Search

Objective: To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses., Methods: A multicenter, retrospective, case-control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10-30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities., Results: In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18-7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79-3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83-18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78-18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25-0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11-0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02-0.78) compared to individuals without these neuroimaging abnormalities., Interpretation: This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: A variety of maternal risk factors for fetal alcohol spectrum disorders (FASD) have been described in the literature. Here, we conducted a multivariate analysis of a large array of potential distal influences on FASD risk., Methods: Interviews were conducted with 2515 mothers of first-grade students whose children were evaluated to assess risk for FASD. Topics included: physical/medical status, childbearing history, demographics, mental health, domestic violence, and trauma. Regression modeling utilized usual level of alcohol consumption by trimester and six selected distal variables (maternal head circumference, body mass index, age at pregnancy, gravidity, marital status, and formal years of education) to differentiate children with FASD from control children., Results: Despite individual variation in distal maternal risk factors among and within the mothers of children with each of the common diagnoses of FASD, patterns emerged that differentiated risk among mothers of children with FASD from mothers whose children were developing typically. Case-control comparisons indicate that mothers of children with FASD were significantly smaller physically, had higher gravidity and parity, and experienced more miscarriages and stillbirths, were less likely to be married, reported later pregnancy recognition, more depression, and lower formal educational achievement. They were also less engaged with a formal religion, were less happy, suffered more childhood trauma and interpersonal violence, were more likely to drink alone or with her partner, and drank to deal with anxiety, tension, and to be part of a group. Regression analysis showed that the predictor variables explain 57.5% of the variance in fetal alcohol syndrome (FAS) diagnoses, 30.1% of partial FAS (PFAS) diagnoses, and 46.4% of alcohol-related neurodevelopmental disorder (ARND) diagnoses in children with FASD compared to controls. While the proximal variables explained most of the diagnostic variance, six distal variables explained 16.7% ( 1 / 6 ) of the variance in FAS diagnoses, 13.9% ( 1 / 7 ) of PFAS, and 12.1% ( 1 / 8 ) of ARND., Conclusions: Differences in distal FASD risks were identified. Complex models to quantify risk for FASD hold promise for guiding prevention/intervention., (© 2023 Research Society on Alcohol.)

Background: Pregnant women participated in multifaceted case management (MCM) to prevent Fetal Alcohol Spectrum Disorders (FASD)., Methods: Women recruited from antenatal clinics for a longitudinal child development study were screened for alcohol use. Forty-four pregnant women were defined as high-risk drinkers on the Alcohol Use Disorder Identification Test (AUDIT) by an AUDIT score ≥8 and participated in 18 months of MCM to facilitate reduction or cessation of alcohol consumption. Forty-one women completed MCM. Fifty-five equally high-risk women who received standard antenatal care comprised the comparison/control group. Development in offspring was evaluated by a blinded interdisciplinary team of examiners through 5 years of age., Results: At five years of age, more children (34%) of MCM participating women did not meet the criteria for FASD vs. non-MCM offspring (22%). Furthermore, a statistically significant ( p  = .01) lower proportion of MCM offspring (24%) was diagnosed with fetal alcohol syndrome (FAS) compared to controls (49%). Children of MCM participants had significantly ( p  < .05) better physical outcomes: lower total dysmorphology scores, larger head circumferences, longer palpebral fissures, and higher midfacial measurements. Neurodevelopment results showed mixed outcomes. While Bayley developmental scores indicated that MCM offspring were performing significantly worse on most domains through 18 months, group scores equalized and were not significantly different on Kaufman Assessment Battery neurobehavioral measures by five years. Regression analyses indicated that offspring of women who received standard antenatal care were associated with significantly more negative outcomes than MCM offspring: a diagnosis of FAS (OR = 3.2; 95% CI: 1.093-9.081), microcephaly (OR = 5.3; 95% CI: 2.1-13.5), head circumference ≤10th centile (OR = 4.3; 95%CI: 1.8-10.4), and short palpebral fissures (OR = 2.5; 95% CI: 1.0-5.8)., Conclusion: At age five, proportionally fewer children of MCM participants qualified for a diagnosis of FAS, and proportionally more had physical outcomes indicating better prenatal brain development. Neurobehavioral indicators were not significantly different from controls by age five.KEY MESSAGESMultifaceted Case Management (MCM) was designed and employed for 18 months during the prenatal and immediate postpartum period to successfully meet multiple needs of women who had proven to be very high risk for birthing children with fetal alcohol spectrum disorders (FASD).Offspring of the women who participated in MCM were followed up through age five years and were found to have significantly better physical outcomes on multiple variables associated with fetal alcohol syndrome (FAS) and FASD, such as larger head circumferences and fewer minor anomalies, than those children born to equally at-risk women not receiving MCM.Fewer children of women receiving MCM were diagnosed with FASD than the offspring of equally-at-risk controls, and significantly ( p  = .01) fewer MCM offspring had FAS, the most severe FASD diagnosis.

Objective: To explore and analyze the significance of proximal influences of maternal and paternal traits associated with bearing a child with a fetal alcohol spectrum disorder (FASD)., Methods: Aggregated, maternal interview-collected data (N = 2515) concerning alcohol, tobacco, and other drug use were examined to determine risk for FASD from seven cross-sectional samples of mothers of first-grade students who were evaluated for a possible diagnosis of FASD., Results: Mothers of children with fetal alcohol syndrome (FAS) reported the highest alcohol use throughout pregnancy, proportion of binge drinking, drinks per drinking day (DDD), drinking days per week, and total drinks per week. Mothers of children with FAS also consumed significantly more alcohol than mothers of children with partial FAS (PFAS), alcohol-related neurodevelopmental disorder (ARND), or typically developing controls. Mothers of children with PFAS and ARND reported similar drinking patterns, which exposed fetuses to 3-4 times more alcohol than mothers of controls, but the PFAS group was more likely than the ARND group to abstain in latter trimesters. Fathers of all children were predominantly drinkers (70%-85%), but more fathers of children with FASD binged heavily on more days than fathers of controls. Compared to the few mothers of controls who used alcohol during pregnancy, the ARND group binge drank more (3+ DDD) throughout pregnancy and drank more DDD before pregnancy and first trimester. Regression analysis, controlling for tobacco use, indicated that mothers who reported drinking <1 DDD were significantly more likely than abstainers to bear a child with FASD (OR = 2.75) as were those reporting higher levels such as 5-5.9 DDD (OR = 32.99). Exclusive, first-trimester maternal drinking increased risk for FASD five times over that of abstinence (p < 0.001, OR = 5.05, 95% CI: 3.88-6.58), first- and second-trimester drinking by 12.4 times, and drinking all trimesters by 16 times (p < 0.001, OR = 15.69, 95% CI: 11.92-20.64). Paternal drinking during and prior to pregnancy, without adjustment, increased the likelihood of FASD significantly (OR = 1.06 and 1.11, respectively), but the significance of both relationships disappeared when maternal alcohol and tobacco use were controlled., Conclusions: Differences in FASD risk emerged from the examination of multiple proximal variables of maternal alcohol and tobacco use, reflecting increased FASD risk at greater levels of maternal alcohol consumption., (© 2023 Research Society on Alcohol.)

