Prenatal Diagnosis of Congenital Heart Disease: The Crucial Role of Perinatal and Delivery Planning.

Although most congenital heart defects (CHDs) are asymptomatic at birth, certain CHD lesions are at significant risk of severe hemodynamic instability and death if emergent cardiac interventions are not performed in a timely fashion. Therefore, accurate identification of at-risk fetuses and appropriate delivery resource planning according to the degree of anticipated hemodynamic instability is crucial. Fetal echocardiography has increased prenatal CHD detection in recent years due to advancements in ultrasound techniques and improved obstetrical cardiac screening protocols, enabling the prediction of newborns' hemodynamic status. This assessment can guide multidisciplinary resource planning for postnatal care, including selection of delivery site, delivery room management, and transport to a cardiac center based on CHD risk severity. This review will discuss fetal cardiovascular physiology and the circulatory changes that occur at the time of and immediately following birth, outline fetal echocardiographic findings used to risk-stratify newborns with CHDs, and outline principles for neonatal resuscitation and initial transitional care in neonates with these complex CHD lesions.

Aligning patient values and code status: Choice of Diction's Effect (CODE) study.

BACKGROUND: Decisions regarding resuscitation after cardiac arrest are critical from ethical, patient satisfaction, outcome, and healthcare cost standpoints. Physician-reported discussion barriers include topic discomfort, fear of time commitment, and difficulty articulating end-of-life concepts. The influence of language used in these discussions has not been tested. This study explored whether utilizing the alternate term "allow (a) natural death" changed code status decisions in hospitalized patients versus "do not resuscitate" (DNR). METHODS: All patients age 65 and over admitted to a general medicine hospital teaching service were screened (English-speaking, not ICU-level care, no active psychiatric illness, no substance misuse, no active DNR). Participants were randomized to resuscitation discussions with either DNR or "allow natural death" as the "no code" phrasing. Outcomes included patient resuscitation decision, satisfaction with and duration of the conversation, and decision correlation with illness severity and predicted resuscitation success. RESULTS: 102 participants were randomized to the "allow natural death" (N = 49) or DNR (N = 53) arms. The overall "no code" rate for our sample of hospitalized general medicine inpatients age >65 was 16.7%, with 13% in the DNR and 20.4% in the "allow natural death" arms (p = 0.35). Discussion length was similar in the DNR and "allow natural death" arms (3.9 + 3.2 vs. 4.9 + 3.9 minutes), and not significantly different (p = 0.53). Over 90% of participants were highly satisfied with their code status decision, without difference between arms (p = 0.49). CONCLUSIONS: Participants' code status discussions did not differ in "no code" rate between "allow natural death" and DNR arms but were short in length and had high patient satisfaction. Previously reported code status discussion barriers were not encountered. It is appropriate to screen code status in all hospitalized patients regardless of phrasing used.

Incidence of Fetal Arrhythmia Before and During the COVID-19 Pandemic: A Single-Center Experience.

Fetal arrhythmias are rare and carry significant morbidity and mortality without appropriate treatment. Initial reports exist of fetal arrhythmia in the setting of maternal COVID-19 infection. Our study sought to evaluate incidence of fetal arrhythmia before and during the COVID-19 pandemic at our institution. This retrospective cohort study from a tertiary care fetal cardiac center utilized the institutional REDCap database to search fetal arrhythmia diagnostic codes. Medical records of mother-fetus dyads were reviewed and data were collected on diagnoses, gestational age, treatment regimen, and postnatal outcomes. Patients were divided into pre-COVID and peri-COVID segments. 8368 total pregnancies were evaluated during the 7.3 years of study period. Forty-five patients (0.5%) had a significant fetal arrhythmia and were included in this study: 19 (42%) in the pre-COVID-19 group and 26 (58%) in the peri-COVID-19 group. No patients had associated congenital heart disease. There was a notable increase in the incidence of fetal supraventricular tachycardia (SVT) (1.82 per 1000 vs 2.65 per 1000 pregnancies) and complete heart block (1.04 per 1000 vs 1.77 per 1000 pregnancies) but no apparent change in other tachyarrhythmias during the COVID era. The proportion of antibody-mediated complete heart block increased from 50 to 87.5%. There was also an increase in the percentage of SVT patients requiring postnatal treatment during COVID-19 (53.8% vs 62.5%). Our experience shows an increased incidence of some fetal arrhythmia diagnoses during the COVID-19 pandemic. Additional multi-center studies will be necessary to fully evaluate the increased burden of fetal arrhythmias during the COVID-19 era as well as to elucidate etiology.

