Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Atrophic changes in thyroid tumors are strong indicators of underlying DICER1 mutations: a bi-institutional genotype-phenotype correlation study.

Somatic and biallelic DICER1 mutations are reported in subsets of thyroid tumors, supporting the role of this gene in thyroid tumor development. As recent studies have brought attention to macrofollicular patterns, atrophic changes, and papillary structures as being associated with DICER1 mutations, we sought to explore these observations in a bi-institutional cohort. A total of 61 thyroid lesions (54 tumors and 7 cases of thyroid follicular nodular disease; TFND), including 26 DICER1 mutated and 35 DICER1 wildtype controls were subjected to histological re-investigation and clinical follow-up. DICER1-mutated lesions showed a statistically significant association with younger age at surgery (29.2 ± 12.5 versus 51.3 ± 18.8, p = 0.0001), a predominant macrofollicular growth pattern (20/26 mutated cases versus 18/35 wildtype; p = 0.01) and atrophic changes (20/26 mutated cases versus 2/35 wildtype; p = 0.0001). Similar results were obtained when excluding TFND cases. We also present clinical and histological triaging criteria for DICER1 sequencing of thyroid lesions, which led to the identification of DICER1 variants in 16 out of 26 cases (62%) when followed. Among these, 3 out of 12 cases with available data were found to carry a constitutional DICER1 mutation. This observation suggests that the majority of DICER1 mutations are somatic-however implies that sequencing of constitutional tissues could be clinically motivated. We conclude that DICER1 mutations are amassed in younger patients with macrofollicular-patterned tumors and, most strikingly, atrophic changes. Given the rate of constitutional involvement, our findings could be of clinical value, allowing the pathologist to triage cases for genetic testing based on histological findings.

Factors associated with parental human papillomavirus vaccination intentions among adolescents from socioeconomically advantaged versus deprived households: a nationwide, cross-sectional survey.

Background: In the USA, HPV vaccine coverage is substantially lower among adolescents from high-income households compared to their low-income counterparts. We examined and compared the factors associated with parental HPV vaccination intentions between socioeconomically divergent groups. Methods: Data from unvaccinated and not fully HPV-vaccinated adolescents from the 2017-2021 National Immunization Survey (NIS)-Teen were analyzed. Socioeconomically advantaged vs. deprived groups were identified based on dichotomized income (material capital) and education (social capital). Parental intent to initiate and complete the HPV vaccine series was compared using bivariable analysis and the factors associated with lacking intent were identified. Findings: The 2017-2021 NIS-Teen included a total of 212,643 participants; the final analytical sample consisted of 105,958 adolescents (an estimated 10.3 million adolescents) who were unvaccinated or not fully vaccinated. In the advantaged group, 64.7% of parents of unvaccinated adolescents (equating to 2.4 million US adolescents) had no intention to initiate the HPV vaccine compared to 40.9% of parents in the deprived group (equating to 0.2 million adolescents) (P < 0.0001; S > 13.29). The most frequent reason for lacking intent in the advantaged group was 'safety concerns' (25.5%). In the deprived group, 'lack of knowledge', 'not recommended', and 'not needed' were common reasons (nearly 15% each). Lack of intent to complete the HPV vaccine series was higher in the advantaged group (43.9%; 1.1 million adolescents) compared to the deprived group (25.2%; 0.08 million adolescents) (P < 0.0001; S > 13.29). More than half in the advantaged group (58.4%) and over a third (37.1%) in the deprived group cited 'already up to date' as the main reason for not completing the HPV vaccine series. Interpretation: Lack of intent to initiate and complete the HPV vaccination series, particularly among socioeconomically advantaged parents is a significant barrier to achieving the national goal in the USA. Funding: The US National Institute on Minority Health and Health Disparities, the National Center for Advancing Translational Sciences, MUSC Hollings Cancer Center Seed funding, and the US National Cancer Institutes.

Comprehensive evaluation of cytomorphologic, histologic, and molecular features of DICER1-altered thyroid lesions on FNA: A multipractice experience.

