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1.
Cell ; 159(1): 69-79, 2014 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-25259921

RESUMEN

The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121-123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Anti-VIH/química , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/química , VIH-1/inmunología , Vacunas contra el SIDA/química , Vacunas contra el SIDA/inmunología , Secuencia de Aminoácidos , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Anti-VIH/metabolismo , Proteína gp120 de Envoltorio del VIH/química , Modelos Moleculares , Datos de Secuencia Molecular , Alineación de Secuencia
2.
Am J Hum Genet ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39299239

RESUMEN

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) in internal organs. HHT is caused by inheritance of a loss of function mutation in one of three genes. Although individuals with HHT are haploinsufficient for one of these genes throughout their entire body, rather than exhibiting a systemic vascular phenotype, vascular malformations occur as focal lesions in discrete anatomic locations. The inconsistency between genotype and phenotype has provoked debate over whether haploinsufficiency or a different mechanism gives rise to the vascular malformations. We previously showed that HHT-associated skin telangiectases develop by a two-hit mutation mechanism in an HHT gene. However, somatic mutations were identified in only half of the telangiectases, raising the question whether a second-hit somatic mutation is a necessary (required) event in HHT pathogenesis. Here, we show that another mechanism for the second hit is loss of heterozygosity across the chromosome bearing the germline mutation. Secondly, we investigate the two-hit mutation mechanism for internal organ AVMs, the source of much of the morbidity of HHT. Here, we identified somatic molecular genetic events in eight liver telangiectases, including point mutations and a loss of heterozygosity event. We also identified somatic mutations in one pulmonary AVM and two brain AVMs, confirming that mucocutaneous and internal organ vascular malformations undergo the same molecular mechanisms. Together, these data argue that bi-allelic loss of function in an HHT gene is a required event in the pathogenesis of HHT-associated vascular malformations.

3.
Arterioscler Thromb Vasc Biol ; 44(6): 1246-1264, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38660801

RESUMEN

BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models. METHODS: We used genetic studies, RNA sequencing, spatial transcriptome, micro-computed tomography, fluorescence-activated cell sorting, multiplex immunofluorescence, coculture studies, and imaging techniques to reveal that sustained mild hypoxia via the CX3CR1-CX3CL1 (CX3C motif chemokine receptor 1/chemokine [CX3C motif] ligand 1) signaling pathway influences cell-specific neuroinflammatory interactions, contributing to heterogeneity in CCM severity. RESULTS: Histological and expression profiles of CCM neurovascular lesions (Slco1c1-iCreERT2;Pdcd10fl/fl; Pdcd10BECKO) in male and female mice found that sustained mild hypoxia (12% O2, 7 days) accelerates CCM disease. Our findings indicate that a small reduction in oxygen levels can significantly increase angiogenesis, neuroinflammation, and thrombosis in CCM disease by enhancing the interactions between endothelium, astrocytes, and immune cells. Our study indicates that the interactions between CX3CR1 and CX3CL1 are crucial in the maturation of CCM lesions and propensity to CCM immunothrombosis. In particular, this pathway regulates the recruitment and activation of microglia and other immune cells in CCM lesions, which leads to lesion growth and thrombosis. We found that human CX3CR1 variants are linked to lower lesion burden in familial CCMs, proving it is a genetic modifier in human disease and a potential marker for aggressiveness. Moreover, monoclonal blocking antibody against CX3CL1 or reducing 1 copy of the Cx3cr1 gene significantly reduces hypoxia-induced CCM immunothrombosis. CONCLUSIONS: Our study reveals that interactions between CX3CR1 and CX3CL1 can modify CCM neuropathology when lesions are accelerated by environmental hypoxia. Moreover, a hypoxic environment or hypoxia signaling caused by CCM disease influences the balance between neuroinflammation and neuroprotection mediated by CX3CR1-CX3CL1 signaling. These results establish CX3CR1 as a genetic marker for patient stratification and a potential predictor of CCM aggressiveness.


