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1.
J Am Coll Radiol ; 21(6S): S310-S325, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38823953

ABSTRACT

Soft tissue vascular anomalies may be composed of arterial, venous, and/or lymphatic elements, and diagnosed prenatally or later in childhood or adulthood. They are divided into categories of vascular malformations and vascular tumors. Vascular malformations are further divided into low-flow and fast-flow lesions. A low-flow lesion is most common, with a prevalence of 70%. Vascular tumors may behave in a benign, locally aggressive, borderline, or malignant manner. Infantile hemangioma is a vascular tumor that presents in the neonatal period and then regresses. The presence or multiple skin lesions in an infant can signal underlying visceral vascular anomalies, and complex anomalies may be associated with overgrowth syndromes. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Subject(s)
Societies, Medical , Vascular Malformations , Humans , Vascular Malformations/diagnostic imaging , United States , Evidence-Based Medicine , Infant , Vascular Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Infant, Newborn , Child , Diagnostic Imaging/methods , Hemangioma/diagnostic imaging , Practice Guidelines as Topic
2.
Res Pract Thromb Haemost ; 7(8): 102238, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38053983

ABSTRACT

Background: Clinical trials have shown success in bleed prevention with emicizumab, but real-world data on the effectiveness of emicizumab in preventing serious bleeds in the pediatric population are lacking. Objectives: To report real-world data on the effectiveness of Emicizumab in pediatric persons with hemophilia A. Methods: We completed a retrospective chart review of 37 pediatric male patients aged ≤18 years on emicizumab prophylaxis for a median duration of 30.5 months at Children's Medical Center in Dallas, Texas. Results: We identified 4 pediatric persons with severe hemophilia A with and without inhibitors who experienced a provoked or unprovoked serious bleed requiring hospitalization. Conclusion: This study highlights that serious bleeds, both provoked and unprovoked, can occur in pediatric persons with severe hemophilia A. These findings are important for clinicians to provide appropriate counseling/education and recommendation of treatment for pediatric persons with severe hemophilia A through shared decision making. Up-titration of emicizumab or factor VIII replacement needs consideration in persons with hemophilia with suboptimal bleeding control or who participate in activities categorized as moderate- to high-risk activities.

3.
J Med Case Rep ; 17(1): 237, 2023 May 31.
Article in English | MEDLINE | ID: mdl-37254165

ABSTRACT

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014). CASE PRESENTATION: A 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease. CONCLUSIONS: Children and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation.


Subject(s)
Chorea , Inflammatory Bowel Diseases , Osteitis , Male , Child , Adolescent , Humans , Osteitis/pathology , Cachexia/complications , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/pathology , Inflammation/complications , Pain , Weight Loss
4.
Pediatr Blood Cancer ; 70 Suppl 4: e30004, 2023 06.
Article in English | MEDLINE | ID: mdl-36308415

ABSTRACT

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.


Subject(s)
Kidney Neoplasms , Radiology , Wilms Tumor , Child , Humans , Rest , Surface Plasmon Resonance , Kidney Neoplasms/pathology , Wilms Tumor/diagnostic imaging , Wilms Tumor/therapy , Wilms Tumor/pathology , Radiography
5.
SLAS Discov ; 27(3): 191-200, 2022 04.
Article in English | MEDLINE | ID: mdl-35124274

ABSTRACT

3D cell models derived from patient tumors are highly translational tools that can recapitulate the complex genetic and molecular compositions of solid cancers and accelerate identification of drug targets and drug testing. However, the complexity of performing assays with such models remains a hurdle for their wider adoption. In the present study, we describe methods for processing and multi-functional profiling of tumoroid samples to test compound effects using a novel flowchip system in combination with high content imaging and metabolite analysis. Tumoroids were formed from primary cells isolated from a patient-derived tumor explant, TU-BcX-4IC, that represents metaplastic breast cancer with a triple-negative breast cancer subtype. Assays were performed in a microfluidics-based device (Pu⋅MA System) that allows automated exchange of media and treatments of tumoroids in a tissue culture incubator environment. Multi-functional assay profiling was performed on tumoroids treated with anti-cancer drugs. High-content imaging was used to evaluate drug effects on cell viability and expression of E-cadherin and CD44. Lactate secretion was used to measure tumoroid metabolism as a function of time and drug concentration. Observed responses included loss of cell viability, decrease in E-cadherin expression, and increase of lactate production. Importantly, the tumoroids were sensitive to romidepsin and trametinib, while showed significantly reduced sensitivity to paclitaxel and cytarabine, consistent with the primary tumor response. These methods for multi-parametric profiling of drug effects in patient-derived tumoroids provide an in depth understanding of drug sensitivity of individual tumor types, with important implications for the future development of personalized medicine.