BACKGROUND: DICER1 mutations, though infrequent, are encountered on preoperative molecular testing of indeterminate adult and pediatric thyroid fine-needle aspiration (FNA) specimens. Yet, published cytomorphologic features of DICER1-altered thyroid lesions are limited. Cytomorphological features of DICER1-altered thyroid lesions were examined in a multipractice FNA cohort with clinical, radiological, and histologic data. METHODS: The cohort comprised 18 DICER1-altered thyroid FNAs, with 14 having slides available and eight having corresponding surgical resections. Smears, ThinPrep, and formalin-fixed cell block slides were reviewed and correlated with histology, when available. Clinical and radiologic data were obtained from the medical record. RESULTS: Most DICER1-altered FNAs were classified as atypia of undetermined significance (94.4%). DICER1 mutations occurred in codons 1709 (50%), 1810 (27.8%), and 1813 (22.2%). One patient had an additional DICER1 p.D1822N variant in both of their FNAs. Lesions were often hypoechoic (35.3%) and solid (47.1%) on ultrasound. Notable cytomorphologic features include mixed but prominent microfollicular or crowded component, variable colloid, and insignificant nuclear atypia. On resection (n = 10), histologic diagnoses ranged from benign follicular adenoma and low-risk follicular thyroid carcinoma to high-grade follicular-derived nonanaplastic thyroid carcinoma. Subcapsular infarct-type change was the most common histologic change. There was no evidence of recurrence or metastasis in eight patients on limited follow-up. CONCLUSION: DICER1-altered thyroid lesions occurred frequently in young females and FNAs show RAS-like cytomorphology including crowded, mixed macro-/microfollicular pattern, and bland nuclear features. On resection, DICER1-altered thyroid lesions include benign (50%), low-risk lesions (30%), or high-risk malignancies (20%).

Consumption of Health-Related Videos and Human Papillomavirus Awareness: Cross-Sectional Analyses of a US National Survey and YouTube From the Urban-Rural Context.

BACKGROUND: Nearly 70% of Americans use the internet as their first source of information for health-related questions. Contemporary data on the consumption of web-based videos containing health information among American adults by urbanity or rurality is currently unavailable, and its link with health topic awareness, particularly for human papillomavirus (HPV), is not known. OBJECTIVE: We aim to describe trends and patterns in the consumption of health-related videos on social media from an urban-rural context, examine the association between exposure to health-related videos on social media and awareness of health topics (ie, HPV and HPV vaccine), and understand public interest in HPV-related video content through search terms and engagement analytics. METHODS: We conducted a cross-sectional analysis of the US Health Information National Trends Survey 6, a nationally representative survey that collects data from civilian, noninstitutionalized adults aged 18 years or older residing in the United States. Bivariable analyses were used to estimate the prevalence of consumption of health-related videos on social media among US adults overall and by urbanity or rurality. Multivariable logistic regression models were used to examine the association between the consumption of health-related videos and HPV awareness among urban and rural adults. To provide additional context on the public's interest in HPV-specific video content, we examined search volumes (quantitative) and related query searches (qualitative) for the terms "HPV" and "HPV vaccine" on YouTube. RESULTS: In 2022, 59.6% of US adults (152.3 million) consumed health-related videos on social media, an increase of nearly 100% from 2017 to 2022. Prevalence increased among adults living in both urban (from 31.4% in 2017 to 59.8% in 2022; P<.001) and rural (from 22.4% in 2017 to 58% in 2022; P<.001) regions. Within the urban and rural groups, consumption of health-related videos on social media was most prevalent among adults aged between 18 and 40 years and college graduates or higher-educated adults. Among both urban and rural groups, adults who consumed health-related videos had a significantly higher probability of being aware of HPV and the HPV vaccine compared with those who did not watch health videos on the internet. The term "HPV" was more frequently searched on YouTube compared with "HPV vaccine." Individuals were most commonly searching for videos that covered content about the HPV vaccine, HPV in males, and side effects of the HPV vaccine. CONCLUSIONS: The consumption of health-related videos on social media in the United States increased dramatically between 2017 and 2022. The rise was prominent among both urban and rural adults. Watching a health-related video on social media was associated with a greater probability of being aware of HPV and the HPV vaccine. Additional research on designing and developing social media strategies is needed to increase public awareness of health topics.

Underreported and underrecognized: a comprehensive imaging review of breast injury.

