RESUMEN
BACKGROUND AND PURPOSE: Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a 'lightbulb sign' on the ASL sequence (diffuse homogenous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors. MATERIALS AND METHODS: In this retrospective comparative observational study, we only included pathology-proven cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proven posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the 'lightbulb sign'. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. Chi-square and Fisher's exact test were used to analyze the data. RESULTS: 95 patients were enrolled in the study; 57 (60%) were male. The median age at diagnosis was 8 years old (IQR: 3-14). Out of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n=31), pilocytic astrocytoma (n=23), posterior fossa ependymoma type A (n=16), and other tumors (n=17). The comparison of hemangioblastoma vs non-hemangioblastoma showed that peripheral edema (p=0.02) and T2 flow void (p=0.02) favors hemangioblastoma, whereas reduced diffusion (low ADC) (p=0.002) and ventricular system extension (p=0.001) favors nonhemangioblastoma tumors.Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (p=0.03), the lightbulb sign shows a complete distinction since all the ASL series of hemangioblastoma cases (n=4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n=38) showed the sign (p<0.001). CONCLUSIONS: Lightbulb-like intense and homogenous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.ABBREVIATIONS ASL = Arterial spin labelling; pASL = Pulsed arterial spin labelling; pCASL = Pseudocontinuous arterial spin labelling; DCE = Dynamic contrast-enhanced; DSC = Dynamic susceptibility contrast; VHL = Von Hippel Lindau.
RESUMEN
Background: Adult spinal deformity (ASD) patients with concurrent sacroiliac joint (SIJ) pain are susceptible to worse postoperative outcomes. There is scarce literature on the impact of ASD realignment surgery on SIJ pain. Methods: Patients undergoing ASD realignment surgery were included and stratified by the presence of SIJ pain at the baseline (SIJP+) or SIJ pain absence (SIJP-). Mean comparison tests via ANOVA were used to assess baseline differences between both cohorts. Multivariable regression analyses analyzed factors associated with SIJ pain resolution/persistence, factoring in BMI, frailty, disability, and deformity. Results: A total of 464 patients were included, with 30.8% forming the SIJP+ cohort. At the baseline (BL), SIJP+ had worse disability scores, more severe deformity, higher BMI, higher frailty scores, and an increased magnitude of lower limb compensation. SIJP+ patients had higher mechanical complication (14.7 vs. 8.2%, p = 0.024) and reoperation rates (32.4 vs. 20.2%, p = 0.011) at 2 years. SIJP+ patients who subsequently underwent SI fusion achieved disability score outcomes similar to those of their SIJ- counterparts. Multivariable regression analysis revealed that SIJP+ patients who were aligned in the GAP lordosis distribution index were more likely to report symptom resolution at six weeks (OR 1.56, 95% CI: 1.02-2.37, p = 0.039), 1 year (OR 3.21, 2.49-5.33), and 2 years (OR 3.43, 2.41-7.12). SIJP- patients who did not report symptom resolution by 1 year and 2 years were more likely to demonstrate PI-LL > 5° (OR 1.36, 1.07-2.39, p = 0.045) and SVA > 20 mm (OR 1.62, 1.24-1.71 p = 0.017). Conclusions: SIJ pain in ASD patients may result in worsened pain and disability at presentation. Symptom resolution may be achieved in affected patients by adequate postoperative lumbar lordosis restoration.
RESUMEN
OBJECTIVE: Youth with neurofibromatosis type I (NF1) demonstrate high rates of Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD), which often have overlapping behaviors. Diagnostic clarity is important to guide services. This study evaluated ASD classification in NF1 using various methods and whether those with ADHD suspicion have more social challenges associated with ASD. METHOD: 34 youth with NF1 (Mage = 10.5 ± 1.6 years), completed ASD assessments that combined direct observation and informant ratings to yield a Clinician Best Estimate (CBE) classification. Caregivers rated ASD-related social challenges using the Social Responsiveness Scale- 2nd Edition (SRS-2). RESULTS: ASD classification varied depending on the method, ranging from 32% using low-threshold SRS-2 cut-scores (T ≥ 60) to under 6% when combining cut scores for diagnostic observational tools and stringent SRS-2 cut-scores (T ≥ 70). 14.7% had a CBE ASD classification. 44% were judged to have autism traits associated with a non-ASD diagnosis. The 52.9% with a suspicion of ADHD had higher SRS-2 scores than those without ADHD, F (7, 26) = 3.45, p < .05, Wilk's lambda = 0.518, partial eta squared = 0.482. CONCLUSIONS: Findings highlight the importance of rigorous diagnostic methodology when evaluating ASD in NF1 to inform the selection of targeted interventions for socialization challenges in NF1.
