Search

Background: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12 to 16 weeks of gestation when there is evidence for its effectiveness, and enables the guidance of appropriate pregnancy care pathways and surveillance., Objective: The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA screening. Secondary outcomes were prediction of early-onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation)., Methods: This secondary analysis of a prospective, multicenter, observational prenatal cell-free DNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and 2 characteristics of cell-free DNA (total cell-free DNA and fetal fraction) were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the "reference" classifier was a shallow logistic regression model. We also explored several feedforward (nonlinear) neural network architectures with ≥1 hidden layers, and compared their performance with the logistic regression model. We selected a simple neural network model built with 1 hidden layer and made up of 15 units., Results: Of the 17,520 participants included in the final analysis, 72 (0.4%) developed early-onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cell-free DNA measurement was 12.6 weeks, and 2155 (12.3%) had their cell-free DNA measurement at ≥16 weeks' gestation. Preeclampsia was associated with higher total cell-free DNA (median, 362.3 vs 339.0 copies/mL cell-free DNA; P<.001) and lower fetal fraction (median, 7.5% vs 9.4%; P<.001). The expected, cross-validated area under the curve scores for early-onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively, for the logistic regression model, and 0.797, 0.800, and 0.713, respectively, for the neural network model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% confidence interval, 0.569-0.599) for the logistic regression model and 59.3% (95% confidence interval, 0.578-0.608) for the neural network model. The contribution of both total cell-free DNA and fetal fraction to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cell-free DNA and fetal fraction features from the neural network model was associated with a 6.9% decrease in sensitivity at a 15% screen-positive rate, from 54.9% (95% confidence interval, 52.9-56.9) to 48.0% (95% confidence interval, 45.0-51.0)., Conclusion: Routinely available patient characteristics and cell-free DNA markers can be used to predict preeclampsia with performance comparable to that of other patient characteristic models for the prediction of preterm preeclampsia. Logistic regression and neural network models showed similar performance., (Copyright © 2024. Published by Elsevier Inc.)

Objective: One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management., Methods: This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort., Results: Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p < 0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p < 0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P < 0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p = 0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P < 0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p = 0.008)., Conclusions: High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes., Objective: This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes., Study Design: This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction., Results: In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30])., Conclusion: Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is estimated that approximately 300,000 people are experiencing homelessness in England. The aim of this study was to evaluate key causes and long-term trends of emergency departments (EDs) and in hospital inpatient admissions of persons experiencing homelessness in England., Methods: ED and hospital inpatient admissions data were obtained from Hospital Episode Statistics (HES) covering all National Health Service (NHS) England hospitals. Anyone identified or declared to be experiencing homelessness during the service usage are recorded in HES datasets. Data were extracted for the 10-year study period and compared to the general population, which includes all patients attending the ED or admitted to inpatient care in England., Results: Drug- and alcohol-related causes contribute to the most frequent reasons for attendance and admissions of persons experiencing homelessness in the ED and inpatient respectively. A total of 30,406 ED attendances were recorded for persons experiencing homelessness in the year 2018/2019 (+ 44.9% rise vs 2009/10) of which injuries and poisoning respectively represented 21.8% and 17.9% of all persons experiencing homelessness presentations to the ED. Poisoning (including drug overdose) represented only 1.9% of all attendances by the general population during the same study year (rate ratio vs general populations 9.2 95% CI 9.0-9.4). High mortality rates were observed in relation to presentations attributed to drug- and alcohol-related causes. A total of 14,858 persons experiencing homelessness inpatient admissions were recorded in 2018/2019 (+ 68.6% vs 2009/2010). Psychoactive substance use constituted 12.7% of all admissions in 2018/2019 compared to 0.4% of in the general populations (rate ratio: 33.3, 95% CI: 31.9-34.7). There was a 44.3% rise in the number of admissions related to poisoning in the study period amongst persons experiencing homelessness in England (vs 14.2% in general population)., Conclusion: Marked disparities around primary causes of ED and inpatient admissions were identified between persons experiencing homelessness and the general population. There is a continued need for prevention measures to reduce the prevalence of drug and alcohol, injury and poisoning-related admissions to the ED, enhanced service provision at the community level, and multisector collaborations. These initiatives should maximise opportunities for early interventions and improve outcomes for persons experiencing homelessness, including increased accessibility of healthcare and mental health services, particularly in areas that demonstrate increasing ED and inpatient attendance rates over time., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation., Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies., Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%., Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes., Competing Interests: Conflict of Interest All site principal investigators (Pe’er Dar, Bo Jacobsson, Fergal Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, Revital Faro, Rajeevi Madankumar, Sina Haeri, Robert M. Silver, Nidhi Vohra, Jon Hyett, Cora MacPherson, and Mary E. Norton) received institutional research support from the funding sponsor (Natera). Melissa Egbert, Zachary Demko, and Matt Rabinowitz are employed by the study’s funding sponsor (Natera) and hold stock or options to hold stock. Kimberly Martin is a consultant to the funding sponsor (Natera) and holds stock and options to hold stock. Jon Hyett has an ongoing research collaboration that includes financial support for biochemical analytes from Perkin Elmer; has earned honoraria and/or given talks that were not compensated from Natera, Roche, and Canon; and has participated in Asian/Australasian expert consultancies for Natera and Roche. Bo Jacobsson collaborated in the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) study where Roche, Perkin Elmer, and Thermo Fisher provide reagents to Placental Growth Factor (PLGF) analyses. Ronald J. Wapner receives research funding from National Institute of Child Health and Human Development and support from Illumina for research reagents. Mary E. Norton is a consultant to Luna Genetics. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Semantic Artificial Intelligence has certain qualities that are advantageous for deep learning-based medical imaging tasks. Medical images can be augmented by injecting semantic context into the underlying classification mechanism, increasing the information density of the scan and ultimately can provide more trust in the result. This work considers an application of semantic AI to segment tissue types from excised breast tumors imaged with pulsed terahertz (THz)-an emerging imaging technology. Prior work has demonstrated traditional data driven methodology for deep learning on THz has two key weaknesses: namely 1) low image resolution compared to other state-of-the-art imaging techniques and 2) a lack of expertly-labeled images due to domain transformation and tissue changes during histopathology. This work seeks to address these limitations through two semantic AI mechanisms. Specifically, we introduce a two stage pipeline using an unsupervised image-to-image translation network and a supervised segmentation network. The combination of these contributions enables enhanced near-real-time visualization of excised tissue through THz scans and a supervised segmentation and classification training strategy using only synthetic THz scans generated by our bi-directional image-to-image translation network.

