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Item Baseline ultrasound and clinical correlates in children with cystic fibrosis.(Elsevier, 2015-10) Leung, Daniel H.; Ye, Wen; Molleston, Jean P.; Weymann, Alexander; Ling, Simon; Paranjape, Shruti M.; Romero, Rene; Schwarzenberg, Sara Jane; Palermo, Joseph; Alonso, Estella M.; Murray, Karen F.; Marshall, Bruce C.; Sherker, Averell H.; Siegel, Marilyn J.; Krishnamurthy, Rajesh; Harned, Roger; Karmazyn, Boaz; Magee, John C.; Narkewicz, Michael R.; Department of Pediatrics, IU School of MedicineObjective: To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design: Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results: Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) hadItem Characteristics of testicular tumors in prepubertal children (age 5–12 years)(Elsevier, 2018) Karmazyn, Boaz; Weatherly, David L.; Lehnert, Stephen J.; Cain, Mark; Fan, Rong; Jennings, S. Gregory; Ouyang, Fangqian; Kaefer, Martin; Radiology and Imaging Sciences, School of MedicineIntroduction Testicular tumors in children have two peaks with different types of tumors; in the first 4 years of life a third to half are benign with increased risk of malignancy during puberty. The pathology of testicular tumors between these peaks, at the age of 5–12 years, is not known. We hypothesized that because of the low level of testosterone at this time, the incidence of malignant tumors is very low. Objective To compare malignancy risk of primary testicular tumors in children in the prepubertal period (5–12 years) compared with younger (0–4 years) and pubertal (13–18 years) children. Study design We retrospectively (2002–2016) identified patients <18 years with surgery for primary testicular tumor. Patients with testicular tumor risk were excluded. Ultrasound studies were reviewed for contralateral testis volume, tumor morphology, and tumor maximal diameter, for three age groups: 0–4, 5–12, and 13–18 years. The Freeman-Halton extension of the Fisher exact probability test was adopted for categorical outcomes, and one-way ANOVA for continuous outcomes. Results Fifty-two patients (mean age 11.0 years, range 6 days–18 years) were identified. Malignant tumor prevalence significantly differed ( p < 0.01) among age groups ( Fig ).: 0–4 (72.7%, 8/11), 5–12 (0%, 0/16), and 13–18 years (44.0%, 11/25). The most common tumor types in 5–12 years were epidermoid cyst (31.3%, 5/16) and tumor mimics (37.5%, 6/16). Prevalence of cystic tumors in 5–12 year olds was not significantly different compared with other age groups. Contralateral testicular volume >4 mL (pubertal surge) significantly ( p < 0.01) differed among groups: 0–4 years (0/11), 5–12 years (3/16), and 13–18 years (19/20). In children aged 13–18 years the mean tumor maximal diameter (29.8 ± 4.4 mm) was significantly larger (p < 0.01) compared with children 5–12 years (9.3 ± 5.5 mm) and all malignant tumors had contralateral testicular volume >4 mL. Discussion We found that preadolescent children between the ages of 5 and 12 years have distinctive characteristics compared with the other age groups. Most importantly, no malignant testicular tumors were found in this age group. About a third of the children presented with an incidental testicular mass. The testicular tumors were significantly smaller (9.3 ± 6.7 mm) compared with those in children aged 13–18 years (29.8 ± 4.4 mm). There were limitations because of the retrospective nature of the study. Conclusion We found no malignant testicular tumors in children aged 5–12 years with no risk factors and prior to pubertal surge. Our study suggests use of more conservative treatment in this group of patients.Item Classic metaphyseal lesion acquired during physical therapy(Elsevier, 2018) Della Grotta, Lynn M.; Marine, Megan B.; Harris, Tara L.; Karmazyn, Boaz; Radiology and Imaging Sciences, School of MedicineA classic metaphyseal lesion (CML) is highly specific for nonaccidental trauma. Missing CMLs can be devastating to the child as the child can continue to be exposed to inflicted trauma. Yet, there are rare case reports on CMLs that occur due to birth trauma, IV line placement, and treatment for clubfoot. We present a case of a CML in the tibia that occurred in the hospital secondary to physical therapy, that also caused a femoral shaft fracture, in a term child with hypertonic lower extremities secondary to myelomeningocele. Radiologists, as well as child abuse