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1.
Pediatr Radiol ; 52(9): 1756-1764, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35441838

RESUMEN

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.


Asunto(s)
COVID-19 , Pandemias , Niño , Demografía , Servicio de Urgencia en Hospital , Humanos , Estudios Retrospectivos
2.
Emerg Radiol ; 29(1): 1-8, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34729649

RESUMEN

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.


Asunto(s)
COVID-19 , Radiología , Niño , Servicio de Urgencia en Hospital , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2
3.
AJR Am J Roentgenol ; 216(4): 1081-1087, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33534622

RESUMEN

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.


Asunto(s)
Internado y Residencia , Cultura Organizacional , Seguridad del Paciente , Mala Conducta Profesional , Radiología/educación , Adulto , Femenino , Humanos , Masculino , Mala Conducta Profesional/psicología , Encuestas y Cuestionarios , Lugar de Trabajo/psicología , Lugar de Trabajo/normas
4.
Pediatr Radiol ; 51(6): 1070-1075, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33999247

RESUMEN

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.


Asunto(s)
Maltrato a los Niños , Médicos , Radiología , Niño , Maltrato a los Niños/diagnóstico , Errores Diagnósticos , Testimonio de Experto , Humanos
5.
Pediatr Radiol ; 51(13): 2461-2469, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34351495

RESUMEN

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.


Asunto(s)
Anomalías Congénitas , Enfermedades Gastrointestinales , Niño , Preescolar , Humanos , Estómago/diagnóstico por imagen
6.
Pediatr Radiol ; 51(7): 1275-1280, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33904950

RESUMEN

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.


Asunto(s)
Testimonio de Experto , Radiología , Niño , Humanos , Radiólogos
7.
Pediatr Radiol ; 50(9): 1180-1190, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32474774

RESUMEN

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.


Asunto(s)
Anomalías del Sistema Digestivo/diagnóstico por imagen , Gastropatías/diagnóstico por imagen , Adolescente , Niño , Preescolar , Medios de Contraste , Diagnóstico Diferencial , Humanos , Lactante , Recién Nacido
8.
J Med Ethics ; 44(4): 234-238, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29018178

RESUMEN

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.


Asunto(s)
Actitud del Personal de Salud , Anomalías Congénitas/cirugía , Enfermedades Fetales/cirugía , Fetoscopía/ética , Asesoramiento Genético/ética , Neonatólogos/psicología , Diagnóstico Prenatal/psicología , Adulto , Estudios Transversales , Femenino , Asesoramiento Genético/estadística & datos numéricos , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Neonatólogos/ética , Relaciones Médico-Paciente , Embarazo , Diagnóstico Prenatal/ética , Religión
9.
Perspect Biol Med ; 61(1): 106-117, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29805151

RESUMEN

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.


Asunto(s)
Bioética , Muerte Encefálica , Encéfalo/embriología , Encéfalo/fisiología , Femenino , Edad Gestacional , Corazón/fisiología , Humanos , Masculino , Estado Vegetativo Persistente , Embarazo , Donantes de Tejidos
10.
Radiology ; 285(2): 601-608, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28631981

RESUMEN

Purpose The objectives of the Radiological Society of North America (RSNA) Patient-Centered Radiology Steering Committee survey were to (a) assess RSNA members' general attitudes and experiences concerning patient-centered radiology, with specific attention paid to radiologist-to-patient communication; (b) examine the members' barriers to communicating more directly with patients; and (c) explore their perceptions of how such barriers can be overcome. Materials and Methods A total of 5999 radiologists were invited by e-mail to complete an anonymous electronic survey developed by the Steering Committee and the RSNA Department of Research. Participants were asked to identify aspects of patient-centered care important to their practice, report on their interactions with patients, and share their opinions on radiologist-patient communication. Statistical analyses were performed by using the χ2 test and analysis of variance. Results The response rate was 12% (n = 694, 109 invitations were undeliverable). Most respondents (89%, 611 of 684) agreed that promoting awareness of the role of radiology in patients' overall health care is important to how they practice. The majority (73%, 421 of 575) reported that time or workload frequently prevented them from communicating directly with patients. The majority (74%, 423 of 572) reported that a personal sense of satisfaction was likely to motivate them to communicate more directly with patients, but many commented that changes to reimbursement and compensation would help them communicate with patients more directly. Conclusion Many radiologists support the concept of communicating more directly with patients but report they are constrained by time or workload. Changes to reimbursement schemes may help mitigate these barriers to one crucial aspect of patient-centered care. © RSNA, 2017 Online supplemental material is available for this article.


