Biomarker screening for pulmonary hypertension in VLBW infants at risk for bronchopulmonary dysplasia.

BACKGROUND: Very low birth weight (VLBW) infants demonstrate altered alveolar and pulmonary vascular development and carry an increased risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Risk stratification for BPD-associated PH (BPD-PH) in at-risk infants may help tailor management, improve outcomes, and optimize resource utilization. METHODS: VLBW infants were screened for PH with blood gas measurements, serum NT-proBNP and bicarbonate (HCO3) levels, and echocardiograms if they remained on respiratory support at 34 weeks corrected gestational age. We then tested 11 models using different cutoffs for NT-proBNP and HCO3 to predict infants at low risk of BPD-PH. RESULTS: We identified PH in 34 of 192 (17.6%) VLBW infants. The median NT-proBNP in VLBWs with PH was 2769 pg/mL versus 917 pg/mL in those without PH (p < 0.0001). A model with NT-proBNP < 950 pg/mL and HCO3 < 32 mmol/L had a sensitivity of 100%, specificity of 34.2%, and negative predictive value of 100%. Using this model, 54 of 192 (28%) of the patients in this study would have been categorized as low risk for PH and could have avoided a screening echocardiogram. CONCLUSION: NT-proBNP and HCO3 together may serve as sensitive and cost-effective screening tools for BPD-PH in VLBW infants. IMPACT: NT-proBNP and HCO3 concentrations obtained together may help identify very low birth weight infants at risk for bronchopulmonary dysplasia who should undergo screening for pulmonary hypertension with echocardiography. This large dataset demonstrates that NT-proBNP and HCO3 levels together are more sensitive than NT-proBNP alone in identifying VLBW infants to undergo echocardiography. The combination of NT-proBNP and HCO3 levels may identify VLBW infants at low risk for pulmonary hypertension and thus those who may be able to avoid screening echocardiography.

Addiction specialists' attitudes toward psychedelics: A National Survey.

BACKGROUND AND OBJECTIVES: In recent years, there has been accelerating scientific and public interest in the use of psychedelics to treat mental health disorders. Our study's objective was to assess the attitudes of addiction specialists regarding therapeutic psychedelics. METHODS: Our study utilized an anonymous online survey to assess the opinions of 145 addiction specialists regarding the therapeutic promise, potential risks, and legalization of psychedelics in the treatment of psychiatric illness and substance use disorders. Psychedelics were defined in the survey as inclusive of nonserotonergic hallucinogens such as ketamine or MDMA in addition to "classic" serotonergic psychedelics. RESULTS: Most respondents expressed positive attitudes to the therapeutic use of psychedelics, but a sizeable minority expressed concern for their addictive potential. Familiarity with psychedelic scientific literature was the strongest positive predictor of belief in the therapeutic potential of psychedelics, while concern for addictive potential was the strongest negative predictor. DISCUSSION AND CONCLUSIONS: Participants overall expressed more positive attitudes to the therapeutic use of psychedelics than we had hypothesized. This may be attributable to the accelerating pace of psychedelics research in recent years. Given the strong influence of concern for addiction risk on attitudes, future study is warranted to explore the findings regarding these concerns. These findings may also represent an opportunity for improved education of physicians regarding the addictive potential, and relative risks/benefits of psychedelics. SCIENTIFIC SIGNIFICANCE: Though there have been several prior studies assessing psychiatrist and psychologist attitudes toward psychedelics, we are unaware of any specifically examining the opinions of addiction specialists.

Prenatal Congenital Heart Disease-It Takes a Multidisciplinary Village.