Breast injury is commonly encountered yet it remains significantly underreported. Injury to the breast may arise from either primary mechanisms or secondary or iatrogenic mechanisms. Primary mechanisms of breast injury include blunt force, seat-belt, penetrating, and thermal injury. Secondary or iatrogenic mechanisms of breast injury include breast biopsy or intervention as well as operative intervention and cardiopulmonary resuscitation. The severity of breast injury arising from these mechanisms is broad, ranging from breast contusion to avulsion. Sequelae of breast injury include fat necrosis and Mondor's disease. Radiologists play an integral role in the evaluation and management of breast injury both in the acute and non-acute settings. In the acute setting, radiologists must be able to recognize breast injury arising from primary mechanisms or iatrogenic or secondary mechanisms and to identify rare but potentially life-threatening complications promptly to ensure timely, appropriate management. In the non-acute setting, radiologists must be able to discern the sequalae of breast injury from other processes to prevent potentially unnecessary further evaluation and intervention. Nonetheless, though breast injury is commonly encountered there remain few guidelines and a lack of established recommendations for the evaluation and management of breast injury. We provide a comprehensive multi-modality imaging review of breast injury arising in the acute setting as well as the sequela of breast injury arising in the non-acute setting. Moreover, we provide an overview of the management of breast injury.

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.

Radiologic-Pathologic Correlation of COVID-19-Associated Acute Disseminated Encephalomyelitis.

A 42-year-old woman presented with drooling, slurred speech, inability to walk and talk, and a recent positive COVID-19 test. She had two prior hospital admissions within the past week for similar symptoms with inconclusive evaluation. MRI of the brain demonstrated multifocal white matter hyperintense lesions on fluid-attenuated inversion recovery (FLAIR)/diffusion with variable enhancement. These imaging findings have been described in recent literature and are associated with inflammatory demyelinating disease, such as acute disseminated encephalomyelitis. The patient subsequently underwent a brain biopsy with a final diagnosis of inflammatory demyelinating lesion. To our knowledge, this is the first radiologic-pathologic correlation of COVID-19-associated acute disseminated encephalomyelitis.

Inflammatory markers are elevated in early pregnancy, but not late pregnancy, in women with overweight and obesity that later develop preeclampsia.

PROBLEM: Obesity and preeclampsia both involve a pathological inflammatory response, which may be how obesity increases preeclampsia risk. Previous studies have failed to assess robust measurements of inflammatory markers across gestation, specifically in overweight/ obese women in the context of preeclampsia. METHOD OF STUDY: We measured 20 inflammatory markers in plasma via multiplex assay (ThermoFisher Inflammation 20 plex Human ProcartaPlex Panel) across the three trimesters of pregnancy in an existing cohort of overweight and obese women who developed preeclampsia (n = 37) and without preeclampsia (n = 74). Mann-Whitney U tests examined differences in inflammatory marker concentrations between cases and controls. Repeated measures ANOVA tests were used to explore differences in inflammatory marker concentrations over time within cases and controls. RESULTS: Pro-inflammatory markers (IL-1α, IL-1ß, IL-6, IFN-α, IFN-γ, GM-CSF, IL-12p70, IL-17α, TNF-α, IL-8) and anti-inflammatory markers (IL-4, IL-10, IL-13) were higher in the first and second trimester in participants who later developed preeclampsia compared to those who did not (p < .05). Only TNF-α and IL-8 remained elevated in the third trimester. Inflammatory markers did not change across pregnancy in preeclampsia cases but did increase across pregnancy in controls. CONCLUSION: Our findings diverge from prior studies, predominantly of non-obese women, that report lower circulating concentrations of anti-inflammatory cytokines in preeclampsia versus normotensive pregnancy, particularly by late pregnancy. We posit that women with overweight and obesity who develop preeclampsia entered pregnancy with a heightened pro-inflammatory state likely related to obesity, which increased risk for preeclampsia. Further studies are needed to investigate if inflammatory maker profiles differ between obese and non-obese women.

PREPARE: A Stepped-Wedge Cluster-Randomized Trial to Evaluate Whether Risk Stratification Can Reduce Preterm Deliveries Among Patients With Suspected or Confirmed Preterm Preeclampsia.

