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

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%-2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.

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

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.

Optimizing Imaging of Pediatric Liver Lesions: Guidelines from the Pediatric LI-RADS Working Group.

A differential diagnosis based on a patient's age, clinical presentation, and serum α-fetoprotein level will help guide the initial imaging workup in children with a liver lesion. Children vary significantly in size, the ability to stay still, and the ability to breath hold for imaging examinations. Choosing and tailoring imaging techniques and protocols for each indication and age group is important for optimal care with minimal invasiveness. The need for sedation or anesthesia can be obviated by using techniques like feed and bundle, distraction, contrast-enhanced US, and motion-insensitive sequences for MRI. US is often the first imaging modality used in children with a suspected abdominal mass. Once a hepatic lesion is confirmed, multiphasic contrast-enhanced MRI is recommended for most lesions as the next imaging modality allowing full characterization of the lesion and assessment of the liver parenchyma. Contrast-enhanced CT can also be performed for assessment of pediatric focal liver lesions, especially in patients who have a contraindication to MRI. Contrast-enhanced US has shown promise to decrease the need for MRI or CT in some lesions such as hemangioma and focal nodular hyperplasia. Children with a history of malignancy can develop multiple types of hepatic lesions at various stages, including infections during an immunocompromised state, manifesting as focal liver lesions. Based on available limited data in the literature and the collective experiences of the Liver Imaging and Reporting Data System Pediatric Working Group, the authors provide guidelines for the imaging workup of pediatric focal liver lesions with an indication- and age-based approach and discuss the selection and performance of various imaging techniques and modalities. ©RSNA, 2022 See the invited commentary by Chojniak and Boaventura in this issue.

Cancer Therapy-related Hepatic Injury in Children: Imaging Review from the Pediatric LI-RADS Working Group.

The liver is the primary organ for the metabolism of many chemotherapeutic agents. Treatment-induced liver injury is common in children undergoing cancer therapy. Hepatic injury occurs due to various mechanisms, including biochemical cytotoxicity, hepatic vascular injury, radiation-induced cytotoxicity, and direct hepatic injury through minimally invasive and invasive surgical treatments. Treatment-induced liver injury can be seen contemporaneous with therapy and months to years after therapy is complete. Patients can develop a combination of hepatic injuries manifesting during and after treatment. Acute toxic effects of cancer therapy in children include hepatitis, steatosis, steatohepatitis, cholestasis, hemosiderosis, and vascular injury. Longer-term effects of cancer therapy include hepatic fibrosis, chronic liver failure, and development of focal liver lesions. Quantitative imaging techniques can provide useful metrics for disease diagnosis and monitoring, especially in treatment-related diffuse liver injury such as hepatic steatosis and steatohepatitis, hepatic iron deposition, and hepatic fibrosis. Focal liver lesions, including those developing as a result of treatment-related vascular injury such as focal nodular hyperplasia-like lesions and hepatic perfusion anomalies, as well as hepatic infections occurring as a consequence of immune suppression, can be anxiety provoking and confused with recurrent malignancy or hepatic metastases, although there often are imaging features that help elucidate the correct diagnosis. Radiologic evaluation, in conjunction with clinical and biochemical screening, is integral to diagnosing and monitoring hepatic complications of cancer therapy in pediatric patients during therapy and after therapy completion for long-term surveillance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material See the invited commentary by Ferraciolli and Gee in this issue.

[Medical students and graduates' perceptions of preparation to face a patient's death]. / Percepción de preparación de los internos y egresados de Medicina para enfrentar la muerte de un paciente.

Historically, death has been socially accepted, but for the last decades it has been hidden in hospitals, transforming physicians into "death specialists". Thus, medical graduates should feel prepared to assume this responsibility accompanying the patient and their family through the process. With this in consideration, the present work explores students' and graduates' perceptions of preparation to face a patient's death (SPEM) in a Chilean Medical school and identifies SPEM-associated characteristics. An observational study was performed using a digital form sent by email to interns and 2018 and 2019 graduates of the Facultad de Medicina CAS-UDD, in which they were asked about their SPEM and possible SPEM-related variables. The results showed that 63% and 31% of interns and graduates reported feeling inadequately prepared or unprepared to address a patient's death, respectively. During the first two years of their profession, 71% of graduates faced a patient's death. There was a significant correlation between the SPEM and death-facing training. Considering these results and the previous evidence of the positive impact that classes and courses have on SPEM, it is suggested that an obligatory course should be added to improve SPEM in medical students.

