Assessing the Diagnostic Accuracy of TI-RADS in Pediatric Thyroid Nodules: A Multi-institutional Review.

PURPOSE: Thyroid nodules are uncommon in children and adolescents but carry an increased risk of malignancy when present. The Thyroid Imaging Reporting and Data System (TI-RADS) is an adult-validated ultrasound-based risk assessment providing a prediction of malignant potential for thyroid nodules, thereby guiding recommendations for fine needle aspiration biopsy (FNAB). Minimal data exist regarding the applicability of TI-RADS to predict malignancy in pediatric thyroid nodules. This study aims to analyze the performance of TI-RADS for children and adolescents with thyroid nodules, hypothesizing that applying TI-RADS criteria would improve accuracy and reduce the number of recommended FNAB compared to American Thyroid Association (ATA) size criteria alone. METHODS: A multi-institutional retrospective analysis was conducted including patients ≤21 years with a thyroid nodule by sonographic thyroid imaging between 2015 and 2020. TI-RADS scores were assigned at each institution by a pediatric radiologist trained in thyroid imaging and TI-RADS criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of TI-RADS scoring were compared to existing ATA size-based recommendation for performing a FNAB. Accounting for relative size differences between adults and children, a novel PED TI-RADS category was developed and tested, recommending FNAB for thyroid nodules with a TI-RADS 3 and ≥ 1.5 cm, TI-RADS 4 and ≥ 1.0 cm, and TI-RADS 5 any feasible size. RESULTS: 291 nodules from 260 patients (median age 14.9 years, 78.8% female) were assessed using TI-RADS. Applying adult TI-RADS criteria resulted in recommendation of FNAB for 35.1% of nodules, in contrast to 76.6% recommended by ATA guidelines (p < 0.0001) (Table). Utilizing the adult TI-RADS score ≥3 as an FNAB indicator resulted in 100% sensitivity and 28.5% specificity, with 0 cases of missed malignant nodules on pathology. When novel PED TI-RADS criteria were applied, 88 patients would have been spared an unnecessary FNAB with improved sensitivity and accuracy over ATA criteria. CONCLUSIONS: The application of adult and PED TI-RADS scoring to thyroid nodules in pediatric patients enhances the accuracy of malignancy prediction compared to current American Thyroid Association size criteria alone. The utilization of PED TI-RADS scoring eliminated unnecessary biopsies in many children while not missing a single thyroid malignancy. LEVEL OF EVIDENCE: Level III.

Shedding light on the social and health realities of care-experienced young people in Western Australia: A population-level study.

BACKGROUND: Young people who were in out-of-home care (OHC) face an accelerated transition to independent adulthood. Current evidence on outcomes for Australian care-leavers is scant. OBJECTIVE: This study aims to develop a better understanding of the outcomes for young people leaving care. PARTICIPANTS AND SETTING: A birth cohort of children and young people born in Western Australia (WA) from 1993 to 2008. Three groups were identified and compared: young people with care-experience (OHC Cohort), those with child protection involvement but not care experience (CP Contact Cohort), and peers in the general population (No Contact Cohort). METHODS: This is a retrospective, population-based study utilising de-identified, linked administrative records provided by the WA state government agencies. Data from the three cohorts were compared through descriptive statistics, independent samples t-tests, and logistic regression modelling. RESULTS: The birth cohort contained records for 414,266 individuals. The smallest comparison group in this study was the OHC Cohort (n = 6526), followed by the CP Contact Cohort (n = 78,095), and the No Contact Cohort (n = 329,645). Care-experienced young people in WA fared significantly worse than their peers across the domains of health (physical and mental), disability, education, social housing and criminal justice involvement. CONCLUSIONS: Those who have had child protection involvement, but have not been placed in care, had better outcomes than those who had been in care. However, their outcomes were still poorer than the population cohort with no child protection contact.

Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

An evaluation of intervention appropriateness from the perspective of parents: A peer-mediated, play-based intervention for children with ADHD.

