Faculty Bibliography
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26
Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci
Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.
PMCID:11071577
PMID: 38712091
CID: 5662722
Quantification of popliteal artery narrowing with QISS MRA during active ankle plantarflexion in healthy, asymptomatic volunteers and its potential application in the diagnosis of popliteal artery entrapment syndrome (PAES)
OBJECTIVE:To assess the degree of narrowing of the popliteal artery during active ankle plantar flexion in healthy volunteers using a non-contrast quiescent-interval single-shot (QISS) magnetic resonance angiography (MRA) technique. MATERIALS AND METHODS/METHODS:Following IRB approval, 10 healthy volunteers were recruited and following informed consent underwent QISS MRA of the lower extremity at rest and during ankle plantarflexion. Two pediatric musculoskeletal radiologists independently reviewed MR images in random order and recorded a number of subjective and objective anatomic variables including branch pattern, proximity of vessel to bony structures, gastrocnemius bulk, and presence of accessory muscle. Arterial narrowing with plantarflexion was recorded by a subjective assessment of 3D reconstructions (negligible or non-negligible) and objectively by measuring the narrowest diameter during plantarflexion and at rest. Agreement between reader scores was assessed using the concordance correlation coefficient (CCC) for continuous variables, and kappa and the proportion of agreement for categorical variables. RESULTS:Mean reduction in arterial diameter during plantar flexion was 17.1% (min 1.9%, max 64.1%, SD 16.7%) for reader 1 and 17.2% (min 1.7%, max 50.0%, SD 14.3%.) for reader 2 with high agreement between readers: CCC = 0.92 and CI = 0.82, 0.96. Arterial narrowing was described subjectively as "non-negligible" in 7/20 legs by reader 1 and 5/20 legs by reader 2 with proportion of agreement = 0.90, CI (0.77, 1.00). CONCLUSION/CONCLUSIONS:We observed a wide range of popliteal arterial narrowing with plantarflexion in asymptomatic volunteers. Larger studies, for which QISS is well suited, may be invaluable for distinguishing physiologic from pathologic arterial narrowing in patients with suspected popliteal artery entrapment syndrome (PAES).
PMID: 33797565
ISSN: 1432-2161
CID: 5155802
Challenges within our current education model and where to direct innovation: the three-strand triquetra approach [Editorial]
PMCID:7692422
PMID: 33245374
ISSN: 1432-1998
CID: 5155872
DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor
The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary "DICER1-associated central nervous system sarcoma" (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3-15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic "organoid" features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.
PMID: 32291395
ISSN: 1530-0285
CID: 5155822
A pandemic offers a silver lining for pediatric radiology training
PMCID:7441304
PMID: 32821993
ISSN: 1432-1998
CID: 5155882
MRI Is Better Than CT Scan for Detection of Structural Pathologies After Traumatic Posterior Hip Dislocations in Children and Adolescents
BACKGROUND:Traumatic posterior hip dislocations in children and adolescents requires emergent closed reduction. Postreduction imaging is necessary to assess the concentricity of reduction and structural injuries to the hip. There is no a consensus for which imaging is a modality of choice in such condition. The purposes of this study are to describe magnetic resonance imaging (MRI) findings of traumatic posterior hip dislocations and to compare the effectiveness of MRI with computerized tomography (CT) in detecting structural abnormalities of the hip that impact patient management. METHODS:This study is a retrospective review of imaging in traumatically dislocated hips in patients who were treated at our institution. All CT and MRI imaging were reviewed and specific osseous and soft tissue injuries documented by consensus among 2 musculoskeletal pediatric radiologists who interpreted the MRI and CT scans of each patient in a blinded manner. RESULTS:In total, 27 patients (23 males, 4 females) with mean age of 12.5 years (range, 2 to 19 y) with postreduction MRI were evaluated. MRI findings revealed femoral head injuries in 17 (62.9%), posterior labral entrapments in 6 (22.2%), posterior labral tears in 17 (62.9%), posterior wall fractures in 15 (55.5%), fracture of the posterior unossified part of acetabulum in 4 (14.8%), and ligamentum teres injuries in 8 (29.6%). Of 16 patients who had postreduction CT scans, 6 (37.5%) had femoral head fractures, 9 (56.3%) had posterior wall fractures, and 8 (50%) had intra-articular osseous entrapments. All bony fractures and intra-articular entrapment could be seen on MRI imaging. In 16 patients with both CT and MRI, posterior acetabular injury was detected in 10/16 (62.5%) on MRI and 9/16 (56.3%) on CT. Three patients with entrapment of labrums identified on MRI could not be seen on CT scan. One patient with persistently unstable hip after reduction had an entrapped unossified portion of acetabular fracture which was seen on MRI but not on CT. CONCLUSIONS:MRI is superior to CT scan for detection of structural injuries in children and adolescents with traumatic hip dislocation. The unique structural injuries included entrapment of posterior labrum and posterior unossified acetabular fractures could be seen only at MRI. These findings will impact surgical decision making of these injuries. LEVEL OF EVIDENCE/METHODS:Level IV.
PMID: 31923168
ISSN: 1539-2570
CID: 5155792
Fetal applications
Philadelphia PA : Wolters Kluwer, 2020
pp. ?-?
