Vineland Adaptive Behavior Scale Second Edition (VABS-II) were administered to the children. The parental Acceptance Rejection/Control Questionnaire (PARQ/Control) and Zarit Burden Inventory (ZBI) were administered to parents. In total, 6 patients and 10 parents were included. Patients showed a significant presence of internalizing behavior in PSC-35 (mean, 7.66 ± 3.67), anxiety symptoms (SCARED: mean, 46.33 ± 17.50) and socialization difficulties (mean, 90.83 ± 10.09). Parents reported a perceived good acceptance (mean, 56.33 ± 1.03) and a moderate control (mean, 24.17 ± 1.83), but the burden level was ranked moderate to severe (mean, 59.33 ± 16.78). It was found that the severity of the burden level reported by parents was related to internalizing behavior (OR = 2.000; 95% CI = 0.479-3.521; p = 0.022) and anxiety symptoms (SCARED total score: OR = 3.000; 95% CI = 1.479-4.521; p = 0.005) of children. During psychological counseling in the context of BWS treatment, it is important to identify specific resources that can support patients and families in dealing with stress and identify any critical areas that could hinder the adaptation process.

Objectives: Comprehensive counseling on prenatal genetic screening and diagnostic testing is challenging for clinicians. We sought to identify baseline clinician knowledge of prenatal genetic screening and diagnostic testing and needs to promote counseling aligned with ACOG recommendations., Methods: We performed an anonymous, cross-sectional survey of clinicians at two unaffiliated, tertiary academic institutions to assess the knowledge of, confidence in, and time spent counseling on prenatal genetic screening and diagnostic testing. Stata (Version 17, College Station, TX) was used to perform descriptive statistics. Deductive and inductive coding was used to analyze responses regarding ideal education resources., Results: The survey response rate was 78% (100/129). Only 36% of respondents correctly answered knowledge questions about prenatal genetic screening and diagnostic testing. A majority, 59% (16/39), of those confident or extremely confident in counseling were unable to answer all questions accurately. Respondents reported a median of 5.6 min (95% CI 4.9-6.4 min) spent counseling. Thematic analysis of free responses revealed desire for visual tools that discuss financial costs and patient values., Conclusions: Surveyed clinicians demonstrated deficiencies in knowledge about prenatal genetic counseling. To provide better and more comprehensive care, we noted a desire for the development of formalized resources for clinician and patient education., (© 2024 John Wiley & Sons Ltd.)

Soybean ( Glycine max ) is one of the most important crops worldwide. This crop is prone to diseases caused by the phytopathogenic fungi Macrophomina phaseolina , Fusarium oxysporum, and the lepidopteran pest Rachiplusia nu . Biological control using entomopathogenic fungi is a sustainable alternative to chemical pesticides. In this study, we assessed the antifungal activity of Beauveria bassiana and Metarhizium anisopliae against phytopathogens and the pathogenicity of B. bassiana as an endophyte against R. nu . The antagonic activity of the fungal entomopathogens was evaluated in vitro by dual culture bioassays. The feeding preference of R. nu was evaluated in a "free choice" assay under laboratory conditions. Entomopathogenic fungi inhibited the mycelial growth of the phytopathogens. The best response in all cases was observed when the antagonists were placed in the culture medium two days before the pathogens. B. bassiana was the best antagonist of F. oxysporum , while both antagonists had similar inhibitory effects on M. phaseolina growth. Additionally, B. bassiana , when grown as an endophyte, reduced insects' food preferences and decreased soybean consumption. Findings suggest that entomopathogenic fungi can fulfill multiple roles in the ecosystem. Therefore, the simultaneous expression of both properties should be considered for their application in integrated pest management programs.

Introduction: Chorionic villus sampling (CVS) remains essential for first-trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use., Methods: We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily available materials costing less than $10 and can be refrigerated and re-used to train maternal-fetal medicine fellows in CVS., Results: All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for 3 months and dozens of simulated procedures each without any apparent qualitative degradation in performance., Discussion/conclusion: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS., (© 2023 S. Karger AG, Basel.)

