A Mouse Model with a Frameshift Mutation in the Nuclear Factor I/X (NFIX) Gene Has Phenotypic Features of Marshall-Smith Syndrome.

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall-Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6-10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix +/Del2, Nfix +/Del24, Nfix +/Del140, Nfix Del24/Del24, and Nfix Del140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but Nfix Del2/Del2 mice had significantly reduced viability (p < 0.002) and died at 2-3 weeks of age. Nfix Del2 was not cleared by NMD, and NfixDel2/Del2 mice, when compared to Nfix +/+ and Nfix +/Del2 mice, had: growth retardation; short stature with kyphosis; reduced skull length; marked porosity of the vertebrae with decreased vertebral and femoral bone mineral content; and reduced caudal vertebrae height and femur length. Plasma biochemistry analysis revealed Nfix Del2/Del2 mice to have increased total alkaline phosphatase activity but decreased C-terminal telopeptide and procollagen-type-1-N-terminal propeptide concentrations compared to Nfix +/+ and Nfix +/Del2 mice. Nfix Del2/Del2 mice were also found to have enlarged cerebral cortices and ventricular areas but smaller dentate gyrus compared to Nfix +/+ mice. Thus, Nfix Del2/Del2 mice provide a model for studying the in vivo effects of NFIX mutants that escape NMD and result in developmental abnormalities of the skeletal and neural tissues that are associated with MSS. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Advanced imaging of disease unrelated to the coronavirus disease 2019 (COVID-19) during the pandemic: effect of patient demographics in a pediatric emergency department.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affected children from underrepresented minorities and marginalized populations, but little is understood regarding the pandemic's effect on non-COVID-19-related illnesses. OBJECTIVE: To examine the effect of the COVID-19 pandemic and related stay-at-home orders on pediatric emergency department (ED) imaging of non-COVID-19-related diseases across patient demographic groups. MATERIALS AND METHODS: We retrospectively reviewed radiology reports from advanced imaging (US, CT, MRI and fluoroscopy) on children in the ED during the month of April for the years 2017, 2018, 2019 and 2020, excluding imaging for respiratory illness and trauma. We used imaging results and the electronic medical record to identify children with positive diagnoses on advanced imaging, and whether these children were admitted to the hospital. Demographic variables included age, gender, race/ethnicity and insurance type. We used multivariable Poisson regression models to report rate ratio (RR) and binomial logistic regression models to report odds ratio (OR) with 95% confidence interval (CI). RESULTS: We included 1,418 ED encounters for analysis. Compared to pre-2020, fewer children underwent ED imaging in April 2020 (RR 0.63, 95% CI 0.52, 0.76). The odds of positive imaging results increased (OR 2.18, 95% CI 1.59, 3.00) overall, and for all racial/ethnic groups except Hispanic patients (OR 0.83, 95% CI 0.34, 2.03). No differences occurred in admission rates for positive imaging results in 2020 compared to pre-2020. CONCLUSION: In April 2020 compared to pre-2020, there were decreased imaging and increased positivity rates for imaging for non-respiratory and non-trauma ED visits. COVID-19 stay-at-home advisories might have resulted in triaging for urgent health care by families or referring clinicians during this month of the pandemic.

Emergency pediatric radiology imaging trends for non-COVID-19-related illnesses through different stages of the pandemic.

PURPOSE: To evaluate how the COVID-19 pandemic affected the imaging utilization patterns for non-COVID-19-related illness in a pediatric emergency department (ED). METHODS: We retrospectively reviewed radiology reports for ultrasound, CT, MRI, and fluoroscopy studies performed at a pediatric ED in April from 2017 to 2021, excluding studies for respiratory symptoms and trauma. Radiology reports and medical records were reviewed to determine if patients had a positive radiology diagnosis, the type of diagnosis, and whether it required hospital admission. Results from during the pandemic were compared to predicted rates based on pre-pandemic years. RESULTS: A total of 2198 imaging studies were included. During the COVID-19 pandemic, fewer ED imaging studies were performed compared to predicted. The decrease was greater in April 2020 (RR = 0.56, p < 0.001) than in April 2021 (RR = 0.80, p = 0.038). The odds of positive diagnosis was higher during the pandemic than before, and higher in 2020 (OR 2.53, p < 0.001) than in 2021 (OR 1.38, p = 0.008). The expected numbers of positive diagnoses and hospital admittances remained within the predicted range during the pandemic (p = 0.505-0.873). CONCLUSIONS: Although imaging volumes decreased during the studied months of the pandemic, the number of positive findings was unchanged compared to prior years. No differences were demonstrated in the percentage of patients admitted to the hospital with positive imaging findings. This suggests that, at our institution, the pandemic did not lead to a substantial number of missed diagnoses or severely delay the diagnosis of non-COVID-related conditions. While still lower than expected, imaging volumes increased in April 2021 suggesting a return towards baseline patient behavior as the pandemic conditions improved.