Asunto(s)
Receptor 1 de Quimiocinas CX3C , Quimiocina CX3CL1 , Modelos Animales de Enfermedad , Hemangioma Cavernoso del Sistema Nervioso Central , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/genética , Receptor 1 de Quimiocinas CX3C/genética , Receptor 1 de Quimiocinas CX3C/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Hipoxia/metabolismo , Hipoxia/complicaciones , Ratones Endogámicos C57BL , Ratones Noqueados , Neovascularización Patológica/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/genética
4.
Stroke ; 55(1): 22-30, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38134268

RESUMEN

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Accidente Cerebrovascular , Adulto , Humanos , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemorragia , Estudios Prospectivos , Calidad de Vida , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
5.
Stroke ; 55(1): 31-39, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38134265

RESUMEN

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Hemorragia , Humanos , Estudios Prospectivos , Hemorragia/etiología , Hemorragia/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Biomarcadores , Imagen por Resonancia Magnética/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones
6.
Radiology ; 311(1): e240219, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38652030

RESUMEN

Climate change adversely affects the well-being of humans and the entire planet. A planetary health framework recognizes that sustaining a healthy planet is essential to achieving individual, community, and global health. Radiology contributes to the climate crisis by generating greenhouse gas (GHG) emissions during the production and use of medical imaging equipment and supplies. To promote planetary health, strategies that mitigate and adapt to climate change in radiology are needed. Mitigation strategies to reduce GHG emissions include switching to renewable energy sources, refurbishing rather than replacing imaging scanners, and powering down unused scanners. Radiology departments must also build resiliency to the now unavoidable impacts of the climate crisis. Adaptation strategies include education, upgrading building infrastructure, and developing departmental sustainability dashboards to track progress in achieving sustainability goals. Shifting practices to catalyze these necessary changes in radiology requires a coordinated approach. This includes partnering with key stakeholders, providing effective communication, and prioritizing high-impact interventions. This article reviews the intersection of planetary health and radiology. Its goals are to emphasize why we should care about sustainability, showcase actions we can take to mitigate our impact, and prepare us to adapt to the effects of climate change. © RSNA, 2024 Supplemental material is available for this article. See also the article by Ibrahim et al in this issue. See also the article by Lenkinski and Rofsky in this issue.


Asunto(s)
Cambio Climático , Salud Global , Humanos , Gases de Efecto Invernadero , Radiología , Servicio de Radiología en Hospital/organización & administración
7.
Childs Nerv Syst ; 40(7): 2101-2108, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38517485

RESUMEN

OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.


Asunto(s)
Angiografía Cerebral , Malformaciones Arteriovenosas Intracraneales , Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico por imagen , Telangiectasia Hemorrágica Hereditaria/epidemiología , Niño , Masculino , Femenino , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/cirugía , Preescolar , Adolescente , Lactante
8.
Pediatr Radiol ; 54(1): 20-26, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37962606

RESUMEN

The global temperature has been increasing resulting in climate change. This negatively impacts planetary health that disproportionately affects the most vulnerable among us, especially children. Extreme weather events, such as hurricanes, tornadoes, wildfires, flooding, and heatwaves, are becoming more frequent and severe, posing a significant threat to our patients' health, safety, and security. Concurrently, shifts in environmental exposures, including air pollution, allergens, pathogenic vectors, and microplastics, further exacerbate the risks faced by children. In this paper, we provide an overview of pediatric illnesses that are becoming more prevalent and severe because of extreme weather events, global temperature increases, and shifts in environmental exposures. As members of pediatric health care teams, it is crucial for pediatric radiologists to be knowledgeable about the impacts of climate change on our patients, and continue to advocate for safe, healthier environments for our patients.