ISBN: 9781496370495
CID: 5155922
Improving Low-Dose Pediatric Abdominal CT by Using Convolutional Neural Networks
Purpose/UNASSIGNED:To evaluate the efficacy of convolutional neural networks (CNNs) to improve the image quality of low-dose pediatric abdominal CT images. Materials and Methods/UNASSIGNED:Images from 11 pediatric abdominal CT examinations acquired between June and July 2018 were reconstructed with filtered back projection (FBP) and an iterative reconstruction (IR) algorithm. A residual CNN was trained using the FBP image as the input and the difference between FBP and IR as the target such that the network was able to predict the residual image and simulate the IR. CNN-based postprocessing was applied to 20 low-dose pediatric image datasets acquired between December 2016 and December 2017 on a scanner limited to reconstructing FBP images. The FBP and CNN images were evaluated based on objective image noise and subjective image review by two pediatric radiologists. For each of five features, readers rated images on a five-point Likert scale and also indicated their preferred series. Readers also indicated their "overall preference" for CNN versus FBP. Preference and Likert scores were analyzed for individual and combined readers. Interreader agreement was assessed. Results/UNASSIGNED:< .001). CNN was preferred for overall image quality for individual and combined readers. For combined Likert scores, at least one of the two score types (Likert or binary preference) indicated a significant favoring of CNN over FBP for low contrast, image noise, artifacts, and high contrast, whereas the reverse was true for spatial resolution. Conclusion/UNASSIGNED:FBP images can be improved in image space by a well-trained CNN, which may afford a reduction in dose or improvement in image quality on scanners limited to FBP reconstruction.© RSNA, 2019.
PMCID:6884028
PMID: 32090205
ISSN: 2638-6100
CID: 5155812
The distal tibial classic metaphyseal lesion: medial versus lateral cortical injury
BACKGROUND:The distal tibia is a common location for the classic metaphyseal lesion (CML). Prior radiologic-pathologic studies have suggested a tendency for medial, as opposed to lateral, cortical injury with the CML, but there has been no formal study of the geographic distribution of this strong indicator of abuse. OBJECTIVE:This study compares medial versus lateral cortical involvement of distal tibial CMLs in a clinical cohort of infants with suspected abuse. MATERIALS AND METHODS:Reports of 1,020 skeletal surveys performed for suspected abuse (July 2005-June 2016) were reviewed. Twenty-six distal tibial CMLs (14 unilateral, 6 bilateral) with anteroposterior (AP) and lateral projections on the initial skeletal survey and at least an AP view on the follow-up survey were identified in 20 infants. Two blinded pediatric radiologists determined if the medial and/or lateral margins of the distal tibial metaphysis were involved by the CML. RESULTS:Average interreader absolute agreement and kappa scores were 0.69-0.90 and 0.45-0.72, respectively. Average intrareader absolute agreement and kappa scores were 0.65-0.88 and 0.44-0.57, respectively. Analyses showed that the distal tibial CML almost always involved the medial cortical margin (reader 1=89%, reader 2=88%, pooled=89%) and the fracture infrequently involved the lateral cortical margin (reader 1=12%, reader 2=38%, pooled=26%). The percentage point difference between fracture involvement in medial and lateral margins was statistically significant from zero (P<0.001). CONCLUSION:The distal tibial CML is most often encountered medially; lateral involvement is uncommon. This observation should help guide the radiologic diagnosis and could have implications for understanding the biomechanics of this distinctive injury.
PMID: 29541806
ISSN: 1432-1998
CID: 5155772
Pediatric radiology malpractice claims - characteristics and comparison to adult radiology claims
Medical malpractice is the primary method by which people who believe they have suffered an injury in the course of medical care seek compensation in the United States and Canada. An increasing body of research demonstrates that failure to correctly diagnose is the most common allegation made in malpractice claims against radiologists. Since the 1994 survey by the Society of Chairmen of Radiology in Children's Hospitals (SCORCH), no other published studies have specifically examined the frequency or clinical context of malpractice claims against pediatric radiologists or arising from pediatric imaging interpretation. We hypothesize that the frequency, character and outcome of malpractice claims made against pediatric radiologists differ from those seen in general radiology practice. We searched the Controlled Risk Insurance Co. (CRICO) Strategies' Comparative Benchmarking System (CBS), a private repository of approximately 350,000 open and closed medical malpractice claims in the United States, for claims related to pediatric radiology. We further queried these cases for the major allegation, the clinical environment in which the claim arose, the clinical severity of the alleged injury, indemnity paid (if payment was made), primary imaging modality involved (if applicable) and primary International Classification of Diseases, 9th revision (ICD-9) diagnosis underlying the claim. There were a total of 27,056 fully coded claims of medical malpractice in the CBS database in the 5-year period between Jan. 1, 2010, and Dec. 31, 2014. Of these, 1,472 cases (5.4%) involved patients younger than 18Â years. Radiology was the primary service responsible for 71/1,472 (4.8%) pediatric cases. There were statistically significant differences in average payout for pediatric radiology claims ($314,671) compared to adult radiology claims ($174,033). The allegations were primarily diagnosis-related in 70% of pediatric radiology claims. The most common imaging modality implicated in pediatric radiology claims was radiography. The highest payouts in pediatric radiology pertained to missed congenital and developmental anomalies (average $1,222,932) such as developmental dysplasia of the hip and congenital central nervous system anomalies. More than half of pediatric radiology claims arose in the ambulatory setting. Pediatric radiology is not immune from claims of medical malpractice and these claims result in high monetary payouts, particularly for missed diagnoses of congenital and developmental anomalies. Our data suggest that efforts to reduce diagnostic error in the outpatient radiology setting, in the interpretation of radiographs, and in the improved diagnosis of fractures and congenital and developmental anomalies would be of particular benefit to the pediatric radiology community.
PMID: 28536766
ISSN: 1432-1998
CID: 5155782
