Arthritis in Children with Psychiatric Deteriorations: A Case Series.

Pediatric acute-onset neuropsychiatric syndrome (PANS), pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, Sydenham chorea, and other postinfectious psychiatric deteriorations are thought to be caused by inflammatory/autoimmune mechanisms, likely involving the basal ganglia based on imaging studies. Patients have a relapsing-remitting course and some develop severe refractory psychiatric disease. We found that 55/193 (28%) of consecutive patients meeting PANS criteria developed chronic arthritis and 25/121 (21%) of those with related psychiatric deteriorations developed chronic arthritis. Here we describe 7 of these patients in detail and one sibling. Many of our patients often have "dry" arthritis (no effusions found on physical exam) but subtle effusions detected by imaging and features of spondyloarthritis, enthesitis, and synovitis. Joint capsule thickening, not previously reported in children, is a common finding in the presented cases and in psoriatic arthritis in adults. Due to the severity of psychiatric symptoms in some cases, which often overshadow joint symptoms, and concomitant sensory dysregulation (making the physical exam unreliable in the absence of effusions), we rely on imaging to improve sensitivity and specificity of the arthritis classification. We also report the immunomodulatory treatments of these 7 patients (initially nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs with escalation to biologic medications) and note any coincidental changes to their arthritis and psychiatric symptoms while on immunomodulation. Patients with overlapping psychiatric syndromes and arthritis may have a unifying cause and pose unique challenges; a multi-disciplinary team can utilize imaging to tailor and coordinate treatment for this patient population.

The varied spectrum of nephroblastomatosis, nephrogenic rests, and Wilms tumors: Review of current definitions and challenges of the field.

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.

Imaging of pediatric renal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper focused on Wilms tumor and nephrogenic rests.

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.

Imaging of pediatric bone tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%-5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.

Magnetic resonance neurography techniques in the pediatric population.

The use of magnetic resonance imaging (MRI) in the evaluation of the central extracranial nervous system, namely the brachial and lumbosacral plexuses, is well established and has been performed for many years. Only recently after numerous advances in MRI, has image quality been sufficient to properly visualize small structures, such as nerves in the extremities. Despite the advances, peripheral MR Neurography remains a complex and difficult examination to perform, especially in the pediatric patient population, in which the risk for motion artifact and compliance is always of concern. Thus, technical aspects of the MR imaging protocol must be flexible but robust, to balance image quality with scan time, in a patient population of varying sizes. An additional important step for reliably performing a successful MR Neurography examination is the non-technical pre-imaging preparation, which includes patient/family education and open communication with referring teams. This paper will discuss in detail the individual technical and non-technical/operational aspects of peripheral MR Neurography, to help guide in building a successful program in the pediatric population.

Volumetric and multispectral DWI near metallic implants using a non-linear phase Carr-Purcell-Meiboom-Gill diffusion preparation.

PURPOSE: DWI near metal implants has not been widely explored due to substantial challenges associated with through-slice and in-plane distortions, the increased encoding requirement of different spectral bins, and limited SNR. There is no widely adopted clinical protocol for DWI near metal since the commonly used EPI trajectory fails completely due to distortion from extreme off-resonance ranging from 2 to 20 kHz. We present a sequence that achieves DWI near metal with moderate b-values (400-500 s/mm2 ) and volumetric coverage in clinically feasible scan times. THEORY AND METHODS: Multispectral excitation with Cartesian sampling, view angle tilting, and kz phase encoding reduce in-plane and through-plane off-resonance artifacts, and Carr-Purcell-Meiboom-Gill (CPMG) spin-echo refocusing trains counteract T2* effects. The effect of random phase on the refocusing train is eliminated using a stimulated echo diffusion preparation. Root-flipped Shinnar-Le Roux refocusing pulses permits preparation of a high spectral bandwidth, which improves imaging times by reducing the number of excitations required to cover the desired spectral range. B1 sensitivity is reduced by using an excitation that satisfies the CPMG condition in the preparation. A method for ADC quantification insensitive to background gradients is presented. RESULTS: Non-linear phase refocusing pulses reduces the peak B1 by 46% which allows RF bandwidth to be doubled. Simulations and phantom experiments show that a non-linear phase CPMG pulse pair reduces B1 sensitivity. Application in vivo demonstrates complementary contrast to conventional multispectral acquisitions and improved visualization compared to DW-EPI. CONCLUSION: Volumetric and multispectral DW imaging near metal can be achieved with a 3D encoded sequence.