Disentangling the role of virus infectiousness and awareness-based human behavior during the early phase of the COVID-19 pandemic in the European Union.

In this work, we manage to disentangle the role of virus infectiousness and awareness-based human behavior in the COVID-19 pandemic. Using Bayesian inference, we quantify the uncertainty of a state-space model whose propagator is based on an unusual SEIR-type model since it incorporates the effective population fraction as a parameter. Within the Markov Chain Monte Carlo (MCMC) algorithm, Unscented Kalman Filter (UKF) may be used to evaluate the likelihood approximately. UKF is a suitable strategy in many cases, but it is not well-suited to deal with non-negativity restrictions on the state variables. To overcome this difficulty, we modify the UKF, conveniently truncating Gaussian distributions, which allows us to deal with such restrictions. We use official infection notification records to analyze the first 22 weeks of infection spread in each of the 27 countries of the European Union (EU). It is known that such records are the primary source of information to assess the early evolution of the pandemic and, at the same time, usually suffer underreporting and backlogs. Our model explicitly accounts for uncertainty in the dynamic model parameters, the dynamic model adequacy, and the infection observation process. We argue that this modeling paradigm allows us to disentangle the role of the contact rate, the effective population fraction, and the infection observation probability across time and space with an imperfect first principles model. Our findings agree with phylogenetic evidence showing little variability in the contact rate, or virus infectiousness, across EU countries during the early phase of the pandemic, highlighting the advantage of incorporating the effective population fraction into pandemic modeling for heterogeneity in both human behavior and reporting. Finally, to evaluate the consistency of our data assimilation method, we performed a forecast that adequately fits the actual data. Statement of significance: Data-driven and model-based epidemiological studies aimed at learning the number of people infected early during a pandemic should explicitly consider the behavior-induced effective population effect. Indeed, the non-isolated, or effective, fraction of the population during the early phase of the pandemic is time-varying, and first-principles modeling with quantified uncertainty is imperative for an adequate analysis across time and space. We argue that, although good inference results may be obtained using the classical SEIR type model, the model posed in this work has allowed us to disentangle the role of virus infectiousness and awareness-based human behavior during the early phase of the COVID-19 pandemic in the European Union from official infection notification records.

The old becomes new: advances in imaging techniques to assess nephron mass in children.

Renal imaging is widely used in the assessment of surrogate markers of nephron mass correlated to renal function. Autopsy studies have tested the validity of various imaging modalities in accurately estimating "true" nephron mass. However, in vivo assessment of nephron mass has been largely limited to kidney volume determination by ultrasonography (US) in pediatric populations. Practical limitations and risks create challenges in incorporating more precise 3D volumetric imaging, like magnetic resonance imaging (MRI), and computed tomography (CT) technologies, compared to US for routine kidney volume assessment in children. Additionally, accounting for structural anomalies such as hydronephrosis when estimating renal parenchymal area in congenital anomalies of the kidney and urinary tract (CAKUT) is important, as it correlates with chronic kidney disease (CKD) progression. 3D imaging using CT and MRI has been shown to be superior to US, which has traditionally relied on 2D measurements to estimate kidney volume using the ellipsoid calculation. Recent innovations using 3D and contrast-enhanced US (CEUS) provide improved accuracy with low risk. Indexing kidney volume to body surface area in children is an important standard that may allow early detection of CKD progression in high-risk populations. This review highlights current understanding of various imaging modalities in assessing nephron mass, discusses applications and limitations, and describes recent advances in the field of imaging and kidney disease. Although renal imaging has been a long-standing, essential tool in assessing kidney disease, innovation and new applications of established technologies provide important tools in the study and management of kidney disease in children.