Prenatal diagnosis of congenital heart disease (CHD) allows for thoughtful multidisciplinary planning about location, timing, and need for medical interventions at birth. We sought to assess the accuracy of our prenatal cardiac diagnosis, and postnatal needs for patients with CHD utilizing a multidisciplinary approach. We performed a retrospective chart review of fetal CHD patients between 1/1/18 and 4/30/19. Maternal and infant charts were reviewed for delivery planning, subspecialty care needs, genetic evaluation, prenatal and postnatal cardiac diagnoses, need for prostaglandin (PGE) and neonatal cardiac intervention. 82 maternal-fetal dyads met inclusion criteria during the study period and delivered at a median of 38w2d gestation. 32 (39%) dyads had CHD and other anomalies or genetic abnormalities. All dyads met with a genetic counselor and neonatologist. 11 patients delivered at outside hospitals as planned (all with isolated CHD not requiring neonatal intervention), and 5 chose a palliative delivery. 30 patients were counseled to expect a neonatal cardiac intervention and 25 (83%) underwent an intervention within the expected time period. No neonates required an uncounseled cardiac intervention. 29 patients planned for PGE at birth and 31 received PGE. Of the 79 postnatal echocardiograms, 60 (76%) were entirely consistent with the fetal diagnosis. A multidisciplinary approach to the prenatal diagnosis of CHD in maternal-fetal dyads is optimal and utilizing this method we were able to accurately predict postnatal physiology and ensure that patients delivered in the correct location with an appropriate supportive structure in place.

Structured Framework for Multidisciplinary Parent Counseling and Medical Interventions for Fetuses and Infants with Trisomy 13 or Trisomy 18.

OBJECTIVE: Trisomy 13 (T13) and 18 (T18) are aneuploidies associated with multiple structural congenital anomalies and high rates of fetal demise and neonatal mortality. Historically, patients with either one of these diagnoses have been treated similarly with exclusive comfort care rather than invasive interventions or intensive care, despite a wide phenotypic variation and substantial variations in survival length. However, surgical interventions have been on the rise in this population in recent years without clearly elucidated selection criterion. Our objective was to create a standardized approach to counseling expectant persons and parents of newborns with T13/T18 in order to provide collaborative and consistent counseling and thoughtful approach to interventions such as surgery. STUDY DESIGN: This article describes our process and presents our resulting clinical care guideline. RESULTS: We formed a multi- and interdisciplinary committee. We used published literature when available and otherwise expert opinion to develop an approach to care featuring individualized assessment of the patient to estimate qualitative mortality risk and potential to benefit from intensive care and/or surgeries centered within an ethical framework. CONCLUSION: Through multidisciplinary collaboration, we successfully created a patient-centered approach for counseling families facing a diagnosis of T13/T18. Other institutions may use our approach as a model for developing their own standardized approach. KEY POINTS: · Trisomy 13 and trisomy 18 are associated with high but variable morbidity and mortality.. · Research on which patients are most likely to benefit from surgery is lacking.. · We present our institution's framework to counsel families with fetal/neonatal T13/T18..

Measuring antenatal counseling skill with a milestone-based assessment tool: a validation study.

BACKGROUND: Antenatal counseling for parents in the setting of expected preterm delivery is an important component of pediatric training. However, healthcare professionals receive a variable amount and quality of formal training. This study evaluated and discussed validity of a practical tool to assess antenatal counseling skills and provide evaluative feedback: the Antenatal Counseling Milestones Scale (ACoMS). METHODS: Experts in antenatal counseling developed an anchored milestone-based tool to evaluate observable skills. Study participants with a range of antenatal counseling skills were recruited to participate in simulation of counseling sessions in person or via video with standardized patient actors presenting with preterm labor at 23 weeks' gestation. Two faculty observers scored each session independently using the ACoMS. Participants completed an ACoMS self-assessment, demographic, and feedback survey. Validity was measured with weighted kappas for inter-rater agreement, Kruskal-Wallis and Dunn's tests for milestone levels between degrees of expertise in counseling, and cronbach's alpha for item consistency. RESULTS: Forty-two participants completed observed counseling sessions. Of the 17 items included in the tool, 15 items were statistically significant with scores scaling with level of training. A majority of elements had fair-moderate agreement between raters, and there was high internal consistency amongst all items. CONCLUSION: This study demonstrates that the internal structure of the ACoMS rubric has greater than fair inter-rater reliability and high internal consistency amongst items. Content validity is supported by the scale's ability to discern level of training. Application of the ACoMS to clinical encounters is needed to determine utility in clinical practice.