Near-Silent and Distortion-Free Diffusion MRI in Pediatric Musculoskeletal Disorders: Comparison With Echo Planar Imaging Diffusion.

BACKGROUND: Diffusion-weighted imaging (DWI) is common for evaluating pediatric musculoskeletal lesions, but suffers from geometric distortion and intense acoustic noise. PURPOSE: To investigate the performance of a near-silent and distortion-free DWI sequence (DW-SD) relative to standard echo-planar DWI (DW-EPI) in pediatric extremity MRI. STUDY TYPE: Prospective validation study. SUBJECTS: Thirty-nine children referred for extremity MRI. FIELD STRENGTH/SEQUENCE: DW-EPI and DW-SD, based on a rotating ultrafast sequence modified with sinusoidal diffusion preparation gradients, at 3T. ASSESSMENT: DW-SD image quality (Sanat ) was assessed from 0 (nondiagnostic) to 5 (outstanding) and comparative image quality (Scomp ) (from -2 = DW-EPI more delineated to +2 = DW-SD more delineated, 0 = same). ADC measured by DW-SD and DW-EPI were compared in bone marrow, muscle, and lesions. STATISTICAL TESTS: Wilcoxon rank-sum test and confidence interval of proportions (CIOP) were calculated for Scomp , Student's t-test, coefficient of variation (COV), and Bland-Altman analysis for ADC values, and intraclass correlation coefficient (ICC) for interreader agreement. RESULTS: DW-SD and DW-EPI ADC values for bone marrow, muscle, and lesions were not significantly different (P = 0.3, P = 0.2, and P = 0.27, respectively) and had an overall ADC COV of 14.8% (95% confidence interval: 12.3%, 16.9%) and no significant proportional bias on Bland-Altman analysis. Sanat CIOP was rated diagnostic or better (score of 3, 4, or 5) in 72-98% of cases for bone marrow, muscle, and soft tissues. DW-SD was equivalent to or preferred over DW-EPI in muscles and soft tissues, with CIOP 86-93% and 93%, respectively. Lesions were equally visualized on DW-SD and DW-EPI in 40-51%, with DW-SD preferred in 44-56% of cases. DW-SD was rated significantly better than DW-EPI across all comparative variables that included bone marrow, muscle, soft tissue, cartilage, and lesions (P < 0.05). Readers had moderate to near-perfect (ICC range = 0.45-0.85). DATA CONCLUSION: DW-SD of the extremities provided similar ADC values and improved image quality compared with conventional DW-EPI. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:504-513.

Zero echo time pediatric musculoskeletal magnetic resonance imaging: initial experience.