Transcatheter Intervention for Treatment of Coronary Stenosis After Unroofing of the Anomalous Left Coronary Artery.

Anomalous origin of left coronary artery (LCA) from the right coronary cusp with an intramural course is usually managed with unroofing of the intramural segment. Available literature demonstrates an uneventful course following surgery in most patients. Coronary stenosis following the unroofing procedure treated with percutaneous coronary intervention has not been described in the past. We describe a case where an 11-year-old girl with anomalous origin of the LCA from the right coronary cusp presented with near syncope. Surgical unroofing of the intramural segment was done without any post-operative complications and the patient remained asymptomatic for 9 months. She then presented with chest pain, abnormal troponin levels, and ST-T wave changes on EKG. A CT angiogram done revealed short segment narrowing of the LCA near its origin. Cardiac catheterization with coronary angiography demonstrated short segment narrowing of the LCA just distal to origin. Stenting of the left main coronary artery was done with a drug eluting stent. She underwent the procedure without complications. The patient continued to be asymptomatic 16 months after placement of the stent and there was no residual stenosis seen on a repeat CT angiogram at 3 months after the procedure.

Performance of Leishmania PFR1 recombinant antigen in serological diagnosis of asymptomatic canine leishmaniosis by ELISA.

BACKGROUND: Leishmania infantum is a protozoan parasite transmitted by phlebotomine sand flies that causes life-threatening disease in humans and dogs. The dog is the primary reservoir of the parasite and early diagnosis of canine leishmaniosis is crucial at the clinical and epidemiological level. The currently available serological tests for CanL diagnostic show limitations therefore the aim of the present study was to investigate the diagnostic performance of an indirect antibody ELISA based on the Leishmania infantum recombinant antigen PFR1 in asymptomatically infected dogs. One hundred fifty-six dogs including Leishmania-free experimental Beagles and pet dogs from England, Scotland and Leishmania-endemic Murcia in Spain, were tested with the assay. The later were also tested with two commercial L. infantum crude antigen ELISAs (INgezim and Civtest, respectively) and a real-time kinetoplast PCR test. RESULTS: Anti-PFR1 antibodies were detected in the four groups of dogs, and the mean log-transformed optical density (OD) values were lowest in Beagles and in dogs from England and highest among dogs from Murcia (p < 0.05). Using the highest OD in beagles as the PFR1 ELISA cut-off point, the estimated seroprevalence was 27% (14-40%) in dogs from Murcia, 4% (0-9%) in dogs from Scotland and 3% (0-8%) in dogs from England (p < 0.05). Seroprevalence in dogs from Murcia according to the INgezim and Civtest ELISAs were 24% (12-37%) and 31% (18-45%), respectively, whilst the prevalence of infection based on PCR in these dogs was 73% (60-86). The percentages of PFR1-positive dogs that tested negative on the INgezim and Civtest ELISAs were 30% and 35%, respectively, and all of them tested positive on the PCR test. Relative to the PCR, the specificity, sensitivity and area under the ROC curve of the PFR1 ELISA were 100%, 36% and 0.74 (0.63-0.86), respectively. CONCLUSIONS: The ability shown by the PFR1 ELISA to detect infected dogs that go undetected by the crude antigen ELISAs is clinically and epidemiologically useful and PFR1 could be considered a candidate for a multi-antigen-based immunoassay for early detection of L. infantum infected dogs.

CT image quality in sinogram affirmed iterative reconstruction phantom study - is there a point of diminishing returns?