Context.—: The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early-stage estrogen receptor-positive breast cancer patients. Cost and unavailability are 2 major disadvantages of the assay. Multiple models have been developed to predict the RS., Objective.—: To predict RS based on histopathologic and biomarker features, and to measure concordance and correlation with RS of the following 3 algorithms: breast cancer prognostic score, Magee0, and Magee2., Design.—: Breast cancer cases with available RSs were reviewed (n = 442). RS categories were stratified by pathologic and biomarker variables. Histopathologic and biomarker data were abstracted from pathology reports, and RS was calculated by each model. Correlation and concordance between models and RS were calculated., Results.—: Less than 5% of breast cancers with lobular features, low-grade tumors, carcinomas with high progesterone receptor content, or luminal A tumors had an RS greater than 25. Breast cancer prognostic score, Magee0, and Magee2 demonstrated correlation coefficients with RS of 0.63, 0.61, and 0.62, respectively. Two-step discordances were uncommon. When an RS of 25 was used to separate high-risk from non-high-risk cases, concordance rates of 86% to 88% were achieved., Conclusions.—: High RS was observed only in a small percentage of pure or mixed lobular carcinomas, low-grade or luminal A tumors, and tumors with high progesterone receptor expression, suggesting that these cancers may not require Oncotype testing. All 3 surrogate models demonstrated comparable correlation and high concordance with the RS when a cutoff of 25 was used, suggesting their utility in cases where the actual RS is unavailable.

Background: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy., Objective: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed., Results: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate., Conclusion: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Persons experiencing homelessness (PEH) often use hospital Emergency Department (ED) as the only source of healthcare. The aim of this study was to undertake a systematic review to identify the prevalence, clinical reasons and outcomes in relation to ED visits by PEH., Methods: A protocol-led (CRD42020189263) systematic review was conducted using search of MEDLINE, EMBASE, CINAHL and Google Scholar databases. Studies that reported either the prevalence of homelessness in the ED or clinical reasons for presentation to ED by PEH and published in English language were included. Definitions of homelessness used by study authors were accepted., Results: From the screening of 1349 unique titles, a total of 36 studies were included. Wide variations in the prevalence and key cause of presentations were identified across the studies often linked to differences in country, study setting, disease classification and data collection methods. The proportion of ED visits contributed by PEH ranged from 0.41 to 19.6%. PEH made an average of 0.72 visits to 5.8 visits per person per year in the ED [rate ratio compared to non-homeless 1.63 to 18.75]. Up to a third and quarter of the visits were contributed by alcohol-related diagnoses and substance poisoning respectively. The percentage of PEH who died in the ED ranged from 0.1 to 0.5%., Conclusions: Drug-, alcohol- and injury-related presentations dominate the ED visits by PEH. Wide variations in the data were observed in regard to attendance and treatment outcomes. There is a need for prevention actions in the community, integrated discharge and referral pathways between health, housing and social care to minimise frequent usage and improve attendance outcomes., (© 2022. The Author(s).)

Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival. Moreover, high levels of gp78 are associated with poor outcomes in both ER+ and ER- tumors, and breast cancers expressing elevated amounts of gp78 protein are enriched in gene expression pathways that influence cell cycle, metabolism, receptor-mediated signaling, and cell stress response pathways. In multivariate analysis adjusted for subtype and grade, gp78 protein is an independent predictor of poor outcomes in women of African ancestry. Furthermore, gene expression signatures, derived from patients stratified by gp78 protein expression, are strong predictors of recurrence and pathological complete response in retrospective clinical trial data and share many common features with gene sets previously identified to be overrepresented in breast cancers based on race. These findings implicate a prominent role for gp78 in tumor progression and offer insights into our understanding of racial differences in breast cancer outcomes.