Background: Plasma levels of vitamin D have been reported to be low in persons with Down syndrome (DS) and existing data is limited to small and homogenous cohorts. This is of particular importance in persons with DS given the high rates of autoimmune disease in this population and the known relationship between vitamin D and immune function. This study sought to investigate vitamin D status in a multi-center cohort of individuals with DS and compare them to individuals with autism spectrum disorder (ASD) and neurotypical (NT) controls., Methods: A retrospective, multi-center review was performed. The three sites were located at latitudes of 42.361145, 37.44466, and 34.05349. Patients were identified by the International Classification of Diseases (ICD)-9 or ICD-10 codes for DS, ASD, or well-child check visits for NT individuals. The first vitamin D 25-OH level recorded in the electronic medical record (EMR) was used in this study as it was felt to be the most reflective of a natural and non-supplemented state. Vitamin D 25-OH levels below 30 ng/mL were considered deficient., Results: In total, 1624 individuals with DS, 5208 with ASD, and 30,775 NT controls were identified. Individuals with DS had the lowest mean level of vitamin D 25-OH at 20.67 ng/mL, compared to those with ASD (23.48 ng/mL) and NT controls (29.20 ng/mL) (p < 0.001, 95% CI: -8.97 to -6.44). A total of 399 (24.6%) individuals with DS were considered vitamin D deficient compared to 1472 (28.3%) with ASD and 12,397 (40.3%) NT controls (p < 0.001, 95% CI: -5.43 to -2.36). Individuals with DS with higher body mass index (BMI) were found to be more likely to have lower levels of vitamin D (p < 0.001, 95% CI: -0.3849 to -0.1509). Additionally, having both DS and a neurologic diagnosis increased the likelihood of having lower vitamin D levels (p < 0.001, 95% CI: -5.02 to -1.28). Individuals with DS and autoimmune disease were much more likely to have lower vitamin D levels (p < 0.001, 95% CI: -6.22 to -1.55). Similarly, a history of autoimmunity in a first-degree relative also increased the likelihood of having lower levels of vitamin D in persons with DS (p = 0.01, 95% CI: -2.45 to -0.63)., Conclusions: Individuals with DS were noted to have hypovitaminosis D in comparison to individuals with ASD and NT controls. Associations between vitamin D deficiency and high BMI, personal autoimmunity, and familial autoimmunity were present in individuals with DS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Mistrust in the information and treatment provided by medical professionals and organizations hinders cancer screening among African Americans. However, its impact on responses to health messaging aimed at bolstering screening uptake is unknown. The present study examined the effects of medical mistrust on message framing and culturally targeted health messaging about colorectal cancer (CRC) screening. Screening eligible African Americans (N = 457) completed the Group-Based Medical Mistrust scale and then viewed an informational video about CRC risks, prevention, and screening, during which all participants received either a gain or loss-framed message about screening. Half of participants received an additional culturally targeted screening message. After messaging, all participants completed Theory of Planned Behavior measures of CRC screening receptivity, as well as items assessing expectations about experiencing racism when obtaining CRC screening (i.e., anticipatory racism). Hierarchical multiple regressions showed that medical mistrust predicted lower screening receptivity and greater anticipatory racism. Additionally, effects of health messaging were moderated by medical mistrust. Among participants high in mistrust, targeted messaging-regardless of message frame-bolstered normative beliefs about CRC. Additionally, only targeted loss-framed messaging bolstered attitudes toward CRC screening. Although targeted messaging reduced anticipatory racism among participants with high mistrust, anticipatory racism did not mediate messaging effects. Findings indicate medical mistrust may be an important culturally-relevant individual difference to attend to in addressing CRC screening disparities, including its potential to impact responses to cancer screening messaging., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2  = 11.82, P = 0.001), abnormal MRI (χ 2  = 7.78, P = 0.005), and abnormal LP (χ 2  = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD., (© 2023. Springer Nature Limited.)

