Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.

QuantiFERON-cytomegalovirus to predict clinically significant cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Controlling cytomegalovirus (CMV) infection through prophylaxis or pre-emptive therapy remains an important contributor to outcomes after allogeneic hematopoetic stem cell transplant (alloHCT). Predicting clinically significant CMV infection (csCMVi) after day 100 remains a challenge. METHODS: We examined the abilty of the QuantiFERON-CMV assay (QFN-CMV) at day 100 (d100) and day 150 (d150) after alloHCT to predict csCMVi after these time points, with median follow-up of 3.1 years (range 1.3-4.3 years). RESULTS: In 46 transplants (donor seropositive (D+) recipient seronegative (R-) = 12, D+R+ = 25, D-R+ = 9; matched related = 13, unrelated donor = 32, haploidentical = 1), for the prediction of freedom from csCMVi >d100, QFN-CMVd100 (positive compared to negative/indeterminate) had sensitivity 62% (23/37), specificity 100% (9/9), positive predictive value 100% (23/23), and negative predictive value 39% (9/23). For the prediction of freedom from csCMVi >d150, QFN-CMVd150 (positive compared to negative/indeterminate) had sensitivity 62% (18/29), specificity 83% (5/6), positive predictive value 95% (18/19), and negative predictive value 31% (5/16). CONCLUSION: Positive QFN-CMV at d100 and d150 strongly predicted freedom from csCMVi after these time points. QFN-CMV could be utilized to predict the need for pre-emptive therapy and CMV viral load monitoring after day 100 post-alloHCT.

Alcohol-induced aggression in Drosophila.

Alcohol-induced aggression is a destructive and widespread phenomenon associated with violence and sexual assault. However, little is understood concerning its mechanistic origin. We have developed a Drosophila melanogaster model to genetically dissect and understand the phenomenon of sexually dimorphic alcohol-induced aggression. Males with blood alcohol levels of 0.04-mg/ml BAC were less aggressive than alcohol-naive males, but when the BAC had dropped to ~0.015 mg/ml, the alcohol-treated males showed an increase in aggression toward other males. This aggression-promoting treatment is referred to as the post-ethanol aggression (PEA) treatment. Females do not show increased aggression after the same treatment. PEA-treated males also spend less time courting and attempt to copulate earlier than alcohol-naive flies. PEA treatment induces expression of the FruM transcription factor (encoded by a male-specific transcript from the fruitless gene), whereas sedating doses of alcohol reduce FruM expression and reduce male aggression. Transgenic suppression of FruM induction also prevents alcohol-induced aggression. In male flies, alcohol-induced aggression is dependent on the male isoform of the fruitless transcription factor (FruM). Low-dose alcohol induces FruM expression and promotes aggression, whereas higher doses of alcohol suppress FruM and suppress aggression.

Supporting positive parenting practices within a community-based music therapy group program: Pilot study findings.

The aim of this study was to evaluate the benefits of a short-term, community-based music therapy group program on positive parenting practices. Parent-child dyads receiving early intervention family services (N = 199) participated in 8 weekly, 45-60 minute, music-based group play sessions. We analyzed pre-post parent self-reports that measured parenting competency and clinician-observed ratings of parental responsiveness that evaluated behavioral domains of play, praise, and consistency. Significant results were found for parent-reported efficacy (p = 0.008, d = 0.21) and satisfaction (p = 0.004, d = 0.19) but not for interest (p = 0.149, d = 0.12). Significant results were found for clinician-rated observations of parental responsiveness, including play (p < 0.001), praise (p < 0.001), and consistency (p < 0.001). Short-term, music-based parenting programs may be an effective way to improve parents' sense of competency and foster greater parental responsiveness for those receiving family services.

Non-immediate heparin and heparinoid cutaneous allergic reactions: a role for fondaparinux.

Non-immediate allergic cutaneous reactions to heparins have been increasingly reported, typically manifesting as large, eczematous plaques at sites of subcutaneous injection. Patients may demonstrate cross-reactivity between unfractionated heparin, low molecular weight heparin and semi-synthetic heparinoids, making finding an alternative difficult. Fondaparinux has been identified as a useful alternative in such patients; here we present the first two documented cases in Australia and a literature review.

Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study.

BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort. METHODS: This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up. RESULTS: DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16-0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up. CONCLUSIONS: Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder: The TIME-A Randomized Clinical Trial.

Importance: Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective: To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants: Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions: Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents' concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child's focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures: The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results: Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0.06 [95% CI, -0.70 to 0.81]; P = .88), with no significant difference in improvement. Of 20 exploratory secondary outcomes, 17 showed no significant difference. Conclusions and Relevance: Among children with autism spectrum disorder, improvisational music therapy, compared with enhanced standard care, resulted in no significant difference in symptom severity based on the ADOS social affect domain over 5 months. These findings do not support the use of improvisational music therapy for symptom reduction in children with autism spectrum disorder. Trial Registration: isrctn.org Identifier: ISRCTN78923965.

Autistic identity: A systematic review of quantitative research.

Autism can be considered both a personal and social identity. Identifying the factors contributing to positive Autistic identity development is crucial given the potential implications for mental health and wellbeing. In this systematic review, we aimed to synthesize quantitative literature on Autistic identity to identify the (individual and environmental) factors associated with Autistic identity, and to ascertain the relationship between Autistic identity and mental health and wellbeing. A total of 3,617 studies were screened and 20 met our inclusion criteria. Results indicated that people developed a more positive Autistic identity when receiving external autism acceptance and external support. The association between individual factors and Autistic identity were largely nonsignificant or inconclusive, highlighting the need for broad support that meets the needs of a range of Autistic people, rather than specific subgroups. Importantly, positive Autistic identity was associated with improved mental health and wellbeing. Peer support and/or self-directed support resources may be valuable mechanisms for supporting Autistic people to cultivate a positive Autistic identity. The evaluation of such support, including the long-term impacts on identity development, will be a critical avenue for future research.

Frailty as a predictor of postoperative outcomes in neurosurgery: a systematic review.

INTRODUCTION: Baseline frailty status has been utilized to predict a wide range of outcomes and guide preoperative decision making in neurosurgery. This systematic review aims to analyze existing literature on the utilization of frailty as a predictor of neurosurgical outcomes. EVIDENCE ACQUISITION: We conducted a systematic review following PRISMA guidelines. Studies that utilized baseline frailty status to predict outcomes after a neurosurgical intervention were included in this systematic review. Studies that utilized sarcopenia as the sole measure of frailty were excluded. PubMed, EMBASE, and Cochrane library was searched from inception to March 1st, 2023, to identify relevant articles. EVIDENCE SYNTHESIS: Overall, 244 studies met the inclusion criteria. The 11-factor modified frailty index (mFI-11) was the most utilized frailty measure (N.=91, 37.2%) followed by the five-factor modified Frailty Index (mFI-5) (N.=80, 32.7%). Spine surgery was the most common subspecialty (N.=131, 53.7%), followed by intracranial tumor resection (N.=57, 23.3%), and post-operative complications were the most reported outcome (N.=130, 53.2%) in neurosurgical frailty studies. The USA and the Bowers author group published the greatest number of articles within the study period (N.=176, 72.1% and N.=37, 15.2%, respectively). CONCLUSIONS: Frailty literature has grown exponentially over the years and has been incorporated into neurosurgical decision making. Although a wide range of frailty indices exist, their utility may vary according to their ability to be incorporated in the outpatient clinical setting.

Exploring Music Therapy Research in Preschool Settings that Include Children with Disabilities: A Scoping Review.