BACKGROUND: Early delivery in preterm preeclampsia may reduce the risks for the patient, but consequences of prematurity may be substantial for the baby. This trial evaluated whether the implementation of a risk stratification model could safely reduce prematurity. METHODS: This was a stepped-wedge cluster-randomized trial in seven clusters. Patients presenting with suspected or confirmed preeclampsia between 20+0 and 36+6 gestational weeks were considered eligible. At the start of the trial, all centers were allocated in the preintervention phase, and patients enrolled in this phase were managed according to local treatment guidance. Subsequently, every 4 months, 1 randomly allocated cluster transitioned to the intervention. Patients enrolled in the intervention phase had sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and preeclampsia integrated estimate of risk assessments performed. If sFlt-1/PlGF ≤38 and preeclampsia integrated estimate of risk <10%, patients were considered low risk and clinicians received recommendations to defer delivery. If sFlt-1/PlGF >38 and preeclampsia integrated estimate of risk ≥10%, patients were considered not low risk, and clinicians received recommendations to increase surveillance. The primary outcome was the proportion of patients with preterm preeclampsia delivered prematurely out of total deliveries. RESULTS: Between March 25, 2017 and December 24, 2019, 586 and 563 patients were analyzed in the intervention and usual care groups, respectively. The event rate was 1.09% in the intervention group, and 1.37% in the usual care group. After prespecified adjustments for variation between and within clusters over time, the adjusted risk ratio was 1.45 ([95% CI, 1.04-2.02]; P=0.029), indicating a higher risk of preterm deliveries in the intervention group. Post hoc analysis including calculation of risk differences did not show evidence of statistical differences. Abnormal sFlt-1/PlGF was associated with a higher rate of identifying preeclampsia with severe features. CONCLUSIONS: The introduction of an intervention based on biomarkers and clinical factors for risk stratification did not lead to reductions in preterm deliveries. Further training on the interpretation of disease severity in preeclampsia and the development of additional risk stratification is needed before adoption into clinical practice. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03073317.

Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

BACKGROUND: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. METHODS: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). RESULTS: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. CONCLUSIONS: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain.

A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy.

Background: While preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study's purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls). Results: In the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×10-8, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×10-5. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample. Conclusions: The discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1-2 and significant DMRs that were not examined in the replication phase.

Enhanced expectancies benefit performance under distraction, but compromise it under stress: Exploring the OPTIMAL theory.

Motor learning can benefit from practice under enhanced expectancies; that is, the belief one can generate an intended positive outcome. According to the OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory, this benefit manifests from a greater coupling between action and its external consequences, which potentially coincides with a more automatic mode of control. The aim of the study was to examine this possibility, and in so doing, understand more about the psycho-motor processes underpinning the influence of expectancies. On Day 1, novice participants practiced a dart-throwing task under enhanced (EE) (n = 11), reduced (RE) (n = 12) or no (control; CTL) (n = 12) expectancies. Enhanced and reduced expectancies were indirectly manipulated by positively reinforcing shots that landed within the large or small circle on the dartboard, respectively. On Day 2, participants transferred to a dual-task (i.e., tone-counting) or stress (i.e., social-comparative threat, false feedback) setting. While there was no evidence of improvement across practice, RE was significantly worse than CTL for the dual-task, but EE was significantly worse than RE and CTL under stress (ps < 0.05). Therefore, the ability of EE to retain performance within the dual-task, but decline under stress, suggests a more automatic mode of control was adopted. Both theoretical and practical implications are discussed.

Evaluation of the First-Year Data from an HPV Vaccination Van Program in South Carolina, U.S.

Human papillomavirus (HPV) infections are linked to at least six different types of cancer. The Medical University of South Carolina (MUSC) Hollings Cancer Center (HCC) and Department of Pediatrics leaders identified suboptimal rates of HPV vaccinations in rural and medically underserved communities in South Carolina (SC). To address this major public health problem in SC, they received funding from the HealthyMe/HealthySC (HMHSC) program and HCC to create a statewide community engagement-focused HPV Vaccination Van Program in October 2021. The Program provides HPV vaccinations and other childhood immunizations in school districts and HMHSC health clinics throughout SC, focusing on children aged 9-18 who are eligible for the U.S. Centers for Disease Control and Prevention's Vaccines for Children Program. As of 14 December 2022, the Program administered vaccinations in 16 counties of SC to 552 participants, 243 of whom received HPV vaccinations and were predominantly female (57.2%), aged 4-18 (95.9%), and self-identified as White (44.0%), Black (33.2%), or Hispanic/Latino (15.1%). Most had Medicaid (53.1%)/no insurance coverage (25.1%). The Program is expected to expand as the Program's relationship with SC's school districts grows. The Program provides a model for delivering mobile HPV vaccinations to rural children, thus reducing their cancer risk.

The Role of Imaging in the Diagnosis of Primary and Secondary Breast Angiosarcoma: Twenty-Five-Year Experience of a Provincial Cancer Institution.