Background: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported., Objective: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome., Study Design: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome., Results: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6)., Conclusion: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Although minimally invasive surgery (MIS) has clearly been associated with improved colorectal surgery outcomes, not all populations benefit from this approach. Using a national database, we analyzed both, the trend in the utilization of MIS for diverticulitis and differences in utilization by race., Methods: Colon-targeted participant user files (PUFs) from 2012 to 18 were linked to respective PUFs in National Surgical Quality Improvement Project. Patients undergoing colectomy for acute diverticulitis or chronic diverticular disease were included. Surgical approach was stratified by race and year. To adjust for confounding and estimate the association of covariates with approach, data were fit using multivariable binary logistic regression main effects model. Using a joint effects model, we evaluated whether the odds of a particular approach over time was differentially affected by race., Results: Of the 46 713 patients meeting inclusion criteria, 83% were white, with 7% black and 10% other. Over the study period, there was a decrease in the rate of open colectomy of about 5% P < .001, and increase in the rate of utilization of laparoscopic and robotic approaches (RC) P < .0001. After adjusting for confounders, black race was associated with open surgery P < .0001., Conclusion: There is disparity in the utilization of MIS for diverticulitis. Further research into the reasons for this disparity is critical to ensure known benefits of MIC are realized across all races.

Terahertz imaging and spectroscopy is an exciting technology that has the potential to provide insights in medical imaging. Prior research has leveraged statistical inference to classify tissue regions from terahertz images. To date, these approaches have shown that the segmentation problem is challenging for images of fresh tissue and for tumors that have invaded muscular regions. Artificial intelligence, particularly machine learning and deep learning, has been shown to improve performance in some medical imaging challenges. This paper builds on that literature by modifying a set of deep learning approaches to the challenge of classifying tissue regions of images captured by terahertz imaging and spectroscopy of freshly excised murine xenograft tissue. Our approach is to preprocess the images through a wavelet synchronous-squeezed transformation (WSST) to convert time-sequential terahertz data of each THz pixel to a spectrogram. Spectrograms are used as input tensors to a deep convolution neural network for pixel-wise classification. Based on the classification result of each pixel, a cancer tissue segmentation map is achieved. In experimentation, we adopt leave-one-sample-out cross-validation strategy, and evaluate our chosen networks and results using multiple metrics such as accuracy, precision, intersection, and size. The results from this experimentation demonstrate improvement in classification accuracy compared to statistical methods, an improvement to segmentation between muscle and cancerous regions in xenograft tumors, and identify areas to improve the imaging and classification methodology., Competing Interests: Conflict of Interest The authors declare no competing interests.

Purpose: We investigate the enhancement in terahertz (THz) images of freshly excised breast tumors upon treatment with an optical clearance agent. The hyperspectral imaging and spectral classifications are used to quantitatively demonstrate the image enhancement. Glycerol solution with 60% concentration is applied to excised breast tumor specimens for various time durations to investigate the effectiveness on image enhancement. Approach: THz reflection spectroscopy is utilized to obtain the absorption coefficient and the index of refraction of untreated and glycerol-treated tissues at each frequency up to 3 THz. Two classifiers, spectral angular mapping (SAM) based on several kernels and Euclidean minimum distance (EMD) are implemented to evaluate the effectiveness of the treatment. The testing raw data is obtained from five breast cancer specimens: two untreated specimens and three specimens treated with glycerol solution for 20, 40, or 60 min. All tumors used in the testing data have healthy tissues adjacent to cancerous ones consistent with the challenge faced in lumpectomy surgeries. Results: The glycerol-treated tissues showed a decrease in the absorption coefficients compared with untreated tissues, especially as the period of treatment increased. Although the sensitivity metric of the classifier presented higher values in the untreated tissues compared with the treated ones, the specificity and accuracy metrics demonstrated higher values for the treated tissues compared with the untreated ones. Conclusions: The biocompatible glycerol solution is a potential optical clearance agent in THz imaging while keeping the histopathology imaging intact. The SAM technique provided a good classification of cancerous tissues despite the small amount of cancer in the training data (only 7%). The SAM exponential kernel and EMD presented classification accuracy of ∼ 80 % to 85% compared with linear and polynomial kernels that provided accuracy ranging from 70% to 80%. Overall, glycerol treatment provides a potential improvement in cancer classification in freshly excised breast tumors., (© 2022 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Aim: This study aimed to examine trends in prescribing of antidementia drugs in primary care in England between 2009 and 2019, and investigate the impact of deprivation, regional demography and disease prevalence on prescribing practices., Methods: Analysis of publicly available government data from various sources pertaining to primary care prescribing and demographics was conducted. All primary care prescription data pertaining to antidementia drugs in England between 2009 and 2019 were extracted and adjusted for inflation and population changes. Data across English clinical commissioning regions were compared to explore the association between prescribing trend, deprivation, regional demography and dementia prevalence., Results: The number of prescription items for antidementia drugs in England increased by approximately 3-fold (195.4%) from 24 items/1000 population in 2009 to 70.9 items/1000 population in 2019. In 2019, the least-deprived areas had approximately twice the rate of prescribing of antidementia drugs compared to the most-deprived areas (median [IQR] values of 46.7 [36.6-64.8] vs 91.23 [76.2-95.1] items/1000 population, respectively). In the multivariable analysis, the number of prescription items showed an inverse relationship with deprivation (coefficient -0.046, 95% CI -0.47 to -0.045) after adjustment for number of populations aged 65+ years and prevalence of dementia., Conclusions: The 3-fold rise in the number of prescription items for antidementia drugs in the study period reflects the policy emphasis on early diagnosis and treatment of dementia. Higher rates of prescribing in the least-deprived areas may be reflective of better and early diagnoses and access to treatments. Such inequality in access to the treatments needs to be investigated further., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Epidemiological studies focused on primary healthcare needs of persons experiencing homelessness (PEH) are often based on data from specialist homeless healthcare services., Aim: To explore the presentation of PEH, coding of homelessness, and associated health conditions in mainstream primary care general practices in England., Design & Setting: EMIS electronic database search of medical records was conducted across 48 general practices in a clinical commissioning group (CCG), representing one of the most socioeconomically deprived regions in England, which also lacks a specialist primary healthcare service for PEH., Method: Key terms and codes were used to identify PEH, their respective diagnoses across 22 health conditions, and prescribed medications over the past 4 years., Results: From a population of approximately 321 000, 43 (0.013%) people were coded as PEH, compared with a homelessness prevalence of 0.5% in the English general population. Mental health conditions were the most prevalent diagnoses among the PEH registrants (56.6%); the recorded prevalence of other common long-term conditions in PEH was lower than the levels observed in PEH registered with specialist homelessness health services., Conclusion: In a population with approximately four times higher rate of statutory homelessness, PEH representation in mainstream general practices was under-represented by several folds. As homelessness overlaps with mental health, substance misuse, and long-term health conditions, consistent coding of homelessness in medical records is imperative in order to offer tailored support and prevention actions when patients present for services., (Copyright © 2021, The Authors.)