With an increasing number of developed nations adopting elements of the social model of disability, early childhood intervention practice has evolved to place greater emphasis on an inclusive, ecological, and strength-based framework. Recent music therapy literature seems to align with this shift in policy and demonstrates how family-centered strategies can be promoted in homes. Although music therapy researchers have conducted studies in kindergartens and childcares, which are also fundamental naturalistic settings for children with disabilities, the overall breadth and nature of practice in these settings is unclear and has not been collated. This scoping review aims to identify the key characteristics of music therapy research in preschool settings that include children with disabilities, subsequently identifying key publication details, participants, therapeutic aims, outcome measures, study designs, preschool settings, delivery models, and choice of music therapy methods. A total of 19 peer-reviewed journal articles from 1988 to 2020 met inclusion and exclusion criteria, with more than half of the studies published during the last 15 years. Evaluation of these 19 studies reveals how funding policies and educational systems seem to inherently inform the application of music therapy research in early learning centers. Developmental perspectives and objectivist study designs underpin many of the included sources, with majority of the outcomes demonstrating music therapy's positive impact upon a child's development. Researchers outside of the United States should give greater focus to early childhood and collect data from preschools within their respective countries to broaden awareness on how music therapy can support children with disabilities in naturalistic settings.

Adeno-associated virus-mediated gene therapy in a patient with Canavan disease using dual routes of administration and immune modulation.

Gene replacement therapy is a rational therapeutic strategy and clinical intervention for neurodegenerative disorders like Canavan disease, a leukodystrophy caused by biallelic mutations in the aspartoacylase (ASPA) gene. We aimed to investigate whether simultaneous intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of rAAV9-CB6-ASPA provides a safe and effective therapeutic strategy in an open-label, individual-patient, expanded-access trial for Canavan disease. Immunomodulation was given prophylactically prior to adeno-associated virus (AAV) treatment to prevent an immune response to ASPA or the vector capsid. The patient served as his own control, and change from baseline was assessed by clinical pathology tests, vector genomes in the blood, antibodies against ASPA and AAV capsids, levels of cerebrospinal fluid (CSF) N-acetylaspartate (NAA), brain water content and morphology, clinical status, and motor function tests. Two years post treatment, the patient's white matter myelination had increased, motor function was improved, and he remained free of typical severe epilepsy. NAA level was reduced at 3 months and remained stable up to 4 years post treatment. Immunomodulation prior to AAV exposure enables repeat dosing and has prevented an anti-transgene immune response. Dual-route administration of gene therapy may improve treatment outcomes.

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition, but an overabundance of genomic virulence factors that have functional consequence on host immune evasion. One Sentence Summary: The severity of sepsis in the aged host is in part mediated by longevity-associated increases in gut microbial virulence.

Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion. IMPORTANCE Older adults suffer more frequent and worse outcomes from sepsis, a critical illness secondary to infection. The reasons underlying this unique susceptibility are incompletely understood. Prior work in this area has focused on how the immune response changes with age. The current study, however, focuses instead on alterations in the community of bacteria that humans live with within their gut (i.e., the gut microbiome). The central concept of this paper is that the bacteria in our gut evolve along with the host and "age," making them more efficient at causing sepsis.

A Systematic Review of Music Interventions to Support Parent-Child Attachment.

Secure attachment in early childhood is important for wellbeing throughout life. Music interventions show promise for supporting early parent-child relationships; however, their effects on attachment security are unclear as few music intervention evaluations have measured attachment outcomes. This systematic literature review aimed to synthesize published empirical literature examining the effects of music interventions on relationship quality between typically developing children aged birth to 5 years old and their parents. The study aimed to: (1) establish whether music interventions were associated with changes in attachment-related outcomes; (2) identify music intervention characteristics likely to support secure attachment; and (3) elucidate processes through which music techniques may have contributed to attachment-related changes. Included interventions focused on the parent-child dyad, involved a substantial music component delivered by a music therapist or an allied health professional, and assessed and/or described relationship outcome/s. A total of 23 studies describing 15 unique interventions met criteria for inclusion and represented approximately 808-815 parent-child dyads. Mothers were the most common caregivers. All interventions demonstrated some effectiveness, including in attachment-related outcomes such as bonding, emotional co-regulation, and parental sensitivity. All interventions involved singing, suggesting it may be especially suitable for supporting parent-child attachment; other music techniques used included instrument playing and movement to music. Findings suggested that music interventions may facilitate attachment-related changes through intervening in psychological processes, including parental sensitivity, reflective functioning, and emotional co-regulation. Future research should develop music interventions aiming specifically to support attachment quality, and music intervention evaluations should use validated attachment assessments and longitudinal study designs.