Subject(s)
Antineoplastic Agents , Triple Negative Breast Neoplasms , Antineoplastic Agents/pharmacology , Cadherins , Humans , Lactic Acid , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics
6.
SLAS Technol ; 26(3): 237-248, 2021 06.
Article in English | MEDLINE | ID: mdl-33783259

ABSTRACT

There is an increasing interest in using three-dimensional (3D) cell structures for modeling tumors, organs, and tissue to accelerate translational research. We describe here a novel automated organoid assay system (the Pu·MA System) combined with microfluidic-based flowchips that can facilitate 3D cell-based assays. The flowchip is composed of sample wells, which contain organoids, connected to additional multiple wells that can hold various assay reagents. Organoids are positioned in a protected chamber in sample wells, and fluids are exchanged from side reservoirs using pressure-driven flow. Media exchange, sample staining, wash steps, and other processes can be performed without disruption to or loss of 3D sample. The bottom of the sample chamber is thin, optically clear plastic compatible with high-content imaging (HCI). The whole system can be kept in an incubator, allowing long-term cellular assays to be performed. We present two examples of use of the system for biological research. In the first example, cytotoxicity effects of anticancer drugs were evaluated on HeLa and HepG2 spheroids using HCI and vascular endothelial growth factor expression. In the second application, the flowchip system was used for the functional evaluation of Ca2+ oscillations in neurospheroids. Neurospheres were incubated with neuroactive compounds, and neuronal activity was assessed using Ca2+-sensitive dyes and fast kinetic fluorescence imaging. This novel assay system using microfluidics enables automation of 3D cell-based cultures that mimic in vivo conditions, performs multidosing protocols and multiple media exchanges, provides gentle handling of spheroids and organoids, and allows a wide range of assay detection modalities.


Subject(s)
Antineoplastic Agents , Vascular Endothelial Growth Factor A , Automation , Microfluidics , Organoids
7.
J Pediatr Urol ; 16(5): 557.e1-557.e7, 2020 10.
Article in English | MEDLINE | ID: mdl-32446678

ABSTRACT

INTRODUCTION: The standard imaging modality for hemodynamically stable blunt abdominal trauma patients is a contrast enhanced CT scan, which is reflected in the current AUA urotrauma guidelines. This comes, however, with radiation exposure and the potential sequalae of IV contrast administration in the pediatric patient. OBJECTIVE: We hypothesize that ultrasound imaging would be able to diagnose and rule out clinically significant renal injuries when compared to the gold standard of CT scan in the setting of pediatric blunt abdominal trauma. STUDY DESIGN: All children <18 years of age who were evaluated for blunt abdominal trauma who had a CT scan and ultrasound imaging of kidneys were identified. The ultrasound images were reviewed by four reviewers who were blinded to CT results and all clinical information. The ability of ultrasound to diagnose and rule out clinically significant renal injury was evaluated by diagnostic test performance characteristics including sensitivity, specificity, negative predictive value and positive predictive value. RESULTS: There were 76 patients identified, 24 of which had a renal injury (1 bilateral) diagnosed by CT scan for a total of 25 injuries in 152 renal units. There were six grade I-II injuries and 19 grade III-V injuries. The sensitivity of the four blinded reviewers by ultrasound alone to detect the 19 grade III-V injuries ranged from 79 to 100% with NPV between 97 and 100%. Three of the four reviewers identified all 19 grade III-V injuries by ultrasound. When combined with significant hematuria, all 19 grade III-IV injuries were identified. Of note, all patients with a grade III-V injury of the kidney had significant hematuria. Of the grade I-II renal injuries, all reviewers identified 1/5 or 2/5 by ultrasound alone. DISCUSSION: The limitations of this study include: its retrospective nature, limited number of patients and reviewers, quality of the ultrasound machine. and experience of technologist, radiologist and urologist. A major limitation is the inability to assess other solid organ injuries during this initial study. CONCLUSIONS: When compared to a CT scan as the gold standard, kidney ultrasound images had a sensitivity of 79-100% to detect grade III-V injuries and NPV of 97-100% by four blinded reviewers. All grade III-V injuries had either an episode of gross hematuria or microscopic hematuria >50 RBC/hpf. A prospective study that includes full abdominal imaging is needed to confirm that ultrasound can safely be used in place of CT scan for evaluation of hemodynamically stable blunt trauma patients.


