Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.

Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.

Cancer progression can be restrained by tumor-infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre-wired, in which innate lymphocytes and innate-like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming-dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming-dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell-directed therapeutic programs, recent studies have revealed that pre-wired cancer immunity mediated by tissue-resident type 1 innate lymphoid cells (ILC1s) and killer innate-like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer-sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed.

Mitochondrial Raf1 Regulates Glutamine Catabolism.

Raf kinases play vital roles in normal mitogenic signaling and cancer, however, the identities of functionally important Raf-proximal proteins throughout the cell are not fully known. Raf1 proximity proteomics/BioID in Raf1-dependent cancer cells unexpectedly identified Raf1-adjacent proteins known to reside in the mitochondrial matrix. Inner-mitochondrial localization of Raf1 was confirmed by mitochondrial purification and super-resolution microscopy. Inside mitochondria, Raf1 associated with glutaminase (GLS) in diverse human cancers and enabled glutaminolysis, an important source of biosynthetic precursors in cancer. These impacts required Raf1 kinase activity and were independent of canonical MAP kinase pathway signaling. Kinase-dead mitochondrial matrix-localized Raf1 impaired glutaminolysis and tumorigenesis in vivo. These data indicate that Raf1 localizes inside mitochondria where it interacts with GLS to engage glutamine catabolism and support tumorigenesis.

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.

Epigenetic priming targets tumor heterogeneity to shift transcriptomic phenotype of pancreatic ductal adenocarcinoma towards a Vitamin D susceptible state.

As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state. Increasing overall H3K27 acetylation with GTA and reducing overall DNA methylation with 5-Aza not only elevated the Vitamin D receptor (VDR) expression but also reprogrammed the Vitamin D-responsive genes. Consequently, Vitamin D inhibited cell viability and migration in the epigenetically primed PDAC cells by activating genes involved in apoptosis as well as genes involved in negative regulation of cell proliferation and migration, while the opposite effect of Vitamin D was observed in unprimed cells. Studies in genetically engineered mouse PDAC cells further validated the effects of epigenetic priming for enhancing the anti-tumor activity of Vitamin D. Using gain- and loss-of-function experiments, we further demonstrated that VDR expression was necessary but not sufficient for activating the favorable transcriptomic phenotype in respond to Vitamin D treatment in PDAC, highlighting that both the VDR and Vitamin D-responsive genes were prerequisites for Vitamin D response. These data reveal a previously undefined mechanism in which epigenetic state orchestrates the expression of both VDR and Vitamin D-responsive genes and determines the therapeutic response to Vitamin D in PDAC.

Serine starvation silences estrogen receptor signaling through histone hypoacetylation.

Loss of estrogen receptor (ER) pathway activity promotes breast cancer progression, yet how this occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in breast cancer, represses estrogen receptor alpha (ERα) signaling by reprogramming glucose metabolism and epigenetics. Using isotope tracing and time-resolved metabolomic analyses, we demonstrate that serine is required to maintain glucose flux through glycolysis and the TCA cycle to support acetyl-CoA generation for histone acetylation. Consequently, limiting serine depletes histone H3 lysine 27 acetylation (H3K27ac), particularly at the promoter region of ER pathway genes including the gene encoding ERα, ESR1. Mechanistically, serine starvation impairs acetyl-CoA-dependent gene expression by inhibiting the entry of glycolytic carbon into the TCA cycle and down-regulating the mitochondrial citrate exporter SLC25A1, a critical enzyme in the production of nucleocytosolic acetyl-CoA from glucose. Consistent with this model, total H3K27ac and ERα expression are suppressed by SLC25A1 inhibition and restored by acetate, an alternate source of acetyl-CoA, in serine-free conditions. We thus uncover an unexpected role for serine in sustaining ER signaling through the regulation of acetyl-CoA metabolism.

Rare but life-threatening cause of massive haemoptysis in an adolscent with tuberculosis: Rasmussen's aneurysm.

Rasmussen's aneurysm is a rare yet fatal cause of massive haemoptysis in pulmonary tuberculosis. Early identification and timely intervention are of utmost importance to reduce the associated mortality. A girl in early adolescence presented with persistent fever and massive haemoptysis who required intubation and was subsequently confirmed to have tuberculosis. CT pulmonary angiogram showed the presence of pseudoaneurysms in the left upper and lower lobes. The haemoptysis resolved following the embolisation of the culprit's vessel. Residual lung destruction was evident on CT after a 12-month course of antituberculosis therapy. Rasmussen's aneurysm is a significant vascular complication of cavitary tuberculosis and needs to be considered in patients presenting with massive haemoptysis.