BACKGROUND: Breast angiosarcoma may arise spontaneously (primary breast angiosarcoma (PBA)) or may arise secondary to a biological insult, such as radiation therapy (secondary breast angiosarcoma (SBA)). We evaluated the imaging findings of patients diagnosed with PBA and SBA within the province of British Columbia, Canada. MATERIALS AND METHODS: This was a multi-center, retrospective study of patients diagnosed with PBA and SBA over a 25-year period. Patients were identified via a provincial database which registers all cases of sarcoma. Patients diagnosed with histologically proven PBA and SBA were eligible for inclusion. Multimodal breast imaging reviewed included mammography, ultrasound, magnetic resonance imaging, and computed tomography. RESULTS: Thirteen patients were diagnosed with PBA and 22 patients were diagnosed with SBA. The median (interquartile range (IQR)) age of patients diagnosed with PBA (45.5 years (19.7 years)) was less than that of patients diagnosed with SBA (75.8 years (13.8 years), P < .001). Patients diagnosed with PBA (90.9%) were more likely to present with a parenchymal mass clinically and radiographically than those with SBA (28.6%, P < .002). Patients diagnosed with SBA (71.4%) were more likely to present with cutaneous findings than patients diagnosed with PBA (0.0%, P < .05). Without specific clinical context, the imaging findings of PBA and SBA were observed to be non-specific. CONCLUSION: This is the only study which evaluated the imaging findings of patients diagnosed with PBA and SBA within a large, defined geographical area. Given non-specific imaging findings, awareness of the disease and clear and timely communication between radiologists and clinicians is required to ensure appropriate diagnosis and management.

Cytomorphologic features of thyroid nodules harboring thyroid adenoma-associated fusion: A single institutional review of 11 cases.

BACKGROUND: Thyroid adenoma-associated (THADA) fusions are being identified more frequently with increased preoperative molecular testing on indeterminate thyroid fine-needle aspirates (FNA). However, data on cytomorphologic features of THADA-fusion thyroid lesions are limited. We examined cytomorphologic features of a THADA-fusion thyroid FNA cohort with clinical, radiologic, and histologic data. METHODS: Our THADA fusion FNA cohort included 11 specimens from 11 patients with a mean age and F:M ratio of 56.5 years and 2.7:1, respectively. Ten cases had FNA slides available for review and five cases had histopathology. Air-dried Diff-Quik and alcohol-fixed Papanicolaou smears, and formalin-fixed cell blocks were reviewed and findings were correlated with the matched resection, when available. Clinical and radiologic data were obtained from the medical record. RESULTS: THADA fusion thyroid lesions were hypoechoic or isoechoic (80%), solid (80%) with well-demarcated margins (100%) on ultrasound. Notable cytomorphologic features include crowded or prominent microfollicular groups (100%), scant colloid (91%), and mild nuclear atypia with nuclear grooves (100%), insignificant nuclear pleomorphism (100%), and without intranuclear pseudoinclusions (100%). All cases were classified as either atypia of undetermined significance (91%) or suspicious for follicular neoplasm (9%). Five resected cases were all low-risk lesions (benign and malignant) with no evidence of recurrence in the limited available follow-up. CONCLUSION: THADA-fusion thyroid FNAs show a crowded or prominent microfollicular pattern with mild nuclear atypia and without intranuclear pseudoinclusions, which overlaps with the cytomorphology of other RAS-like thyroid lesions. In our cohort, resected THADA lesions were low risk on histologic analysis.

Predicting HPV vaccination among Tdap vaccinated adolescents in Georgia at the county level☆.

PURPOSE: Vaccinations are reported at the state level, but services are delivered at the county level through health departments (HD). This research contributes statistical models to predict county level HPV vaccination. METHODS: Using a cross sectional study design, secondary data were analyzed for the years 2016-2018 for all counties of GA. Study population was male and female adolescents aged 13-17 who received the tetanus, diphtheria and pertussis (Tdap) vaccine. The number of administered HPV vaccine doses and HPV vaccination coverage rate were modeled using indicators of HD clinic access, age, sex, race/ethnicity, socioeconomic status, education, median household income, health insurance, and urban/rural residence. RESULTS: By county the number of administered HPV vaccine doses showed a statistically significant positive association with indicators of HD clinic access: public transit and the number of HD private clinics. HPV vaccination coverage showed a statistically significant negative association with White race and rural residency. CONCLUSION: Examining Tdap vaccinated adolescents conservatively predicted HPV vaccination and controlled for multiple confounders such as vaccination ineligibility, vaccine exemption, and vaccine opposition. Within this population, public health professionals and clinicians could use these statistical models to target HPV vaccination efforts among non-Hispanic whites and rural communities at the county level.

Latent class analysis of placental histopathology: a novel approach to classifying early and late preterm births.

