Electrocardiographic intervals in foetuses with CHD.

OBJECTIVES: To assess foetal electrocardiographic intervals across gestational age among foetuses with and without congenital heart disease, and to investigate differences between groups. DESIGN: A prospective observational cohort study. SETTING: Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York-Presbyterian. Population or sample A total of 92 participants with singleton pregnancies, 41 with normal anatomy and 51 with congenital heart disease were included in this study. METHODS: Using a maternal abdominal monitor, foetal electrocardiogram was obtained serially from foetuses with and without congenital heart disease at 20-24 weeks (F1), 28-32 weeks (F2), and 34-38 weeks (F3) of gestation. A signal-averaged waveform was calculated, and PR, QRS, and QT intervals were measured. Intervals from controls were compared with gestational age norms. Using Pearson's correlation coefficient, we analysed the relationship between gestational age and foetal electrocardiographic intervals. Intervals from control and congenital heart disease foetuses were compared by Student's t-test. RESULTS: PR (r=0.333, p=0.02) and QRS (r=0.248, p=0.05) intervals correlated with gestational age only among controls. QRS intervals in foetuses with congenital heart disease were significantly longer than controls at F1 (63 ± 6 versus 52 ± 5 ms, p<0.001), F2 (61 ± 8 versus 56 ± 7 ms, p=0.02), and F3 (64 ± 10 versus 56 ± 9 ms, p=0.007). CONCLUSIONS: PR and QRS intervals lengthen across gestational age among foetuses with normal cardiac anatomy but not in foetuses with congenital heart diseases. As early as 20 weeks of gestation, differences between foetuses with and without congenital heart disease are discernible, with congenital heart disease foetuses demonstrating longer QRS intervals compared with controls.

Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.