Asunto(s)
Biodiversidad , Radiología , Humanos , Niño , Plásticos , Temperatura , Cambio Climático
9.
Pediatr Transplant ; 27(2): e14429, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36345140

RESUMEN

BACKGROUND: Although voiding cystourethrogram (VCUG) is currently the gold standard in VUR evaluation, there is ionizing radiation exposure. Contrast-enhanced voiding urosonography (CEVUS) uses ultrasound contrast agents to visualize the urinary tract and has been reported to be safe and effective in VUR evaluation in children. CEVUS application has yet to be specifically described in VUR evaluation in the pediatric kidney transplant population. The purpose of this study was to report the use of CEVUS and VCUG in evaluating and managing VUR in pediatric renal transplant patients. METHODS: Retrospective review was conducted for pediatric kidney transplant patients (18 years and younger) who underwent VCUG or CEVUS to assess for transplant VUR from July 2019 through June 2021. Demographic information, reason for VUR evaluation, fluoroscopy time, and postimaging complications were evaluated. Costs of imaging modalities were also considered. RESULTS: Eight patients were evaluated for transplant VUR during the study period. Of the 3 patients who underwent VCUG, all 3 had VUR (median grade 3). Median fluoroscopy time was 18 s and dose-area product was 18.7 uGy*m2 . Of the 5 patients who underwent CEVUS, 4 had VUR (median grade 4). There were no complications for either modality. Based on clinical and radiographic findings, patients were recommended no intervention, behavioral modification, or ureteral reimplantation. The total cost of CEVUS was $800 less than that of VCUG. CONCLUSION: CEVUS can provide an alternate means of safely evaluating VUR in kidney transplant patients with similar outcomes, potentially lower costs, and no exposure to ionizing radiation.


Asunto(s)
Trasplante de Riñón , Reflujo Vesicoureteral , Niño , Humanos , Lactante , Reflujo Vesicoureteral/diagnóstico por imagen , Medios de Contraste , Cistografía/métodos , Micción , Ultrasonografía/métodos
10.
Nature ; 545(7654): 305-310, 2017 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-28489816

RESUMEN

Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have yet to be identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment.


Asunto(s)
Microbioma Gastrointestinal/inmunología , Hemangioma Cavernoso del Sistema Nervioso Central/inmunología , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Inmunidad Innata , Receptor Toll-Like 4/inmunología , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Susceptibilidad a Enfermedades , Células Endoteliales/metabolismo , Femenino , Vida Libre de Gérmenes , Bacterias Gramnegativas/inmunología , Hemangioma Cavernoso del Sistema Nervioso Central/microbiología , Humanos , Inyecciones Intravenosas , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/inmunología , Masculino , Ratones , Transducción de Señal , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/deficiencia , Receptor Toll-Like 4/genética
11.
Pediatr Radiol ; 53(12): 2380-2385, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37773443

RESUMEN

BACKGROUND: MR arthrography is an essential diagnostic tool to assess and guide management of labral, ligamentous, fibrocartilaginous, and capsular abnormalities in children. While fluoroscopy is traditionally used for intra-articular contrast administration, ultrasound offers advantages of portability and lack of ionizing radiation exposure for both the patient and proceduralist. OBJECTIVE: The purpose of this retrospective study is to quantify technical success and frequency of complications of ultrasound-guided arthrogram injections at our institution. MATERIALS AND METHODS: This retrospective analysis investigates the results of 217 ultrasound-guided arthrograms of the shoulder, elbow, and hip in patients aged 5-18 years. Successful injection of contrast into the target joint, clinical indication for MR arthrography, and complications were reviewed. RESULTS: Accurate ultrasound-guided intra-articular administration of contrast into the target joint was successful for 100% of shoulder cases (90/90), 97% of elbow cases (77/79), and 98% of hip cases (47/48). Leak of contrast outside the target joint occurred in 1.4% (3/217) of cases. No major side effects including excessive bleeding, paresthesia, allergic reactions, or infection occurred during or after the procedure. Additionally, no major vessel, nerve, or tendon complications were observed on MR images. CONCLUSION: Ultrasound guidance is a reliable, effective, and safe approach to arthrography in children.