A Novel Targeted Amplicon Next-Generation Sequencing Gene Panel for the Diagnosis of Common Variable Immunodeficiency Has a High Diagnostic Yield: Results from the Perth CVID Cohort Study.

With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.

Cross With Caution: Antibiotic Cross-Reactivity and Co-Reactivity Patterns in Severe Cutaneous Adverse Reactions.

Current understanding of cross-reactivity in severe cutaneous adverse reactions to beta-lactam antibiotics is limited, thereby making recommendations for future prescribing difficult. The underlying immunopathogenesis of these reactions is not completely understood but involves interactions between small molecule drugs, T cells and HLA molecules. Historically, these reactions were considered to be specific to the inciting antibiotic and therefore likely to have minimal cross-reactivity. We assessed patients presenting with non-SJS/TEN severe cutaneous adverse reactions to a tertiary hospital drug allergy clinic. In our case series cross-reactivity or co-reactivity commonly occurred among the beta-lactam antibiotic class, however further research is required to investigate and understand patterns of cross-reactivity. Based on our experience we provide clinicians with a practical algorithm for testing for cross-reactivity in non-SJS/TEN severe cutaneous adverse reactions.

Music Therapists' Perceptions of the Therapeutic Potentials Using Music When Working With Verbal Children on the Autism Spectrum: A Qualitative Analysis.

While there are numerous descriptions of the use of music and its therapeutic potential by music therapists working with nonverbal children on the autism spectrum, only limited literature focuses on exploring how music therapists use music and perceive its therapeutic potential when working with children on the spectrum who have verbal skills. This qualitative study aimed to explore music therapists' descriptions of the use of music and its therapeutic potential in their work with children on the autism spectrum who have verbal skills. Semi-structured interviews were conducted with six qualified music therapists from Israel and then analyzed according to the principles of interpretative phenomenological analysis (IPA). Three main themes were identified: (a) musical infrastructure, which describes how the music therapists facilitated musical experiences to support the children's ability to regulate their arousal, attention and emotions; (b) the meeting point between musical and verbal playfulness, which reflects the music therapists' beliefs about how musical experiences add vitality and support the development of both verbal and nonverbal imaginative play; and (c) musical responses, which describes the different ways music therapists use their voice and songs to interact musically with verbal children. The experiences described by the participants emphasize the importance of the therapist musically attuning to the child's emotional, physiological, creative, and playful qualities, even when the child has verbal skills. These musical interactions help to create a shared experience between the child and therapist that are perceived to help the child's different forms of regulation, continuity, and vitality within the play.

Supporting Breastfeeding in Infants Hospitalized for Jaundice.

BACKGROUND: Infants readmitted for neonatal hyperbilirubinemia requiring phototherapy are less likely to exclusively breastfeed than infants who are not readmitted for phototherapy. Our aim for this study was to increase breastfeeding exclusivity for infants admitted for neonatal hyperbilirubinemia. METHODS: Using the Model for Improvement, we conducted 3 plan-do-study-act cycles to improve exclusive breastfeeding (EB). Our outcome measure was to increase the percentage of EB for infants hospitalized for phototherapy from 30% to 80% in 12 months. Our process measure was to increase lactation consultations from 60% to 80%. Balancing measures included the development of >10% weight loss, acute bilirubin encephalopathy, readmissions, and length of stay. Interventions involved staff breastfeeding education, automated orders for lactation consultations, and use of bilirubin blankets during breastfeeding. Data were analyzed by using run charts and statistical process control. RESULTS: A total of 92 infants with neonatal hyperbilirubinemia were admitted from December 2016 to August 2019, with 61 in the postintervention period. After implementation of an automated order for lactation consultation, EB improved from 30% to 60% and completed lactation consultations increased from 60% to 90%. Infants who received a lactation consultation within the first shift during their hospitalization were 4 times more likely to have EB during hospitalization than infants who did not (odds ratio 3.8; confidence interval: 1.17-12.39.) No infant experienced >10% weight loss, acute bilirubin encephalopathy, or a readmission, and length of stay did not significantly change. CONCLUSIONS: Early involvement of trained lactation consultants safely improves rates of EB for infants hospitalized with neonatal hyperbilirubinemia.

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population.

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.