BACKGROUND: Projection radiography (XR) is often supplemented by both CT (to evaluate osseous structures with ionizing radiation) and MRI (for marrow and soft-tissue assessment). Zero echo time (ZTE) MR imaging produces a "CT-like" osseous contrast that might obviate CT. OBJECTIVE: This study investigated our institution's initial experience in implementing an isotropic ZTE MR imaging sequence for pediatric musculoskeletal examinations. MATERIALS AND METHODS: Pediatric patients referred for extremity MRI at 3 tesla (T) underwent ZTE MR imaging to yield images with contrast similar to that of CT. A radiograph-like image was also created with ray-sum image processing. We assessed ZTE-CT/XR anatomical image quality (Sanat) from 0 (nondiagnostic) to 5 (outstanding). Further, we made image comparisons on a 5-point scale (Scomp) (range of -2 = conventional CT/XR greater anatomical delineation to +2 = ZTE-CT/XR greater anatomical delineation; 0=same) for three cohorts: (1) ZTE-XR to conventional radiography, (2) ZTE-CT to conventional CT and (3) pathological lesion assessment on ZTE-XR to conventional radiography. We measured cortical thickness of ZTE-XR and ZTE-CT and compared these with conventional imaging. We calculated confidence interval of proportions, Wilcoxon rank sum test and intraclass correlation coefficients for inter-reader agreement. RESULTS: Cohorts 1, 2 and 3 consisted of 40, 20 and 35 cases, respectively (age range 0.6-23.0 years). ZTE-CT versus CT and ZTE-XR versus radiography of cortical thicknesses were not significantly different (P=0.55 and P=0.31, respectively). Cortical delineation was rated diagnostic or better (score of 3, 4 or 5) in all cases (confidence interval of proportions = 100%) for ZTE-CT/XR. Similarly, intramedullary cavity delineation was rated diagnostic or better in all cases for ZTE-CT, and ZTE-XR was at least diagnostic in 58-63% of cases. For cohort 2, cortex and intramedullary cavity Scomp for ZTE-CT was comparable to those of conventional CT, with confidence interval of proportion (sum of score of -1 to +2) of 93-100% and 95%, respectively. Pathology visualized on ZTE-CT/XR was comparable; Scomp confidence interval of proportions was 95%/97-100%, with improved delineation of non-displaced fractures on ZTE-XR. Readers had moderate to near-perfect intraclass correlation coefficient (range=0.60-0.93). CONCLUSION: Implementation of a diagnostic-quality ZTE MRI sequence in the pediatric population is feasible and can be performed as a complementary pulse sequence to enhance musculoskeletal MRI studies. Compared to conventional CT, ZTE has comparable cortical delineation, intramedullary cavity and pathology visualization. While not intended as a replacement for conventional radiography, ZTE-XR provides similar visualization of pathology.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Near-silent distortionless DWI using magnetization-prepared RUFIS.

PURPOSE: To develop a near-silent and distortionless DWI (sd-DWI) sequence using magnetization-prepared rotating ultrafast imaging sequence. METHODS: A rotating ultrafast imaging sequence was modified with driven-equilibrium diffusion preparation, including eddy-current compensation methods. To compensate for the T1 recovery during readout, a phase-cycling method was used. Both compensation methods were validated in phantoms. The optimized sequence was compared with an EPI diffusion sequence for image distortion, contrast, ADC, and acoustic noise level in phantoms. The sequence was evaluated in 1 brain volunteer, 5 prostate volunteers, and 10 pediatric patients with joint diseases. RESULTS: Combination of several eddy-current compensation methods reduced the artifact to an acceptable level. Phase cycling reduced T1 recovery contamination during readout. In phantom scans, the optimized sequence generated similar image contrast to the EPI diffusion sequence, and ADC maps between the sequences were comparable; sd-DWI had significantly lower acoustic noise (P < .05). In vivo brain scan showed reduced image distortion in sd-DWI compared with the EPI diffusion, although residual motion artifact remains due to brain pulsation. The prostate scans showed that sd-DWI can provide similar ADC compared with EPI diffusion, with no image distortion. Patient scans showed that the sequence can clearly depict joint lesions. CONCLUSION: An sd-DWI sequence was developed and optimized. Compared with conventional EPI diffusion, sd-DWI provided similar diffusion contrast, accurate ADC measurement, improved image quality, and minimal ambient scanning noise. The sequence showed the ability to obtain in vivo diffusion contrast in relatively motion-free body regions, such as prostate and joint.

Imaging Characteristics of Nephrogenic Rests Versus Small Wilms Tumors: A Report From the Children's Oncology Group Study AREN03B2.