Patient-reported barriers to prenatal diagnosis of congenital heart defects: A mixed-methods study.

OBJECTIVE: To ascertain patient-reported, modifiable barriers to prenatal diagnosis of congenital heart defects (CHDs). METHODS: This was a mixed-methods study among caretakers of infants who received congenital heart surgery from 2019 to 2020 in the Chicagoland area. Quantitative variables measuring sociodemographic characteristics and prenatal care utilization, and qualitative data pertaining to patient-reported barriers to prenatal diagnosis were collected from electronic health records and semi-structured phone surveys. Thematic analysis was performed using a convergent parallel approach. RESULTS: In total, 160 caretakers completed the survey, 438 were eligible for survey, and 49 (31%) received prenatal care during the COVID-19 pandemic. When comparing respondents and non-respondents, there was a lower prevalence of maternal Hispanic ethnicity and a higher prevalence of non-English/Spanish-speaking households. Of all respondents, 34% reported an undetected CHD on ultrasound or echocardiogram, while 79% reported at least one barrier to prenatal diagnosis related to social determinants of health. Among those social barriers, the most common were difficulty with appointment scheduling (n = 12, 9.5%), far distance to care/lack of access to transportation (n = 12, 9.5%) and difficulty getting time off work to attend appointments (n = 6, 4.8%). The latter two barriers were correlated. CONCLUSION: While technical improvements in the detection of CHDs remain an important area of research, it is equally critical to produce evidence for interventions that mitigate barriers to prenatal diagnosis due to social determinants of health.

Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer.

OBJECTIVE: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer. METHODS: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30). RESULTS: After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66-1.06; p = 0.13); median OS was not estimable with atezolizumab versus 49.2 months with placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78-1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed ≥10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother. CONCLUSIONS: Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients. CLINICALTRIALS: gov registration: NCT03038100.

Survivor engagement: Experience with an advocacy-based model in Washington, D.C.

INTRODUCTION: As an IRCT member organization supporting survivors of torture, the Torture Abolition and Survivor Support Coalition (TASSC) International places survivor engagement at the core of their work, aiming to provide safe and inclusive spaces for survivors to speak out and take meaningful action to prevent torture. This article describes TASSC's model for engaging survivors in advocacy and presents evidence on the personal impacts such engagement can have. METHOD: Each year from 2016-2019, TASSC administered a simple survey with questions for survivors to complete after their annual "Advocacy Day" in Washington D.C. Quantitative and qualitative data was collected to inform internal service provision and the design of future events. RESULTS: Across the four years a total of 140 survivors and compatriot human rights advocates participated in the annual Advocacy Day, and a majority completed the surveys. In their survey responses, survivors agreed they had many positive thoughts and feelings after advocacy. Their reported positive experiences included a sense of being listened to and heard by an understanding and responsive audience, the power of feeling part of a group that was speaking out on behalf of themselves and others, and a sense of motivation and hopefulness for the future. DISCUSSION: Although undertaken primarily to inform internal processes, TASSC's surveys with survivors who engaged in advocacy shed light on the potential value of well-designed advocacy experiences. Consistent with past research, survivors reported strong motivations around and compelling benefits from participating, despite the challenges that the deeply personal nature of their engagement could present. This feedback suggests TASSC has a strong model that could be replicated elsewhere, but it would be beneficial to further investigate the experiences of survivors engaging in advocacy in other country settings.

Diagnosis and Management of Aortic Dissection in a Pediatric Patient With Turner Syndrome: A Simulation.