RESUMEN
In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.
RESUMEN
BACKGROUND: With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies. METHODS: Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue. RESULTS: Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested. CONCLUSION: The current recommendations from multiple sources were reviewed in discussion.
Asunto(s)
Eliminación de Componentes Sanguíneos , Humanos , Eliminación de Componentes Sanguíneos/métodos , Leucocitos Mononucleares/citología , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos , Células Madre Hematopoyéticas/citologíaRESUMEN
OBJECTIVE: This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). METHODS: EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. RESULTS: Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. INTERPRETATION: Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024;96:175-186.
Asunto(s)
Electroencefalografía , Síndrome de Rett , Índice de Severidad de la Enfermedad , Humanos , Femenino , Electroencefalografía/métodos , Niño , Adolescente , Síndrome de Rett/fisiopatología , Síndrome de Rett/diagnóstico , Adulto Joven , Adulto , Ondas Encefálicas/fisiología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND/OBJECTIVE: To evaluate the visual performance of a purely refractive extended depth of focus (EDF) intraocular lens (IOL). SUBJECTS/METHODS: A prospective, multi-center, randomized, subject/evaluator-masked study. Subjects were bilaterally implanted with the EDF test (Model ZEN00V, N = 60) or an enhanced monofocal control (Model ICB00, N = 57) IOL. Monocular corrected distance (CDVA), intermediate (DCIVA), near acuities (DCNVA) and patient reported visual symptoms were evaluated at the 6-month visit. Monocular mesopic contrast sensitivity (CS) and depth of focus (DOF) testing were assessed at 3 months. RESULTS: CDVA (Mean ± SD) was -0.06 ± 0.08 for test and -0.05 ± 0.08 logMAR for control groups. DCIVA was 0.13 ± 0.08 for test and 0.18 ± 0.14 logMAR for control groups (p = 0.0127). DCNVA was 0.37 ± 0.10 for test and 0.43 ± 0.16 logMAR for control groups (p = 0.0137). Test lens was statistically superior for intermediate and near. Overall, 91.7% (halos), 95.0% (starbursts) and 95.0% (glare) of test lens patients reported that they did not experience, were not bothered, or were slightly bothered by specific visual symptoms, compared to 98.2%, 100% and 96.5% in the control group. The DOF range over which monocular visual acuity was 0.20 logMAR or better was -1.6 D for the test lens. Mesopic CS was comparable between both groups, falling within 0.11 log units for all measured cycles per degree with and without glare. CONCLUSION: The EDF IOL demonstrated extended range of vision and statistically superior intermediate and near performance compared to the monofocal IOL. Distance visual acuity, contrast sensitivity and dysphotopsia profile were similar to the monofocal IOL.
Asunto(s)
Sensibilidad de Contraste , Percepción de Profundidad , Implantación de Lentes Intraoculares , Lentes Intraoculares , Seudofaquia , Agudeza Visual , Humanos , Estudios Prospectivos , Agudeza Visual/fisiología , Femenino , Masculino , Sensibilidad de Contraste/fisiología , Anciano , Persona de Mediana Edad , Percepción de Profundidad/fisiología , Seudofaquia/fisiopatología , Diseño de Prótesis , Refracción Ocular/fisiología , Facoemulsificación , Método Doble Ciego , Satisfacción del PacienteRESUMEN
Aims: Perthes' disease (PD) is a relatively rare syndrome of idiopathic osteonecrosis of the proximal femoral epiphysis. Treatment for Perthes' disease is controversial due to the many options available, with no clear superiority of one treatment over another. Despite having few evidence-based approaches, many patients with Perthes' disease are managed surgically. Positive outcome reporting, defined as reporting a study variable producing statistically significant positive (beneficial) results, is a phenomenon that can be considered a proxy for the strength of science. This study aims to conduct a systematic literature review with the hypothesis that positive outcome reporting is frequent in studies on the treatment of Perthes' disease. Methods: We conducted a systematic review of all available abstracts associated with manuscripts in English or with English translation between January 2000 and December 2021, dealing with the treatment of Perthes' disease. Data collection included various study characteristics, surgical versus non-surgical management, treatment modality, mean follow-up time, analysis methods, and clinical recommendations. Results: Our study included 130 manuscripts. Overall, 110 (85%) reported positive (beneficial) results, three (2%) reported negative results, and 17 (13%) reported no significant difference. Despite only 10/130 studies (8%) having a testable hypothesis, 71 (55%) recommended the use of their studied treatment methods for the patients, five (4%) made recommendations against the use of the studied treatment modality, and 54 (42%) did not make any recommendations. Conclusion: The overall rate for positive outcomes among included manuscripts regarding different treatment methods for Perthes' disease (85%) is higher than the 74% positive outcome rate found among studies for other surgically treated disorders and significantly higher than most scientific literature. Despite the lack of testable hypotheses, most manuscripts recommended their studied treatment method as a successful option for managing patients solely based on the reporting of retrospective data.