Subject(s)
Abdominal Injuries , Wounds, Nonpenetrating , Abdominal Injuries/diagnostic imaging , Child , Diagnostic Tests, Routine , Humans , Kidney/diagnostic imaging , Kidney/injuries , Prospective Studies , Retrospective Studies , Tomography, X-Ray Computed , Ultrasonography , Wounds, Nonpenetrating/diagnostic imaging
8.
JBJS Rev ; 8(3): e0121, 2020 03.
Article in English | MEDLINE | ID: mdl-32224640

ABSTRACT

A team approach is optimal in the evaluation and treatment of musculoskeletal infection in pediatric patients given the complexity and uncertainty with which such infections manifest and progress, particularly among severely ill children. The team approach includes emergency medicine, pediatric intensive care, pediatric hospitalist medicine, infectious disease service, orthopaedic surgery, radiology, anesthesiology, pharmacology, and hematology. These services follow evidence-based clinical practice guidelines with integrated processes of care so that children and their families may benefit from data-driven continuous process improvement. Important principles based on our experience in the successful treatment of pediatric musculoskeletal infection include relevant information gathering, pattern recognition, determination of the severity of illness, institutional workflow management, closed-loop communication, patient and family-centered care, ongoing dialogue among key stakeholders within and outside the context of direct patient care, and periodic data review for programmatic improvement over time. Such principles may be useful in almost any setting, including rural communities and developing countries, with the understanding that the team composition, institutional capabilities or limitations, and specific approaches to treatment may differ substantially from one setting or team to another.


Subject(s)
Osteomyelitis/therapy , Patient Care Team , Shock, Septic/therapy , Child , Humans , Magnetic Resonance Imaging , Male , Osteomyelitis/complications , Osteomyelitis/diagnostic imaging , Shock, Septic/etiology , Tibia/diagnostic imaging
9.
J Bone Joint Surg Am ; 101(18): 1679-1688, 2019 Sep 18.
Article in English | MEDLINE | ID: mdl-31567805