INTRODUCTION: A peer-mediated, play-based intervention has been developed to address social participation challenges experienced by children with ADHD. To facilitate implementation into clinical practice, interventions should be evaluated for appropriateness to the end-user, as well as effectiveness. Previous research demonstrated the approach is effective for improving children's social play skills. This study aimed to evaluate the appropriateness of the intervention for children with ADHD and their families. METHODS: Parents of children with ADHD who participated in the play-based intervention were interviewed 1 month after completion. Parents were asked about their perspective of parent and children's experiences of the intervention, the perceived benefits for children and parents, the logistics of participating, and recommended adaptations to the intervention. Interviews were analysed thematically, and themes were mapped to the elements of the adopted definition of appropriateness to understand whether parents supported the appropriateness of the intervention for their families. CONSUMER AND COMMUNITY INVOLVEMENT: Consumers were not directly involved in the decisions made about this study. FINDINGS: One core theme, 'collaborative efforts', emerged from the data. Major themes comprising the core theme were 'on the same page', 'therapeutic relationship', and 'getting the job done'. Three sub-themes of 'engagement and motivation', 'the effort was worth it for the reward', and 'Rome wasn't built in a day' were nested within the major themes. CONCLUSION: Parents largely supported the appropriateness of the intervention, indicating it addressed an important goal for their child, participation was a positive experience, and they perceived the intervention to be beneficial. Future adaptions of the intervention are needed to increase its ecological validity and to generalise the strategies to other social environments and playmates, such as peers at school. PLAIN LANGUAGE SUMMARY: This study looked at an intervention that uses play with peers to help children with ADHD develop their play skills. The researchers wanted to know if parents thought the intervention was a good fit for their families and if it helped their children. Parents gave an interview a month after the intervention ended. They were asked about their thoughts on the intervention, how it helped their children and themselves, how easy it was to take part, and what changes could be made to make the intervention better. After analysing parents' answers, the researchers found parents mostly agreed that the intervention was a good fit. They said it helped their children to play with their peers, and they had a good time doing it. Parents thought the intervention was helpful, they liked that it was a joint effort between them and the occupational therapist, and they felt it was worth the effort. However, they also suggested some changes. They wanted the intervention to fit into other real-life social situations, such as school, so their children could use the skills they learned in other places. Overall, parents thought the intervention was helpful and suitable for their children and themselves, but some changes might make it more helpful.

Correction: Research using population-based administration data integrated with longitudinal data in child protection settings: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0249088.].

Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study.

BACKGROUND: Dupilumab, a human monoclonal antibody targeting the interleukin 4 alpha receptor, is used for treatment of moderate to severe atopic dermatitis (AD). Previous studies have reported diagnoses of cutaneous T cell lymphoma (CTCL) after dupilumab use. OBJECTIVE: Investigate the risk of CTCL after dupilumab use in patients with AD. METHODS: Using the TrinetX database, incidence of cutaneous and lymphoid malignancies including CTCL was compared between a cohort of patients with AD who used dupilumab and a cohort of patients with AD who never used dupilumab. A second analysis excluding prior disease-modifying antirheumatic drug use was performed. Propensity score matching was performed to control for covariates. RESULTS: An increased risk of CTCL was found in the cohort of AD patients who used dupilumab (odds ratio 4.1003, 95% confidence interval 2.055-8.192). The increased risk persisted after exclusion of prior disease-modifying antirheumatic drug use. Risk was not increased for other cutaneous or lymphoid malignancies. Most (27/41) cases of CTCL were diagnosed more than 1 year after dupilumab use. LIMITATIONS: There is potential for misclassification in the database. Severity of AD could not be assessed. Association between dupilumab and CTCL does not prove causality. CONCLUSION: Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Friendship interventions for children with neurodevelopmental needs: A systematic review and meta-analysis.