Asunto(s)
Enfermedad de Legg-Calve-Perthes , Humanos , Enfermedad de Legg-Calve-Perthes/terapia , Enfermedad de Legg-Calve-Perthes/cirugía , Ortopedia , Procedimientos Ortopédicos/métodos , Resultado del TratamientoRESUMEN
PURPOSE: To demonstrate J-difference coediting of glutamate using Hadamard encoding and reconstruction of Mescher-Garwood-edited spectroscopy (HERMES). METHODS: Density-matrix simulations of HERMES (TE 80 ms) and 1D J-resolved (TE 31-229 ms) of glutamate (Glu), glutamine (Gln), γ-aminobutyric acid (GABA), and glutathione (GSH) were performed. HERMES comprised four sub-experiments with editing pulses applied as follows: (A) 1.9/4.56 ppm simultaneously (ONGABA /ONGSH ); (B) 1.9 ppm only (ONGABA /OFFGSH ); (C) 4.56 ppm only (OFFGABA /ONGSH ); and (D) 7.5 ppm (OFFGABA /OFFGSH ). Phantom HERMES and 1D J-resolved experiments of Glu were performed. Finally, in vivo HERMES (20-ms editing pulses) and 1D J-resolved (TE 31-229 ms) experiments were performed on 137 participants using 3 T MRI scanners. LCModel was used for quantification. RESULTS: HERMES simulation and phantom experiments show a Glu-edited signal at 2.34 ppm in the Hadamard sum combination A+B+C+D with no overlapping Gln signal. The J-resolved simulations and phantom experiments show substantial TE modulation of the Glu and Gln signals across the TEs, whose average yields a well-resolved Glu signal closely matching the Glu-edited signal from the HERMES sum spectrum. In vivo quantification of Glu show that the two methods are highly correlated (p < 0.001) with a bias of â¼10%, along with similar between-subject coefficients of variation (HERMES/TE-averaged: â¼7.3%/â¼6.9%). Other Hadamard combinations produce the expected GABA-edited (A+B-C-D) or GSH-edited (A-B+C-D) signal. CONCLUSION: HERMES simulation and phantom experiments show the separation of Glu from Gln. In vivo HERMES experiments yield Glu (without Gln), GABA, and GSH in a single MRS scan.
Asunto(s)
Ácido Glutámico , Imagen por Resonancia Magnética , Humanos , Espectroscopía de Resonancia Magnética/métodos , Glutamina , Glutatión/química , Ácido gamma-Aminobutírico/químicaRESUMEN
BACKGROUND AND PURPOSE: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12 R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients, which may require platelet transfusion in emergency situations. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12 R. EXPERIMENTAL APPROACH: Studies were performed in human platelets, with P2Y12 R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were undertaken to assess G protein-subunit activation downstream of P2Y12 R activation. KEY RESULTS: Initial studies revealed that a range of P2Y12 R ligands, including ticagrelor, displayed inverse agonist activity at P2Y12 R. Only ticagrelor was resistant to washout and, in human platelet and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12 R function. The P2Y12 R agonist 2MeSADP, which was also resistant to washout, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12 R than other P2Y12 R ligands. CONCLUSION AND IMPLICATIONS: Ticagrelor binding to P2Y12 R is prolonged and more akin to that of an irreversible antagonist, especially versus the endogenous P2Y12 R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding, and for bleeding associated with urgent invasive procedures.