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) is a heavily utilized resource to evaluate children suspected to have a musculoskeletal infection. Complex interdisciplinary workflows are involved with decision-making with regard to indications, anesthesia, contrast use, and procedural timing relative to the scan. This study assesses the impact of a quality improvement endeavor on MRI workflows at a tertiary pediatric medical center. METHODS: A registry of consecutively enrolled children for a multidisciplinary musculoskeletal infection program identified those evaluated with MRI from 2012 to 2018. Annual MRI process improvement feedback was provided to the key stakeholders. Demographic characteristics, laboratory parameters, MRI indications, anesthesia use, MRI findings, final diagnoses, scan duration, imaging protocol, surgical intervention following MRI, and length of stay were retrospectively compared between the 3 cohorts (initial, middle, and final) representing 2-year increments to assess the impact of the initiative. RESULTS: There were 526 original MRI scans performed to evaluate 1,845 children with suspected musculoskeletal infection. Anesthesia was used in 401 children (76.2%). When comparing the initial, middle, and final study period cohorts, significant improvement was demonstrated for the number of sequences per scan (7.5 sequences for the initial cohort, 5.8 sequences for the middle cohort, and 4.6 sequences for the final cohort; p < 0.00001), scan duration (73.6 minutes for the initial cohort, 52.1 minutes for the middle cohort, and 34.9 minutes for the final cohort; p < 0.00001), anesthesia duration (94.1 minutes for the initial cohort, 68.9 minutes for the middle cohort, and 53.2 minutes for the final cohort; p < 0.00001), and the rate of contrast use (87.6% for the initial cohort, 67.7% for the middle cohort, and 26.3% for the final cohort; p < 0.00001). There was also a trend toward a higher rate of procedures under continued anesthesia immediately following the MRI (70.2% in the initial cohort, 77.8% in the middle cohort, and 84.6% in the final cohort). During the final 6-month period, the mean scan duration was 24.4 minutes, anesthesia duration was 40.9 minutes, and the rate of contrast administration was 8.5%. CONCLUSIONS: Progressive quality improvement through collaborative interdisciplinary communication and workflow redesign led to improved utilization of MRI and minimized contrast use for suspected musculoskeletal infection. There was a high rate of procedural intervention under continued anesthesia for children with confirmed musculoskeletal infection. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Hospitals, Pediatric/standards , Infections/diagnostic imaging , Magnetic Resonance Imaging/standards , Musculoskeletal Diseases/diagnostic imaging , Quality Improvement/organization & administration , Tertiary Care Centers/standards , Workflow , Adolescent , Child , Child, Preschool , Clinical Protocols , Contrast Media , Female , Hospitals, Pediatric/organization & administration , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Registries , Retrospective Studies , Tertiary Care Centers/organization & administration , Texas , Time Factors , Young Adult
10.
Skeletal Radiol ; 48(1): 77-88, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30123946

ABSTRACT

With the rising participation of girls in sports at both the recreational and elite levels, there has also been increased awareness of injuries common in this athlete population. Anatomic differences between boys and girls cause girl athletes to be predisposed to certain injuries. Certain behavioral patterns, such as eating disorders, also cause problems specific to girl athletes that may result in injury. Imaging plays a large role in diagnosis and ongoing management, but there has been only scant literature dedicated to the specific topic of imaging in girl athletes. The purpose of this article is to review the imaging findings and recommendations for injuries and other conditions affecting the adolescent girl athlete. This article first provides an overview of the key anatomic differences between boys and girls, including both static and dynamic factors, as well as non-anatomic differences, such as hormonal factors, and discusses how these differences contribute to the injury patterns that are seen more typically in girls. The article then reviews the imaging findings in injuries that are commonly seen in girl athletes. There is also a discussion of the "female athlete triad," which consists of osteoporosis, disordered eating, and amenorrhea, and the role of imaging in this condition.


Subject(s)
Athletic Injuries/diagnostic imaging , Musculoskeletal System/diagnostic imaging , Musculoskeletal System/injuries , Adolescent , Female , Female Athlete Triad Syndrome/complications , Female Athlete Triad Syndrome/diagnostic imaging , Humans , Risk Factors
11.
Oral Maxillofac Surg Clin North Am ; 30(1): 25-34, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29153235

ABSTRACT

Imaging of the temporomandibular joint in pediatric patients is a critical component in the evaluation and treatment of children with temporomandibular joint symptoms. MRI can provide detailed joint anatomy and identify inflammation, sometimes before symptom onset. Ultrasound scan is a convenient emerging modality to evaluate the joint and guide therapeutic injections. Radiography and computed tomography offer osseous detail to recognize early morphologic changes of the mandibular condyle and provide operative planning. Imaging promises to direct treatment to prevent future joint destruction and maintain function.


Subject(s)
Diagnostic Imaging , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint/diagnostic imaging , Child , Humans
12.
J Physiol ; 595(22): 6887-6903, 2017 11 15.
Article in English | MEDLINE | ID: mdl-28862330

ABSTRACT

KEY POINTS: The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. ABSTRACT: Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 µs) over 14 months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as 'neural fulcrum') during which HRR ≈ 0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy.