Preclinical murine platform to evaluate therapeutic countermeasures against radiation-induced gastrointestinal syndrome.

Radiation-induced gastrointestinal syndrome (RIGS) is a limiting factor for therapeutic abdominopelvic radiation and is predicted to be a major source of morbidity in the event of a nuclear accident or radiological terrorism. In this study, we developed an in vivo mouse-modeling platform that enables spatial and temporal manipulation of potential RIGS targets in mice following whole-abdomen irradiation without the confounding effects of concomitant hematopoietic syndrome that occur following whole-body irradiation. We then tested the utility of this platform to explore the effects of transient Wnt pathway activation on intestinal regeneration and animal recovery following induction of RIGS. Our results demonstrate that intestinal epithelial suppression of adenomatous polyposis coli (Apc) mitigates RIGS lethality in vivo after lethal ionizing radiation injury-induced intestinal epithelial damage. These results highlight the potential of short-term Wnt agonism as a therapeutic target and establish a platform to evaluate other strategies to stimulate intestinal regeneration after ionizing radiation damage.

Incidental Findings from Deep Phenotyping Research in Psychiatry: Legal and Ethical Considerations.

Substantial advancement in the diagnosis and treatment of psychiatric disorders may come from assembling diverse data streams from clinical notes, neuroimaging, genetics, and real-time digital footprints from smartphones and wearable devices. This is called "deep phenotyping" and often involves machine learning. We argue that incidental findings arising in deep phenotyping research have certain special, morally and legally salient features: They are specific, actionable, numerous, and probabilistic. We consider ethical and legal implications of these features and propose a practical ethics strategy for managing them.

Pulmonary Function Tests in Very Low Birth Weight Infants Screened for Pulmonary Hypertension: A Pilot Study.

OBJECTIVE: To compare pulmonary function tests (PFTs), specifically respiratory system resistance (Rrs) and compliance (Crs), in very low birth weight (VLBW) infants with and without pulmonary hypertension. STUDY DESIGN: Infants were included who underwent PFTs at 34-38 weeks postmenstrual age (PMA) as part of our pulmonary hypertension screening guidelines for infants born at ≤1500 g requiring respiratory support at ≥34 weeks PMA. One pediatric cardiologist reviewed and estimated right ventricular or pulmonary arterial pressure and defined pulmonary hypertension as an estimated pulmonary arterial pressure or right ventricular pressure greater than one-half the systemic pressure. Rrs and Crs were measured with the single breath occlusion technique and functional residual capacity with the nitrogen washout method according to standardized criteria. RESULTS: Twelve VLBW infants with pulmonary hypertension and 39 without pulmonary hypertension were studied. Those with pulmonary hypertension had significantly lower birth weight and a trend toward a lower gestational age. There were no other demographic differences between the groups. The infants with pulmonary hypertension had significantly higher Rrs (119 vs 78 cmH2O/L/s; adjusted P = .012) and significantly lower Crs/kg (0.71 vs 0.92 mL/cmH2O/kg; P = .04). CONCLUSIONS: In this pilot study of VLBW infants screened for pulmonary hypertension at 34-38 weeks PMA, those with pulmonary hypertension had significantly increased Rrs and decreased Crs compared with those without pulmonary hypertension. Additional studies are needed to further phenotype infants with evolving BPD and pulmonary hypertension.

Diagnostic accuracy and clinical outcomes associated with prenatal diagnosis of fetal absent cavum septi pellucidi.