Background: Cancer clinical trial participation is low and inequitable. Partnering Around Cancer Clinical Trials (PACCT) addressed systemic and interpersonal barriers through an observational study of eligibility and an intervention to improve patient-physician communication and trial invitation rates., Methods: Physicians at two comprehensive cancer centers and Black and White men with prostate cancer participated. Patients were followed for 2 years to determine whether they became potentially eligible for an available therapeutic trial. Potentially eligible patients were randomized to receive a trials-focused Question Prompt List or usual care. Patient-physician interactions were video-recorded. Outcomes included communication quality and trial invitation rates. Descriptive analyses assessed associations between sociodemographic characteristics and eligibility and effects of the intervention on outcomes., Results: Only 44 (22.1%) of participating patients (n = 199) became potentially eligible for an available clinical trial. Patients with higher incomes were more often eligible (>$80,000 vs. <$40,000, adjusted OR = 6.06 [SD, 1.97]; $40,000-$79,000 vs. <$40,000, adjusted OR = 4.40 [SD, 1.81]). Among eligible patients randomized to the intervention (n = 19) or usual care (n = 25), Black patients randomized to the intervention reported participating more actively than usual care patients, while White intervention patients reported participating less actively (difference, 0.41 vs. -0.34). Intervention patients received more trial invitations than usual care patients (73.7% vs. 60.0%); this effect was greater for Black (80.0% vs. 30.0%) than White patients (80.0% vs. 66.7%)., Conclusions: Findings suggest the greatest enrollment barrier is eligibility for an available trial, but a communication intervention can improve communication quality and trial invitation rates, especially for eligible Black patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The current study investigated whether culturally targeted message frames alter preferences for specific colorectal cancer (CRC) screening modalities among African Americans., Method: African Americans who were eligible for CRC screening ( N = 457) viewed a video about CRC risks, prevention, and recommended screening options. Participants then received a gain or loss-framed message about screening, with half of participants viewing an additional culturally targeted message about overcoming disparities in CRC through screening. Participants reported their desired thoroughness in CRC screening and preferences for being screened using colonoscopy, sigmoidoscopy, or stool-based fecal immunochemical testing., Results: Relative to gain-framing, loss-framed messaging enhanced desired thoroughness in CRC screening. Targeted loss-framing enhanced preferences for colonoscopy and decreased preferences for stool-based FIT screening., Conclusions: Findings demonstrate that message framing and culturally targeted messaging can impact CRC screening preferences. Altering preferences may carry implications for reducing CRC screening disparities among African Americans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: This study is the ninth cross-sectional community study of fetal alcohol spectrum disorders (FASD) conducted by the multidisciplinary Fetal Alcohol Syndrome Epidemiology Research team in the Western Cape Province of South Africa. It is the third comprehensive study of FASD in a rural, agricultural region of South Africa., Methods: Population-based, active case ascertainment methods were employed among a school-based cohort to assess child physical and neurobehavioral traits, and maternal risk factor interviews were conducted to identify all children with FASD to determine its prevalence., Results: Consent was obtained for 76.7% of 1158 children attending first grade in the region's public schools. Case-control results are presented for 95 with fetal alcohol syndrome (FAS), 64 with partial fetal alcohol syndrome (PFAS), 77 with alcohol-related neurodevelopmental disorder (ARND), 2 with alcohol-related birth defects (ARBD), and 213 randomly-selected controls. Four techniques estimating FASD prevalence from in-person examinations and testing yielded a range of total FASD prevalence of 206-366 per 1000. The final weighted, estimated prevalence of FAS was 104.5 per 1000, PFAS was 77.7 per 1000, ARND was 125.2 per 1000, and total FASD prevalence was 310 per 1000 (95% CI = 283.4-336.7). Expressed as a percentage, 31% had FASD. Although the rate of total FASD remained steady over 9 years, the proportion of children within the FASD group has changed significantly: FAS trended down and ARND trended up. A detailed evaluation is presented of the specific child physical and neurobehavioral traits integral to assessing the full continuum of FASD. The diagnosis of a child with FASD was significantly associated with maternal proximal risk factors such as: co-morbid prenatal use of alcohol and tobacco (OR = 19.1); maternal drinking of two (OR = 5.9), three (OR = 5.9), four (OR = 38.3), or more alcoholic drinks per drinking day; and drinking in the first trimester (OR = 8.4), first and second trimesters (OR = 17.7), or throughout pregnancy (OR = 18.6). Distal maternal risk factors included the following: slight or small physical status (height, weight, and head circumference), lower BMI, less formal education, late recognition of pregnancy, and higher gravidity, parity, and older age during the index pregnancy., Conclusion: The prevalence of FASD remained a significant problem in this region, but the severity of physical traits and anomalies within the continuum of FASD is trending downwards., (© 2022 Research Society on Alcoholism.)

We compared growth, physical features, and minor anomalies in 131 first-grade children with fetal alcohol spectrum disorders (FASD) to those of a representative comparison group of typically developing children from the same populations (n = 1212). The data were collected from three regional sites in the NIAAA-funded Collaboration on FASD Prevalence (CoFASP). Dysmorphology examinations were performed by a team of expert clinical geneticists, and FASD diagnoses were assigned according to the Revised Institute of Medicine Guidelines, which include assessments of growth, dysmorphology, neurobehavior, and maternal risk interviews. We present detailed data on 32 physical traits, minor anomalies, and a summary dysmorphology score for children within each of the four diagnostic categories in the continuum of FASD. There were few differences in the frequency of FASD diagnoses by race or Hispanic ethnicity. Children with FASD were born to mothers who reported using alcohol, tobacco (28.3%), and other drugs (14.2%) during pregnancy. Controlling for tobacco and other drug use, risk analysis indicated that women with a drinking pattern of 3 drinks per drinking day prior to pregnancy were 10 times more likely (p < 0.001, OR = 9.92, 95% CI: 4.6-21.5) to bear a child with FASD than those who reported abstinence prior to pregnancy., (© 2022 Wiley Periodicals LLC.)

Background: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention., Methods: A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms., Results: Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective., Conclusions: This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology., (© 2022. The Author(s).)

Splenic lesions are commonly discovered incidentally at imaging, without clinical signs or symptoms that may aid in diagnosis. As such, the differential diagnosis and subsequent management are based primarily on imaging characteristics. Much has been written about the myriad pathologic conditions that can occur in the spleen; however, there is little guidance on the approach to an incidental splenic mass. Applying an approach frequently used in imaging to the splenic mass-based on the number and consistency of lesions and refined by supplementary imaging features-allows formulation of a useful differential diagnosis. Solitary cystic masses include true cysts, pseudocysts, and parasitic cysts. When multiple cystic lesions are present, the differential diagnosis expands to include infectious lesions (abscess or microabscesses) and lymphangioma (a benign cystic neoplasm). Hemangioma is the most common solitary solid mass, although other vascular lesions (hamartoma, sclerosing angiomatoid nodular transformation) and nonvascular lesions (inflammatory pseudotumor, lymphoma) manifest as solitary and solid. When multiple solid masses are present, diffuse inflammatory disease (sarcoidosis), littoral cell angioma, and lymphoma should be considered. Malignancies, such as angiosarcoma or metastasis, can manifest as solitary or multiple and solid or cystic masses but are typically associated with symptoms or widespread primary malignancy. Careful assessment of the multimodality imaging characteristics of splenic lesions based on this approach aids the radiologist faced with the incidental splenic lesion. Online supplemental material is available for this article. Work of the U.S. Government published under an exclusive license with the RSNA.