Subject(s)
Heart Rate , Heart/physiology , Vagus Nerve Stimulation , Vagus Nerve/physiology , Adrenergic beta-Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Benzazepines/pharmacology , Dogs , Female , Heart/innervation , Ivabradine , Male , Muscarinic Antagonists/pharmacology , Vagus Nerve/drug effects
13.
Auton Neurosci ; 208: 57-65, 2017 12.
Article in English | MEDLINE | ID: mdl-28919363

ABSTRACT

BACKGROUND: Autonomic regulation therapy involving either vagus nerve stimulation (VNS) or spinal cord stimulation (SCS) represents emerging bioelectronic therapies for heart disease. The objective of this study was to determine if VNS and/or SCS modulate primary cardiac afferent sensory transduction of the ischemic myocardium. METHODS: Using extracellular recordings in 19 anesthetized canines, of 88 neurons evaluated, 36 ventricular-related nodose ganglia sensory neurons were identified by their functional activity responses to epicardial touch, chemical activation of their sensory neurites (epicardial veratridine) and great vessel (descending aorta or inferior vena cava) occlusion. Neural responses to 1min left anterior descending (LAD) coronary artery occlusion (CAO) were then evaluated. These interventions were then studied following either: i) SCS [T1-T3 spinal level; 50Hz, 90% motor threshold] or ii) cervical VNS [15-20Hz; 1.2× threshold]. RESULTS: LAD occlusion activated 66% of identified nodose ventricular sensory neurons (0.33±0.08-0.79±0.20Hz; baseline to CAO; p<0.002). Basal activity of cardiac-related nodose neurons was differentially reduced by VNS (0.31±0.11 to 0.05±0.02Hz; p<0.05) as compared to SCS (0.36±0.12 to 0.28±0.14, p=0.59), with their activity response to transient LAD CAO being suppressed by either SCS (0.85±0.39-0.11±0.04Hz; p<0.03) or VNS (0.75±0.27-0.12±0.05Hz; p<0.04). VNS did not alter evoked neural responses of cardiac-related nodose neurons to great vessel occlusion. CONCLUSIONS: Both VNS and SCS obtund ventricular ischemia induced enhancement of nodose afferent neuronal inputs to the medulla.


Subject(s)
Myocardial Ischemia/physiopathology , Nodose Ganglion/physiopathology , Sensory Receptor Cells/physiology , Spine/physiopathology , Sympathetic Nervous System/physiopathology , Action Potentials , Animals , Disease Models, Animal , Dogs , Electric Stimulation , Immunohistochemistry , Microelectrodes , Myocardial Ischemia/pathology , Nodose Ganglion/pathology , Sensory Receptor Cells/pathology , Spine/pathology , Sympathetic Nervous System/pathology , Thoracic Vertebrae
14.
Assay Drug Dev Technol ; 15(6): 280-296, 2017.
Article in English | MEDLINE | ID: mdl-28837356

ABSTRACT

Development of more complex, biologically relevant, and predictive cell-based assays for compound screening is a major challenge in drug discovery. The focus of this study was to establish high-throughput compatible three-dimensional (3D) cardiotoxicity assays using human induced pluripotent stem cell-derived cardiomyocytes. Using both high-content imaging and fast kinetic fluorescence imaging, the impact of various compounds on the beating rates and patterns of cardiac spheroids was monitored by changes in intracellular Ca2+ levels with calcium-sensitive dyes. Advanced image analysis methods were implemented to provide multiparametric characterization of the Ca2+ oscillation patterns. In addition, we used confocal imaging and 3D analysis methods to characterize compound effects on the morphology of 3D spheroids. This phenotypic assay allows for the characterization of parameters such as beating frequency, amplitude, peak width, rise and decay times, as well as cell viability and morphological characteristics. A set of 22 compounds, including a number of known cardioactive and cardiotoxic drugs, was assayed at different time points, and the calculated EC50 values for compound effects were compared between 3D and two-dimensional (2D) model systems. A significant concordance in the phenotypes was observed for compound effects between the two models, but essential differences in the concentration responses and time dependencies of the compound-induced effects were observed. Together, these results indicate that 3D cardiac spheroids constitute a functionally distinct biological model system from traditional flat 2D cultures. In conclusion, we have demonstrated that phenotypic assays using 3D model systems are enabled for screening and suitable for cardiotoxicity assessment in vitro.