RATIONALE: Children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual disability (ID), and social (pragmatic) communication disorder (SPCD) experience difficulties with social functioning due to differences in their social, emotional and cognitive skills. Previous systematic reviews have focussed on specific aspects of social functioning rather than broader peer functioning and friendships. OBJECTIVE: To systematically review and methodologically appraise the quality and effectiveness of existing intervention studies that measured friendship outcomes for children with ADHD, autism, DLD, ID, and SPCD. METHOD: Following PRISMA guidelines, we searched five electronic databases: CINAHL, Embase, Eric, PsycINFO, and PubMed. Two independent researchers screened all abstracts and disagreements were discussed with a third researcher to reach consensus. The methodological quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomised Trials. RESULTS: Twelve studies involving 15 interventions were included. Studies included 683 children with a neurodevelopmental disorder and 190 typically-developing children and diagnosed with either autism or ADHD. Within-group meta-analysis showed that the pooled intervention effects for friendship across all interventions were small to moderate (z = 2.761, p = 0.006, g = 0.485). The pooled intervention effect between intervention and comparison groups was not significant (z = 1.206, p = 0.400, g = 0.215). CONCLUSION: Findings provide evidence that some individual interventions are effective in improving social functioning and fostering more meaningful friendships between children with neurodevelopmental disorders and their peers. Effective interventions involved educators, targeted child characteristics known to moderate peer functioning, actively involved peers, and incorporated techniques to facilitate positive peer perceptions and strategies to support peers. Future research should evaluate the effectiveness of friendship interventions for children with DLD, ID and SPCD, more comprehensively assess peer functioning, include child self-report measures of friendship, and longitudinally evaluate downstream effects on friendship.

The friendships of children and youth with attention-deficit hyperactivity disorder: A systematic review.

BACKGROUND: Children with attention-deficit hyperactivity disorder (ADHD) experience substantial difficulty maintaining meaningful friendships, which has implications for social functioning and mental health. No systematic review has investigated their friendship difficulties. OBJECTIVES: To systematically review and methodologically appraise the quality of existing studies reporting on friendships of children with ADHD. To compare their friendships to typically-developing children, and examine associations between friendship and children's social-emotional wellbeing and mental health. METHOD: Six databases were searched. The methodological quality of studies was assessed using the QualSyst appraisal tool and the Appraisal tool for Cross-Sectional Studies. Aspects of friendships measured were charted, along with comparisons between children with ADHD and typically-developing children and the associations between friendships and social-emotional wellbeing and mental health. RESULTS: Twenty-three cross-sectional studies and one longitudinal follow-up study were included. Studies included 1509 participants with ADHD, with 1197 typically-developing participants used as a companion in 19 of the 24 studies. Friendship quantity was the most investigated aspect of friendship. Children and youth with ADHD had significantly fewer friends, lower quality friendships and poorer friendship interactions. There were mixed findings from studies investigating the role or impact of friendship on social-emotional wellbeing and mental health. Twenty-two had strong methodological quality. CONCLUSION: Limited longitudinal studies, small sample sizes and variability in measurement restrict the interpretations of friendship over time and the causal impact of friendship on social and emotional outcomes. Further research should investigate the role and impact of friendships on the social-emotional wellbeing of children and youth with ADHD.

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. Methods: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Results: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. Conclusions: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

Putting It All Together: Postmortem Diagnosis of a Rare Ichthyosis Syndrome.

Neu-Laxova syndrome (NLS) is a rare lethal disorder with autosomal recessive inheritance and is characterized by multiple congenital anomalies. Our case of NLS presented with severe intrauterine growth restriction (IUGR), abnormal facial features, severe central nervous system malformations, skeletal muscle contractures, and the hallmark signs of NLS: ichthyotic skin and excessive subcutaneous tissue with edema. Additionally, testing amniotic fluid from a prior pregnancy with a fetus showing similar abnormalities revealed several regions of homozygosity; one of these regions involved chromosome 1p13.2-p11.2, where the PHGDH gene is located. Based on the pattern of findings on serial fetal ultrasounds, postmortem neonatal exams, gross and microscopic exams, radiographs, and genetic analysis in conjunction with the clinical history and the prior pregnancy with the above-described molecular alteration, a final diagnosis of NLS was made. This rare developmental disorder is characterized by heterogenous neuroectodermal defects. Fetal ultrasound in the second trimester can help diagnose it. It is postulated to be caused by loss-of-function mutations in the PHGDH (phosphoglycerate dehydrogenase), PSAT1 (phosphoserine aminotransferase 1), and PSPH (phosphoserine phosphatase) genes, which are responsible for de novo L-serine synthesis.

Identification of D-arabinan-degrading enzymes in mycobacteria.