In this paper we describe a coupled model for flow and microbial growth as well as nutrient utilization. These processes occur within and outside the biofilm phase formed by the microbes. The primary challenge is to address the volume constraint of maximum cell density but also to allow some microbial presence outside the contiguous biofilm phase. Our model derives from the continuum analogues of the mechanism of cell shoving introduced in discrete biomass models, and in particular from the models exploiting singular diffusivity as well as from models of variational inequality type which impose explicit constraints. We blend these approaches and propose a new idea to adapt the magnitude of the diffusivity automatically so as to ensure the volume constraint without affecting the reactions; this construction can be implemented in many variants without deteriorating the overall efficiency. The second challenge is to account for the flow and transport in the bulk fluid phase adjacent to the biofilm phase. We use the Brinkman flow model with a spatially variable permeability depending on biomass amount. The fluid flow allows some advection of the nutrient within the biofilm phase as well as for the flow even when the pores are close to being plugged up. Our entire model is monolithic and computationally robust even in complex pore-scale geometries, and extends to multiple species. We provide illustrations of our model and of related approaches. The results of the model can be easily post-processed to provide Darcy scale properties of the porous medium, e.g., one can predict how the permeability changes depending on the biomass growth in many realistic scenarios.

Purpose: The objective of this study is to quantitatively evaluate terahertz (THz) imaging for differentiating cancerous from non-cancerous tissues in mammary tumors developed in response to injection of N-ethyl-N-nitrosourea (ENU) in Sprague Dawley rats. Approach: While previous studies have investigated the biology of mammary tumors of this model, the current work is the first study to employ an imaging modality to visualize these tumors. A pulsed THz imaging system is utilized to experimentally collect the time-domain reflection signals from each pixel of the rat's excised tumor. A statistical segmentation algorithm based on the expectation-maximization (EM) classification method is implemented to quantitatively assess the obtained THz images. The model classification of cancer is reported in terms of the receiver operating characteristic (ROC) curves and the areas under the curves. Results: The obtained low-power microscopic images of 17 ENU-rat tumor sections exhibited the presence of healthy connective tissue adjacent to cancerous tissue. The results also demonstrated that high reflection THz signals were received from cancerous compared with non-cancerous tissues. Decent tumor classification was achieved using the EM method with values ranging from 83% to 96% in fresh tissues and 89% to 96% in formalin-fixed paraffin-embedded tissues. Conclusions: The proposed ENU breast tumor model of Sprague Dawley rats showed a potential to obtain cancerous tissues, such as human breast tumors, adjacent to healthy tissues. The implemented EM classification algorithm quantitatively demonstrated the ability of THz imaging in differentiating cancerous from non-cancerous tissues., (© 2021 Society of Photo-Optical Instrumentation Engineers (SPIE).)

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso's subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso's role in breast cancer progression.