Subject(s)
Induced Pluripotent Stem Cells/drug effects , Myocytes, Cardiac/drug effects , Phenotype , Spheroids, Cellular/drug effects , Calcium/metabolism , Cells, Cultured , High-Throughput Screening Assays , Humans , Induced Pluripotent Stem Cells/metabolism , Myocytes, Cardiac/metabolism , Spheroids, Cellular/metabolism
15.
J Pediatr Urol ; 13(4): 401.e1-401.e7, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28511888

ABSTRACT

BACKGROUND: MAG3 diuretic renal scan remains the gold standard for determination of improvement in renal drainage following pyeloplasty for ureteropelvic junction obstruction. We hypothesized that (i) a change in geometric measurements between pre-operative and post-operative renal ultrasound (RUS) images and (ii) blinded simple visual review of images both would predict pyeloplasty success. OBJECTIVE: To determine if simple visual review and/or novel geometric measurement of renal ultrasounds can detect pyeloplasty failure. STUDY DESIGN: This study was a retrospective, blinded comparison with a gold standard. Included were children aged ≤18 years undergoing pyeloplasty at our institution from 2009 to 2015. For each kidney, representative pre-operative and post-operative RUS images were chosen. Our standard for pyeloplasty success was improved drainage curve on MAG3 and lack of additional surgery. Measurements for collecting system circularity, roundness, and renal parenchymal to collecting system area ratio (RPCSR) were obtained by three raters (Figure), who were blinded to the outcome of the pyeloplasty. Changes in geometric measurements were analyzed as a diagnostic test for MAG3-defined pyeloplasty success using ROC curve analysis. In addition, six reviewers blinded to pyeloplasty success reviewed pre-operative and post-operative images visually for improved hydronephrosis and categorized pyeloplasty as success or failure based on simple visual review of RUS. RESULTS: Fifty-three repaired renal units were identified (50 children). There were five pyeloplasty failures, four of which underwent revision or nephrectomy. While all geometric measurements could discriminate pyeloplasty failure and success, the geometric measurements that discriminated best between pyeloplasty failure and success were change in collecting system roundness and change in RPCSR. Consensus opinion among six blinded reviewers using simple visual review had a sensitivity of 94% and PPV of 100% with respect to identifying pyeloplasty success (AUC 0.97 (95% CI 0.93-1.0)). This was not significantly different from AUC for change in roundness (p = 0.09) or change in RPCSR (p = 0.1). DISCUSSION: Change in collecting system roundness and change in RPCSR were the most accurate geometric measurements in predicting pyeloplasty success. Simple visual review of ultrasound images for pyeloplasty success performed as well or better than geometric measurements. However, geometric measurements remain useful as a research tool or to communicate findings between clinicians. CONCLUSIONS: Complex geometric measurements of hydronephrosis or post-operative MAG3 scans are not needed if hydronephrosis is visually significantly improved, as simple visual review is highly sensitive for detecting pyeloplasty failure.


Subject(s)
Hydronephrosis/diagnostic imaging , Kidney Pelvis/surgery , Postoperative Complications/diagnostic imaging , Ureteral Obstruction/surgery , Child , Female , Humans , Hydronephrosis/etiology , Male , Postoperative Complications/etiology , Predictive Value of Tests , Retrospective Studies , Treatment Failure , Ultrasonography , Ureteral Obstruction/diagnostic imaging
16.
J Pediatr Orthop ; 37(2): 121-126, 2017 Mar.
Article in English | MEDLINE | ID: mdl-26165554