Background: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance., Objective: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance., Study Design: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders., Results: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance., Conclusion: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context and Background: The prevalence of uterine fibroids is estimated to be approximately 80%. Fibroids can be associated with abnormal uterine bleeding, pressure symptoms, and infertility. Given this high prevalence, approximately 30,000 myomectomies are performed in the United States per year. Minimally invasive approaches are preferred, if feasible. The minimally invasive techniques include laparoscopic, robot-assisted, hysteroscopic, and mini-laparotomy., Objective: To discuss the multiple techniques for optimizing the use of mini-laparotomy in minimally invasive myomectomy., Design: We use intraoperative surgical video to demonstrate techniques that optimize the use of the mini-laparotomy for myomectomy., Setting: Cleveland Clinic., Patient(s): Patient's undergoing fertility preserving, minimally invasive myomectomy at the Cleveland Clinic. The patient(s) included in this video gave consent for publication of the video and posting of the video online, including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, and Scopus), and other applicable sites., Intervention(s): After the surgeon has selected to proceed with mini-laparotomy myomectomy, different techniques can be employed to optimize management. We demonstrate and discuss these techniques to ensure that surgeons have a set of tools to tackle a fibroid uterus. These techniques include direct palpation of the fibroids, use of a uterine manipulator to visualize the endometrial cavity, use of the uterine manipulator to aid in repair of the cavity if entered, suturing technique that avoids the endometrial cavity and therefore limits foreign body exposure and decreases intrauterine adhesion formation, utilization of barbed suture in a layered fashion, in-situ debulking to avoid injury to fallopian tubes and other critical uterine structures, easy identification of the optimal enucleation plane, use of single hysterotomy for multiple fibroids, visualization of the "Tortuga" sign, and evaluation of the abdominal cavity using the mini-laparotomy site as a port site. To limit postoperative adhesion formation, the investigators place cellulose-based adhesion barriers with peritoneum closure. Although the need for prolonged postoperative observation can be made on a case-by-case basis, we consider this as an outpatient surgery and anticipate same-day discharge for our patients., Main Outcome Measure(s): In this video, we perform a mini-laparotomy myomectomy optimally and describe the techniques employed., Result(s): Specific techniques employed in mini-laparotomy myomectomy make the case safe, effective, and can lead to same-day discharge., Conclusion(s): Mini-laparotomy myomectomy is a technique used to perform minimally invasive myomectomy. Following the discussed steps, surgeons can be more confident in performing this method of myomectomy., Competing Interests: Declaration of interests C.R.K. reports travel supports from AAGL 2022, AUGS 2022 Clinical course, SGS 2022, Creighton residency graduation speech, Society of Robotic Surgery conference, and SGS Strategic planning meeting outside the submitted work. M.L.D. has nothing to disclose. T.G. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aortic dissection (AD) associated with pregnancy can have catastrophic consequences for the mother and/or fetus. AD occurs in 4-5 per 1,000,000 pregnancies and, despite its rarity, is the third most frequent maternal cardiovascular cause of death. AD associated with pregnancy is most likely to occur in the third trimester or postpartum period. In individuals with genetic aortopathy, pregnancy is considered a high-risk time for AD. There are management strategies in the preconception, antepartum, delivery and postpartum periods to optimize patient care. A multi-disciplinary team that includes capability to perform cardiovascular surgery is critical. Imaging modalities including maternal echocardiogram and magnetic resonance imaging can be safely performed in pregnancy for surveillance of the aortic size. Computed tomography (CT) scan is reserved for scenarios where there is a high index of suspicion for AD in a pregnant person to limit fetal exposure to radiation. After counseling about the potential risks of a pregnancy, the decision to pursue pregnancy is ultimately at the discretion of the individual. The duty of the cardio-obstetric team is to ensure that the patient and their family understand the risks of a pregnancy and the plan of care., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2023 Annals of Cardiothoracic Surgery. All rights reserved.)

COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge., (© 2023. Springer Nature Limited.)