Aortic dissection is exceedingly rare in the pediatric population. However, it is much more common among children and adolescents with certain underlying syndromes, including Turner syndrome. Furthermore, aortic dissection carries significant mortality without prompt diagnosis and management. Therefore, pediatric emergency providers should know how to recognize and treat pediatric aortic dissection in a patient with Turner syndrome. We designed this simulation for pediatric emergency medicine fellows. A simulated adolescent female patient with a known history of Turner syndrome presents with chest pain, tachycardia, and hypertension. Participants must order and interpret the appropriate diagnostics, diagnose aortic dissection, and manage aortic dissection adequately. This simulation was completed by six pediatric emergency medicine fellows and one pediatric resident. After completing the simulation, six participants (85.7%) provided anonymous feedback on a five-point Likert scale (one = strongly disagree, five = strongly agree). Feedback was positive, and participants agreed that the case content was relevant to their clinical practice and that the event will improve their clinical practice. This simulation encourages participants to recognize and manage pediatric aortic dissection in patients with Turner syndrome. Participants felt that the simulation was relevant and will improve their clinical practice.

To screen or not to screen: Exploring and addressing effective screening processes for trauma among forced migrants.

Background: Existing literature points to higher rates of trauma disorders for forced migrants than general or immigrant populations. The process of identification and screening for trauma in this population however is not straightforward and is actually controversial in some circles. Furthermore there are no definitive guidelines for mental health and social service providers on the "when" "who", "what" "why", "where", and "how" of trauma screening. Objectives: Importantly, few studies have included insights into the screening process from service providers and forced migrants themselves through participatory research methods. This study investigates effective screening processes for trauma and examines benefits and pitfalls of current practices from the perspectives of both migrants themselves as well as health service providers that serve them. Design: We used a qualitative approach to identify and analyze key themes from focus group interviews with key informants (service providers and trauma experts providing social and medical services in the community) and forced migrants (from Cameroon, Ethiopia, Honduras, and Tanzania). Results: Our results comprise forced migrant definitions of and approaches to coping with trauma, reservations about engaging with providers, positive experiences with and impacts of screening, limitations and negative aspects of screening, helpful screening practices, and effective tools and questions for screening. Conclusions: Drawing on these themes, we offer recommendations that may help inform future screening approaches and trauma-informed service provision. The study ultimately helps those in the field to reflect on current trauma screening practices for forced migrants and consider how new insights derived from rich discussions with migrants and their service providers may alter existing screening processes- which few.

Fetal Congenital Complete Heart Block: A Rare Case with an Extremely Low Ventricular Rate and Review of Current Management Strategies.

Congenital complete heart block (CCHB) is associated with high intrauterine and post-natal mortality. Prenatal detection and management, as well as appropriate delivery planning, may improve the outcomes in CCHB. We describe a rare case of CCHB that initially presented with fetal ascites and high-grade second-degree heart block noted on fetal echocardiography. The mother was noted to be positive for anti-SSA antibodies, and treatment with maternal steroids was started in an effort to reverse the fetal cardiac conduction abnormality. However, the fetal cardiac rhythm progressed to complete heart block by the follow up evaluation and the fetus had a continual declination of heart rate throughout the pregnancy to a low fetal heart rate of 25 beats per minute (bpm). This case demonstrates the lowest fetal ventricular rate documented in the literature and illustrates a severe presentation of a rare disease process. An overview of the existing knowledge related to etiology, prenatal evaluation with fetal echocardiography and fetal magnetocardiography, prenatal management, and delivery planning in fetuses with prenatally detected CCHB is included.

Laparoscopic Toupet fundoplication: a safe and effective anti-reflux option in lung transplant recipients.

BACKGROUND: Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients. METHODS: A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms. RESULTS: Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2 months post-fundoplication. CONCLUSIONS: Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.

Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

Cardiovascular Manifestations of Turner Syndrome: Phenotypic Differences Between Karyotype Subtypes.

Turner syndrome (TS) is a genetic disorder presenting in phenotypic females with total or partial monosomy of the X chromosome. Cardiovascular abnormalities are common, including congenital heart defects (CHD) and aortic dilation. Although mosaic TS is suspected to have less severe phenotype as compared to non-mosaic TS, differences in cardiovascular manifestations between karyotypes are not well studied. This is a single-center retrospective cohort study including patients with TS seen from 2000 to 2022. Demographic data, chromosomal analysis, and imaging were reviewed. Karyotypes were categorized as monosomy X (45X), 45X mosaicism, isochromosome Xq, partial X deletions, ring X (r(X)), TS with Y material, and others. Prevalence of CHD and aortic dilation were compared between monosomy X and other subtypes using Pearson's chi-square test and Welch two-sample t-test. We included 182 TS patients with median age 18 (range 4-33) years. CHD was more common in monosomy X as compared with others (61.4% vs. 26.8%, p < 0.001), including bicuspid aortic valve (44.3% vs. 16.1%, p < 0.001), partial anomalous pulmonary venous return (12.9% vs. 2.7%, p = 0.023), persistent left superior vena cava (12.9% vs. 1.8%, p = 0.008), and coarctation of the aorta (20.0% vs. 4.5%, p = 0.003). Cardiac surgery (24.3% vs. 8.9%, p = 0.017) was more prevalent in the monosomy X group. There was no statistically significant difference for presence of aortic dilation (7.1% vs 1.8%, p = 0.187). Although CHD and need for cardiac surgery are more common in TS with monosomy X as compared to others, all TS subtypes may have similar risk of developing aortic dilation. All TS patients should have similar cardiovascular surveillance testing to monitor for aortic dilation.