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan. Using one of these isolates with exo-D-galactofuranosidase activity, we generated enriched D-arabinan and used it to identify a strain of Dysgonomonas gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo-D-arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo-D-arabinanases with different preferences for the D-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.

Reliability and Validity of Non-Instrumental Clinical Assessments for Adults with Oropharyngeal Dysphagia: A Systematic Review.

This systematic review on non-instrumental clinical assessment in adult oropharyngeal dysphagia (OD) provides an overview of published measures with reported reliability and validity. In alignment with PRISMA, four databases (CINAHL, Embase, PsycINFO, and PubMed) were searched, resulting in a total of 16 measures and 32 psychometric studies included. The included measures assessed any aspect of swallowing, consisted of at least one specific subscale relating to swallowing, were developed by clinical observation, targeted adults, and were developed in English. The included psychometric studies focused on adults, reported on measures for OD-related conditions, described non-instrumental clinical assessments, reported on validity or reliability, and were published in English. Methodological quality was assessed using the standard quality assessment QualSyst. Most measures targeted only restricted subdomains within the conceptual framework of non-instrumental clinical assessments. Across the 16 measures, hypothesis testing and reliability were the most reported psychometrics, whilst structural validity and content validity were the least reported. Overall, data on the reliability and validity of the included measures proved incomplete and frequently did not meet current psychometric standards. Future research should focus on the development of comprehensive non-instrumental clinical assessments for adults with OD using contemporary psychometric research methods.

A pairwise randomised controlled trial of a peer-mediated play-based intervention to improve the social play skills of children with ADHD: Outcomes of the typically-developing playmates.

To examine the effectiveness of a play-based intervention for improving social play skills of typically-developing playmates of children with ADHD. Children (5-11 years) were randomised to an intervention (n = 15) or waitlisted control group (n = 14). The Test of Playfulness was scored by a blinded rater. Between-group statistics compared the change of the intervention (10-week intervention) and waitlisted control (10-week wait) groups. Change in the intervention group following intervention was significantly greater than the change in the waitlisted control group. When combining data from the groups, playmates' (n = 29) mean ToP scores improved significantly following intervention, with a large effect pre- to post-intervention and pre-intervention to follow-up. Typically-developing playmates of children with ADHD benefited from participation in a peer-mediated intervention.

Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's oncology group (COG) renal tumour studies: Similarities and differences.

Excellent outcomes for patients with Wilms' tumour (WT), >90% for all stages together, have been achieved through researching WT in multicentre and multinational trials and studies in the last 50 years, led by two major groups-the International Society of Paediatric Oncology (SIOP) and the Children's Oncology Group (COG) (previously the National Wilms' Tumour Study Group). Despite the two groups having different approaches, the survival outcomes are remarkably similar. In general, in the SIOP approach, which is followed in Europe and most other countries around the world, patients are first treated with preoperative chemotherapy; this is followed by surgery and, if necessary, postoperative chemotherapy and radiotherapy. In the COG approach, which is mainly followed in North America, patients are treated with upfront surgery, followed, if necessary, by postoperative chemotherapy and radiotherapy. In both groups, postoperative treatment primarily depends on tumour histological classification and stage, although, in recent studies, other prognostic factors have also been included (tumour volume, response to preoperative chemotherapy, and molecular markers). Owing to separate initial treatments, there are differences in histological assessment and subtyping of WT, and, more importantly, in staging criteria. In this review, we discuss the similarities and differences between the two groups in order to help pathologists who are dealing with WT to understand and follow the pathological protocol that is appropriate for a particular case, because, in many centres, both approaches may be followed, depending on individual case/patient circumstances.