Background: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity., Objective: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13., Study Design: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome., Results: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %., Conclusion: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Endometriosis involving the colon and/or rectum (CRE) is operatively managed using various methods. We aimed to determine if a more limited excision is associated with 30-day complications, symptom improvement, and/or recurrence., Methods: This is a retrospective review of consecutive cases of patients who underwent surgical management of CRE between 2010 and 2018. Primary outcomes were the associations between risk factors and symptom improvement, 30-day complications, and time to recurrence. Multivariable logistic regression assessed the independent risk factors., Results: Of 2681 endometriosis cases, 142 [5.3% of total, mean age 35.4 (31.0; 39.0) years, 73.9% stage IV] underwent CRE excision (superficial partial = 66.9%, segmental = 27.5%, full thickness = 1.41%). Minor complications (14.8%) were associated with blood loss [150 (112; 288) vs. 100 (50.0; 200) mls, p = 0.046], Sigmoid involvement [45.5% vs. 12.2%, HR 5.89 (1.4; 22.5), p = 0.01], stoma formation [52.6% vs. 8.9%, HR 10.9 (3.65; 34.1), p < 0.001], and segmental resection [38.5% vs. 5.8%, HR 9.75 (3.54; 30.4), p < 0.001]. Superficial, partial-thickness resections were associated with decreased risk [(4.2% vs. 36.2%), HR 0.08 (0.02; 0.24), p < 0.001]. Factors associated with major complications (8.5%) were blood loss [250 (100; 400) vs. 100 (50.0; 200) mls, p = 0.03], open surgery [31.6% vs. 4.9%, HR 8.74 (2.36; 32.9), p = 0.001], stoma formation [42% vs. 3.3%, HR 20.3 (5.41; 90.0), p < 0.001], and segmental colectomy [28.2% vs. 0.9%, HR 34.6 (6.25; 876), p < 0.001]. Partial-thickness resection was associated with decreased risk ([.05% vs. 23.4%, HR 8.74 (2.36; 32.9), p < 0.001]. 19.1% experienced recurrence. Open surgery [5.2% vs. 21.3%, HR 0.14 (0.02; 1.05), p = 0.027] and superficial partial thickness excision [23.4% vs. 10.6%, HR 2.86 (1.08; 7.59), p = 0.027] were associated. Segmental resection was associated with decreased recurrence risk [7.6% vs. 23.5%, HR 0.27 (0.08; 0.91), p = 0.024]., Conclusion: Limiting resection to partial-thickness or full-thickness disc excision compared to bowel resection may improve complications but increase recurrence risk., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The utilization of cell-free DNA (cfDNA) screening has expanded rapidly across the age spectrum of pregnant persons. With cfDNA's widespread adoption, genetic fetal sex is now often known before a phenotypic assessment on anatomic survey. CfDNA detects sex discordance in 1/1500 to 2000 pregnancies. Upon detection of sex discordance, lab error or other factors should first be assessed. Once other causes have been ruled out, this may indicate an underlying disorder/difference in sex development. A multidisciplinary team should coordinate diagnosis, treatment, and support for the family. This review discusses the diagnostic workup, emphasizing the multidisciplinary counseling and management of disorder/differences in sex development., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Access to vaccination for newly arrived migrants (NAMs) is a relevant concern that requires urgent attention in EU/EEA countries. This study aimed to develop a General Conceptual Framework (GCF) for understanding how to improve vaccination coverage for NAMs, by characterizing and critically analyzing system barriers and possible strategies to increase vaccination. Methods: A theoretical conceptualization of the GCF was hypothesized based on conceptual hubs in the immunization process. Barriers and solutions were identified through a non-systematic desktop literature review and qualitative research. The GCF guided the activities and facilitated the integration of results, thereby enriching the GCF with content. Results: The study explores the vaccination of NAMs and proposes strategies to overcome barriers in their vaccination process. It introduces a framework called GCF, which consists of five interconnected steps: entitlement, reachability, adherence, achievement, and evaluation of vaccination. The study also presents barriers and solutions identified through literature review and qualitative research, along with strategies to enhance professionals' knowledge, improve reachability, promote adherence, achieve vaccination coverage, and evaluate interventions. The study concludes by recommending strategies such as proximity, provider training, a migrant-sensitive approach, and data collection to improve vaccination outcomes for NAMs. Conclusion: Ensuring equitable access to healthcare services, including vaccination, is crucial not only from a humanitarian perspective but also for the overall public health of these countries., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Scarso, Marchetti, Russo, D’Angelo, Tosti, Bellini, De Marchi, Ferrari, Gatta, Caminada, Papaevgeniou, Dalma, Karnaki, Marceca and Declich.)

Vascular surgical emergencies are common in vascular surgical care and require complex decision making and multidisciplinary care. They are especially challenging when they occur in patients with unique physiological characteristics, such as pediatric, pregnant, and frail patients. Among the pediatric and pregnant population, vascular emergencies are rare. This rarity challenges accurate and timely diagnosis of the vascular emergency. This landscape review summarizes these three unique populations' epidemiology and emergency vascular considerations. Understanding the epidemiology is the foundation for accurate diagnosis and subsequent management. Considering each population's unique characteristics is crucial to the emergent vascular surgical interventions decision making. Collaborative and multidisciplinary care is vital in gaining expertise in managing these special populations and achieving optimal patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recently, a tool based on two different artificial neural networks has been developed. The first network predicts kidney failure (KF) development while the second predicts the time frame to reach this outcome. In this study, we conducted a post-hoc analysis to evaluate the discordant results obtained by the tool., Methods: The tool performance was analyzed in a retrospective cohort of 1116 adult IgAN patients, as were the causes of discordance between the predicted and observed cases of KF., Results: There was discordance between the predicted and observed KF in 216 IgAN patients (19.35%) all of whom were elderly, hypertensive, had high serum creatinine levels, reduced renal function and moderate or severe renal lesions. Many of these patients did not receive therapy or were non-responders to therapy. In other IgAN patients the tool predicted KF but the outcome was not reached because patients responded to therapy. Therefore, in the discordant group (prediction did not match the observed outcome) the proportion of patients having or not having KF was strongly associated with treatment (P < 0.0001)., Conclusions: The post-hoc analysis shows that discordance in a low number of patients is not an error, but rather the effect of positive response to therapy. Thus, the tool could both help physicians to determine the prognosis of the disease and help patients to plan for their future., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics., (© 2023. The Author(s).)