BACKGROUND: In our pediatric practice, we have observed qualitatively limited improvement in the image quality of images generated with sinogram affirmed iterative reconstruction (SAFIRE) compared to series generated with filtered back projection (FBP), particularly in cases near or below a CT dose index volume (CTDIvol) of 1-mGy. OBJECTIVE: To determine whether the image quality advantage of SAFIRE remains constant across clinically used CT dose levels in an American College of Radiology (ACR) CT accreditation phantom including the lower dose range used in pediatric imaging. MATERIALS AND METHODS: An exemption from institutional review board approval was obtained for this phantom-based study. An ACR quality phantom was scanned in incremental kV steps and effective tube current intervals. Acquisitions were reconstructed with FBP and SAFIRE strengths of 1, 3 and 5. Image quality measures were calculated including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), low-contrast resolution and high-contrast resolution. Peak SNR was also calculated. Descriptive and nonparametric statistics were used to compare these image quality metrics while normalizing to CT dose index (CTDI). RESULTS: The percent improvement in SNR and peak SNR of SAFIRE reconstructions compared to FBP decreased from about 70% for image sets acquired above a 1.42 mGy CTDI to 25% at a 0.25 mGy CTDI. CNR improvement with SAFIRE did not vary with dose. No significant difference was seen in the low-contrast resolution or high-contrast resolution of SAFIRE images compared to FBP. CONCLUSION: SNR did not improve equally after applying SAFIRE across a spectrum clinically used CTDIs. Below a threshold CTDI, the incremental improvement of SAFIRE compared to FBP decreased.

Cardiac Physiology for Radiologists: Review of Relevant Physiology for Interpretation of Cardiac MR Imaging and CT.

Cardiac computed tomography (CT) and magnetic resonance (MR) imaging provide clinicians with important insights into cardiac physiology and pathology. However, not all radiologists understand the language and concepts of cardiac physiology that are used daily by cardiologists. This review article covers basic cardiac physiology as it relates to cardiac CT and MR imaging. Topics include a review of the cardiac cycle and left ventricular pressure-volume loops as they relate to different pathologic states, evaluation of cardiac function, and calculation of key parameters such as left ventricular volumes and the ejection fraction. The hemodynamics of cardiac shunts are covered, with an emphasis on factors important to cardiologists, including the ratio of pulmonary flow to systemic flow. Additionally, valvular physiologic function is reexamined, with a focus on understanding pressure gradients within the heart and also the changes associated with valvular pathologic conditions, including measurement of regurgitant fractions in patients with valvular insufficiency. Understanding these basic concepts will help radiologists tailor the reporting of cardiac studies to clinically relevant information.

Focal nodular hyperplasia within accessory liver: imaging findings at computed tomography and magnetic resonance imaging.

Accessory liver tissue is a rare but probably underreported entity that may harbor the same spectrum of pathology as that of the parent organ. The rarity and aberrant locations of such lesions cause confusion and may lower diagnostic confidence despite otherwise classic radiographic appearances. Focal nodular hyperplasia (FNH) is the most common non-hemangiomatous benign hepatic tumor, but to our knowledge, ectopic FNH has been reported only once before in the gastroenterology literature. We present the first case of ectopic FNH in the radiology literature.

Repeated dose toxicity study of Vibrio cholerae-loaded gastro-resistant microparticles.

CONTEXT: Microencapsulation of antigens has been extensively studied over the last decades aiming at improving the immunogenicity of vaccine candidates. OBJECTIVE: Addressing microparticles (MPs) toxicity in rats. MATERIAL AND METHODS: Spray-dried Eudragit® L 30 D-55 MPs and Eudragit® L 30 D-55 alginate MPs were elaborated and characterized. MPs obtained were administered to rats, three groups were defined: G1, control group; G2, administered with Vibrio cholerae (VC)-loaded MPs; G3, receiving VC-loaded alginate MPs. Animals received three vaccine doses. Body weight, food and water intake were controlled during the study. Haematological parameters, vibriocidal titres, organ weight and histology in necropsy were also analyzed. RESULTS: All animals grew healthy. Body weight gain, food and water intake and haematological parameters remained within physiological values, showing no treatment-related differences. Moreover, organ weight changes were not detected and animals developed protective vibriocidal titres. CONCLUSION: VC-loaded MPs and VC-loaded alginate MPs have proved to be safe and effective in the assessed conditions.

Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis.

BACKGROUND: Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. METHODS: The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. RESULTS: The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. CONCLUSION: The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations.