OBJECTIVE. Distinguishing nephrogenic rests from small Wilms tumors can be challenging. This retrospective study was performed to determine if imaging characteristics can be used to distinguish nephrogenic rests from Wilms tumors. MATERIALS AND METHODS. All cases of pathologically confirmed nephrogenic rests and Wilms tumors smaller than 5 cm in maximum dimension on imaging in patients younger than 5 years old were identified from the Children's Oncology Group AREN03B2 study (July 2006-August 2016). Exclusion criteria were chemotherapy before pathologic evaluation or more than 30 days between imaging and surgery; in addition, patients with nephrogenic rests occurring within or juxtaposed to a Wilms tumor and patients with diffuse hyperplastic perilobar nephroblastomatosis were excluded. Two radiologists who were blinded to pathology results assessed all lesions. The two-sample t test was used for continuous variables, and the Fisher exact test was used for categoric variables. ROC analysis was performed to determine the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors. RESULTS. Thirty-one pathologically confirmed rests (20 perilobar, 11 intralobar) and 26 Wilms tumors smaller than 5 cm met the eligibility criteria for study inclusion. The median diameter of the nephrogenic rests was 1.3 cm (range, 0.7-3.4 cm) and the median diameter of the Wilms tumor was 3.2 cm (range, 1.8-4.9 cm) (p < 0.001). Imaging findings supportive of Wilms tumors were spherical (p < 0.001) and exophytic (p < 0.001) lesions. Perilobar rests (17/20) were more likely to be homogeneous than intralobar rests (3/11) or Wilms tumor (3/26) (p < 0.001). ROC analysis showed that the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors was 1.75 cm. CONCLUSION. In children younger than 5 years old, the diagnosis of a Wilms tumor should be favored over a nephrogenic rest when a renal mass is spherical, exophytic, or larger than 1.75 cm. Homogeneity favors the diagnosis of perilobar nephrogenic rests, whereas intralobar rests and Wilms tumors are more likely to be inhomogeneous.

Targeted rapid knee MRI exam using T2 shuffling.

BACKGROUND: MRI is commonly used to evaluate pediatric musculoskeletal pathologies, but same-day/near-term scheduling and short exams remain challenges. PURPOSE: To investigate the feasibility of a targeted rapid pediatric knee MRI exam, with the goal of reducing cost and enabling same-day MRI access. STUDY TYPE: A cost effectiveness study done prospectively. SUBJECTS: Forty-seven pediatric patients. FIELD STRENGTH/SEQUENCE: 3T. The 10-minute protocol was based on T2 Shuffling, a four-dimensional acquisition and reconstruction of images with variable T2 contrast, and a T1 2D fast spin-echo (FSE) sequence. A distributed, compressed sensing-based reconstruction was implemented on a four-node high-performance compute cluster and integrated into the clinical workflow. ASSESSMENT: In an Institutional Review Board-approved study with informed consent/assent, we implemented a targeted pediatric knee MRI exam for assessing pediatric knee pain. Pediatric patients were subselected for the exam based on insurance plan and clinical indication. Over a 2-year period, 47 subjects were recruited for the study and 49 MRIs were ordered. Date and time information was recorded for MRI referral, registration, and completion. Image quality was assessed from 0 (nondiagnostic) to 5 (outstanding) by two readers, and consensus was subsequently reached. STATISTICAL TESTS: A Wilcoxon rank-sum test assessed the null hypothesis that the targeted exam times compared with conventional knee exam times were unchanged. RESULTS: Of the 49 cases, 20 were completed on the same day as exam referral. Median time from registration to exam completion was 18.7 minutes. Median reconstruction time for T2 Shuffling was reduced from 18.9 minutes to 95 seconds using the distributed implementation. Technical fees charged for the targeted exam were one-third that of the routine clinical knee exam. No subject had to return for additional imaging. DATA CONCLUSION: The targeted knee MRI exam is feasible and reduces the imaging time, cost, and barrier to same-day MRI access for pediatric patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2019.

Case 253: Thrombosed Umbilical Venous Varix in an Infant.