Asunto(s)
Síndrome Coronario Agudo , Difosfatos , Humanos , Ticagrelor/farmacología , Ticagrelor/metabolismo , Ticagrelor/uso terapéutico , Difosfatos/metabolismo , Difosfatos/farmacología , Difosfatos/uso terapéutico , Adenosina/farmacología , Agonismo Inverso de Drogas , Antagonistas del Receptor Purinérgico P2Y/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Adenosina Difosfato/farmacología , Adenosina Difosfato/metabolismo , Plaquetas , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/complicaciones , Receptores Purinérgicos P2Y12/metabolismoRESUMEN
Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan. Materials and Methods In this secondary analysis of preexisting data, clinical brain MRI SLIPs from an urban pediatric health care system (individuals aged ≤22 years) were scanned across nine 3.0-T MRI scanners. The curation process included manual review of signed radiology reports and automated and manual quality review of images without gross pathology. Global and regional volumetric imaging phenotypes were measured using two image segmentation pipelines, and clinical brain growth charts were quantitatively compared with charts derived from a large set of research controls in the same age range by means of Pearson correlation and age at peak volume. Results The curated clinical data set included 532 patients (277 male; median age, 10 years [IQR, 5-14 years]; age range, 28 days after birth to 22 years) scanned between 2005 and 2020. Clinical brain growth charts were highly correlated with growth charts derived from research data sets (22 studies, 8346 individuals [4947 male]; age range, 152 days after birth to 22 years) in terms of normative developmental trajectories predicted by the models (median r = 0.979). Conclusion The clinical indication of the scans did not significantly bias the output of clinical brain charts. Brain growth charts derived from clinical controls with limited imaging pathology were highly correlated with brain charts from research controls, suggesting the potential of curated clinical MRI scans to supplement research data sets. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ertl-Wagner and Pai in this issue.
Asunto(s)
Encéfalo , Gráficos de Crecimiento , Humanos , Masculino , Niño , Recién Nacido , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , CabezaRESUMEN
Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03-mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9-mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches.
Asunto(s)
Enfermedades Renales , Síndrome Nefrótico , Ratones , Humanos , Animales , Síndrome Nefrótico/genética , Síndrome Nefrótico/terapia , Dependovirus/genética , Albuminuria , Modelos Genéticos , Terapia Genética/métodos , Modelos Animales de Enfermedad , Ratones Noqueados , Vectores GenéticosRESUMEN
Introduction: The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed). Methods: The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome. Results: Non-linear TD support vector regression modeling methods accounted for considerably more M50 latency variance than linear models, likely due to the non-linear dependence on neuroimaging factors such as GABA MRS. While SVR models accounted for ~80% of the M50 latency variance in TD and the genetically homogenous XYY syndrome, a similar approach only accounted for ~20% of the M50 latency variance in ASD, implicating the insufficiency of diffusion MR, GABA MRS, and age factors alone. Biologically based stratification of ASD was performed by assessing the conformance of the ASD population to the TD SVR model and identifying a sub-population of children with unexpectedly long M50 latency. Discussion: Multimodal integration of neuroimaging data can help build a mechanistic understanding of brain connectivity. The unexplained M50 latency variance in ASD motivates future hypothesis generation and testing of other contributing biological factors.
RESUMEN
The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by â¼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left-right hemisphere P2m maturation is associated with language performance.