It Takes a Village: Providing International Pediatric Pathology Services in a Resource-Limited Setting

OBJECTIVES: Partnerships between low- to middle-income countries (LMICs) and high-income countries (HICs) is one strategy to mitigate observed health disparities. Cambodia's Angkor Hospital for Children (AHC), an LMIC institution, faces shortages in health care resources, including pathology services. A partnership was created with Children's Wisconsin (CW), an HIC hospital, including provision of pathology services. We describe our established pathology workflow, examine cases seen in AHC patients, and evaluate the impact of CW's interpretations. METHODS: AHC provides clinical history and impression and ships samples to CW, which processes the samples, and pathologists provide interpretations, sending reports electronically to AHC. For analysis, final diagnoses were considered "concordant," "refined," or "discordant" based on agreement with the clinical impression. Cases were also classified as "did not change management" or "changed management" based on how CW interpretation affected clinical management. RESULTS: We included 347 specimens (177 malignant, 146 benign, 24 insufficient for diagnosis). Of these cases, 31% were discordant and 44% of cases with clinical follow-up had a change in management with CW interpretation. CONCLUSIONS: Inclusion of pathology services in LMIC-HIC partnerships is crucial for resolving health disparities between the institutions involved. The described partnership and established pathology workflow can be adapted to the needs and resources of many institutions.

Research using population-based administration data integrated with longitudinal data in child protection settings: A systematic review.

INTRODUCTION: Over the past decade there has been a marked growth in the use of linked population administrative data for child protection research. This is the first systematic review of studies to report on research design and statistical methods used where population-based administrative data is integrated with longitudinal data in child protection settings. METHODS: The systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. The electronic databases Medline (Ovid), PsycINFO, Embase, ERIC, and CINAHL were systematically searched in November 2019 to identify all the relevant studies. The protocol for this review was registered and published with Open Science Framework (Registration DOI: 10.17605/OSF.IO/96PX8). RESULTS: The review identified 30 studies reporting on child maltreatment, mental health, drug and alcohol abuse and education. The quality of almost all studies was strong, however the studies rated poorly on the reporting of data linkage methods. The statistical analysis methods described failed to take into account mediating factors which may have an indirect effect on the outcomes of interest and there was lack of utilisation of multi-level analysis. CONCLUSION: We recommend reporting of data linkage processes through following recommended and standardised data linkage processes, which can be achieved through greater co-ordination among data providers and researchers.

Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center.

BACKGROUND: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.

Wilms Tumor: Challenges and Newcomers in Prognosis.

Wilms tumor is the most common renal tumor of childhood. It is a biologically and morphologically diverse entity, with ongoing studies contributing to our understanding of the pathobiology of various subgroups of patients with Wilms tumor. The interplay of histologic examination and molecular interrogation is integral in prognostication and direction of therapy. This review provides an overview of some of the challenging aspects and pitfalls in pathologic assessment of Wilms tumor, along with discussion of current and up-and-coming markers of biological behavior with prognostic significance.

Research protocol of a multifaceted prospective mixed-method longitudinal study: Navigating Through Life - Western Australian study of transitions from out-of-home care.

BACKGROUND: Developing robust evidence is a challenge for researchers working with disadvantaged or vulnerable populations. For example, research shows that young people who have transitioned from out-of-home care (OOHC) to independent adulthood often experience poor long-term outcomes. However, evidence for the aetiology of those outcomes is weak due to methodological limitations such as small sample sizes and a lack of longitudinal data. This paper details the protocol for Navigating Through Life, a study that utilises novel research methods to better understand the pathways and outcomes of young people as they leave OOHC in Western Australia (WA). METHODS: Navigating Through Life is a longitudinal, mixed methods, population-based study. A prospective longitudinal study of young people aged 15-25 years will follow participants' experiences and outcomes over a two-year period. Quantitative and qualitative data is being collected from participants five times over 2 years, using standardised outcome measures and individual interviews. Outcome measures focus on key dimensions of young people's lives (e.g., social inclusion, well-being, resilience, self-determination). Interviews examine important influences and the variable contexts into which young people have transitioned from care. In addition, retrospective population-level data for young people transitioning from OOHC will be obtained from linked Western Australian government administrative records. Using a multitude of data sources, analysis will map pathways and outcomes of young people with care experience, and comparisons will be made with other population groups within WA. DISCUSSION: Navigating Through Life exemplifies a novel utilisation of multiple data sources to research outcomes for vulnerable and difficult to reach populations, and offers insights for other complex mixed-methods longitudinal studies. Results will provide new and more comprehensive data about specific pathways that may be influential to a range of post-care outcomes. Findings will extend evidence to inform better service-delivery models that improve outcomes and reduce disparities for vulnerable young people.