Pathogenic variants in RPS6KA3 are associated with Coffin-Lowry syndrome (CLS), an X-linked semidominant disorder characterized by intellectual disability, stimulus-induced drop attacks, distinctive facial features, progressive kyphoscoliosis, and digit anomalies in hemizygous males. Heterozygous females may also have features of CLS; however, there can be considerable phenotypic variation, often attributed to ratios of X-inactivation in various tissue types. Although skeletal anomalies and short stature are hallmarks of CLS, hypercalcemia has not been reported. Here we describe a 30-month-old girl with gross motor delays, short stature, dysmorphic features, bilateral duplicated renal collecting systems, and no family history of hypercalcemia who required multiple admissions for idiopathic hypercalcemia necessitating bisphosphonate infusions at 12.5 and 15 months of age. A maternally inherited likely-pathogenic variant in RPS6KA3 was identified by trio exome sequencing, consistent with the diagnosis of CLS in the proband and her mother. Maternal history was notable only for decreased height compared to first-degree relatives, bilateral genu valgum, and a bicornuate uterus; she was later found to also have a partially duplicated left renal collecting system. Subsequent X-inactivation studies in blood aligned with the phenotypic variation between mother and daughter. Although hypercalcemia is not a reported feature in CLS, there is evidence of interrupted osteoblast differentiation, providing a potential mechanism for hypercalcemia in this genetic condition. The hypercalcemia in this case may represent a severe presentation of an unrecognized clinical feature in CLS that resolves with age. This case further highlights the intrafamilial phenotypic variation of CLS among females, suggesting X-inactivation as the underlying mechanism, and demonstrates the value of exome sequencing in patients for whom a genetic disorder is highly suspected but not identified despite thorough evaluation.

Purpose: Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS, with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single-institution designs. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Preoperative Radiosurgery for Brain Metastases [PROPS-BM])., Methods and Materials: Patients with brain metastases (BM) from solid cancers who had at least 1 lesion treated with preoperative SRS and underwent a planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease (MD) was categorized as either nodular or classical "sugarcoating" (cLMD)., Results: The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection, and 98.8% were treated with a single fraction to a median dose of 15 Gray to a median gross tumor volume of 9.9 cc. Cavity local recurrence (LR) rates at 1 and 2 years were 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio, 9.1; P < .001). One and 2-year rates of MD were 6.1% and 7.6% and of any grade ARE were 4.7% and 6.8% , respectively. The median overall survival (OS) duration was 16.9 months and the 2-year OS rate was 38.4%. The majority of MD was cLMD (13 of 19 patients with MD; 68.4%). Of 242 patients, 10 (4.1%) experienced grade ≥3 postoperative surgical complications., Conclusions: To our knowledge, this multicenter study represents the largest cohort treated with preoperative SRS. The favorable outcomes previously demonstrated in single-institution studies, particularly the low rates of MD and ARE, are confirmed in this expanded multicenter analysis, without evidence of an excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and is currently being designed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Utilize a random sample to estimate the prevalence, child traits, and maternal risk for fetal alcohol spectrum disorders (FASD) in a Southeastern United States county., Methods: From all first-grade students (n = 1073) a simple random sample was drawn, and 32 % (n = 231) were consented. All 231 children were examined for dysmorphology and growth, 84 were tested and rated on neurobehavior, and 72 mothers were interviewed for maternal risk., Results: Significant differences (α = .05) between the physical traits of children diagnosed with FASD and the entire sample were height, weight, head circumference, body mass index, and total dysmorphology scores, and all three cardinal features of fetal alcohol syndrome: palpebral fissure length, smooth philtrum, and narrow vermilion. Intellectual function and inhibition were not significantly different between FASD and typically-functioning children, but two executive function measures and one visual/spatial measure approached significance (α = .10). Three behavioral measures were significantly worse for the FASD group: parent-rated problems of communication, daily living, and socialization. Significant maternal risk factors reported were postpartum depression, frequency of drinking, and recovery from problem drinking. The prevalence of FASD was 71.4 per 1,000 or 7.1 %. This rate falls clearly within the prevalence range identified in eight larger samples of other communities in the Collaboration on FASD Prevalence (CoFASP) study in four regions of the United States., Conclusion: Careful and detailed clinical evaluation of children from small random samples can be useful for estimating the prevalence and traits of FASD in a community., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To determine if elevated rates of autoimmune disease are present in children with both Down syndrome and moyamoya disease given the high rates of autoimmune disease reported in both conditions and unknown etiology of angiopathy in this population. Methods: A multi-center retrospective case-control study of children with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome without cerebrovascular disease was performed. Outcome measures included presence of autoimmune disease, presence of autoantibodies and angiopathy severity data. Comparisons across groups was performed using the Kruskal-Wallis, χ2 and multivariate Poisson regression. Results: The prevalence of autoimmune disease were 57.7, 20.3, and 35.3% in persons with Down syndrome and moyamoya syndrome, idiopathic moyamoya disease, and Down syndrome only groups, respectively ( p < 0.001). The prevalence of autoimmune disease among children with Down syndrome and moyamoya syndrome is 3.2 times ( p < 0.001, 95% CI: 1.82-5.58) higher than the idiopathic moyamoya group and 1.5 times ( p = 0.002, 95% CI: 1.17-1.99) higher than the Down syndrome only group when adjusting for age and sex. The most common autoimmune diseases were thyroid disorders, type I diabetes and Celiac disease. No individuals with idiopathic moyamoya disease had more than one type of autoimmune disorder while 15.4% of individuals with Down syndrome and moyamoya syndrome and 4.8% of individuals with Down syndrome only had >1 disorder ( p = 0.05, 95%CI: 1.08-6.08). Interpretation: This study reports elevated rates of autoimmune disease in persons with Down syndrome and moyamoya syndrome providing a nidus for study of the role of autoimmunity in angiopathy in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Santoro, Lee, Wang, Ho, Nagesh, Khoshnood, Tanna, Durazo-Arvizu, Manning, Skotko, Steinberg and Rafii.)

Cystic lesions found in and around the peritoneal cavity can often be challenging to diagnose owing to significant overlap in imaging appearance between the different entities. When the cystic lesion can be recognized to arise from one of the solid abdominal organs, the differential considerations can be more straightforward; however, many cystic lesions, particularly when large, cannot be clearly associated with one of the solid organs. Cystic lesions arising from the mesentery and peritoneum are less commonly encountered and can be caused by relatively rare entities or by a variant appearance of less-rare entities. The authors provide an overview of the classification of cystic and cystic-appearing lesions and the basic imaging principles in evaluating them, followed by a summary of the clinical, radiologic, and pathologic features of various cystic and cystic-appearing lesions found in and around the peritoneal cavity, organized by site of origin. Emphasis is given to lesions arising from the mesentery, peritoneum, or gastrointestinal tract. Cystic lesions arising from the liver, spleen, gallbladder, pancreas, urachus, adnexa, or soft tissue are briefly discussed and illustrated with cases to demonstrate the overlap in imaging appearance with mesenteric and peritoneal cystic lesions. When approaching a cystic lesion, the key imaging features to assess include cyst content, locularity, wall thickness, and presence of internal septa, solid components, calcifications, or any associated enhancement. While definitive diagnosis is not always possible with imaging, careful assessment of the imaging appearance, location, and relationship to adjacent structures can help narrow the differential diagnosis. Online supplemental material is available for this article. © RSNA, 2021.