Background: Telehealth has been successfully implemented for the delivery of obstetrical care. However, little is known regarding the attitudes and acceptability of patients and providers in high-risk obstetrics and whether the implementation of a telehealth model improves access to care in nonrural settings., Objective: This study aimed to describe patient and provider attitudes toward telehealth for the delivery of high-risk obstetrical care in a large healthcare system with both urban and suburban settings and to determine whether the implementation of a telehealth model improves patient adherence to scheduled appointments in this patient population., Study Design: Two self-administered surveys were designed. The first survey was sent to all high-risk obstetrical patients who received a telehealth visit between March 1, 2020, and May 30, 2020. The second survey was designed for providers who participated in these visits. We also compared the attended, cancelled, and no-show visit rates before (March 1 to May 30, 2019) and after (March 1 to May 30, 2020) the telehealth implementation and telehealth vs in-person visits in 2020. We reviewed scheduled high-risk prenatal care appointments, diabetes mellitus education sessions, and genetic counseling and Maternal-Fetal Medicine consultations., Results: A total of 91 patient surveys and 33 provider surveys were analyzed. Overall, 86.9% of patients were satisfied with the care they received and 78.3% would recommend telehealth visits to others. Notably, 87.8% of providers reported having a positive experience using telehealth, and 90.9% believed that telehealth improved patients' access to care. When comparing patient and provider preference regarding future obstetrical care after experiencing telehealth, 73.8% of patients desired a combination of in-person and telehealth visits during their pregnancy. However, a significantly higher rate of providers preferred in-person than telehealth visits (56% vs 23%, P =.024, respectively). When comparing visits between 2019 and 2020, there was a significantly lower rate of no-show appointments (8.49% vs 4.61%, P <.001), patient-cancelled appointments (7.06% vs 4.96%, P <.001), and patient same-day cancellations (2.30% vs 1.35%, P <.001) with the implementation of telehealth. There was also a significantly lower rate of patient-cancelled appointments (3.82% vs 5.44%, P =.021) and patient same-day cancellations (0.60% vs 1.65%, P =.002) with those receiving telehealth visits than in-person visits in 2020., Conclusion: The implementation of a telehealth model in high-risk obstetrics has the potential to improve access to high-risk obstetrical care, by reducing the rate of missed appointments. Both patients and providers surveyed expressed a high rate of satisfaction with telehealth visits and a desire to integrate telehealth into the traditional model of high-risk obstetrical care.

We report the complete genome sequencing of novel Pseudomonas stutzeri strain MP4687 isolated from cattle rumen. Various strains of P. stutzeri have been reported from different environmental samples including oil-contaminated sites, crop roots, air, and human clinical samples, but not from rumen samples, which is being reported here for the first time. The genome of P. stutzeri MP4687 has a single replicon, 4.75 Mb chromosome and a G + C content of 63.45%. The genome encodes for 4,790 protein coding genes including 164 CAZymes and 345 carbohydrate processing genes. The isolate MP4687 harbors LCB hydrolyzing potential through endoglucanase (4.5 U/mL), xylanase (3.1 U/mL), β-glucosidase (3.3 U/mL) and β-xylosidase (1.9 U/mL) activities. The pangenome analysis further revealed that MP4687 has a very high number of unique genes (>2100) compared to other P. stutzeri genomes, which might have an important role in rumen functioning., (© 2020 The Authors. Published by Elsevier B.V.)

The rapid progression of the coronavirus disease 2019 (COVID-19) outbreak presented extraordinary challenges to the US health care system, particularly straining resources in hard hit areas such as the New York metropolitan region. As a result, major changes in the delivery of obstetrical care were urgently needed, while maintaining patient safety on our maternity units. As the largest health system in the region, with 10 hospitals providing obstetrical services, and delivering over 30,000 babies annually, we needed to respond to this crisis in an organized, deliberate fashion. Our hospital footprint for Obstetrics was dramatically reduced to make room for the rapidly increasing numbers of COVID-19 patients, and established guidelines were quickly modified to reduce potential staff and patient exposures. New communication strategies were developed to facilitate maternity care across our hospitals, with significantly limited resources in personnel, equipment, and space. The lessons learned from these unexpected challenges offered an opportunity to reassess the delivery of obstetrical care without compromising quality and safety. These lessons may well prove valuable after the peak of the crisis has passed.

This manuscript presents a protocol to handle, characterize, and image freshly excised human breast tumors using pulsed terahertz imaging and spectroscopy techniques. The protocol involves terahertz transmission mode at normal incidence and terahertz reflection mode at an oblique angle of 30°. The collected experimental data represent time domain pulses of the electric field. The terahertz electric field signal transmitted through a fixed point on the excised tissue is processed, through an analytical model, to extract the refractive index and absorption coefficient of the tissue. Utilizing a stepper motor scanner, the terahertz emitted pulse is reflected from each pixel on the tumor providing a planar image of different tissue regions. The image can be presented in time or frequency domain. Furthermore, the extracted data of the refractive index and absorption coefficient at each pixel are utilized to provide a tomographic terahertz image of the tumor. The protocol demonstrates clear differentiation between cancerous and healthy tissues. On the other hand, not adhering to the protocol can result in noisy or inaccurate images due to the presence of air bubbles and fluid remains on the tumor surface. The protocol provides a method for surgical margins assessment of breast tumors.