History A 3-month-old previously healthy girl presented to an outside institution with a 4-day history of low-grade fever, irritability, and a tender "knot" in the upper abdomen. Ultrasonography (US) was performed at an outside hospital. US images were not available for review; however, they showed a mass in the left hepatic lobe, per the outside report, and the patient was referred to our institution for further evaluation. Her parents reported a normal full-term pregnancy, with regular prenatal care and normal prenatal US findings. The baby was born after an uncomplicated gestation. She was delivered at term via an uncomplicated cesarean section due to a maternal history of cesarean section. The perinatal course was uncomplicated, and there was no history of umbilical catheterization, per the parents. On arrival at our institution, the patient had a temperature of 38.2°C. All other vital signs were normal. Palpation revealed a tender and firm mass in the periumbilical region; otherwise, physical examination findings were normal. Results of laboratory work-up were normal, except for elevated white blood cell count (26 600/mm3 [26.6 × 109/L]; normal, 6000-17 500/mm3 [6-17.5 × 109/L]). The patient underwent US followed by intravenous contrast material-enhanced (10 mL ioversol, Optiray 320; Medtronic, Santa Rosa, Calif) computed tomography (CT) on the same day.

Percutaneous Cryoablation for the Treatment of Recurrent Malignant Pleural Mesothelioma: Safety, Early-Term Efficacy, and Predictors of Local Recurrence.

PURPOSE: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of recurrent mesothelioma and assess risk factors for local recurrence. MATERIALS AND METHODS: During the period 2008-2012, 24 patients underwent 110 cryoablations for recurrent mesothelioma tumors in 89 sessions. Median patient age was 69 years (range, 48-82 y). Median tumor size was 30 mm (range, 9-113 mm). Complications were graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Recurrence was diagnosed on CT or positron emission tomography/CT by increasing size, nodular enhancement, or hypermetabolic activity and analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine covariates associated with local tumor recurrence. RESULTS: Median duration of follow-up was 14.5 months. Complications occurred in 8 of 110 cryoablations (7.3%). All but 1 complication were graded CTCAE v4.0 1 or 2. No procedure-related deaths occurred. Freedom from local recurrence was observed in 100% of cases at 30 days, 92.5% at 6 months, 90.8% at 1 year, 87.3% at 2 years, and 73.7% at 3 years. Tumor recurrence was diagnosed 4.5-24.5 months after cryoablation (mean 5.7 months). Risk of tumor recurrence was associated with a smaller ablative margin from the edge of tumor to iceball ablation margin (multivariate hazard ratio 0.68, CI 0.48-0.95, P = .024). CONCLUSIONS: CT-guided cryoablation is safe for local control of recurrent mesothelioma, with a low rate of complications and promising early-term efficacy. A smaller ablative margin may predispose to tumor recurrence.

Imaging of renal medullary carcinoma in children and young adults: a report from the Children's Oncology Group.

BACKGROUND: Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children. OBJECTIVE: To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation. MATERIALS AND METHODS: We retrospectively analyzed images of 25 pediatric patients with renal medullary carcinoma enrolled in the Children's Oncology Group renal tumors classification, biology and banking study (AREN03B2) from March 2006 to August 2016. Imaging findings of the primary mass, and patterns of locoregional and distant spread were evaluated in correlation with pathological and surgical findings. RESULTS: Median age at presentation was 13 years (range: 6-21 years), with a male predominance (3.2:1). The overall stage of disease at initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with a slight right side predilection (1.5:1). Enlarged (>1 cm short axis) retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%) cases, 10 of which were histologically confirmed while the others did not undergo surgical sampling. Enlarged lymph nodes were also identified in the mediastinum (14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1 unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic carcinomatosis had associated enlarged mediastinal lymph nodes. CONCLUSION: Renal medullary carcinoma in children and young adults presents at an advanced local and distant stage in the majority of patients. The diagnosis of renal medullary carcinoma should be considered when a child or young adult presents with a poorly defined/infiltrative, centrally located renal mass, especially in the setting of known sickle cell hemoglobinopathy. Distant metastases are common at initial presentation in the lungs, distant lymph nodes and liver and often involve multiple sites simultaneously. Pulmonary lymphangitic carcinomatosis, a distinctive and uncommon form of lung metastasis in children, is common in this patient population.

The density-threshold affinity: Calculating lipid binding affinities from unbiased coarse-grained molecular dynamics simulations.