BACKGROUND: Absence of the cavum septi pellucidi (CSP) on prenatal imaging is historically associated with additional anomalies; however, recent cases of isolated absent CSP have also been identified. This study seeks to assess the accuracy of prenatal imaging in evaluating isolated absent CSP and to describe the spectrum of clinical outcomes. METHODS: This is a retrospective observational study of all prenatally diagnosed absent CSP cases between 2011 and 2016 at our institution. Cases with additional structural parenchymal abnormalities were excluded. Clinical outcomes were abstracted from available records. RESULTS: We identified 15 cases of prenatally diagnosed isolated absent CSP. All patients were initially diagnosed on ultrasound (US) and 11/15 patients had fetal magnetic resonance imaging (MRI) confirming the diagnosis. Prenatal US and MRI were concordant in all cases. Of the continuing pregnancies, 2 neonatal deaths occurred related to extreme prematurity. Two cases of septo-optic dysplasia were identified in our cohort. DISCUSSION: In this study, fetal MRI and US had a high degree of accuracy with concordant postnatal imaging. Our study is similar to other case series suggesting that a range of clinical outcomes is possible with isolated absent CSP, but long-term patient follow up is necessary.

Global health reciprocal innovation: ethical, legal and regulatory considerations.

Global health reciprocal innovation (GHRI) is a recent and more formalised approach to conducting research that recognises and develops innovations (eg, medicines, devices, methodologies) from low- and middle-income countries (LMICs). At present, studies using GHRI most commonly adapt innovations from LMICs for use in high-income countries (HICs), although some develop innovations in LMICs and HICs. In this paper, we propose that GHRI implicitly makes two ethical commitments: (1) to promote health innovations from LMICs, especially in HICs, and (2) to conduct studies on health innovations from LMICs in equitable partnerships between investigators in LMICs and HICs. We argue that these commitments take a significant step towards a more equal global health research enterprise while helping to ensure that populations and investigators in LMICs receive equitable benefits from studies using GHRI. However, studies using GHRI can raise potential ethical concerns and face legal and regulatory barriers. We propose ethical, legal and regulatory considerations to help address these concerns and barriers. We hope our recommendations will allow GHRI to move the global health research enterprise forward into an era where all people are treated equally as knowers and learners, while populations in both LMICs and HICs benefit equitably from studies using GHRI.

Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals.

Autism Spectrum Disorder is a developmental condition associated with impairments in communication and social interactions, and repetitive and restricted behavior or interests. Autistic individuals are more likely to experience gastrointestinal (GI) symptoms than neurotypical individuals. This may be partially due to dysbiosis of the gut microbiome. In this article, we describe the interaction of the microbiome and immune system on autism etiology. We also summarize the links between the microbiome and gastrointestinal and related symptoms among autistic individuals. We report that microbial interventions, including diet, probiotics, antibiotics, and fecal transplants, and immune-modulating therapies such as cytokine blockade during the preconception, pregnancy, and postnatal period may impact the neurodevelopment, behavior, and gastrointestinal health of autistic individuals.

Perinatal Stressors and Consequences for Neonates with Critical Congenital Heart Disease.

INTRODUCTION: The prenatal diagnosis of congenital heart disease (CHD) is a traumatic event that can cause expectant parents to experience anxiety, depression, and toxic stress. Prenatal exposure to stress may impact neonatal postoperative outcomes. In addition, expectant parents may have other psychosocial stressors that may compound maternal stress. We investigated the relationship between stress in pregnancies complicated by prenatally diagnosed CHD and their neonatal outcomes. METHODS: A pilot retrospective cohort study of pregnancies with prenatally diagnosed critical CHD (2019-2021) was performed. The collected data included pregnancy characteristics and neonatal and postoperative outcomes (including the need for exogenous corticosteroid treatment (ECT)). In order to quantify prenatal stressors, a composite prenatal stress score (PSS) was established and utilized. RESULTS: In total, 41 maternal-fetal dyads were evaluated. Thirteen (32%) neonates had single-ventricle anatomy. The need for ECT after CHD surgery was associated with higher pregnant patient PSS (p = 0.01). PSS did not correlate with birthweight, infection, or hypoglycemia in the neonatal period. CONCLUSIONS: Prenatal stress is multifactorial; higher PSS is correlates with post-bypass ECT, suggesting that a stressful intrauterine environment may be associated with worse neonatal postoperative outcomes.