Phage display of functional αß single-chain T-cell receptor molecules specific for CD1b:Ac2SGL complexes from Mycobacterium tuberculosis-infected cells.

The development of molecules specific for M. tuberculosis-infected cells has important implications, as these tools may facilitate understanding of the mechanisms regulating host pathogen interactions in vivo. In addition, development of new tools capable to targeting M. tuberculosis-infected cells may have potential applications to diagnosis, treatment, and prevention of tuberculosis (TB). Due to the lack of CD1b polymorphism, M. tuberculosis lipid-CD1b complexes could be considered as universal tuberculosis infection markers. The aim of the present study was to display on the PIII surface protein of m13 phage, a human αß single-chain T-cell receptor molecule specific for CD1b:2-stearoyl-3-hydroxyphthioceranoyl-2´-sulfate-α-α´-D-trehalose (Ac2SGL) which is a complex presented by human cells infected with M. tuberculosis. The results showed the pIII fusion particle was successfully displayed on the phage surface. The study of the recognition of the recombinant phage in ELISA and immunohistochemistry showed the recognition of CD1b:Ac2SGL complexes and cells in human lung tissue from a tuberculosis patient respectively, suggesting the specific recognition of the lipid-CD1b complex.

Evaluation of the humoral immune response and cross reactivity against Mycobacterium tuberculosis of mice immunized with liposomes containing glycolipids of Mycobacterium smegmatis.

Mycobacterium smegmatis (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.

Measuring Persistence in the US Equity Gender Diversity Index.

An analysis of the SPDR SSGA Gender Diversity Index ETF using fractional integration or I(d) techniques and daily data from 8 March 2016 to 8 January 2021, reveals that the series is highly persistent with an order of integration smaller than, though very close to 1. However, when estimating d recursively across subsamples, two peaks can be observed. The first peak appears in the sample with 679 observations (ending at 26 December 2018) and the second one occurs in the sample with 974 observations and ending at 28 February 2020, which shows the most significant change in d, moving from values within the I(1) interval to values significantly above 1. The findings indicate that the Covid-19 pandemic has had a significant impact on the persistence of the SPDR SSGA Gender Diversity Index ETF, increasing its magnitude and thus the level of persistence.

Tetralogy of Fallot Associated With Right Aortic Arch and Isolated Left Brachiocephalic Artery.

A newborn presented with tetralogy of Fallot (TOF), right aortic arch (RAA), and isolated left brachiocephalic artery. The RAA supplied the right common carotid artery, right vertebral artery, and right subclavian artery, in that order. The left common carotid and left subclavian arteries were in continuity with no aortic origin. Ultrasound demonstrated retrograde flow in the left vertebral artery supplying antegrade flow to the diminutive left subclavian artery (ie, "steal phenomenon"). The patient underwent repair of TOF without intervention on the left common carotid or left subclavian arteries and is being followed conservatively.

Activator-independent transcription of Snf1-dependent genes in mutants lacking histone tails.

Transcriptional regulation of Snf1-dependent genes occurs in part by histone-acetylation-dependent binding of the transcription factor Adr1. Analysis of previously published microarray data indicated unscheduled transcription of a large number of Snf1- and Adr1-dependent genes when either the histone H3 or H4 tail was deleted. Quantitative real-time PCR confirmed that the tails were important to preserve stringent transcriptional repression of Snf1-dependent genes when glucose was present. The absence of the tails allowed Adr1 and RNA Polymerase II to bind promoters in normally inhibitory conditions. The promoters escaped glucose repression to a limited extent and the weak constitutive ADH2 transcription induced by deletion of the histone tails was transcription factor- and Snf1-independent. These effects were apparently due to a permissive chromatin structure that allowed transcription in the absence of repression mediated by the histone tails. Deleting REG1, and thus activating Snf1 in the H3 tail mutant enhanced transcription in repressing conditions, indicating that Snf1 and the H3 tail influence transcription independently. Deleting REG1 in the histone H4 tail mutant appeared to be lethal, even in the absence of Snf1, suggesting that Reg1 and the H4 tail have redundant functions that are important for cell viability.