Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy.

BACKGROUND: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks. OBJECTIVE: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy. STUDY DESIGN: Hospitalized patients with hypertensive disorders of pregnancy between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to January 2024 after the implementation of serum soluble fms-like tyrosine kinase-1/placental growth factor testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (placental growth factor and soluble fms-like tyrosine kinase-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines on the basis of biomarkers but made pragmatic management decisions independently. Results of soluble fms-like tyrosine kinase-1/placental growth factor tests were available to clinicians within 24 hours of venipuncture. The association between soluble fms-like tyrosine kinase-1/placental growth factor ≥40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. RESULTS: Of the 65 patient encounters, 36 had a soluble fms-like tyrosine kinase-1/placental growth factor <40 (55.4%). The rate of delivery for indications related to hypertensive disorders of pregnancy within 2 weeks was significantly lower among encounters with a low ratio vs high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted hazard ratio, 7.52; 95% confidence interval, 3.05-18.54; P<.001). A diagnosis of preeclampsia with severe features within 2 weeks of testing was also less likely among the encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 when compared with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (2/36 [5.6%] vs 23/29 [79.3%], P<.001; positive predictive value of 79% [95% confidence interval, 0.65-0.94] and negative predictive value of 0.94 [95% confidence interval, 0.87-1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within 2 weeks of testing were 6.13 and 0.09, respectively. Encounters with a soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 were less likely to experience a maternal or fetal adverse event as compared with encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], P=.01). Among 36 encounters involving low soluble fms-like tyrosine kinase-1/placental growth factor values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed on the basis of biomarkers, and none developed preeclampsia with severe features or adverse outcomes at 2 weeks. The median latency defined as days between biomarker measurement and delivery in patients with a low biomarker ratio was 33 (interquartile ratio, 23-47) vs 7 (interquartile ratio, 4-14) days among patients with a high ratio (P<.001). Corticosteroid use within 2 weeks was also significantly reduced in the low biomarker group when compared with the high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], P<.001). CONCLUSION: In this study, the incorporation of soluble fms-like tyrosine kinase-1/placental growth factor ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with hypertensive disorders of pregnancy in the United States. Among patients with a low ratio, pregnancy may be prolonged, which results in better neonatal outcomes without harm to the mother.

Preterm birth among women with and without severe acute respiratory syndrome coronavirus 2 infection.

INTRODUCTION: Studies directly comparing preterm birth rates in women with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Our objective was to determine whether preterm birth was affected by SARS-CoV-2 infection within a large integrated health system in New York with a universal testing protocol. MATERIAL AND METHODS: This retrospective cohort study evaluated data from seven hospitals in New York City and Long Island between March 2020 and June 2021, incorporating both the first and second waves of the coronavirus disease 2019 (COVID-19) pandemic in the USA. All patients with live singleton gestations who had SARS-CoV-2 polymerase chain reaction (PCR) testing at delivery were included. Deliveries before 20 weeks of gestation were excluded. The rate of preterm birth (before 37 weeks) was compared between patients with positive and negative SARS-CoV-2 test results. This analysis was performed separately for resolved prenatal infections and infections at delivery, with the latter group subdivided by symptom status. Multiple logistic regression analysis was used to examine the association between SARS-CoV-2 infection and preterm birth, adjusting for maternal age, race-ethnicity, parity, history of preterm birth, body mass index, marital status, insurance type, medical co-morbidities, month of delivery, and wave of pandemic. RESULTS: A total of 31 550 patients were included and 2473 (7.8%) had laboratory-confirmed infection. Patients with symptomatic COVID-19 at delivery were more likely to deliver preterm (19.0%; adjusted odds ratio 2.76, 95% CI 1.92-3.88) compared with women with asymptomatic infection (8.8%) or without infection (7.1%). Among preterm births associated with symptomatic infection, 72.5% were medically indicated compared with 44.1% among women without infection (p < 0.001). Risk of preterm birth in patients with resolved prenatal infection was unchanged when compared with women without infection. Among women with infection at delivery, preterm birth occurred more frequently during the second wave compared with the first wave (13.6% vs. 8.7%, respectively; p < 0.006). However, this was not significant on multiple regression analysis after adjusting for other explanatory variables. CONCLUSIONS: Pregnant women with symptomatic COVID-19 are more than twice as likely to have a preterm delivery than patients without infection. Asymptomatic infection and resolved prenatal infection are not associated with increased risk.

The effect of perceptual decision-making on the interpretation of twin fetal heart rate tracings.