Asunto(s)
Atención Dirigida al Paciente , Relaciones Médico-Paciente , Radiólogos/estadística & datos numéricos , Radiología , Actitud del Personal de Salud , Comunicación , Estudios Transversales , Humanos , América del Norte , Encuestas y Cuestionarios
12.
AJR Am J Roentgenol ; 209(2): 351-357, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28537754

RESUMEN

OBJECTIVE: The purpose of this study was to develop and test a standardized communication skills assessment instrument for radiology. MATERIALS AND METHODS: The Delphi method was used to validate the Kalamazoo Communication Skills Assessment instrument for radiology by revising and achieving consensus on the 43 items of the preexisting instrument among an interdisciplinary team of experts consisting of five radiologists and four nonradiologists (two men, seven women). Reviewers assessed the applicability of the instrument to evaluation of conversations between radiology trainees and trained actors portraying concerned parents in enactments about bad news, radiation risks, and diagnostic errors that were video recorded during a communication workshop. Interrater reliability was assessed by use of the revised instrument to rate a series of enactments between trainees and actors video recorded in a hospital-based simulator center. Eight raters evaluated each of seven different video-recorded interactions between physicians and parent-actors. RESULTS: The final instrument contained 43 items. After three review rounds, 42 of 43 (98%) items had an average rating of relevant or very relevant for bad news conversations. All items were rated as relevant or very relevant for conversations about error disclosure and radiation risk. Reliability and rater agreement measures were moderate. The intraclass correlation coefficient range was 0.07-0.58; mean, 0.30; SD, 0.13; and median, 0.30. The range of weighted kappa values was 0.03-0.47; mean, 0.23; SD, 0.12; and median, 0.22. Ratings varied significantly among conversations (χ26 = 1186; p < 0.0001) and varied significantly by viewing order, rater type, and rater sex. CONCLUSION: The adapted communication skills assessment instrument is highly relevant for radiology, having moderate interrater reliability. These findings have important implications for assessing the relational competencies of radiology trainees.


Asunto(s)
Competencia Clínica , Comunicación , Evaluación Educacional/métodos , Radiólogos , Radiología/educación , Técnica Delphi , Educación Médica , Femenino , Humanos , Masculino , Relaciones Médico-Paciente , Reproducibilidad de los Resultados , Grabación en Video
13.
J Med Ethics ; 43(10): 679-683, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28235884

RESUMEN

This article addresses whether cardiopulmonary resuscitation (CPR) and sustained physiological support should ever be permitted in individuals who are diagnosed as brain dead and who had held previously expressed moral or religious objections to the currently accepted criteria for such a determination. It contrasts how requests for care would normally be treated in cases involving a brain-dead individual with previously expressed wishes to donate and a similarly diagnosed individual with previously expressed beliefs that did not conform to a brain-based conception of death. The paper first focuses narrowly on requests for CPR and then expands its scope to address extended physiological support. It describes how refusing the brain-dead non-donor's requests for either CPR or extended support would represent enduring harm to the antemortem or previously autonomous individual by negating their beliefs and self-identity. The paper subsequently discusses potential implications of policy that would allow greater accommodations to those with conscientious objections to currently accepted brain-based death criteria, such as for cost, insurance, higher brain formulations and bedside communication. The conclusion is that granting wider latitude to personal conceptions around the definition of death, rather than forcing a contested definition on those with valid moral and religious objections, would benefit both individuals and society.


Asunto(s)
Muerte Encefálica , Reanimación Cardiopulmonar , Defensa del Paciente/ética , Derecho a Morir/ética , Privación de Tratamiento/ética , Actitud del Personal de Salud , Actitud Frente a la Muerte , Muerte Encefálica/legislación & jurisprudencia , Reanimación Cardiopulmonar/ética , Características Culturales , Ética Médica , Humanos , Principios Morales , Defensa del Paciente/legislación & jurisprudencia , Formulación de Políticas , Religión y Medicina , Derecho a Morir/legislación & jurisprudencia , Privación de Tratamiento/legislación & jurisprudencia
14.
Pediatr Radiol ; 46(5): 591-600, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26886911

RESUMEN

This paper addresses significant misconceptions regarding the etiology of fractures in infants and young children in cases of suspected child abuse. This consensus statement, supported by the Child Abuse Committee and endorsed by the Board of Directors of the Society for Pediatric Radiology, synthesizes the relevant scientific data distinguishing clinical, radiologic and laboratory findings of metabolic disease from findings in abusive injury. This paper discusses medically established epidemiology and etiologies of childhood fractures in infants and young children. The authors also review the body of evidence on the role of vitamin D in bone health and the relationship between vitamin D and fractures. Finally, the authors discuss how courts should properly assess, use, and limit medical evidence and medical opinion testimony in criminal and civil child abuse cases to accomplish optimal care and protection of the children in these cases.