BACKGROUND: Neonatal morbidity attributable to prematurity predominantly occurs among early preterm births (<32 weeks) rather than late preterm births (32 to <37 weeks). Methods to distinguish early and late preterm births are lacking given the heterogeneity in pathophysiology and risk factors, including maternal obesity. Although preterm births are often characterized by clinical presentation (spontaneous or clinically indicated), classifying deliveries by placental features detected on histopathology reports may help identify subgroups of preterm births with similar etiology and risk factors. Latent class analysis is an empirical approach to characterize preterm births on the basis of observed combinations of placental features. OBJECTIVE: To identify histopathologic markers that can distinguish early (<32 weeks) and late preterm births (32 to <37 weeks) that are also associated with maternal obesity and neonatal outcomes. STUDY DESIGN: Women with a singleton preterm birth at University of Pittsburgh Medical Center Magee-Womens Hospital (Pittsburgh, PA) from 2008 to 2012 and a placental evaluation (89% of preterm births) were stratified into early (n=900, 61% spontaneous) and late preterm births (n=3362, 57% spontaneous). Prepregnancy body mass index was self-reported at first prenatal visit and 16 abstracted placental features were analyzed. Placental subgroups (ie, latent classes) of early and late preterm births were determined separately by latent class analysis of placental features. The optimal number of latent classes was selected by comparing fit statistics. The probability of latent class membership across prepregnancy body mass indexes was estimated in early preterm births and in late preterm births by an extension of multinomial regression called pseudo-class regression, adjusting for race, smoking, education, and parity. The frequencies of severe neonatal morbidity (composite outcome: respiratory distress, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, patent ductus arteriosus, and retinopathy of prematurity), small-for-gestational-age, and length of neonatal intensive care unit stay were compared across latent classes by chi-square and Kruskal-Wallis tests. RESULTS: Early preterm births were grouped into 4 latent classes based on placental histopathologic features: acute inflammation (38% of cases), maternal vascular malperfusion with inflammation (29%), maternal vascular malperfusion (25%), and fetal vascular thrombosis with hemorrhage (8%). As body mass index increased from 20 to 50kg/m2, the probability of maternal vascular malperfusion and fetal vascular thrombosis with hemorrhage increased, whereas the probability of maternal vascular malperfusion with inflammation decreased. There was minimal change in the probability of acute inflammation with increasing body mass index. Late preterm births also had 4 latent classes: maternal vascular malperfusion (22%), acute inflammation (12%), fetal vascular thrombosis with hemorrhage (9%), and low-risk pathology (58%). Body mass index was not associated with major changes in likelihood of the latent classes in late preterm births. Associations between body mass index and likelihood of the latent classes were not modified by type of delivery (spontaneous or indicated) in early or late preterm births. Maternal malperfusion and fetal vascular thrombosis with hemorrhage were associated with greater neonatal morbidity than the other latent classes in early and late preterm births. CONCLUSION: Obesity may predispose women to early but not late preterm birth through placental vascular impairment. Latent class analysis of placental histopathologic data provides an evidence-based approach to group preterm births with shared underlying etiology and risk factors.

Spatial patterns of HPV and Tdap vaccine dose administration and the association of health department clinic access in Georgia counties.

OBJECTIVE: To characterize counties in GA by quantifying administered doses of the HPV and Tdap vaccines collected by the state health department immunization registry and indicators of Health Department (HD) clinic access. METHODS: Using a cross sectional study design, secondary data were collected from public health data sources for the years 2016 to 2018 for 159 counties of Georgia. The study population was male and female adolescents aged 13-17. The number of administered HPV and Tdap vaccine doses were modeled in relation to number of private and public HD clinics, number of HD clinics registered in the VFC program and the availability of public transportation using Poisson regression, negative binomial regression, and Bayesian spatial analysis. RESULTS: Choropleth maps showed similar clustering patterns between administered doses of the HPV vaccine and Tdap vaccine and increased counts of administered vaccine doses in counties with both public and private clinics. Administered doses of HPV and Tdap vaccines were found to exhibit spatial dependence across counties. Accounting for spatial dependence, the availability of public transit had a significant positive effect on administered HPV vaccine doses, while the number of private HD clinics had a significant positive effect on administered Tdap vaccine doses. CONCLUSIONS: Maps at the county level show vaccination variability, clustering patterns and provide additional insights on the access to health care. Bayesian spatial models are needed to accurately identify and estimate factors associated with administering doses of the HPV and Tdap vaccines. Future work is needed to further examine the utilization of HPV vaccination services among urban groupings.

Association between gestational PFAS exposure and Children's adiposity in a diverse population.

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (ß = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (ß = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (ß = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.