OBJECTIVE: Decision-making is an integrative process during which multiple sources of available evidence are combined into a singular response. Importantly, subconscious processes occur in perceptual decisions that may influence interpretations of visually displayed data such as fetal heart rate tracings (FHRT), which are typically presented together for twins. To examine the potential impact of subconscious perceptual influences on fetal well-being, differences in assessments of FHRTs for twin gestations presented singly or paired were evaluated for baseline fetal heart rate, variability, accelerations, decelerations, and overall concern. STUDY DESIGN: Obstetrical nurses (N = 27) assessed FHRTs from 20 twin gestations (each of which had at least one live birth with a 5-min Apgar <7) presented either on the same tracing or as singletons on separate tracings. Nurses were naïve to the fact that the fetal heart rate tracings presented in the unpaired condition were the same as those presented in the paired condition. Assessments were then compared between the two conditions. RESULTS: Each nurse participant completed ratings on five metrics for each of 20 twin gestations across two conditions (80 FHRT assessments, 400 metrics total per participant). The intraobserver impact of visual context was calculated as the frequency of changed opinions regarding an individual metric (e.g. variability) between the paired and unpaired contexts for each individual fetal heart rate. Assessments of variability (average Kappa = 0.59), decelerations (average Kappa = 0.34), and overall level of concern (average Kappa = 0.33) were moderately to heavily impacted by viewing condition (unpaired vs. paired FHRT). Analysis of interobserver agreement using intraclass correlations (two-way random effect, absolute agreement) indicates poor agreement on unpaired assessments for both accelerations (ICC = 0.01, 95% CI -0.01-0.04) and decelerations (ICC = 0.22, 95% CI 0.15-0.33). These results are mirrored in poor agreement on paired assessments for both accelerations (ICC = 0.00, 95% CI -0.01-0.03) and decelerations (ICC = 0.27, 95% CI 0.19-0.39). There was moderate agreement on overall level of concern for unpaired assessments (ICC = 0.55, 95% CI 0.44-0.67) and near moderate agreement for the paired condition (ICC = 0.45, 95% CI 0.34-0.58). CONCLUSIONS: The simultaneous presentation of fetal heart rate tracings in twin gestations introduces both intraobserver and interobserver variances in the interpretation of variability, accelerations, and decelerations, likely due to the influence of subconscious perceptual decision-making. This may theoretically affect outcomes in cases in which visual information is nuanced. More research is necessary to determine whether the standard protocol of simultaneous assessment of FHRT in twins is subliminally affected by perceptual decision-making.

Abnormalities in white matter connections between orbitofrontal cortex and anterior cingulate cortex and their associations with negative symptoms in schizophrenia: a DTI study.

INTRODUCTION: The medial orbitofrontal cortex (mOFC) and rostral part of the anterior cingulate cortex (rACC) are brain regions that are important in the neural network involving emotional processing and decision making, as well as playing an important role in social behavior and interaction. Considering the schizophrenia dysconnectivity hypothesis, observed abnormalities in emotional response and social behavior in schizophrenia might be associated with connectivity abnormalities between mOFC and rACC. METHODS: Twenty-seven patients with chronic schizophrenia and 26 healthy controls were examined using diffusion tensor imaging (DTI). White matter properties in bilateral mOFC-rACC connections were examined using stochastic tractography, which has been shown to be among the most effective DTI methods for examining tracts between adjacent gray matter regions. RESULTS: Reductions in fractional anisotropy (FA) were observed in left anterior mOFC-rACC connections (p<0.0001), and bilateral posterior mOFC-rACC connections (left: p<0.0001; right: p<0.0001) in patients compared to controls. In addition, reduced FA in left posterior mOFC-rACC connections was associated with more severe anhedonia-asociality (R=-0.396, p=0.041) and avolition-apathy (R=-0.426, p=0.027) using the Scale for the Assessment of Negative Symptoms. DISCUSSION: White matter abnormalities within connections between mOFC and rACC are associated with more severe anhedonia-asociality and avolition-apathy, which suggest that these brain regions may be important in understanding abnormal emotional responses and social behavior in patients with schizophrenia.

Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging.

AIM: With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. MATERIALS & METHODS: Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. RESULTS: We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. CONCLUSION: Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs.

Fiber geometry in the corpus callosum in schizophrenia: evidence for transcallosal misconnection.

BACKGROUND: Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. AIMS: To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients by using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named Shape-Normalized Dispersion (SHD). METHODS: DTIs (3T, 51 gradient directions, 1.7mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. RESULTS: The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. CONCLUSIONS: The results suggest that the transcallosal misconnectivity thought to be associated with schizophrenia could reflect abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by neurodevelopmental irregularities.