pediatricians, should be aware of the rare exception when CML is secondary to non-abusive injury.Item Compliance With Skeletal Surveys for Child Abuse in General Hospitals: A Statewide Quality Improvement Process(ARRS, 2019-05) Wanner, Matthew R.; Marine, Megan B.; Hibbard, Roberta A.; Ouyang, Fangqian; Jennings, S. Gregory; Shea, Lindsey; Karmazyn, Boaz; Radiology and Imaging Sciences, School of MedicineOBJECTIVE. The purpose of this study is to perform a statewide quality improvement process to improve compliance with the American College of Radiology (ACR) guidelines in performing skeletal surveys for suspected child abuse. SUBJECTS AND METHODS. We prospectively identified all outside hospital skeletal surveys for suspected child abuse in children younger than 3 years referred to our tertiary children's hospital in 2016–2017. We included a 3-month baseline and 21-month intervention period. The quality improvement process was based on sending educational material to all ACR member radiologists in the state and making telephone calls to radiology technologist team leaders whenever the surveys were not compliant, followed by e-mails with guidance on performing skeletal surveys. We documented the views obtained and compared them with the ACR guidelines. The percentage of compliance with each individual view was assessed with the chi-square test. The total number of compliant views per survey was evaluated with ANOVA. RESULTS. Two hundred twenty-seven patients (105 female) with a mean age of 0.8 year (SD, 0.67 year; range, 0.01–3 years) were evaluated. These 227 surveys (baseline, n = 27; postintervention, n = 200) were performed at 69 different outside hospitals. Compliance significantly (p = 0.006) improved from 25.9% (7/27) during baseline to 54.0% (108/200) after intervention. There was a nonsignificant trend of improved compliance between the first (51.9%; 41/79) and last 7-month (62.3%; 33/53) periods of intervention. Among individual views, only rib oblique views showed significantly (p = 0.02) improved compliance after the intervention, from 51.9% (14/27) to 73.5% (147/200). CONCLUSION. The compliance rate with ACR guidelines for skeletal surveys in suspected child abuse at outside general hospitals significantly increased after implementation of a quality improvement process.Item Diagnosis and Follow-up of Incidental Liver Lesions in Children(Wolters Kluwer, 2022-03) Karmazyn, Boaz; Rao, Girish S.; Johnstone, Lindsey S.; Severance, Tyler S.; Ferguson, Michael J.; Marshalleck, Francis E.; Molleston, Jean P.; Radiology and Imaging Sciences, School of MedicineABSTRACT: Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH) and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was FDA-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and AFP should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and when biopsy is not feasible.Item Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children(Wiley, 2022) Schwarzenberg, Sarah Jane; Palermo, Joseph J.; Ye, Wen; Huang, Suiyuan; Magee, John C.; Alazraki, Adina; Freeman, A. Jay; Harned, Roger; Karmazyn, Boaz; Karnsakul, Wikrom; Leung, Daniel H.; Ling, Simon C.; Masand, Prakash; Molleston, Jean P.; Murray, Karen F.; Navarro, Oscar M.; Nicholas, Jennifer L.; Otto, Randolph K.; Paranjape, Shruti M.; Siegel, Marilyn J.; Stoll, Janis; Towbin, Alexander J.; Narkewicz, Michael R.; Alonso, Estella M.; CFLD NET; Pediatrics, School of MedicineObjectives: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. Methods: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. Results: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. Conclusions: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.Item Health-related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis-related Liver Disease in Children(Wiley, 2022-09-06) Schwarzenberg, Sarah Jane; Palermo, Joseph J.; Ye, Wen; Huang, Suiyuan; Magee, John C.; Alazraki, Adina; Freeman, A. Jay; Harned, Roger; Karmazyn, Boaz; Karnsakul, Wikrom; Leung, Daniel H.; Ling, Simon C.; Masand, Prakash; Molleston, Jean P.; Murray, Karen F.; Navarro, Oscar M.; Nicholas, Jennifer L.; Otto, Randolph K.; Paranjape, Shruti M.; Siegel , Marilyn J.; Stoll, Janis; Towbin, Alexander J.; Narkewicz, Michael R.; Alonso, Estella M.; Pediatrics, School of MedicineBackground: Cystic fibrosis-related liver disease (CFLD) begins early in life. Symptoms may be vague, mild or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of