Mental health diagnoses and services utilization vary by wage level.

OBJECTIVES: The relationship between employee wage status and mental health care utilization has not been characterized in large-scale analyses. This study assessed health care utilization and cost patterns for mental health diagnoses according to wage category among employees with health insurance. STUDY DESIGN: This was an observational, retrospective cohort study for the year 2017 among 2,386,844 adult full-time employees (254,851 with mental health disorders; subgroup of 125,247 with depression) enrolled in self-insured plans in the IBM Watson Health MarketScan research database. METHODS: Participants were stratified into annual wage categories: $34,000 or less; more than $34,000 to $45,000; more than $45,000 to $69,000; more than $69,000 to $103,000; and more than $103,000. Health care utilization and costs were analyzed via regression analyses. RESULTS: Prevalence of diagnosed mental health disorders was 10.7% (9.3% in the lowest-wage category); prevalence of depression was 5.2% (4.2% in the lowest-wage category). Severity of mental health, and specifically depression episodes, was greater in lower-wage categories. All-cause utilization of health care services was higher in patients with mental health diagnoses vs the total population. Among patients with mental health diagnoses, specifically depression, utilization was highest in the lowest- vs highest-wage category for hospital admissions, emergency department visits, and prescription drug supply (all P < .0001). All-cause health care costs were higher in the lowest- vs highest-wage category among patients with mental health diagnoses ($11,183 vs $10,519; P < .0001), specifically depression ($12,206 vs $11,272; P < .0001). CONCLUSIONS: Lower mental health condition prevalence and greater use of high-intensity health care resources highlight the need to more effectively identify and manage mental health conditions among lower-wage workers.

Fetal Echocardiographic Variables Associated with Pre-Surgical Mortality in Truncus Arteriosus: A Pilot Study.

Truncus arteriosus (TA) is a rare congenital heart defect that can be prenatally detected by fetal echocardiography. However, prognostication and prenatal counseling focus primarily on surgical outcomes due to limited fetal and neonatal pre-surgical mortality data. We aimed to describe the incidence and identify predictors of pre-surgical mortality in prenatally detected TA. This two-center, retrospective cohort study included fetuses diagnosed with TA between 01/2010 and 04/2020. The primary outcome was pre-surgical mortality, defined by fetal or neonatal pre-surgical death or primary listing for transplantation prior to discharge. Univariable regression modeling, Chi-square tests, and t tests assessed for associations between prenatal clinical, demographic, and fetal echocardiographic (fetal-echo) variables and pre-surgical mortality. Of 23 pregnancies with prenatal diagnosis of TA, 4 (17%) were terminated. Of the remaining 19, pre-surgical mortality occurred in 4 (26%), including 2 (11%) fetal deaths and 2 (11%) neonatal pre-surgical deaths. No transplantation listings. Of liveborn fetuses (n = 17), 15 (88%) underwent a neonatal surgery, and 1 (6%) required ECMO. As compared to the survivors, the pre-surgical mortality group had a higher likelihood of having left ventricular dysfunction (0% vs. 40%; p = 0.01), right ventricular dysfunction (0% vs. 60%; p = 0.002), cardiovascular profile score < 7 (0% vs. 40%; p = 0.01), skin edema (0% vs. 40%; p = 0.01), and abnormal umbilical venous (UV) Doppler (0% vs. 60%; p = 0.002). The presence of truncal valve regurgitation or stenosis neared significance. In this cohort with prenatally diagnosed TA, there is significant pre-surgical mortality, including fetal death and neonatal pre-surgical death. Termination rate is also high. Fetal-echo variables associated with pre-surgical mortality in this cohort include ventricular dysfunction, low CVP, skin edema, and abnormal UV Doppler. Knowledge about prenatal risk factors for pre-surgical mortality may guide parental counseling and postnatal planning in prenatally diagnosed TA.

