The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro, and a clinically relevant 1.8 mg oral loading dose administered over one hour in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations, but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28% [22–57] to 22% [19–31], p=0.05) and NPA (19% [16–59] to 15% [11–30], p=0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p=0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p=0.03), and platelet adhesion to collagen (10.2% [2.5–32.6] to 2.0% [0.2–9.5], p=0.09) 2 hours post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation, but does not inhibit homotypic platelet aggregation.

The diagnostic yield (pathogenic or likely pathogenic (P/LP) variants) was compared in fetuses with one structural anomaly, multiple structural anomalies, and effusions or nonimmune hydrops (NIHF) with or without a concurrent structural anomaly. Cases with a single structural anomaly + polyhydramnios or growth restriction (FGR) were categorized as multiple anomalies, and cases with an effusion or NIHF and a structural anomaly were categorized as hydrops. We also compared the proportion of variants of uncertain significance that were thought to potentially be associated with the phenotype across these subgroups (VUS). Chi square or Fisher's exact test compared proportions and logistic regression generated odds ratios. RESULTS: The cohort included 315 pregnancies with median age 33 years (IQR 29-36), 45.1% (142/315) nulliparous, and median gestational age at diagnosis of anomaly of 22.3 weeks (IQR 20.0-25.7). In all, 19.7% (62/315) had a single structural anomaly, 25.4% (80/315) had multiple anomalies, and 54.9% (173/315) had effusions/NIHF. The overall diagnostic yield of ES was 22.9% (72/315). The yield for isolated anomalies was 16.1% (10/62), for multiple anomalies was 17.5% (14/80), and for effusions/NIHF was 27.8% (48/173) (p¼0.07) (Table ). The OR for diagnostic yield of ES (P/LP) for multiple anomalies vs a single anomaly was 1.31 (95% CI 0.54-3.16) and for effusions/NIHF vs a single anomaly was 1.47 (95% CI 1.03-2.11). CONCLUSION: The diagnostic yields of ES for single or multiple structural anomalies are similar, while the yield in cases of NIHF is higher. Further study is needed to identify optimal candidates for prenatal ES.

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INTRODUCTION: In 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) revised the guidelines for abnormal blood pressure (BP): elevated (120-129/<80), stage 1 (130-139/80-89) and stage 2 hypertension (≥140/90) on ≥2 occasions in adults. This study aims to determine a relationship between elevated and stage 1 ACC/AHA hypertension in the second trimester and pregnancy-induced hypertensive disorders (PIH). METHODS: In this IRB approved retrospective cohort study, we collected the highest two blood pressure measurements in second trimester for singleton pregnancies prior to the ACOG diagnosis of PIH (gestational hypertension, preeclampsia, HELLP, eclampsia). Patients were grouped by ACC/AHA criteria and compared using Pearson chi-square tests, Fisher’s exact tests, T-tests or Mann-Whitney U tests. RESULTS: 200 patients were included; 54.9% had normal BP, 10.5% had elevated BP, and 34% had stage 1 ACC/AHA hypertension. There was no association between the severity of PIH and normal versus elevated/stage 1 BP in second trimester. Among those with elevated/stage 1 hypertension, gestational age was significantly lower at diagnosis of PIH (P<.001) and delivery (P<.001) compared to normotensive patients. CONCLUSION: Gestational age at PIH diagnosis and delivery were significantly lower among women with ACC/AHA elevated or stage 1 hypertension in second trimester compared to normotensive women. Therefore, further research is warranted to determine a relationship between the ACC/AHA guidelines for hypertension and PIH with the possibility of earlier recognition of the disease and intervention.

In the original publication the initial sentences of the legends for Figs. 4 and 5 were inadvertently reversed. They should read as follows: Figure 4. Effect of a 1.8 mg load of colchicine on extent of monocyte-and neutrophil-platelet aggregate. Extent of monocyte-platelet aggregate (Panel A) and neutrophil-platelet aggregate (Panel B) were assessed before and 2 and 24 h after completion of the 1.8 mg load of colchicine in healthy subjects (n=10). Medians shown via dashed line.Figure 5. Effect of a 1.8 mg load of colchicine on platelet surface expression of PAC-1 and P-selectin. Platelet surface expression of PAC-1 in response to 0.4 μM epinephrine (Panel A) and P-selectin in response to 0.025 U thrombin (Panel B) were assessed before and 2 and 24 h after completion of the 1.8 mg load of colchicine in healthy subjects (n=10). Medians shown via dashed line.The online version of the original article can be found at http://dx.