ABSTRACT

BACKGROUND: Femoroacetabular impingement (FAI) can lead to acetabular chondrolabral damage and has been theorized as a causative factor in the development of osteoarthritis. The pathogenesis of FAI is unknown. The purpose of this study was to determine the prevalence of FAI morphology in asymptomatic adolescents. METHODS: We identified children 10 to 18 years of age who had undergone a pelvic CT between 2007 and 2012. Exclusion criteria included hip pain, any hip pathology, bone tumor, long-term steroid use, history of chemotherapy or radiation therapy, nonambulatory status, neuromuscular disorder, chromosomal abnormality, and metabolic bone disease. Multiplanar reformatted images were created from axial images to calculate α angles and lateral center-edge angles (LCEA). Cam morphology was defined as an α-angle ≥55 degrees and pincer morphology as a LCEA≥40 degrees. RESULTS: We analyzed 558 patients (1116 hips). There were 276 males and 282 females. The average age was 14.4 years (range, 10.0 to 18.2 y). The mean α-angle was 47.9 degrees (range, 25.7 to 78 degrees) and the mean LCEA was 34.4 degrees (range, 3.9 to 58.6 degrees). Males had a significantly higher mean α-angle (49.7 vs. 46.0 degrees) (P<0.0005) and females had a significantly higher mean LCEA (35.7 vs. 33.0 degrees) (P<0.0005). Ninety-four adolescents (16.8%) had an α-angle ≥55 degrees. Cam morphology was significantly more common in males (23.9% vs. 9.9%) (P<0.001). A total of 181 adolescents (32.4%) had a LCEA≥40 degrees. Pincer morphology was equally common in males and females (29.7% vs. 35.1%) (P=0.17). Thirty-four adolescents (6.1%) had mixed morphologies. Mixed morphologies were found in 21 males (7.6%) and 13 females (4.6%) (P=0.19). The prevalence of pincer morphology increased significantly with increased age in males (P<0.001). CONCLUSIONS: The prevalence of cam-type FAI morphology in asymptomatic adolescents is similar to the reported prevalence in asymptomatic adults. Pincer morphology may be more common than cam morphology in adolescents. Cam morphology is more prevalent in males, whereas pincer and mixed morphologies are equally prevalent in both sexes. LEVEL OF EVIDENCE: Level III-diagnostic.


Subject(s)
Asymptomatic Diseases , Femoracetabular Impingement/diagnosis , Hip Joint/diagnostic imaging , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Retrospective Studies , Sex Factors , Tomography, X-Ray Computed
17.
Emerg Radiol ; 24(2): 207-213, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27832341

ABSTRACT

Non-accidental trauma is a significant source of morbidity and mortality in the pediatric population. Given the vulnerable state of the child, the radiologist can often provide valuable diagnostic information in the setting of suspected abuse. This review focuses on common findings of abusive trauma and serves as a guide to aid in clinical decision-making for providers of emergency medicine and pediatrics. Amid this discussion is an assessment of modern controversies regarding reported mimicking pathologies, recapitulation of the current state of evidence with respect to radiologic findings of abuse, and examination of the contribution that spine imaging may add to the diagnosis of possible abusive head trauma in the acutely injured child. Recommendations for avoiding pitfalls regarding the dating of intracranial injuries are discussed, and illustrated depictions of perpetrator-induced pathology are provided to aid in the understanding of these injuries. Through the use of the appropriate approach to imaging and evidence-based guidelines regarding radiologic findings, the role of radiology is to provide fundamental clues to diagnose and prevent recurrence of abusive injury in patients who cannot speak for themselves.


Subject(s)
Child Abuse/diagnosis , Craniocerebral Trauma/diagnostic imaging , Diagnostic Imaging , Child , Decision Making , Diagnosis, Differential , Humans
18.
Radiographics ; 36(2): 464-78, 2016.
Article in English | MEDLINE | ID: mdl-26871986

ABSTRACT

Ultrasonography (US) is commonly used to assess the peripheral nerves of the lower extremity because of its many advantages over magnetic resonance (MR) imaging. The most obvious advantages over MR imaging are superior soft-tissue resolution, low cost, portability, lack of magnetic susceptibility artifact, and the ability to image patients who cannot undergo MR imaging. US has been shown to have equal specificity and greater sensitivity than MR imaging in the evaluation of peripheral nerves. Additional benefits are the capability of real-time and dynamic imaging, and the ability to scan an entire extremity quickly without the need for a patient to lie motionless for long periods of time, as with MR imaging. Any abnormal findings can be easily compared against the contralateral side. Published literature has shown that US has clinical utility in patients suspected of having peripheral nerve disease: US can be used to guide diagnostic and therapeutic decisions, as well as help confirm electrodiagnostic findings. Common indications for lower extremity peripheral nerve US are the evaluation for injury due to penetrating trauma, entrapment by scar tissue, or tumor. To confidently perform US of the peripheral nerves of the lower extremity, it is important to gain a thorough knowledge of anatomic landmarks and the course of each nerve. Readers who may not be familiar with US will be introduced to the basics of scanning the peripheral nerves of the lower extremity. Important anatomic landmarks and common sites of injury and entrapment will be reviewed.