This paper proposes a new dimension reduction algorithm based on low-dimension ordered orthogonal projection (LOOP), which is used for cancer detection with terahertz (THz) images of freshly excised human breast cancer tissues. A THz image can be represented by a data cube with each pixel containing a high dimension spectrum vector covering several THz frequencies, where each frequency represents a different dimension in the vector. The proposed algorithm projects the high-dimension spectrum vector of each pixel within the THz image into a low-dimension subspace that contains the majority of the unique features embedded in the image. The low-dimension subspace is constructed by sequentially identifying its orthonormal basis vectors, such that each newly chosen basis vector represents the most unique information not contained by existing basis vectors. A multivariate Gaussian mixture model is used to represent the statistical distributions of the low-dimension feature vectors obtained from the proposed dimension reduction algorithm. The model parameters are iteratively learned by using unsupervised learning methods such as Markov chain Monte Carlo or expectation maximization, and the results are used to classify the various regions within a tumor sample. Experiment results demonstrate that the proposed method achieves apparent performance improvement in human breast cancer tissue over existing approaches such as one-dimension Markov chain Monte Carlo. The results confirm that the dimension reduction algorithm presented in this paper is a promising technique for breast cancer detection with THz images, and the classification results present a good correlation with respect to the histopathology results of the analyzed samples.

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking. Functional screening of these drugs identified 4 compounds with low toxicity and high water solubility. Micro molar concentrations of these CtBP inhibitors produces significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurs through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. In functional assays, CtBP inhibition disrupts CtBP dimerization, decreases cell migration, abolishes cellular invasion, and improves DNA repair. Combinatorial use of CtBP inhibitors with the LSD1 inhibitor pargyline has synergistic influence. Finally, integrated correlation of gene expression in breast cancer patients with nuclear levels of CtBP1 and LSD1, reveals new potential therapeutic vulnerabilities. These findings implicate a broad role for this class of compounds in strategies for epigenetically targeted therapeutic intervention.

Cancer has become the leading cause of death in North Carolina (NC) (North Carolina DHHS, State Center for Health Statistics 2015) and the eastern region of North Carolina (ENC) has experienced greater cancer mortality than the remainder of the state. The Pitt County Breast Wellness Initiative-Education (PCBWI-E) provides culturally tailored breast cancer education and navigation to screening services for uninsured/underinsured women in Pitt and Edgecombe Counties in ENC. PCBWI-E created a network of 23 lay breast health educators, and has educated 735 women on breast health and breast cancer screening guidelines. Navigation services have been provided to 365 women, of which 299 were given breast health assessments, 193 were recommended for a mammogram, and 138 were screened. We have identified five lessons learned to share in the successful implementation of a community-based breast cancer screening intervention: (1) community partnerships are critical for successful community-based cancer screening interventions; (2) assuring access to free or low-cost screening and appropriate follow-up should precede interventions to promote increased use of breast cancer screening; (3) the reduction of system-based barriers is effective in increasing cancer screening; (4) culturally tailored interventions can overcome barriers to screening for diverse racial/ethnic and socioeconomic groups; and (5) multi-component interventions that include multiple community health strategies are effective in increasing screening.

Terahertz imaging and spectroscopy characterization of freshly excised breast cancer tumors are presented in the range 0.15 to 3.5 THz. Cancerous breast tissues were obtained from partial or full removal of malignant tumors while healthy breast tissues were obtained from breast reduction surgeries. The reflection spectroscopy to obtain the refractive index and absorption coefficient is performed on experimental data at each pixel of the tissue, forming tomographic images. The transmission spectroscopy of the refractive index and absorption coefficient are retrieved from experimental data at few tissue points. The average refractive index and absorption coefficients for cancer, fat, and collagen tissue regions are compared between transmission and reflection modes. The reflection mode offers the advantage of retrieving the electrical properties across a significantly greater number of points without the need for sectioning or altering the freshly excised tissue as in the transmission mode. The terahertz spectral power images and the tomographic images demonstrated good qualitative comparison with pathology.

Terahertz imaging and spectroscopy has demonstrated a potential for differentiating tissue types of excised breast cancer tumors. Pulsed terahertz technology provides a broadband frequency range from 0.1 THz to 4 THz for detecting cancerous tissue. Tumor tissue types of interest include cancer typically manifested as infiltrating ductal or lobular carcinomas, fibro-glandular (healthy connective tissues) and fat. In this work, images of breast tumors excised from human and animal models are reviewed. In addition to alternate fresh tissues, breast cancer tissue phantoms are developed to further evaluate terahertz imaging and the potential use of contrast agents. Terahertz results are successfully validated with pathology images, showing strong differentiation between cancerous and healthy tissues for all freshly excised tissues and types. The advantages, challenges and limitations of THz imaging of breast cancer are discussed., Competing Interests: Conflict of interest The authors have no conflict of interest to report.

Objective: To evaluate if presence of extreme maternal serum biochemical analytes recurs in consecutive pregnancies. We hypothesized that presence of >1 extreme analyte in prior pregnancy is associated with increased risk of adverse pregnancy outcome in subsequent pregnancy., Methods: Retrospective cohort study of singleton pregnancies evaluated and delivered in 2 consecutive pregnancies (2011-2015). Adverse outcomes were defined as indicated preterm delivery before 37 completed weeks due to preeclampsia, fetal growth restriction or other complications., Results: First and second trimester maternal serum analytes were assessed in 1434 patients in 2 consecutive pregnancies. The presence of >1 extreme serum analyte in prior pregnancy significantly increased likelihood of >1 extreme analyte in subsequent pregnancy. The likelihood increased as number of prior extreme markers increased. In patients with normal outcomes and 2 or more extreme serum analytes in prior pregnancy, there was an increased incidence of adverse pregnancy outcomes in subsequent pregnancy with relative risk (RR) of 5.42 [95% CI 1.6-18.3]., Conclusions: The presence of more than 1 extreme serum marker in one pregnancy increases likelihood of recurrence in subsequent pregnancies. Risk of adverse outcomes in subsequent pregnancy can be evaluated based on biochemistry results as well as prior pregnancy outcomes.