Objective: To investigate gestational age and growth at birth as predictors of fetal alcohol spectrum disorders (FASD)., Methods: The sample analyzed here comprises 737 randomly selected children who were assessed for growth, dysmorphology, and neurobehavior at 7 years of age. Maternal interviews were conducted to ascertain prenatal alcohol exposure and other maternal risk factors. Birth data originated from clinic records and the data at 7 years of age originated from population-based, in-school studies. Binary linear regression assessed the relationship between preterm birth, small for gestational age (SGA), and their combination on the odds of a specific FASD diagnosis or any FASD., Results: Among children diagnosed with FASD at 7 years of age (n = 255), a review of birth records indicated that 18.4% were born preterm, 51.4% were SGA, and 5.9% were both preterm and SGA. When compared to non-FASD controls (n = 482), the birth percentages born preterm, SGA, and both preterm and SGA were respectively 12.0%, 27.7%, and 0.5%. Mothers of children with FASD reported more drinking during all trimesters, higher gravidity, lower educational attainment, and older age at pregnancy. After controlling for usual drinks per drinking day in the first trimester, number of trimesters of drinking, maternal education, tobacco use, and maternal age, the odds ratio of an FASD diagnosis by age 7 was significantly associated with SGA (OR = 2.16, 95% CI: 1.35 to 3.45). SGA was also significantly associated with each of the 3 most common specific diagnoses within the FASD continuum: fetal alcohol syndrome (FAS; OR = 3.1), partial FAS (OR = 2.1), and alcohol-related neurodevelopmental disorder (OR = 2.0)., Conclusion: SGA is a robust early indicator for FASD in this random sample of children assessed at 7 years of age., (© 2021 by the Research Society on Alcoholism.)

A new route to azocines and benzoazocines from furopyridinones is described through a photochemically induced [1,3]-sigmatropic rearrangement. The method gives access to these 8-membered nitrogen heterocycles from dimethyl squarate in four stages and with excellent atom economy by sequencing thermal and photochemical ring expansion steps under continuous flow.

Purpose: To assess the ability of the ring-enhancing sign and focal necrosis to diagnose adenosquamous carcinoma (ASqC), a variant of pancreatic ductal adenocarcinoma (PDAC), on MRI and CT., Methods: The following features of ASqC and conventional PDAC were evaluated on CT and MRI: tumor size, location, margins, borders (non-exophytic, exophytic), and T1 signal intensity. Two readers, blinded to histopathology results, rated their confidence in detecting ring-enhancement and focal necrosis (FN) on a 5-point Likert scale on both MRI and CT. Inter-reader agreement was assessed with Cohen's kappa (k)., Results: A total of 24 patients were included: eight patients with treatment naïve and histologically proven ASqC (six women, mean age: 63, range: 40-75) and 16 patients with PDAC (eight women, mean age: 67, range: 47-83). Statistically significant differences between ASqC and PDAC were seen in tumor size, location, presence of FN, and ring enhancement (p = 0.01-0.037). The readers were more confident in depicting the key differentiating feature ring-enhancement in ASqC on MRI compared to CT (confidence 1.71 ± 0.49 vs. 0.88 ± 0.35, p = 0.017) with moderate inter-reader agreement (k = 0.46 and 0.5, respectively). FN showed substantial inter-reader agreement on MR and moderate agreement on CT (k = 0.67 and 0.5, respectively)., Conclusions: Compared to CT, MRI depicts ring-enhancement in ASqC with greater reader confidence and FN in ASqC with higher inter-reader agreement. The concurrent presence of these two imaging features should raise high suspicion for ASqC., (Published by Elsevier Inc.)

The epidemiology and clinical management of esophageal carcinomas are changing, and clinical imagers are required to understand both the imaging appearances of common cancers and the pathologic diagnoses that drive management. Rare esophageal malignancies and benign esophageal neoplasms have distinct imaging features that may suggest a diagnosis and guide the next steps clinically. Furthermore, these imaging features have a basis in pathology, and this article focuses on the relationship between pathologic features and imaging manifestations that will help an informed imager maintain clinical relevance., Competing Interests: Disclosure J.P. Lichtenberger—Author, Elsevier. A.R. Dulberger—The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Army, Navy, Air Force, or Defense., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described., Methods and Materials: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT., Results: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92)., Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation., (© 2021 The Authors.)