Asunto(s)
Artrografía , Articulación del Hombro , Humanos , Niño , Artrografía/métodos , Estudios Retrospectivos , Medios de Contraste , Inyecciones Intraarticulares , Articulación del Hombro/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ultrasonografía Intervencional/métodos
12.
J Genet Couns ; 31(1): 269-278, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34318970

RESUMEN

Prior research has found that many genetic counselors (GCs) experience burnout. Studies of other clinicians have demonstrated that burnout can have significant detrimental consequences for clinicians, patients, and the healthcare system. We sought to explore the prevalence of, contributors to, and consequences of burnout among GCs. We performed a secondary data analysis of baseline data from Me-GC, a randomized controlled trial of meditation for GCs. We applied a systems model of burnout proposed by the National Academy of Medicine (NAM), which depicts burnout arising from a combination of contributors that include both work system and individual mediating factors, and then leading to consequences. Validated self-report scales were used to measure burnout and most contributors and consequences. Female and white GCs were over-represented in our sample. Over half (57.2%) of the 397 participants had Professional Fulfillment Index scores indicative of burnout. Multiple potential contributors were associated with burnout, consistent with its known multifactorial nature. Among work system factors, higher levels of burnout were associated with insufficient administrative support, lack of autonomy, and not feeling valued by non-GC colleagues. Individual mediating factors associated with greater burnout included higher levels of anxiety, depression, and stress. Participants with lower levels of burnout reported greater mindfulness, resilience, and use of professional self-care behaviors. Among variables categorized as consequences, higher levels of burnout were associated with lower levels of empathy, counseling alliance, and positive unconditional regard, as well as higher reactive distress, and a greater desire to reduce the amount of time spent on clinical care. Given the prevalence and potential consequences of burnout observed here, it is imperative that the field take steps to mitigate burnout risk.


Asunto(s)
Agotamiento Profesional , Consejeros , Atención Plena , Agotamiento Profesional/epidemiología , Agotamiento Psicológico , Empatía , Femenino , Humanos , Estados Unidos
13.
Matern Child Health J ; 26(2): 289-298, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34993753

RESUMEN

OBJECTIVES: Adverse childhood experiences (ACEs) can detrimentally impact perinatal mental health, birth outcomes, and parenting behaviors. Proximal psychosocial stressors also increase risks to perinatal health and wellbeing. Additional research on effective perinatal mental health programs is needed, especially for individuals and families with historical and concurrent adversity, and those with moderate to severe symptoms. METHODS: The Mother-Baby Day Hospital at Hennepin County Medical Center provides trauma-informed, multi-generation treatment for perinatal women. Data were collected from patients between January 2016 and September 2019. Self-reported depression, anxiety, and maternal functioning assessments were administered pre- and post-treatment. Patients completed the ACE questionnaire and indicators of current psychosocial stressors (i.e., food insecurity, housing insecurity, and social support) at intake. A series of bivariate tests and hierarchical regression models examined relationships among variables, including whether distal and proximal adversity predicted post-treatment symptoms. RESULTS: 159 Perinatal patients consented to research and completed the ACEs questionnaire at first admission. High proportions of patients reported 4+ ACEs and current psychosocial stressors. Effect sizes for associations between ACEs, psychosocial stressors, and self-report symptoms were small to moderate. Individuals with food or housing insecurity entered treatment with higher anxiety. In regression models, the most robust predictors of post-treatment symptoms were pre-treatment symptoms. Effects of ACEs on post-treatment depression and food insecurity on post-treatment maternal functioning approached the adjusted significance cut-off (p < .01). CONCLUSIONS FOR PRACTICE: Current psychosocial stressors and ACEs did not substantially limit post-treatment depression, anxiety, and maternal functioning outcomes. High prevalence of ACEs and psychosocial stressors highlight the need for trauma-informed, multi-generation treatments to improve maternal mental health and parenting capacity.


