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.

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..

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.

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.

A rectal cancer organoid platform to study individual responses to chemoradiation.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.

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.

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.

Cholangiocarcinoma: aggressive surgical intervention remains justified.

Cholangiocarcinoma (CCA) continues to be a difficult disease to both diagnose and treat. Optimal treatment includes resection to histologically negative margins. In recent years, advanced imaging, including magnetic resonance cholangiography and endoscopic ultrasound, has presumably improved the accuracy of determining resectability. From 2004 to 2009, a total of 61 patients with cholangiocarcinoma were evaluated for resection. The majority were men (37) and ages ranged from 29 to 87 years (mean, 67 years). Only 31 per cent were found to be obviously unresectable based on imaging alone. The remaining 69 per cent underwent exploration, at which time resection was found unfeasible in an additional 25 per cent (overall 56% unresectable). Although all resection specimens had grossly negative margins, 37 per cent were ultimately found to be microscopically positive. The overall 5-year actuarial survival for patients undergoing resection was 39.2 per cent with no survival difference between those with positive and negative margins. Despite advances in diagnostic imaging, more than half of patients with CCA presenting for surgical evaluation are ultimately found to be unresectable. However, the final determination can still only be made at the time of exploration. Even in the presence of microscopic residual disease, surgical intervention results in improved survival. An aggressive stance toward surgical intervention in patients with CCA remains justified.

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.

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.