Rationing and Disparities in Health Care: Implications for Radiology Clinical Practice Guidelines.

We examine the relationship between the rationing of health care resources and disparities in health care delivery and the specific implications for radiologic resource allocation frameworks such as the ACR Appropriateness Criteria. We explore what rationing is in this context and how it is manifested in radiology. We review how rationing has taken many forms and how rationing has influenced the development of disparities in access and outcomes within health care and specifically within the context of radiology. We describe how the relationship between rationing and health care delivery disparities manifested during the coronavirus disease 2019 pandemic and the corrective measures that were proposed to established rationing frameworks to facilitate more equitable pandemic-related resource distribution. We offer suggestions regarding how such solutions might be brought into radiologic resource allocation schemes to help mitigate disparities in radiologic care in the future.

The pediatric stomach - congenital abnormalities.

Diagnostic imaging of the pediatric stomach often provides a challenge for practicing radiologists. Radiologists should be aware of relatively unusual congenital pathology, especially when imaging very young children with gastrointestinal symptoms. We review congenital pathology of the pediatric stomach.

Ethical challenges in child abuse: what is the harm of a misdiagnosis?

In this article the author examines ethical tensions inherent to balancing harms of false-negative and false-positive child abuse diagnoses, and he describes how such tensions manifest in courtroom proceedings. Child abuse physicians, including pediatric radiologists, shoulder heavy responsibilities weighing the potential consequences of not diagnosing child abuse when it could have been diagnosed (false negatives) against the consequences of making the diagnosis when it has not occurred (false positives). These physicians, who practice under ethical obligations to serve children's best interests and protect them from harm, make daily practice decisions knowing that, on balance, abuse is substantially more underdiagnosed than over diagnosed. Legal justice advocates, however, emphasize that clinical decision-making around abuse is not disassociated from endemic injustices that unduly incriminate individuals from socioeconomically underprivileged populations. Some defense advocates charge that child abuse physicians are insufficiently sensitive to harms of erroneous diagnoses, and they have characterized these clinicians as frankly biased. To support their claims in court, defense advocates have enlisted likeminded physician witnesses whose credentials as experts flout professional standards and who provide consistently flawed testimony based upon deficiently peer-reviewed literature. This article concludes that, to help mitigate these unhealthy circumstances, child abuse physicians might build trust with criminal defense advocates by instituting measures to alleviate perceptions of biases and by more explicitly acknowledging the potential harms of erroneous diagnoses. Professional societies representing these physicians, such as the Society for Pediatric Radiology, could take concurrent measures to help better prepare their constituent clinicians for expert testimony and make them more available to testify.

Guidelines for expert testimony in pediatric radiology.

Pediatric radiologists have the professional and ethical duty to assist, inform and educate the legal system in regard to matters involving medical imaging in children. These guidelines, drafted by the Society for Pediatric Radiology Ethics Committee and approved by the Society for Pediatric Radiology Board of Directors, provide recommendations for expert legal testimony in pediatric radiology and codify minimal ethical norms for the pediatric radiology expert witness in legal proceedings.

Radiology Trainees' Perceptions of Speaking up Culture Related to Safety and Unprofessional Behavior in Their Work Environments.

OBJECTIVE. The purpose of this study was to compare radiology trainees' perceptions of the culture regarding speaking up about patient safety and unprofessional behavior in the clinical environment and to assess the likelihood that they will speak up in the presence of a medical hierarchy. MATERIALS AND METHODS. The study included radiology trainees from nine hospitals who attended a communication workshop. Trainees completed questionnaires assessing their perceptions of the support provided by their clinical environment regarding speaking up about patient safety and unprofessional behavior. We also queried their likelihood of speaking up within a team hierarchy about an error presented in a hypothetical clinical vignette. RESULTS. Of 61 participants, 58 (95%) completed questionnaires. Of these 58 participants, 84% felt encouraged by colleagues to speak up about safety concerns, and 57% felt encouraged to speak up about unprofessional behavior (p < .001). Moreover, 17% and 34% thought speaking up about safety concerns and unprofessional behavior, respectively, was difficult (p < .02). Trainees were less likely to agree that speaking up about unprofessional behavior (compared with speaking up about safety concerns) resulted in meaningful change (66% vs 95%; p < .001). In a vignette describing a sterile technique error, respondents were less likely to speak up to an attending radiologist (48%) versus a nurse, intern, or resident (79%, 84%, and 81%, respectively; p < .001). Significant predictors of the likelihood of trainees speaking up to an attending radiologist included perceived potential for patient harm as a result of the error (odds ratio [OR], 6.7; p < .001), perceptions of safety culture in the clinical environment (OR, 5.0; p = .03), and race or ethnicity (OR, 3.1; p = .03). CONCLUSION. Radiology trainees indicate gaps in workplace cultures regarding speaking up, particularly concerning unprofessional behavior and team hierarchy.