Background: Prevalence and characteristics of fetal alcohol spectrum disorders (FASD) have been described previously in this community., Methods: Active case ascertainment methods were employed in a new cross-sectional study with Revised Institute of Medicine criteria among first grade students (n = 735) via dysmorphology examinations and neurobehavioral assessments. Their mothers were interviewed regarding risk factors. Final diagnoses were assigned via structured case conferences., Results: Children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and alcohol related-neurodevelopmental disorder (ARND) were significantly different from controls on all cardinal variables, multiple dysmorphology traits and neurobehavioral performance. Mothers of children with FASD reported significantly more drinking before and during pregnancy (mothers of children with FAS reported 7.8 (±6.1) drinks per drinking day (DDD) prior to pregnancy and 5.1 (±5.9) after pregnancy recognition). Distal risk variables for a diagnosis on the continuum of FASD were: lower maternal height, weight, and body mass index; higher gravidity; lower education and household income; and later pregnancy recognition. Alcohol and tobacco remain the only commonly used drugs. Women reporting first trimester drinking of two DDD were 13 times more likely (95 % CI:1.3-133.4) to have a child with FASD than non-drinkers; and those who reported drinking throughout pregnancy were 19.4 times more likely (95 % CI:8.2-46.0) to have a child with FASD., Conclusion: Seventeen years after the first study in this community, FASD prevalence remains high at 16 %-31 %. The FAS rate may have declined somewhat, but rates of PFAS and ARND seemed to plateau, at a high rate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Family history (FH) remains one of the strongest risk factors for many common cancers and is used to determine cancer genetic counseling (CGC) eligibility, but the understanding of familial cancer patterns in African Americans is limited., Methods: This study evaluated cancer FH among African Americans with invasive breast cancer, prostate cancer, lung cancer, or colorectal cancer (CRC) in the Detroit Research on Cancer Survivors (ROCS) cohort. Associations between participant cancer type, site-specific FH, and meeting national guidelines for CGC were evaluated via logistic regression. Cancer FH patterns were evaluating via hierarchical clustering., Results: Among 1500 ROCS participants, 71% reported at least 1 first-degree relative or grandparent with cancer. FHs of breast cancer, CRC, lung cancer, and prostate cancer were most common among participants with the same diagnosis (odds ratio [OR] for breast cancer, 1.14; P < .001; OR for CRC, 1.08; P = .003; OR for lung cancer, 1.09; P = .008; OR for prostate cancer, 1.14; P < .001). Nearly half of the participants (47%) met national CGC guidelines, and 24.4% of these participants met CGC criteria on the basis of their cancer FH alone. FH was particularly important in determining CGC eligibility for participants with prostate cancer versus breast cancer (OR for FH vs personal history alone, 2.91; 95% confidence interval, 1.94-4.35; P < .001). In clustering analyses, breast and prostate cancer FH-defined clusters were common across all participants. Clustering of CRC and breast cancer FHs was also observed., Conclusions: ROCS participants reported high rates of cancer FH. The high rate of eligibility for CGC among ROCS participants supports the need for interventions to increase referrals and uptake of CGC among African Americans., (© 2020 American Cancer Society.)

Importance: Black individuals are underrepresented in cancer clinical trials., Objective: To examine whether Black and White men with prostate cancer differ in their willingness to discuss clinical trials with their physicians and, if so, whether patient-level barriers statistically mediate racial differences., Design, Setting, and Participants: This cross-sectional survey study used baseline data from Partnering Around Cancer Clinical Trials, a randomized clinical trial to increase Black individuals' enrollment in prostate cancer clinical trials. Data were collected from 2016 through 2019 at 2 National Cancer Institute-designated comprehensive cancer centers; participants were Black and White men with intermediate-risk to high-risk prostate cancer. In mediation analysis, path models regressed willingness onto race and each potential mediator, simultaneously including direct paths from race to each mediator. Significant indirect effect sizes served as evidence for mediation., Exposures: Race was the primary exposure. Potential mediators included age, education, household income, perceived economic burden, pain/physical limitation, health literacy, general trust in physicians, and group-based medical suspicion., Main Outcomes and Measures: The primary outcome was the answer to a single question: "If you were offered a cancer clinical trial, would you be willing to hear more information about it?", Results: A total of 205 participants were included (92 Black men and 113 White men), with a mean (range) age of 65.7 (45-89) years; 32% had a high school education or lower, and 27.5% had a household income of less than $40 000. Most (88.3%) reported being definitely or probably willing to discuss trials, but White participants were more likely to endorse this highest category of willingness than Black participants (82% vs 64%; χ22 = 8.81; P = .01). Compared with White participants, Black participants were younger (F1,182 = 8.67; P < .001), less educated (F1,182 = 22.79; P < .001), with lower income (F1,182 = 79.59; P < .001), greater perceived economic burden (F1,182 = 42.46; P < .001), lower health literacy (F1,184 = 9.84; P = .002), and greater group-based medical suspicion (F1,184 = 21.48; P < .001). Only group-based medical suspicion significantly mediated the association between race and willingness to discuss trials (indirect effect, -0.22; P = .002)., Conclusions and Relevance: In this study of men with prostate cancer, most participants were willing to discuss trials, but Black men were significantly less willing than White men. Black men were more likely to believe that members of their racial group should be suspicious of the health care system, and this belief was associated with lower willingness to discuss trials. Addressing medical mistrust may improve equity in clinical research.

Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and neurologic deficits in individuals exposed to alcohol prenatally. Reduced palpebral fissure length is one of the cardinal facial features of FASD. However, other ocular measurements have not been studied extensively in FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how inner canthal distance (ICD), interpupillary distance (IPD), and outer canthal distance (OCD) centiles differed between FASD and non-FASD individuals. We compared ocular measurement centiles in children with FASD to non-FASD individuals and observed reductions in all three centiles for ICD, IPD, and OCD. However, when our non-FASD children who had various forms of growth deficiency (microcephaly, short-stature, or underweight) were compared to controls, we did not observe a similar reduction in ocular measurements. This suggests that reductions in ocular measurements are a direct effect of alcohol on ocular development independent of its effect on growth parameters, which is consistent with animal models showing a negative effect of alcohol on developing neural crest cells. Interpupillary distance centile appeared to be the most significantly reduced ocular measure we evaluated, suggesting it may be a useful measure to be considered in the diagnosis of FASD., (© 2020 Wiley Periodicals LLC.)

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.