Subject(s)
Leg/innervation , Peripheral Nerves/diagnostic imaging , Peripheral Nervous System Diseases/diagnostic imaging , Ultrasonography/methods , Femoral Nerve/diagnostic imaging , Humans , Leg/diagnostic imaging , Magnetic Resonance Imaging , Morton Neuroma/diagnostic imaging , Peripheral Nerve Injuries/diagnostic imaging , Peroneal Nerve/diagnostic imaging , Sciatic Nerve/diagnostic imaging , Tibial Nerve/diagnostic imaging , Ultrasonography/instrumentation
19.
Pediatr Radiol ; 45(12): 1788-95, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26216155

ABSTRACT

BACKGROUND: MR Urography (MRU) is an increasingly used imaging modality for the evaluation of pediatric genitourinary obstruction. OBJECTIVE: To determine whether pediatric MR urography (MRU) reliably detects crossing vessels in the setting of suspected ureteropelvic junction (UPJ) obstruction. The clinical significance of these vessels was also evaluated. MATERIALS AND METHODS: We identified pediatric patients diagnosed with UPJ obstruction by MRU between May 2009 and June 2014. MRU studies were evaluated by two pediatric radiologists for the presence or absence of crossing vessels. Ancillary imaging findings such as laterality, parenchymal thinning/scarring, trapped fluid in the proximal ureter, and presence of renal parenchymal edema were also evaluated. Imaging findings were compared to surgical findings. We used the Mann-Whitney U test to compare continuous data and the Fisher exact test to compare proportions. RESULTS: Twenty-four of 25 (96%) UPJ obstructions identified by MRU were surgically confirmed. MRU identified crossing vessels in 10 of these cases, with 9 cases confirmed intraoperatively (κ = 0.92 [95% CI: 0.75, 1.0]). Crossing vessels were determined to be the primary cause of UPJ obstruction in 7/9 children intraoperatively, while in two children the vessels were deemed incidental and noncontributory to the urinary tract obstruction. There was no significant difference in age or the proportions of ancillary findings when comparing children without and with obstructing vessels. CONCLUSION: MRU allows detection of crossing vessels in pediatric UPJ obstruction. Although these vessels are the primary cause of obstruction in some children, they are incidental and non-contributory in others. Our study failed to convincingly identify any significant predictors (e.g., age or presence of renal parenchymal edema) that indicate when a crossing vessel is the primary cause of obstruction.


Subject(s)
Magnetic Resonance Imaging , Ureter/blood supply , Ureter/pathology , Ureteral Obstruction/pathology , Adolescent , Child , Child, Preschool , Contrast Media , Female , Gadolinium , Heterocyclic Compounds , Humans , Image Enhancement , Imaging, Three-Dimensional , Infant , Male , Organometallic Compounds , Reproducibility of Results , Retrospective Studies
20.
Magn Reson Imaging Clin N Am ; 21(4): 813-28, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24183527

ABSTRACT

Noninvasive, nonionizing, multiparametric magnetic resonance (MR) imaging of the pelvis using a field strength of 3 T now provides a comprehensive assessment of perineal involvement in pediatric Crohn disease. MR imaging accurately evaluates inflammatory disease activity, and allows determination of the number and course of fistula tracts as well as their relationships to vital perianal structures, including the external anal sphincter, helping to guide surgical management and improve outcomes. This article provides an up-to-date review of perineal MR imaging findings of Crohn disease in the pediatric population, including fistulous disease, abscesses, and skin manifestations. Imaging technique is also discussed.


Subject(s)
Anal Canal/pathology , Crohn Disease/pathology , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Patient Positioning/methods , Perineum/pathology , Proctitis/pathology , Adolescent , Child , Female , Humans , Male
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