Objectives: To determine whether a novel, noninvasive quantitative ultrasound (US) technique can detect differences in proximal and distal cervical tissue echogenicity in women with and without a shortened cervical length (CL)., Methods: We conducted a retrospective case-control study of singleton pregnancies at 16 to 26 weeks' gestation in which a transvaginal US examination was performed to measure CL from 2013 to 2015. Initial CLs in cases and controls were less than 2.5 cm and 2.5 cm or greater, respectively. For each US image, a region of interest was selected in the proximal and distal cervical stroma, in both the anterior and posterior cervical lips. The Floyd-Steinberg dithering algorithm transformed grayscale pixels in each region of interest into a binary map. A histogram tabulated the number of black and white pixels, allowing determination of the percent echogenicity. The difference in the percent echogenicity was calculated by subtracting the distal cervical echogenicity (average of anterior and posterior lips) from the proximal cervical echogenicity (average of anterior and posterior lips)., Results: Ultrasound images from 177 women were analyzed. There was a difference in the percent echogenicity (P < .0001) when comparing women with a short cervix (mean ± SD, 9.8 ± 10.1; n = 102) to women with a normal CL (17.2 ± 9.5; n = 75). Differences were attributable to changes in proximal (P < .008) rather than distal cervical echogenicity. Regardless of CL, the proximal cervix was more echogenic than the distal cervix., Conclusions: A quantitative US analysis of cervical tissue can detect differences in echogenicity between the proximal and distal cervix in the second trimester. Proximal cervical echogenicity is lower with CL of less than 2.5 cm compared to a normal CL., (© 2018 by the American Institute of Ultrasound in Medicine.)

We report the use of reflection-mode terahertz (THz) imaging in a transgenic mouse model of breast cancer. Unlike tumor xenografts that are grown from established cell lines, these tumors were spontaneously generated in the mammary fat pad of mice, and are a better representation of human breast cancer. THz imaging results from 7 tumors that recapitulate the compartmental complexity of breast cancer are presented here. Imaging was first performed on freshly excised tumors within an hour of excision and then repeated after fixation with formalin and paraffin. These THz images were then compared with histopathology to determine reflection-mode signals from specific regions within tumor. Our results demonstrate that the THz signal was consistently higher in cancerous tissue compared with fat, muscle, and fibrous tissue. Almost all tumors presented in this work demonstrated advanced stages where cancer infiltrated other tissues like fat and fibrous stroma. As the first known THz investigation in a transgenic model, these results hold promise for THz imaging at different stages of breast cancer.

Objective: The objective of this study was to determine the effect, if any, of maternal body mass index (BMI) and amniotic fluid index (AFI) on the accuracy of sonographic estimated fetal weight (EFW) at 40 to 42 weeks' gestation., Methods: This was a retrospective cohort study of singleton gestations with ultrasound performed at 40 to 42 weeks from 2010 to 2013. In this study, patients with documented BMI and sonographic EFW and AFI, concurrently, within 7 days of delivery were included. Chronic medical conditions and fetal anomalies were excluded from this study. The primary variable of interest was the rate of substantial error in EFW, defined as absolute percentage error (APE) >10%., Results: A total of 1,000 pregnancies were included. Overall, the APE was 6.0 ± 4.5% and the rate of substantial error was 17.4% ( n  = 174). There was no significant difference in APE or rate of substantial error between BMI groups. In the final multivariable logistic regression model, the rate of substantial error was increased in women with oligohydramnios (OR 1.79; 95% CI: 1.10-2.92). Furthermore, oligohydramnios was significantly more likely to overestimate EFW while polyhydramnios was more likely to underestimate EFW. Maternal BMI did not affect the accuracy of sonographic EFW., Conclusion: Sonographic EFW may be affected by extremes of AFI in the postdates period. Maternal BMI does not affect EFW accuracy at 40 to 42 weeks., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: To determine the effect, if any, of an increasing maternal body mass index (BMI) on sonographically diagnosed oligohydramnios in late gestation and how it subsequently affects obstetric and neonatal outcomes., Methods: This retrospective cohort study evaluated all women with singleton gestations who had a sonographic examination at 40 to 42 weeks' gestational age at North Shore University Hospital from 2010 through 2013. Underweight women (prepregnancy BMI < 18.5 kg/m 2 ) were excluded because of higher rates of oligohydramnios and fetal growth restriction. Patients were classified into 5 groups by late-pregnancy BMI. The primary variable of interest was the diagnosis of oligohydramnios (amniotic fluid index < 5 cm). Secondary variables of interest included the mode of delivery and indication for primary cesarean delivery. A multivariable logistic regression analysis was performed., Results: Oligohydramnios was identified in 189 of 1671 patients (11.3%). There was no significant difference in the amniotic fluid index between BMI groups. The rate of primary cesarean delivery increased with each successive BMI group (P < .001) such that women in the class III obesity group had an approximately 3-fold higher rate of primary cesarean delivery than women in the normal BMI group and a 2-fold higher rate than women in the overweight BMI group. In the final multivariable logistic regression model, a high BMI, nulliparity, and excessive gestational weight gain were associated with primary cesarean delivery. However, oligohydramnios did not contribute significantly to the model., Conclusions: The maternal BMI is not associated with oligohydramnios in late gestation. An increasing maternal BMI significantly increases the risk of primary cesarean delivery., (© 2017 by the American Institute of Ultrasound in Medicine.)