Prevalence of Abnormal Hemoglobin A1c Values in Single Ventricle Patients Following Fontan Palliation.

Fontan palliation has improved survival in single ventricle patients. However, Fontan patients are subject to long-term morbidity. A few previous studies suggest Fontan patients have an increased risk of abnormal glucose metabolism without a clear mechanism. We aim to evaluate the prevalence and severity of abnormal hemoglobin A1c (HbA1c) values in Fontan patients and identify associated factors. Single-center retrospective cross-sectional cohort study including Fontan patients and documented HbA1c testing. Univariate demographic, anthropometric, and laboratory variable comparisons were completed and a stepwise selection multivariate regression model was attempted. The study included 414 Fontan patients, median age of 19 years (range 3-59 years). Of these, 190 patients (60.5% male) had at least one HbA1c. Abnormal HbA1c (> 5.6%) was found in 36% (n = 70) and diabetic-range HbA1c (≥ 6.5%) in 4.7% (n = 9). Factors associated with abnormal HbA1c included non-white race (63% vs 45%, p = 0.018), female sex (49% vs 34%, p = 0.050), elevated adult BMI [29.6 (± 8.4) vs 24.8 (± 4.8), p = < 0.0001], elevated blood glucose [108.7 (± 47.3) vs 91.1 (± 17.9), p = < 0.0001], and elevated triglycerides [101.5 (± 52.9) vs 84.1 (± 50.9), p = 0.029]. There were no significant differences found between the two HbA1c groups regarding cardiac diagnoses or surgical factors including type of stage 1 procedure, type of stage 3 procedure, or fenestration of Fontan. Patient age at time of initial Fontan procedure and time since initial Fontan showed no association with abnormal glucose metabolism. Obesity (BMI z-score ≥ 1.6 in children and BMI ≥ 30 in adults) was correlated with abnormal HbA1c (p = 0.008, 95%CI 0.069-0.45). There is a high prevalence of elevated HbA1c values in Fontan patients with modifiable associated factors, such as obesity and hypertriglyceridemia. Further investigation is needed to identify additional associated factors for abnormal glucose metabolism and determine its clinical significance. Lastly, we propose a new management protocol to screen for abnormal glucose metabolism.

Utility of Fetal Echocardiography with Acute Maternal Hyperoxygenation Testing in Assessment of Complex Congenital Heart Defects.

Fetal echocardiography is an excellent tool for accurately assessing the anatomy and physiology of most congenital heart defects (CHDs). Knowledge gathered from a thorough initial fetal echocardiogram and serial assessment assists with appropriate perinatal care planning, resulting in improved postnatal outcomes. However, fetal echocardiography alone provides limited information about the status of the pulmonary vasculature, which can be abnormal in certain complex CHDs with obstructed pulmonary venous flow (hypoplastic left heart syndrome with restrictive atrial septum) or excessive pulmonary artery flow (d-transposition of the great arteries, usually with a restrictive ductus arteriosus). Fetuses with these CHDs are at high risk of developing severe hemodynamic instability with the immediate transition from prenatal to postnatal circulatory physiology at the time of birth. Adjunctive use of acute maternal hyperoxygenation (MH) testing in such cases can help determine pulmonary vascular reactivity in prenatal life and better predict the likelihood of postnatal compromise and the need for emergent intervention. This comprehensive review discusses the findings of studies describing acute MH testing in a diverse spectrum of CHDs and congenital diagnoses with pulmonary hypoplasia. We review historical perspectives, safety profile, commonly used clinical protocols, limitations, and future directions of acute MH testing. We also provide practical tips on setting up MH testing in a fetal echocardiography laboratory.

Patient-reported outcomes from a randomized trial of neoadjuvant atezolizumab-chemotherapy in early triple-negative breast cancer.