Asunto(s)
Maltrato a los Niños/diagnóstico , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Deficiencia de Vitamina D/complicaciones , Niño , Preescolar , Consenso , Femenino , Medicina Legal , Humanos , Lactante , Recién Nacido , Masculino , Factores de Riesgo
15.
Radiographics ; 35(6): 1779-88, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26466185

RESUMEN

Modern radiology is at the forefront of technological progress in medicine, a position that often places unique challenges on its professional character. This article uses "Medical Professionalism in the New Millennium: A Physician Charter," a document published in 2002 and endorsed by several major radiology organizations, as a lens for exploring professional challenges in modern radiology. The three main tenets of the Charter emphasize patient welfare, patient autonomy, and the reduction of disparities in health care distribution. This article reviews the ways in which modern technology and financial structures potentially create stressors on professionalism in radiology, while highlighting the opportunities they provide for radiologists seeking to fulfill the professional goals articulated in the Charter. Picture archiving and communication systems (PACS) and voice recognition systems have transformed the speed of radiology and enhanced the ability of radiologists to improve patient care but also have brought new tensions to the workplace. Although teleradiology may improve global access to radiologists, it may also promote the commoditization of radiology, which diminishes the professional stature of radiologists. Social media and patient portals provide radiologists with new forums for interacting with the public and patients, potentially promoting patient welfare. However, patient privacy and autonomy are important considerations. Finally, modern financial structures provide radiologists with both entrepreneurial opportunities as well as the temptation for unprofessional conduct. Each of these advances carries the potential for professional growth while testing the professional stature of radiology. By considering the risks and benefits of emerging technologies in the modern radiology world, radiologists can chart an ethical and professional future path.


Asunto(s)
Práctica Profesional , Radiología , Control de Costos , Atención a la Salud/tendencias , Disparidades en Atención de Salud , Humanos , Relaciones Interprofesionales , Uso Excesivo de los Servicios de Salud/economía , Uso Excesivo de los Servicios de Salud/prevención & control , Sistemas de Registros Médicos Computarizados , Derechos del Paciente , Seguridad del Paciente , Autonomía Personal , Práctica Profesional/economía , Práctica Profesional/ética , Práctica Profesional/tendencias , Relaciones Profesional-Paciente , Radiología/economía , Radiología/ética , Radiología/métodos , Radiología/tendencias , Servicio de Radiología en Hospital/organización & administración , Sistemas de Información Radiológica , Telerradiología
16.
18.
J Med Ethics ; 40(2): 117-22, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23572566

RESUMEN

BACKGROUND: To determine (1) whether fetal care paediatric (FCP) and maternal-fetal medicine (MFM) specialists harbour differing attitudes about pregnancy termination for congenital fetal conditions, their perceived responsibilities to pregnant women and fetuses, and the fetus as a patient and (2) whether self-perceived primary responsibilities to fetuses and women and views about the fetus as a patient are associated with attitudes about clinical care. METHODS: Mail survey of 434 MFM and FCP specialists (response rates 60.9% and 54.2%, respectively). RESULTS: MFMs were more likely than FCPs to disagree with these statements (all p values<0.005): (1) 'the presence of a fetal abnormality is not an appropriate reason for a couple to consider pregnancy termination' (MFM : FCP-78.4% vs 63.5%); (2) 'the effects that a child born with disabilities might have on marital and family relationships is not an appropriate reason for a couple to consider pregnancy termination' (MFM : FCP-80.5% vs 70.2%); and (3) 'the cost of healthcare for the future child is not an appropriate reason for a couple to consider pregnancy termination' (MFM : FCP-73.5% vs 55.9%). 65% MFMs versus 47% FCPs disagreed that their professional responsibility is to focus primarily on fetal well-being (p<0.01). Specialists did not differ regarding the fetus as a separate patient. Responses about self-perceived responsibility to focus on fetal well-being were associated with clinical practice attitudes. CONCLUSIONS: Independent of demographic and sociopolitical characteristics, FCPs and MFMs possess divergent ethical sensitivities regarding pregnancy termination, pregnant women and fetuses, which may influence clinical care.


Asunto(s)
Aborto Inducido/ética , Actitud del Personal de Salud , Anomalías Congénitas , Personas con Discapacidad , Relaciones Familiares , Feto , Matrimonio , Médicos/ética , Médicos/estadística & datos numéricos , Mujeres Embarazadas , Adulto , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Obstetricia , Pediatría , Médicos/psicología , Embarazo , Encuestas y Cuestionarios , Recursos Humanos
19.
Am J Bioeth ; 19(4): 75-77, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31544663
20.
JBMR Plus ; 7(6): e10739, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37283649

RESUMEN

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.

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