Many membrane proteins are sensitive to their local lipid environment. As structural methods for membrane proteins have improved, there is growing evidence of direct, specific binding of lipids to protein surfaces. Unfortunately the workhorse of understanding protein-small molecule interactions, the binding affinity for a given site, is experimentally inaccessible for these systems. Coarse-grained molecular dynamics simulations can be used to bridge this gap, and are relatively straightforward to learn. Such simulations allow users to observe spontaneous binding of lipids to membrane proteins and quantify localized densities of individual lipids or lipid fragments. In this chapter we outline a protocol for extracting binding affinities from these localized distributions, known as the "density threshold affinity." The density threshold affinity uses an adaptive and flexible definition of site occupancy that alleviates the need to distinguish between "bound'' lipids and bulk lipids that are simply diffusing through the site. Furthermore, the method allows "bead-level" resolution that is suitable for the case where lipids share binding sites, and circumvents ambiguities about a relevant reference state. This approach provides a convenient and straightforward method for comparing affinities of a single lipid species for multiple sites, multiple lipids for a single site, and/or a single lipid species modeled using multiple forcefields.

Development of Autoimmune Diseases Among Children With Pediatric Acute-Onset Neuropsychiatric Syndrome.

Importance: Epidemiologic studies indicate a high rate of autoimmune conditions among patients with obsessive-complusive disorder and other psychiatric conditions. Furthering the understanding of the inflammatory diatheses of psychiatric conditions may open doors to new treatment paradigms for psychiatric disorders. Objectives: To evaluate whether pediatric acute-onset neuropsychiatric syndrome (PANS) is associated with an inflammatory diathesis by assessing signs of immune activation and vasculopathy during a psychiatric symptom exacerbation (flare), estimating the risk of developing arthritis and other autoimmune diseases, and characterizing subtypes of arthritis. Design, Setting, and Participants: This retrospective cohort study used longitudinal clinical data on 193 consecutive patients with PANS followed up within the Stanford Immune Behavioral Health Clinic from September 1, 2012, to December 31, 2021. Main Outcomes and Measures: Medical records were reviewed, and a predefined set of immune markers that were measured during a flare and the features and imaging findings of arthritis and other autoimmune diseases were collected. Immune activation markers included (1) autoimmunity signs (antinuclear antibody, antihistone antibody, antithyroglobulin antibody, C1q binding assay, and complement levels [C3 and C4]); (2) immune dysregulation or inflammation signs (leukopenia, thrombocytosis, C-reactive protein, and erythrocyte sedimentation rate); and (3) vasculopathy signs (livedo reticularis, periungual redness and swelling, abnormally prominent onychodermal band, palatal petechiae, high von Willebrand factor antigen, and high d-dimer). Last, the cumulative risk of developing arthritis and autoimmune diseases was estimated using product limit (Kaplan-Meier) survival probability. Results: The study included data from 193 children (112 boys [58.0%]) who had PANS at a mean (SD) age of 7.5 (3.5) years. They were followed up for a mean (SD) of 4.0 (2.1) years. Among those tested for immune activation markers, 54.2% (97 of 179) had nonspecific markers of autoimmunity, 12.0% (22 of 184) had nonspecific signs of immune dysregulation or inflammation, and 35.8% (69 of 193) had signs of vasculopathy. By 14 years of age, the estimated cumulative incidence of arthritis was 28.3% (95% CI, 20.8%-36.3%), and the estimated cumulative incidence of another autoimmune disease was 7.5% (95% CI, 4.0%-12.4%). Novel findings in the subgroup with arthritis include joint capsule thickening (55.0% [22 of 40]), distal interphalangeal joint tenderness (81.8% [45 of 55]), and spinous process tenderness (80.0% [44 of 55]). Among the 55 patients with arthritis, the most common subtypes of arthritis included enthesitis-related arthritis (37 [67.3%]), spondyloarthritis (27 [49.1%]), and psoriatic arthritis (10 [18.2%]). Conclusions and Relevance: This study found that patients with PANS show signs of immune activation and vasculopathy during psychiatric symptom flares and have an increased risk of developing arthritis and other autoimmune diseases compared with the general pediatric population. The most common arthritis subtype was enthesitis-related arthritis. These findings suggest that PANS may be part of a multisystem inflammatory condition rather than an isolated psychiatric or neuroinflammatory disorder.

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.