Patient-reported outcomes data assessing patients' experience of immunotherapy treatment burden in potentially curable early-stage triple-negative breast cancer (TNBC) are lacking. These patient-reported data inform clinical benefit and decision-making for adding atezolizumab to neoadjuvant chemotherapy in early-stage TNBC. IMpassion031 (NCT03197935) randomly assigned patients with stage II/III TNBC (T2-T4d primary tumors) to 5 cycles (4 weeks/cycle) of every 2-week neoadjuvant atezolizumab 840 mg or placebo with weekly nab-paclitaxel (3 cycles) followed by every 2-week dose-dense doxorubicin+cyclophosphamide (2 cycles). After surgery, the atezolizumab-chemotherapy arm received atezolizumab 1200 mg every 3 weeks (11 cycles). The placebo-chemotherapy arm was observed under standard of care. To assess treatment burden from the patients' perspective, which comprised measures of the treatment-related impact on patients' functioning and health-related quality of life (HRQoL), as well as patients' experience of treatment-related symptoms plus their associated bother, patients completed the EORTC QLQ-C30 and FACT-G single-item GP5. Predefined secondary endpoints included mean and mean change from baseline values in the QLQ-C30 function (role and physical) and global health status/quality of life scales. Exploratory endpoints included mean and mean change from baseline in treatment-related symptoms, and treatment side effect bother. Mean physical, role function, and HRQoL were similar between arms at baseline and throughout treatment. In the neoadjuvant period, both arms exhibited clinically meaningful declines of similar magnitude from baseline in physical, role function, and HRQoL, and reported similar treatment side effect to bother at each visit. Improved pathologic complete response from adding atezolizumab to neoadjuvant chemotherapy for early-stage TNBC occurred without imposing additional treatment burden on patients.

Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome.

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, cell-free DNA screening for sex chromosome anomalies and monosomy X in particular is associated with high false-positive rates and low positive predictive value. A cell-free DNA result positive for monosomy X may represent fetal Turner syndrome, maternal Turner syndrome, or confined placental mosaicism. A positive screen for monosomy X with discordant results of diagnostic fetal karyotype presents unique interpretation and management challenges because of potential implications for previously unrecognized maternal Turner syndrome. The current international consensus clinical practice guidelines for the care of individuals with Turner syndrome throughout the lifespan do not specifically address management of individuals with a cell-free DNA screen positive for monosomy X. This study aimed to provide context and expert-driven recommendations for maternal and/or fetal evaluation and management when cell-free DNA screening is positive for monosomy X. We highlight unique challenges of cell-free DNA screening that is incidentally positive for monosomy X, present recommendations for determining if the result is a true-positive, and discuss when diagnosis of Turner syndrome is applicable to the fetus vs the mother. Whereas we defer the subsequent management of confirmed Turner syndrome to the clinical practice guidelines, we highlight unique considerations for individuals initially identified through cell-free DNA screening.

Ocular findings in pediatric turner syndrome.

OBJECTIVE: Turner syndrome (TS) is associated with abnormalities across several organ systems, including the visual system. There is a relative paucity of literature describing ophthalmic manifestations of TS. We sought to investigate eye manifestations in our cross-sectional population of pediatric TS patients. METHODS: All patients managed by the TS program of a tertiary children's hospital were identified. Patients with documentation of at least one eye exam were included for analysis. Chart review was retrospectively performed to identify all documented ocular abnormalities as well as patient demographics, including TS karyotype. Statistical analysis was performed to identify any association between karyotype and ocular abnormality. RESULTS: A total of 187 patients with TS were identified. The mean age of the cohort was 14.3 ± 7.2 years. Ametropia was the most common ocular abnormality, occurring in 79 patients (42%), followed by strabismus in 25 (13%). Of the patients with strabismus, 17 had exotropia and 8 had esotropia, with only 2 patients requiring surgical intervention. Posterior segment abnormalities were identified in five patients without accompanying visual deficits. Two patients had ocular tumors: one with retinoblastoma and one with retinal astrocytic hamartoma. There was no association between TS karyotype and occurrence of ocular abnormalities. CONCLUSION: Ophthalmic manifestations of TS were common, particularly ametropia and strabismus. Management of strabismus was conservative in the vast majority of patients. Ocular manifestations were not associated with TS karyotype. Early screening and routine ophthalmic evaluation of patients with TS is needed to prevent progression of potentially vision-threatening abnormalities.