How accurate is transcutaneous bilirubin testing in newborns with darker skin tones?

Fairly accurate. Photometric transcutaneous bilirubin (TcB) testing may overestimate total serum bilirubin (TSB) in neonates with darker skin tones by a mean of 0.68 to > 2 mg/dL (strength of recommendation [SOR]: C, diagnostic cohort studies with differing reference standards).Overall, TcB meters retain accept able accuracy in infants of all skin tones across a range of bilirubin levels, despite being more likely to underestimate lighter skin tones and overestimate darker ones (SOR: C, diagnostic cohort studies with differing reference standards). It is unclear if the higher readings prompt an increase in blood draws or otherwise alter care.

Fetal counseling for congenital heart disease: is communication effective?

PURPOSE: To assess the accuracy of maternal understanding of fetal cardiac defects following initial fetal counseling. METHODS: Pregnant women with a fetal diagnosis of congenital heart disease (CHD) were surveyed regarding understanding of their fetus's heart defect. The survey asked: (1) for a description of the heart condition; (2) how confident they were in the diagnosis; (3) whether their fetus would require heart surgery. Two fetal cardiologists evaluated the maternal qualitative description. Partners were excluded from the study. RESULTS: Fifty-one participants consented and 39 completed the survey. Mean age was 31 years, 60% had some college level or post-graduate education, 48% had Medicaid insurance, and 81% were Caucasian. More than three-quarters of participants, stated they had either "quite a bit" or "very much" understanding of their fetus's diagnosis. Maternal assessment matched the physician's assessment of accuracy with 77% (N = 30) demonstrating either "quite a bit" or a "very accurate" description of the diagnosis. All women correctly understood if their fetus would require heart surgery. Highest level of maternal education positively correlated with the accuracy of diagnosis (regression coefficient 0.48, p < .002). However, confidence in the diagnosis was independent of both education (0.30, p = .167) and maternal age (-0.03, p = .234). CONCLUSIONS: Fetal counseling is effective in conveying anatomy and the need for surgery; however, accuracy amongst women with lower levels of education and maternal confidence in understanding can be improved.

Depression and socioeconomic stressors in expectant parents with fetal congenital anomalies.

OBJECTIVE: Congenital anomalies are increasingly diagnosed before birth, which may lead to psychological distress in expectant parents. While the presence of significant symptoms of depression and stress in these parents is established, understanding their context within parents' other life stressors has not been fully investigated. We sought to characterize the socioeconomic profile and depression symptoms of expectant parents in a quaternary care academic hospital's fetal care clinic. METHODS: This prospective observational study enrolled pregnant persons and their partners in our fetal care clinic. The Edinburgh Postpartum Depression Scale (EPDS), Tool Assessing Patient Stress (TAPS), and a sociodemographic survey were utilized to assess parent psychological distress and socioeconomic stressors. Results were analyzed by the severity of the fetal anomaly. EPDS was repeated at two weeks postpartum. RESULTS: 21.7% of pregnant subjects and 25.0% of co-parents had a positive screen on the EPDS at enrollment during their pregnancy. Mothers' EPDS scores correlated with the severity of the fetal anomaly. Many parents reported socioeconomic stressors including: living remotely from the medical center, low household income, food insecurity, unemployment, or other employment concerns, and difficulty affording living expenses. Most also reported factors that can mitigate psychological distress including social support and participation in a religion or faith. CONCLUSIONS: Expectant parents with fetal anomalies should be screened for depression as well as social and economic risk factors that place them and their infants at higher risk for poor health outcomes. Further work is needed to determine the optimum interventions for addressing their depression symptoms and reducing socioeconomic stressors.

Teaching Antenatal Counseling Skills via Video Conference.