Background: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies., Methods: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle., Results: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively., Conclusions: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020., (© 2022. The Author(s).)

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Background: Laboratories offering cell-free DNA often reserve the right to share prenatal genetic data for research or even commercial purposes, and obtain this permission on the patient consent form. Although it is known that nonpregnant patients are often reluctant to share their genetic data for research, pregnant patients' knowledge of, and opinions about, genetic data privacy are unknown., Objective: We investigated whether pregnant patients who had already undergone cell-free DNA screening were aware that genetic data derived from cell-free DNA may be shared for research. Furthermore, we examined whether pregnant patients exposed to video education about the Genetic Information Nondiscrimination Act-a federal law that mandates workplace and health insurance protections against genetic discrimination-were more willing to share cell-free DNA-related genetic data for research than pregnant patients who were unexposed., Study Design: In this randomized controlled trial (ClinicalTrials.gov Identifier: NCT04420858), English-speaking patients with singleton pregnancies who underwent cell-free DNA and subsequently presented at 17 0/7 to 23 6/7 weeks of gestation for a detailed anatomy scan were randomized 1:1 to a control or intervention group. Both groups viewed an infographic about cell-free DNA. In addition, the intervention group viewed an educational video about the Genetic Information Nondiscrimination Act. The primary outcomes were knowledge about, and willingness to share, prenatal genetic data from cell-free DNA by commercial laboratories for nonclinical purposes, such as research. The secondary outcomes included knowledge about existing genetic privacy laws, knowledge about the potential for reidentification of anonymized genetic data, and acceptability of various use and sharing scenarios for prenatal genetic data. Eighty-one participants per group were required for 80% power to detect an increase in willingness to share data from 60% to 80% (α=0.05)., Results: A total of 747 pregnant patients were screened, and 213 patients were deemed eligible and approached for potential study participation. Of these patients, 163 (76.5%) consented and were randomized; one participant discontinued the intervention, and two participants were excluded from analysis after the intervention when it was discovered that they did not fulfill all eligibility criteria. Overall, 160 (75.1%) of those approached were included in the final analysis. Most patients in the control group (72 [90.0%]) and intervention (76 [97.4%]) group were either unsure about or incorrectly thought that cell-free DNA companies could not share prenatal genetic data for research. Participants in the intervention group were more likely to incorrectly believe that their prenatal genetic data would not be shared for nonclinical purposes than participants in the control group (28.8% in the control group vs 46.2% in the intervention; P=.03). However, video education did not increase participant willingness to share genetic data in multiple scenarios. Non-White participants were less willing than White participants to allow sharing of genetic data specifically for academic research (P<.001)., Conclusion: Most participants were unaware that their prenatal genetic data may be used for nonclinical purposes. Pregnant patients who were educated about the Genetic Information Nondiscrimination Act were not more willing to share genetic data than those who did not receive this education. Surprisingly, video education about the Genetic Information Nondiscrimination Act led patients to falsely believe that their data would not be shared for research, and participants who identified as racial minorities were less willing to share genetic data. New strategies are needed to improve pregnant patients' understanding of genetic privacy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: During the initial wave of the COVID-19, there was uncertainty related to whether the pandemic would affect pregnancy delivery outcomes. We sought to identify whether changes in hospital policies and provider practices, driven by COVID-19, would influence delivery outcomes in nulliparous, term, singleton, vertex (NTSV) pregnancies in Rhode Island., Objective: We compare the delivery outcomes and associated factors for NTSV deliveries during the first wave of the COVID-19 pandemic in Rhode Island compared to patients who delivered the year prior., Study Design: This is a retrospective cohort study of patients who presented to Women & Infants Hospital for NTSV deliveries during April 2019, pre-COVID-19, and April 2020, during COVID-19., Results: During COVID-19, patients were more likely to have abnormal electronic fetal monitoring (AEFM) as an indication for cesarean section (p<.02) and less likely to have an elective cesarean delivery (p<.01). Patients during COVID-19 were more likely to have a midwife involved in their care compared to pre-COVID-19 (p<.001). The cesarean section rate was not statistically different between the two time periods., Conclusion: Those delivering during the pandemic were more likely to have AEFM as an indication for cesarean delivery and less likely to have elective cesareans. They were more likely to have a midwife involved in their care. Further investigation into factors associated with changes in NTSV cesarean rates is warranted.