Asunto(s)
Corteza Auditiva , Masculino , Humanos , Lactante , Anciano , Corteza Auditiva/fisiología , Potenciales Evocados Auditivos/fisiología , Estudios Transversales , Magnetoencefalografía , Estimulación AcústicaRESUMEN
BACKGROUND: Noninvasive alternatives to biopsy for assessment of interstitial fibrosis and tubular atrophy (IFTA), the major determinant of kidney transplant failure, remain profoundly limited. Elastography is a noninvasive technique that propagates shear waves across tissues to measure their stiffness. We aimed to test utility of elastography for early detection of IFTA in pediatric kidney allografts. METHODS: We compared ultrasound (USE) and MR elastography (MRE) stiffness measurements, performed on pediatric transplant recipients referred for clinically indicated biopsies, and healthy controls. RESULTS: Ten transplant recipients (median age 16 years) and eight controls (median age 16.5 years) were enrolled. Three transplant recipients had "stable" allografts and seven had Banff Grade 1 IFTA. Median time from transplantation to biopsy was 12 months. Mean estimated glomerular filtration rate was 61.5 mL/min/1.73m2 by creatinine-cystatin-C CKiD equation at time of biopsy. Mean stiffness, calculated through one-way ANOVA, was higher for IFTA allografts (23.4 kPa USE/5.6 kPa MRE) than stable allografts (13.7 kPa USE/4.4 kPa MRE) and controls (9.1 kPa USE/3.6 kPa MRE). Pearson's coefficient between USE and MRE stiffness values was strong (r = .97). AUC for fibrosis prediction in transplanted kidneys was high for both modalities (0.91 USE and 0.89 MRE), although statistically nonsignificant (p > .05). Stiffness cut-off values for USE and MRE were 13.8 kPa and 4.6 kPa, respectively. Both values yielded a sensitivity of 100% but USE specificity (72%) was slightly higher than MRE (67%). CONCLUSION: Elastography shows potential for detection of low-grade IFTA in allografts although a larger sample is imperative for clinical validation.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Enfermedades Renales , Trasplante de Riñón , Enfermedades Pulmonares Intersticiales , Humanos , Niño , Adolescente , Proyectos Piloto , Fibrosis , Riñón/diagnóstico por imagen , Riñón/patología , Diagnóstico por Imagen de Elasticidad/métodos , Imagen por Resonancia Magnética/métodos , Cirrosis Hepática/patologíaRESUMEN
Academic and community investigators conducting community-engaged research (CEnR) are often met with challenges when seeking Institutional Review Board (IRB) approval. This scoping review aims to identify challenges and recommendations for CEnR investigators and community partners working with IRBs. Peer-reviewed articles that reported on CEnR, specified study-related challenges, and lessons learned for working with IRBs and conducted in the United States were included for review. Fifteen studies met the criteria and were extracted for this review. Four challenges identified (1) Community partners not being recognized as research partners (2) Cultural competence, language of consent forms, and literacy level of partners; (3) IRBs apply formulaic approaches to CEnR; & (4) Extensive delays in IRB preparation and approval potentially stifle the relationships with community partners. Recommendations included (1) Training IRBs to understand CEnR principles to streamline and increase the flexibility of the IRB review process; (2) Identifying influential community stakeholders who can provide support for the study; and (3) Disseminating human subjects research training that is accessible to all community investigator to satisfy IRB concerns. Findings from our study suggest that IRBs can benefit from more training in CEnR requirements and methodologies.
RESUMEN
Improving race and ethnicity (hereafter, race/ethnicity) data quality is imperative to ensure underserved populations are represented in data sets used to identify health disparities and inform health care policy. We performed a scoping review of methods that retrospectively improve race/ethnicity classification in secondary data sets. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searches were conducted in the MEDLINE, Embase, and Web of Science Core Collection databases in July 2022. A total of 2â 441 abstracts were dually screened, 453 full-text articles were reviewed, and 120 articles were included. Study characteristics were extracted and described in a narrative analysis. Six main method types for improving race/ethnicity data were identified: expert review (n = 9; 8%), name lists (n = 27, 23%), name algorithms (n = 55, 46%), machine learning (n = 14, 12%), data linkage (n = 9, 8%), and other (n = 6, 5%). The main racial/ethnic groups targeted for classification were Asian (n = 56, 47%) and White (n = 51, 43%). Some form of validation evaluation was included in 86 articles (72%). We discuss the strengths and limitations of different method types and potential harms of identified methods. Innovative methods are needed to better identify racial/ethnic subgroups and further validation studies. Accurately collecting and reporting disaggregated data by race/ethnicity are critical to address the systematic missingness of relevant demographic data that can erroneously guide policymaking and hinder the effectiveness of health care practices and intervention.