Asunto(s)
Experiencias Adversas de la Infancia , Femenino , Hospitales , Humanos , Lactante , Salud Mental , Madres , Responsabilidad Parental , Embarazo
14.
Pediatr Radiol ; 52(10): 1963-1973, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35316339

RESUMEN

Pediatric chest wall lesions are varied in etiology ranging from normal and benign to aggressive and malignant. When palpable, these lesions can alarm parents and clinicians alike. However, most palpable pediatric chest lesions are benign. Familiarity with the various entities, their incidences, and how to evaluate them with imaging is important for clinicians and radiologists. Here we review the most relevant palpable pediatric chest entities, their expected appearance and the specific clinical issues to aid in diagnosis and appropriate treatment.


Asunto(s)
Pared Torácica , Niño , Humanos , Imagen por Resonancia Magnética/métodos , Pared Torácica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos
15.
Pediatr Radiol ; 52(3): 549-558, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34535807

RESUMEN

Hydrocephalus is the most common neurosurgical disorder in children, and cerebrospinal fluid (CSF) diversion with shunt placement is the most commonly performed pediatric neurosurgical procedure. CT is frequently used to evaluate children with suspected CSF shunt malfunction to assess change in ventricular size. Moreover, careful review of the CT images is important to confirm the integrity of the imaged portions of the shunt system. Subtle shunt disruptions can be missed on multiplanar two-dimensional (2-D) CT images, especially when the disruption lies in the plane of imaging. The use of volume-rendered CT images enables radiologists to view the extracranial shunt tubing within the field of view as a three-dimensional (3-D) object. This allows for a rapid and intuitive method of assessing the integrity of the extracranial shunt tubing. The purpose of this pictorial essay is to discuss how volume-rendered CT images can be generated to evaluate CSF shunts in the pediatric population and to provide several examples of their utility in diagnosing shunt disruption. We also address the potential pitfalls of this technique and ways to avoid them.


Asunto(s)
Derivaciones del Líquido Cefalorraquídeo , Hidrocefalia , Niño , Cabeza/cirugía , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Derivación Ventriculoperitoneal
16.
Stroke ; 52(12): 3829-3838, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34525838

RESUMEN

BACKGROUND AND PURPOSE: Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. METHODS: This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. RESULTS: As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. CONCLUSIONS: These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Hemorragia Cerebral/etiología , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Adulto , Anciano , Neoplasias Encefálicas/patología , Estudios de Cohortes , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen
17.
Cerebrovasc Dis ; 50(3): 296-302, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33640891

RESUMEN

BACKGROUND: Sporadic brain arteriovenous malformations (BAVM) are a major cause of hemorrhagic stroke in younger persons. Prior studies have reported contradictory results regarding the risk of hemorrhage during pregnancy, and there are no standard guidelines for the management of pregnant women who present with BAVM rupture. The purpose of this study is to describe maternal and fetal outcomes and treatment strategies in patients with BAVM hemorrhage during pregnancy. METHODS: We performed a retrospective review of the University of California, San Francisco Brain AVM Project database for female patients who were pregnant at the time of BAVM hemorrhage between 2000 and 2017. Clinical and angiographic characteristics at presentation, BAVM treatment, and maternal outcomes using modified Rankin scale (mRS) score at presentation and 2-year follow-up were recorded. Fetal outcomes were abstracted from medical records and maternal reports. RESULTS: Sixteen patients presented with BAVM hemorrhage during pregnancy, 81% (n = 13) of whom were in their second or third trimester. Three patients (19%) who were in their first trimester terminated or miscarried pregnancy prior to BAVM intervention. Of the remaining 13 patients, 77% (n = 10) received emergent BAVM treatment at time of hemorrhage prior to delivery, and 85% of patients achieved BAVM obliteration and good maternal outcomes (mRS 0-2) at 2-year follow-up. All patients had uncomplicated deliveries (69% cesarean and 23% vaginal) with no reports of postnatal cognitive or developmental delays in infants at 2-year follow-up. CONCLUSIONS: Our study shows good long-term maternal and fetal outcomes in ruptured BAVM patients presenting during pregnancy, the majority who received BAVM interventional treatment prior to delivery.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales/complicaciones , Hemorragias Intracraneales/etiología , Complicaciones Cardiovasculares del Embarazo , Aborto Espontáneo/etiología , Adulto , Bases de Datos Factuales , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/terapia , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/terapia , Nacimiento Vivo , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Rotura Espontánea , San Francisco , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
18.
Matern Child Health J ; 25(11): 1776-1786, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34427835