Background:  In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening., Objective:  The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth., Study Design:  This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue., Results:  A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively ( p  < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth., Conclusion:  Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Primary tumor surgery (PTS) is not a standard treatment modality in stage IV breast cancer. Retrospective studies in female breast cancer show improved survival in women undergoing PTS; however, data regarding the impact of surgery in male breast cancer are lacking. The objective of this study was to analyze the impact of PTS on survival among men with metastatic breast cancer., Methods: A retrospective study was conducted of men diagnosed with metastatic breast cancer at diagnosis were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2011. Cox proportional hazards regression models were used to compare the differences in survival in men who did and did not undergo PTS., Results: A total of 439 men with stage IV breast cancer at diagnosis were identified, of which 222 (51%) underwent PTS, 171 (77%) mastectomy, and 51 (23%) partial mastectomy. The median age was 65 years; 74% of participants were white, 51% had tumors ≤ T2, 65% had estrogen receptor (ER)-positive tumor, and 24% had unknown ER status. Univariate analysis between the surgery and no-surgery arms showed that white race (P = .04), lower T stage and grade (P = .0003, P = .004), ER positivity (P = .0002), and later year of diagnosis (P < .0001) were associated with better survival. PTS was associated with improvement in median overall survival (29 vs. 11 months, P < .0001). On Cox regression analysis, ER negativity (hazard ratio = 2.08; 95% confidence interval, 1.41-3.01; P < .0003) and not undergoing PTS were associated with diminished survival (hazard ratio = 1.81; 95% confidence interval, 1.42-2.31; P < .0001)., Conclusion: PTS among men with metastatic breast cancer was associated with improved survival in this retrospective analysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Multicenter selective lymphadenectomy trial 1 (MSLT-I) defined the prognostic and potential therapeutic values of sentinel lymph node biopsy (SLNB) for intermediate-thickness melanoma. The role of completion lymphadenectomy (CLND) is, however, unclear and the subject of the ongoing MSLT-II trial., Methods: From 2003 to 2012, patients with tumors 1-4 mm thick with positive SLNB were identified in the Surveillance Epidemiology and End Results Program registry. The patients were divided into two groups: group 1 (CLND) and group 2 (observation)., Results: The study enrolled 2172 patients, the majority of whom were white and male with extremity primaries, no ulceration, Clark level 4 invasion, and nodes 2.01-4.0 mm deep. In the univariate analysis, CLND was associated with lower mean age, male gender, primary site, number of positive nodes, and geographic region (p < 0.05). In the multivariate analysis, male gender [odds ratio (OR), 1.27] and geographic area (Michigan OR, 2.31; Iowa OR, 1.69) were associated with CLND (p < 0.05). In the survival analysis, male gender, primary site, ulceration, Clark level, and depth and number of positive nodes were associated with survival (p < 0.05), but CLND was not (p = 0.83). In the Cox regression analysis, the relationship between male gender [hazard ratio (HR), 1.14], primary site trunk versus extremity (HR, 1.3), ulceration (HR, 1.79), Clark level (2 vs. 4 HR, 3.51; 2 vs. 5 HR, 6.48), depth (HR, 1.43) and number of nodes (1 vs. 2: HR, 1.23; 1 vs. ≥3: HR, 2.52) persisted (p < 0.05). However, when CLND was included in this model, it was not associated with improved survival., Conclusions: Age, gender, and geographic area predict the likelihood of CLND. In this retrospective study, CLND did not add survival benefit.

Objective: To determine whether women with sonographically identified uterine fibroids are at higher risk for a short cervix., Methods: This retrospective cohort study evaluated all women with singleton gestations who had a routine second-trimester ultrasound at 17-23 weeks gestational age from 2010 to 2013. When fibroids were noted, their presence, number, location and size were recorded. Exclusion criteria included a history of cervical conization or loop electrosurgical excision procedure (LEEP), uterine anomalies, maternal age greater than 40 years, and a previously placed cerclage. The primary variable of interest was short cervix (<25 mm). Secondary variables of interest included gestational age at delivery, mode of delivery, indication for cesarean, malpresentation, birth weight, and Apgar scores. A multivariable logistic regression analysis was performed., Results: Fibroids were identified in 522/10 314 patients (5.1%). In the final multivariable logistic regression model, short cervix was increased in women with fibroids (OR 2.29, 95% CI: 1.40, 3.74). The number of fibroids did not affect the frequency of short cervix. Fibroids were significantly associated with preterm delivery (<37 weeks), primary cesarean, breech presentation, lower birth weight infants, and lower Apgar scores., Conclusions: Women with uterine fibroids may be at higher risk for a short cervix. Fibroids are also associated with several adverse obstetric and neonatal outcomes.