Asunto(s)
Exactitud de los Datos , Etnicidad , Grupos Raciales , Humanos , Área sin Atención Médica , Estudios RetrospectivosRESUMEN
In a relaxed and awake state with the eyes closed, 8-12 Hz neural oscillations are the dominant rhythm, most prominent in parietal-occipital regions. Resting-state (RS) alpha is associated with processing speed and is also thought to be central to how networks process information. Unfortunately, the RS eyes-closed (EC) exam can only be used with individuals who can remain awake with their eyes closed for an extended period. As such, infants, toddlers, and individuals with intellectual disabilities are usually excluded from RS alpha studies. Previous research suggests obtaining RS alpha measures in a dark room with the eyes open as a viable alternative to the traditional RS EC exam. To further explore this, RS EC and RS dark room (DR) eyes-open alpha activity was recorded using magnetoencephalography in children with typical development (TD; N = 37) and children with autism spectrum disorder (ASD; N = 30) 6.9-12.6 years old. Findings showed good reliability for the RS EC and DR peak alpha frequency (frequency with strongest alpha power; interclass correlation (ICC) = 0.83). ICCs for posterior alpha power were slightly lower (ICCs in the 0.70 s), with an ~ 5% reduction in posterior alpha power in the DR than EC condition. No differences in the EC and DR associations were observed between the TD and ASD groups. Finally, age was associated with both EC and DR peak alpha frequency. Findings thus indicate the DR exam as a viable way to obtain RS alpha measures in populations frequently excluded from electrophysiology RS studies.
Asunto(s)
Trastorno del Espectro Autista , Lactante , Humanos , Niño , Reproducibilidad de los Resultados , Magnetoencefalografía , Lóbulo Occipital , Lóbulo ParietalRESUMEN
Resting-state alpha brain rhythms provide a foundation for basic as well as higher-order brain processes. Research suggests atypical maturation of the peak frequency of resting-state alpha activity (= PAF) in autism spectrum disorder (ASD). The present study examined resting-state alpha activity in young school-aged children, obtaining magnetoencephalographic (MEG) eyes-closed resting-state data from 47 typically developing (TD) males and 45 ASD males 6.0 to 9.3 years old. Results confirmed a higher PAF in ASD versus TD, and demonstrated that alpha power differences between groups were linked to the shift of PAF in ASD. Additionally, a higher PAF was associated with better cognitive performance in TD but not ASD. Finding thus suggested functional consequences of group differences in resting-state alpha activity.
RESUMEN
BACKGROUND: Developing biomarkers is a priority for drug development for all conditions, but vital in the rare neurodevelopmental disorders where sensitive outcome measures are lacking. We have previously demonstrated the feasibility and tracking of evoked potentials to disease severity in Rett syndrome and CDKL5 deficiency disorder. The aim of the current study is to characterize evoked potentials in two related developmental encephalopathies, MECP2 duplication syndrome and FOXG1 syndrome, and compare across all four groups to better understand the potential of these measures to serve as biomarkers of clinical severity for the developmental encephalopathies. METHODS: Visual and auditory evoked potentials were acquired from participants with MECP2 duplication syndrome and FOXG1 syndrome across five sites of the Rett Syndrome and Rett-Related Disorders Natural History Study. A group of age-matched individuals (mean = 7.8 years; range = 1-17) with Rett syndrome, CDKL5 deficiency disorder, and typically-developing participants served as a comparison group. The analysis focused on group-level differences as well as associations between the evoked potentials and measures of clinical severity from the Natural History Study. RESULTS: As reported previously, group-level comparisons revealed attenuated visual evoked potentials (VEPs) in participants with Rett syndrome (n = 43) and CDKL5 deficiency disorder (n = 16) compared to typically-developing participants. VEP amplitude was also attenuated in participants with MECP2 duplication syndrome (n = 15) compared to the typically-developing group. VEP amplitude correlated with clinical severity for Rett syndrome and FOXG1 syndrome (n = 5). Auditory evoked potential (AEP) amplitude did not differ between groups, but AEP latency was prolonged in individuals with MECP2 duplication syndrome (n = 14) and FOXG1 syndrome (n = 6) compared to individuals with Rett syndrome (n = 51) and CDKL5 deficiency disorder (n = 14). AEP amplitude correlated with severity in Rett syndrome and CDKL5 deficiency disorder. AEP latency correlated with severity in CDKL5 deficiency disorder, MECP2 duplication syndrome, and FOXG1 syndrome. CONCLUSIONS: There are consistent abnormalities in the evoked potentials in four developmental encephalopathies some of which correlate with clinical severity. While there are consistent changes amongst these four disorders, there are also condition specific findings that need to be further refined and validated. Overall, these results provide a foundation for further refinement of these measures for use in future clinical trials for these conditions.