cystic fibrosis-related liver disease (CFLD) to determine the impact of early CFLD on general and disease-specific QOL. Methods: US patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age≥5 y) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1-year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. Results: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. Conclusions: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.Item Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease(Elsevier, 2023) Siegel, Marilyn J.; Leung, Daniel H.; Molleston, Jean P.; Ye, Wen; Paranjape, Shruti M.; Freeman, A. Jay; Palermo, Joseph J.; Stoll, Janis; Masand, Prakash; Karmazyn, Boaz; Harned, Roger; Ling, Simon C.; Navarro, Oscar M.; Karnsakul, Wikrom; Alazraki, Adina; Schwarzenberg, Sarah Jane; Towbin, Alex J.; Alonso, Estella M.; Nicholas, Jennifer L.; Green, Nicole; Otto, Randolph K.; Magee, John C.; Narkewicz, Michael R.; CFLD Network; Pediatrics, School of MedicineBackground: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). Methods: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. Results: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. Conclusions: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD.Item Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study(Elsevier, 2020-04) Siegel, Marilyn J.; Freeman, A. Jay; Ye, Wen; Palermo, Joseph J.; Molleston, Jean P.; Paranjape, Shruti M.; Stoll, Janis; Leung, Daniel; Masand, Prakash; Karmazyn, Boaz; Harned, Roger; Ling, Simon C.; Navarro, Oscar M.; Karnsakul, Wikrom; Alazraki, Adina; Schwarzenberg, Sarah Jane; Seidel, F. Glen; Towbin, Alex; Alonso, Estella M.; Nicholas, Jennifer L.; Murray, Karen F.; Otto, Randolph K.; Sherker, Averell H.; Magee, John C.; Narkewicz, Michael R.; Pediatrics, School of MedicineObjective: To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. Study design: Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. Results: There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P < .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P < .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). Conclusions: Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.Item Osteomyelitis of the ribs in children: a rare and potentially challenging diagnosis(Springer, 2020) Crone, Allison M.; Wanner, Matthew R.; Cooper, Matthew L.; Fox, Thomas G.; Jennings, S. Gregory; Karmazyn, Boaz; Radiology and Imaging Sciences, School of MedicineBackground Rib osteomyelitis is rare in children and can mimic other pathologies. Imaging has a major role in the diagnosing rib osteomyelitis. Objective To evaluate clinical presentation and imaging findings in children with rib osteomyelitis. Materials and methods We performed a retrospective (2009–2018) study on children with rib osteomyelitis verified by either positive culture or pathology. We excluded children with multifocal osteomyelitis or empyema necessitans. We reviewed medical charts for clinical, laboratory and pathology data, and treatment. All imaging modalities for rib abnormalities were evaluated for presence and location of osteomyelitis and abscess. We calculated descriptive statistics to compare patient demographics, clinical presentation and imaging findings. Results The study group included 10 children (6 boys, 4 girls), with an average age of 7.3 years (range, 3 months to 15.9 years). The most common clinical presentations were fever (n=8) and pain (n=5). Eight children had elevated inflammatory indices (leukocytosis, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]). Localized chest wall swelling was found initially in six children and later in two more children. Rib osteomyelitis was suspected on presentation in only two children. All children had chest radiographs. Rib lytic changes were found on only one chest radiograph, in two of the four ultrasound studies, and in four of eight CTs. Bone marrow signal abnormalities were seen in all eight MRIs. In nine children the osteomyelitis involved the costochondral junction. Six children had an associated abscess. Staphylococcus aureus was cultured in eight children. Osteomyelitis was diagnosed based on pathology in one child with negative cultures. Conclusion While rib osteomyelitis is rare, imaging findings of lytic changes at the costochondral junction combined with a history of fever, elevated inflammatory markers or localized soft-tissue swelling in the chest should raise suspicion for this disease.