RESUMEN

PURPOSE: The Hennepin Healthcare Mother-Baby Day Hospital is a partial hospital program for pregnant and postpartum women with moderate to severe psychiatric illness. Based in an urban safety net hospital, the Day Hospital provides trauma-informed, multigenerational, group-based therapy and psychiatric care. This report describes the program and preliminary data regarding maternal mental health and functioning at treatment entry and discharge. METHODS: Data include information on pregnant and postpartum women who were admitted to the Day Hospital between April 2013 and September 2019 and completed at least 4 days of treatment. We describe patient demographics and changes in mental health and maternal functioning. RESULTS: 328 women consented to participation in research, representing 364 unique admissions. Primary diagnoses included major depression (55.6%; n = 202); generalized anxiety (36.4%; n = 132); bipolar spectrum (28%; n = 102); and trauma-related disorders (20.6%; n = 75). Patients reported significant improvements (p < 0.001) in self-report scales assessing depression, anxiety, and maternal functioning. CONCLUSIONS: A mother-baby day hospital based in an urban safety net hospital is effective in improving mental health and parenting functioning in perinatal women with moderate to severe psychiatric illness. The high acuity and prevalence of comorbid depression, anxiety, bipolar spectrum, and trauma-related disorders support the need for trauma-informed, multigenerational approaches that address perinatal mental health and attachment-based parenting support.


Asunto(s)
Depresión Posparto , Madres , Niño , Femenino , Hospitales , Humanos , Lactante , Relaciones Madre-Hijo , Embarazo , Proveedores de Redes de Seguridad , Resultado del Tratamiento
19.
Pediatr Radiol ; 51(10): 1783-1797, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34117521

RESUMEN

Pathologies involving the ribs are diverse in nature, including entities specific to the pediatric population as well as shared pathologies with adults. These can be either localized within or adjacent to the rib, but may also cause rib alteration as a component of a systemic process. To better understand these disorders, we discuss several common rib pathologies in the context of their clinical presentation and pertinent imaging findings. In addition, we review the imaging modalities that may be used to evaluate the ribs. Encompassing both the clinical and imaging aspects of pediatric rib pathologies, this review aims to increase pediatric and musculoskeletal radiologists' awareness of the spectrum of disease and how to leverage a pattern-based approach.


Asunto(s)
Diagnóstico por Imagen , Costillas , Adulto , Niño , Diagnóstico Diferencial , Humanos , Costillas/diagnóstico por imagen
20.
Pediatr Radiol ; 51(3): 338-352, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33544190

RESUMEN

In skeletally immature patients, the presence of growth plates and articular cartilage of the shoulder can create a predisposition for unique injuries not observed in adults. Furthermore, increasing participation in sports by children and adolescents appears to be leading to a corresponding increase in the number of sports-related injuries. The importance of radiologists being familiar with pediatric shoulder imaging and its associated injuries is therefore growing. In this article, we review the normal development and maturation pattern of ossification centers of the shoulder from the early gestational period through adolescence. Brachial plexus birth palsy, physeal injuries, shoulder dislocation, and internal impingement are discussed within the context of the child's age and the mechanism of injury to guide radiologists to a correct diagnosis.


Asunto(s)
Traumatismos del Nacimiento , Neuropatías del Plexo Braquial , Luxación del Hombro , Articulación del Hombro , Adolescente , Adulto , Niño , Humanos , Imagen por Resonancia Magnética , Hombro , Lesiones del Hombro , Articulación del Hombro/diagnóstico por imagen
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