Background: Reports continue to show that Blacks with curable lung or breast cancer complete treatment less often than similar Whites contributing to worse survival. ACCURE is an intervention trial designed to address this problem., Patients and Methods: A pragmatic, quality improvement trial comparing an intervention group to retrospective and concurrent controls. Patients with early stage breast or lung cancer aged 18 to 85 were enrolled (N = 302) at 2 cancer centers between April 2013 and March 2015 for the intervention component. Data from patients seen between January 2007 and December 2012 with these diagnoses were obtained to establish control completion rates. Concurrent data for non-study patients were used to identify secular trends. The intervention included: a real time registry derived from electronic health records of participants to signal missed appointments or unmet care milestones, a navigator, and clinical feedback. The primary outcome was "Treatment Complete", a composite variable representing completion of surgery, recommended radiation and chemotherapy for each patient., Results: The mean age in the intervention group was 63.1 years; 37.1% of patients were Black. Treatment completion in retrospective and concurrent controls showed significant Black-White differences (Blacks (B) 79.8% vs. Whites (W) 87.3%, p < 0.001; 83.1% B vs. 90.1% W, p < 0.001, respectively). The disparity lessened within the intervention (B 88.4% and W 89.5%, p = 0.77). Multivariate analyses confirmed disparities reduction. OR for Black-White disparity within the intervention was 0.98 (95% CI 0.46-2.1); Black completion in the intervention compared favorably to Whites in retrospective (OR 1.6; 95% CI 0.90-2.9) and concurrent (OR 1.1; 95% CI 0.59-2.0) controls., Conclusion: A real time registry combined with feedback and navigation improved completion of treatment for all breast and lung cancer patients and narrowed disparities. Similar multi-faceted interventions could mitigate disparities in the treatment of other cancers and chronic conditions., (Copyright © 2019 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC), an epithelial neoplasm derived from the pancreatic ductal tree, is the most common histologic type of pancreatic cancer and accounts for 85%-95% of all solid pancreatic tumors. As a highly lethal malignancy, it is the seventh leading cause of cancer death worldwide and is responsible for more than 300 000 deaths per year. PDAC is highly resistant to current therapies, affording patients a 5-year overall survival rate of only 7.2%. It is characterized histologically by its highly desmoplastic stroma embedding tubular and ductlike structures. On images, it typically manifests as a poorly defined hypoenhancing mass, causing ductal obstruction and vascular involvement. Little is known about the other histologic subtypes of PDAC, mainly because of their rarity and lack of specific patterns of disease manifestation. According to the World Health Organization, these variants include adenosquamous carcinoma, colloid carcinoma, hepatoid carcinoma, medullary carcinoma, signet ring cell carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, and undifferentiated carcinoma. Depending on the subtype, they can confer a better or even worse prognosis than that of conventional PDAC. Thus, awareness of the existence and differentiation of these variants on the basis of imaging and histopathologic characteristics is crucial to guide clinical decision making for optimal treatment and patient management.

Objective: To detail the characteristic traits of children with fetal alcohol spectrum disorders (FASDs) and maternal risk factors in a southeastern U.S. County., Methods: Independent samples were drawn from 2 different cohorts of first-grade students. All consented children (49.8%) were measured for height, weight, and head circumference, and those ≤ 25th centile entered the study along with a random sample drawn from all enrolled students. Study children were examined for physical growth, dysmorphology, and neurobehavior, and their mothers were interviewed., Results: Total dysmorphology scores discriminated well the physical traits of children across the FASD continuum: fetal alcohol syndrome (FAS) = 15.8, partial FAS (PFAS) = 10.8, alcohol-related neurobehavioral disorder (ARND) = 5.2, and typically developing controls = 4.4. Additionally, a neurobehavioral battery distinguished children with each FASD diagnosis from controls. Behavioral problems qualified more children for FASD diagnoses than cognitive traits. Significant proximal maternal risk variables were as follows: reports of prepregnancy drinking, drinking in any trimester, and comorbid use of other drugs in lifetime and during pregnancy, especially alcohol and marijuana (14.9% among mothers of children with FASD vs. 0.4% for controls). Distal maternal risks included reports of other health problems (e.g., depression), living unmarried with a partner during pregnancy, and a lower level of spirituality. Controlling for other drug use during pregnancy, having a child diagnosed with a FASD was 17.5 times greater for women who reported usual consumption of 3 drinks per drinking day prior to pregnancy than for nondrinking mothers (p < 0.001, 95% CI = 5.1 to 59.9). There was no significant difference in the prevalence of FASD by race, Hispanic ethnicity, or socioeconomic status. The prevalence of FASD was not lower than 17.3 per 1,000, and weighted estimated prevalence was 49.0 per 1,000 or 4.9%., Conclusion: This site had the second lowest rate in the CoFASP study, yet children with FASD are prevalent., (© 2020 by the Research Society on Alcoholism.)

Objective: To determine the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers in a Midwestern city., Methods: Case-control samples were drawn from 2 separate first-grade cohorts (combined N = 4,047) in every city school using different methods. In Cohort Sample 1, all consented small children (≤25th centile on height, weight, and/or head circumference) entered the study along with a random sample from all enrolled students. Cohort Sample 2 was drawn totally at random. Child growth, dysmorphology, and neurobehavior were assessed using the Collaboration on FASD Prevalence (CoFASP) criteria, and mothers were interviewed., Results: For the samples combined, 891 children received dysmorphology examinations, and 692 were case-conferenced for final diagnosis. Forty-four children met criteria for FASD. Total dysmorphology scores differentiated diagnostic groups: fetal alcohol syndrome (FAS), 16.7; partial FAS, 11.8; alcohol-related neurodevelopmental disorder (ARND), 6.1; and typically developing controls, 4.2. Neurobehavioral tests distinguished children with FASD from controls, more for behavioral problems than cognitive delay. Children with ARND demonstrated the poorest neurobehavioral indicators. An adjusted regression model of usual prepregnancy drinking indicated that maternal reports of 3 drinks per drinking day (DDD) were significantly associated with a FASD diagnosis (p = 0.020, OR = 10.1, 95% CI = 1.44 to 70.54), as were 5 or more DDD (p < 0.001, OR = 26.47, 95% CI = 4.65 to 150.62). Other significant maternal risk factors included the following: self-reported drinking in any trimester; smoking and cocaine use during pregnancy; later pregnancy recognition and later and less prenatal care; lower maternal weight, body mass index (BMI), and head circumference; and unmarried status. There was no significant difference in FASD prevalence by race, Hispanic ethnicity, or socioeconomic status at this site, where the prevalence of FASD was 14.4 to 41.2 per 1,000 (1.4 to 4.1%)., Conclusion: This city displayed the lowest prevalence of FASD of the 4 CoFASP sites. Nevertheless, FASD were common, and affected children demonstrated a common, recognizable, and measurable array of traits., (© 2020 by the Research Society on Alcoholism.)