Neonatologists provide counseling to expectant parents to prepare them for the birth and subsequent medical care that their extremely preterm, or otherwise medically complex newborn may require. The skills required to conduct these sensitive conversations are often taught to neonatology trainees via direct observation or simulated scenarios in advance of counseling actual patients. This technical report details how we taught antenatal counseling skills to junior neonatal-perinatal medicine (NPM) fellows via video conferencing during the coronavirus disease 2019 (COVID-19) pandemic. This approach could be used to effectively prepare future trainees to perform antenatal counseling.

Current surgical management of infected pancreatic necrosis.

Infected pancreatic necrosis (IPN) continues to be a challenging problem for the surgeon. We reviewed the experience on a hepatobiliary surgical service with patients who required operative intervention for IPN with emphasis on surgical approach, timing of surgery, and complications. Between 2002 and 2008, 21 patients underwent surgery for IPN. The initial surgical approach in these 21 patients included either direct pancreatic débridement (DPD, n=13) or transgastric débridement using cyst-gastrostomy (CG, n=8). Fifteen patients (71%) required only a single procedure, whereas three (14%) required two procedures and three (14%) required three procedures. The mean time from onset of pancreatitis to operation was 77 days. Patients requiring a single intervention had a longer interval from onset of pancreatitis to surgery compared with those requiring multiple interventions. When comparing CG and DPD groups, there was a longer interval from onset of pancreatitis to débridement, a lower chance of needing multiple débridements, and fewer pancreatic fistulae in the CG group. Overall survival was 95 per cent. Our results demonstrate that CG can be successfully used in select patients with IPN. Patients undergoing CG are less likely to require repeat surgical debridement and to develop pancreatic fistulae compared with patients undergoing DPD.

Psychedelic-assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports.

Functional neurological disorders (FNDs), which are sometimes also referred to as psychogenic neurological disorders or conversion disorder, are common disabling neuropsychiatric disorders with limited treatment options. FNDs can present with sensory and/or motor symptoms, and, though they may mimic other neurological conditions, they are thought to occur via mechanisms other than those related to identifiable structural neuropathology and, in many cases, appear to be triggered and sustained by recognizable psychological factors. There is intriguing preliminary evidence to support the use of psychedelic-assisted therapy in a growing number of psychiatric illnesses, including FNDs. We review the theoretical arguments for and against exploring psychedelic-assisted therapy as a treatment for FNDs. We also provide an in-depth discussion of prior published cases detailing the use of psychedelics for psychosomatic conditions, analyzing therapeutic outcomes from a contemporary neuroscientific vantage as informed by several recent neuroimaging studies on psychedelics and FNDs.

Pancreatic neuroendocrine tumors: presentation, management, and outcomes.

Pancreatic neuroendocrine tumors (pNETs) are an uncommon pancreatic neoplasm. We reviewed the presentation, management, and outcome of patients with pNETs treated at a single center by a multidisciplinary approach between 2004 and 2008. Over this time period, 154 patients with carcinoid and neuroendocrine tumors were treated, which included 46 patients (30% of total) with pNETs. The most common presentations included abdominal pain (20 of 46 [43%]), systemic symptoms such as hypoglycemia (15 of 46 [33%]), and incidental mass (7 of 46 [15%]). Fourteen patients had functional tumors. At the time of diagnosis, 22 patients (48%) presented without metastases and 24 (52%) had metastatic disease. Median follow up for the entire group was 42 months. All patients with nonmetastatic pNET underwent pancreatic resection with 95 per cent postoperative survival. Overall survival in this group at 3 years was 86 per cent and disease-free survival was 81 per cent. In patients presenting with metastatic pNET, multiple treatment modalities were used, including liver resection or ablation (n = 15), hepatic chemoembolization (n = 17), pancreatic resection (n = 12), and systemic treatments (n = 7). Three-year survival was 70 per cent. Pancreatic resection results in greater than 80 per cent 3-year survival in nonmetastatic pNET. In patients presenting with metastatic pNET, excellent survival rates are also achievable using a multidisciplinary multimodal approach.