The pediatric stomach - masses and mass-like pathology.

Diagnostic imaging of pediatric gastric masses often provides a challenge for the practicing radiologist. Radiologists should be aware of this relatively unusual pathology, particularly in cross-sectional imaging findings. We will review pediatric gastric masses and mass-like lesions, focusing on neoplastic and inflammatory etiologies.

"I Sleep, But My Heart Is Awake": Negotiating marginal states in life and death.

This article compares a six-week fetus to a brain-dead boy to illustrate multiple inconsistencies and flaws in various prominent frameworks for determination of death by neurological criteria ("brain death"). The authors critically examine the biological and normative assumptions that distinguish these ethically ambiguous "marginal states" at the beginning and end of life and find no consistent biological or ethical criteria that coherently define the fetus as alive and the boy as dead. The authors note important contradictions in how medicine, bioethics, and society treat these marginal states, despite their striking biological and philosophical similarities, and conclude that these contradictions are ultimately untenable. They propose that rigid societal policy regarding brain death be abandoned in favor of more permissive policy that resembles those governing actions at the beginning of life, such as around abortion and embryonic stem cell research.

A Review of Resources and Methodologies Available for Teaching and Assessing Patient-Related Communication Skills in Radiology.

ACGME expectations for radiology trainees' proficiencies in communication skills pose a challenge to program directors who wish to develop curricula addressing these competencies. Numerous educational resources and pedagogical approaches have emerged to address such competencies specifically for radiology, but have yet to be systematically catalogued. In this paper, we review and compile these resources into a toolkit that will help residencies develop curricula around patient-centered communication. We describe numerous web-based resources and published models that have incorporated innovative, contemporary pedagogical techniques. In undertaking this compilation, our hope is to kindle discussion about the development of formalized or standardized communication curricula or guides for radiology residencies.

Attitudes of paediatric and obstetric specialists towards prenatal surgery for lethal and non-lethal conditions.

BACKGROUND: While prenatal surgery historically was performed exclusively for lethal conditions, today intrauterine surgery is also performed to decrease postnatal disabilities for non-lethal conditions. We sought to describe physicians' attitudes about prenatal surgery for lethal and non-lethal conditions and to elucidate characteristics associated with these attitudes. METHODS: Survey of 1200 paediatric surgeons, neonatologists and maternal-fetal medicine specialists (MFMs). RESULTS: Of 1176 eligible physicians, 670 (57%) responded (range by specialty, 54%-60%). In the setting of a lethal condition for which prenatal surgery would likely result in the child surviving with a severe disability, most respondents either disagreed (59%) or strongly disagreed (19%) that they would recommend the surgery. Male physicians were twice as likely to recommend surgery for the lethal condition, as were physicians who believe that abortion is morally wrong (OR 1.75; 95%CI 1.0 to 3.05). Older physicians were less likely to recommend surgery (OR 0.57; 95%CI 0.36 to 0.88). For non-lethal conditions, most respondents agreed (66% somewhat, 4% strongly) that they would recommend prenatal surgery, even if the surgery increases the risk of prematurity or fetal death. Compared with MFMs, surgeons were less likely to recommend such surgery, as were physicians not affiliated with a fetal centre, and physicians who were religious (ORs range from 0.45 to 0.64). CONCLUSION: Physician's attitudes about prenatal surgery relate to physicians' beliefs about disability as well as demographic, cultural and religious characteristics. Given the variety of views, parents are likely to receive different recommendations from their doctors about the preferable treatment choice.

Weighing the Social and Ethical Considerations of Maternal-Fetal Surgery.

OBJECTIVES: The ethics of maternal-fetal surgery involves weighing the importance of potential benefits, risks, and other consequences involving the pregnant woman, fetus, and other family members. We assessed clinicians' ratings of the importance of 9 considerations relevant to maternal-fetal surgery. METHODS: This study was a discrete choice experiment contained within a 2015 national mail-based survey of 1200 neonatologists, pediatric surgeons, and maternal-fetal medicine physicians, with latent class analysis subsequently used to identify groups of physicians with similar ratings. RESULTS: Of 1176 eligible participants, 660 (56%) completed the discrete choice experiment. The highest-ranked consideration was of neonatal benefits, which was followed by consideration of the risk of maternal complications. By using latent class analysis, we identified 4 attitudinal groups with similar patterns of prioritization: "fetocentric" (n = 232), risk-sensitive (n = 197), maternal autonomy (n = 167), and family impact and social support (n = 64). Neonatologists were more likely to be in the fetocentric group, whereas surgeons were more likely to be in the risk-sensitive group, and maternal-fetal medicine physicians made up the largest percentage of the family impact and social support group. CONCLUSIONS: Physicians vary in how they weigh the importance of social and ethical considerations regarding maternal-fetal surgery. Understanding these differences may help prevent or mitigate disagreements or tensions that may arise in the management of these patients.