Background: Lung cancer is the leading cause of cancer death in the US, and significant racial disparities exist in lung cancer outcomes. For example, Black men experience higher lung cancer incidence and mortality rates than their White counterparts. New screening recommendations for low-dose computed tomography (LDCT) promote earlier detection of lung cancer in at-risk populations and can potentially help mitigate racial disparities in lung cancer mortality if administered equitably. Yet, little is known about the extent of racial differences in uptake of LDCT., Objective: To evaluate potential racial disparities in LDCT screening in a large community-based cancer center in central North Carolina., Methods: We conducted a retrospective study of the initial patients undergoing LDCT in a community-based cancer center (n = 262). We used the Pearson chi-squared test to assess potential racial disparities in LDCT screening., Results: Study results suggest that Black patients may be less likely than White patients to receive LDCT screening when eligible (χ2 = 51.41, p < 0.0001)., Conclusion: Collaboration among healthcare providers, researchers, and decision makers is needed to promote LDCT equity., (Copyright © 2020 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To document prevalence and traits of children with fetal alcohol spectrum disorders (FASD) and maternal risk factors in a Rocky Mountain city., Methods: Variations on active case ascertainment methods were used in 2 first-grade cohorts in all city schools. The consent rate was 59.2%. Children were assessed for physical growth, dysmorphology, and neurobehavior and their mothers interviewed., Results: Thirty-eight children were diagnosed with FASD and compared with 278 typically developing controls. Total dysmorphology scores summarized well the key physical indicators of FASD and defined specific diagnostic groups. On average, children with FASD performed significantly poorer than controls on intellectual, adaptive, learning, attention, and behavioral tasks. More mothers of children with FASD reported drinking prior to pregnancy and in the first and second trimesters, and had partners with drinking problems than mothers of controls; however, reports of comorbid alcohol use and 6 other drugs were similar for mothers of children with FASD and mothers of controls. Mothers of children with FASD were significantly younger at pregnancy, had lower average weight before pregnancy and less education, initiated prenatal clinic visits later, and reported more health problems (e.g., stomach ulcers and accidents). Children with FASD had significantly lower birth weight and more problems at birth, and were less likely to be living with biological mother and father. Controlling for other drug and tobacco use, a FASD diagnosis is 6.7 times (OR = 6.720, 95% CI = 1.6 to 28.0) more likely among children of women reporting prepregnancy drinking of 3 drinks per drinking day (DDD) and 7.6 times (OR = 7.590, 95% CI = 2.0 to 31.5) more likely at 5 DDD. Prevalence of FAS was 2.9-5.8 per 1,000 children, and total FASD was 34.9 to 82.5 per 1,000 children or 3.5 to 8.3% at this site., Conclusion: This site had the second highest prevalence of FASD of the 4 Collaboration on FASD Prevalence sites and clearly identifiable child and maternal risk traits., (© 2020 by the Research Society on Alcoholism.)

Purpose: Cancer clinical trial accrual rates are low, and information about contributing factors is needed. We examined video-recorded clinical interactions to identify circumstances under which patients potentially eligible for a trial at a major cancer center were offered a trial., Methods: We conducted a qualitative directed content analysis of 62 recorded interactions with physicians (n = 13) and patients with intermediate- or high-risk prostate cancer (n = 43). Patients were screened and potentially eligible for a trial. We observed and coded the interactions in 3 steps: (1) classification of all interactions as explicit offer, offer pending, trial discussed/not offered, or trial not discussed; (2) in interactions with no explicit offer, classification of whether the cancer had progressed; (3) in interactions classified as progression but no trial offered, identification of factors discussed that may explain the lack of an offer., Results: Of the 62 interactions, 29% were classified as explicit offer, 12% as offer pending, 18% as trial discussed/not offered, and 39% as trial not discussed. Of those with no offer, 57% included information that the cancer had not progressed. In 68% of the remaining interactions with patients whose cancer had progressed but did not receive an offer, reasons for the lack of offer were identified, but in 32%, no explanation was provided., Conclusion: Even in optimal circumstances, few patients were offered a trial, often because their cancer had not progressed. Findings support professional recommendations to broaden trial inclusion criteria. Findings suggest accrual rates should reflect the proportion of eligible patients who enroll.

Xq22 deletions that encompass PLP1 (Xq22-PLP1-DEL) are notable for variable expressivity of neurological disease traits in females ranging from a mild late-onset form of spastic paraplegia type 2 (MIM# 312920), sometimes associated with skewed X-inactivation, to an early-onset neurological disease trait (EONDT) of severe developmental delay, intellectual disability, and behavioral abnormalities. Size and gene content of Xq22-PLP1-DEL vary and were proposed as potential molecular etiologies underlying variable expressivity in carrier females where two smallest regions of overlap (SROs) were suggested to influence disease. We ascertained a cohort of eight unrelated patients harboring Xq22-PLP1-DEL and performed high-density array comparative genomic hybridization and breakpoint-junction sequencing. Molecular characterization of Xq22-PLP1-DEL from 17 cases (eight herein and nine published) revealed an overrepresentation of breakpoints that reside within repeats (11/17, ~65%) and the clustering of ~47% of proximal breakpoints in a genomic instability hotspot with characteristic non-B DNA density. These findings implicate a potential role for genomic architecture in stimulating the formation of Xq22-PLP1-DEL. The correlation of Xq22-PLP1-DEL gene content with neurological disease trait in female cases enabled refinement of the associated SROs to a single genomic interval containing six genes. Our data support the hypothesis that genes contiguous to PLP1 contribute to EONDT., (© 2019 Wiley Periodicals, Inc.)

Gastroesophageal reflux disease (GERD) is a common condition and impairs the quality of life for millions of patients, accounts for considerable health care spending, and is a primary risk factor for esophageal adenocarcinoma. There have been substantial advances in understanding the pathogenesis of GERD and its complications and much progress in diagnosis and management of GERD; however, these have not been comprehensively discussed in the recent radiology literature. Understanding the role of imaging in GERD and its complications is important to aid in multidisciplinary treatment of GERD. GERD results from prolonged or recurrent reflux of gastric contents into the esophagus. Common symptoms include heartburn or regurgitation. Prolonged reflux of gastric contents into the esophagus can cause erosive esophagitis. Over time, the inflammatory response related to esophagitis can lead to deposition of fibrous tissue and development of strictures. Alternatively, the esophageal mucosa can undergo metaplasia (Barrett esophagus), a precursor to dysplasia (which can lead to adenocarcinoma). Conventional barium esophagography has long been considered the primary imaging modality for the esophagus, and the fluoroscopic findings for diagnosis of GERD have been well established. Multimodality imaging has a clear role in detection and assessment of the complications of GERD, specifically reflux esophagitis and Barrett esophagus; differentiation of benign and malignant strictures; and detection, staging, and posttreatment surveillance of esophageal adenocarcinoma. Given the dramatic changes in utilization of abdominal imaging during the past 2 decades, with significantly declining volume of fluoroscopic procedures and concomitant increase in CT and MRI studies, it is crucial that modern radiologists appreciate the value of barium esophagography in the workup of GERD and recognize the key imaging features of GERD and its complications at CT and MRI.