Applicability of the Global Lung Function Initiative prediction equations in Hong Kong Chinese children.

BACKGROUND AND OBJECTIVE: This study aimed to assess the applicability of the Global Lung Function Initiative (GLI) prediction equations for spirometry in Hong Kong children and to develop prediction equations based on the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modeling. METHODS: Healthy Chinese children and adolescents aged 6-17 years old were recruited from randomly selected schools to undergo spirometry. The measurements were transformed to z-score according to the GLI-2012 equations for South East (SE) Asians and the GLI-2022 global race-neutral equations. Prediction equations for spirometric indices were developed with GAMLSS modeling to identify predictors. RESULTS: A total of 886 children (477 boys) with a mean age of 12.5 years (standard deviation [SD] 3.3 years) were included. By the GLI-2012 SE Asian equations, positive mean z-scores were observed in forced expiratory volume in 1 s (FEV1 ) (boys: 0.138 ± SD 0.828; girls: 0.206 ± 0.823) and forced vital capacity (FVC) (boys: 0.160 ± 0.930; girls: 0.310 ± 0.895) in both sexes. Negative mean z-scores were observed in FEV1 /FVC ratio (boys: -0.018 ± 0.998; girls: -0.223 ± 0.897). In contrast, negative mean z-scores in FEV1 and FVC, and positive mean z-scores in FEV1 /FVC were observed when adopting the GLI-2022 race-neutral equations. The mean z-scores were all within the range of ±0.5. By GAMLSS models, age and height were significant predictors for all four spirometric indices, while weight was an additional predictor for FVC and FEV1 . CONCLUSION: Our study provided data supporting the applicability of the GLI prediction equations in Hong Kong Chinese children. The GLI-2012 equations may underestimate FEV1 and FVC, while the GLI-2022 equations may overestimate the parameters, but the differences lie within the physiological limits. By GAMLSS modeling, weight was an additional predictor for FVC and FEV1 .

Mitochondrial Uncoupling Inhibits Reductive Carboxylation in Cancer Cells.

When the electron transport chain (ETC) function is impaired, cancer cells rely on reductive carboxylation (RC) to convert α-ketoglutarate (αKG) to citrate for macromolecular synthesis, thereby promoting tumor growth. Currently, there is no viable therapy to inhibit RC for cancer treatment. In this study, we demonstrate that the mitochondrial uncoupler treatment effectively inhibits RC in cancer cells. Mitochondrial uncoupler treatment activates the ETC and increases the NAD+/NADH ratio. Using U-13C-glutamine and 1-13C-glutamine tracers, we show that mitochondrial uncoupling accelerates the oxidative tricarboxylic acid (TCA) cycle and blocks RC under hypoxia, in von Hippel-Lindau (VHL) tumor suppressor-deficient kidney cancer cells, or under anchorage-independent growth condition. Together, these data demonstrate that mitochondrial uncoupling redirects α-KG from RC back to the oxidative TCA cycle, highlighting that the NAD+/NADH ratio is one key switch that determines the metabolic fate of α-KG. Inhibiting RC could be a key mechanism by which mitochondrial uncouplers inhibit tumor growth. IMPLICATIONS: Mitochondrial uncoupling is a novel strategy to target RC in cancer.

Effect of surgical intervention for childhood OSA on blood pressure: A randomized controlled study.

OBJECTIVE: To investigate the effect of surgical intervention on 24-h ABP in children with OSA. It was hypothesized that blood pressure would improve following adenotonsillectomy. METHODS: This was a two-centered investigator-blinded randomized controlled trial. Non-obese pre-pubertal children aged 6-11 years with OSA (obstructive apnea-hypopnea index, OAHI >3/h) underwent 24-h ABP monitoring at baseline and 9 months after the randomly assigned intervention, i.e. Early Surgery (ES) or Watchful Waiting (WW). Intention-to-treat analysis was performed. RESULTS: 137 subjects were randomized. Sixty-two (Age: 7.9y ± 1.3, 71% boys) and 47 (Age: 8.5y ± 1.6, 77% boys) participants from the ES and WW groups, respectively completed the study. Changes in ABP parameters were similar in the ES and WW groups (nighttime systolic BP z-scores: +0.03 ± 0.93 vs. -0.06 ± 1.04, p = 0.65; nighttime diastolic BP z-scores: -0.20 ± 0.95 vs. -0.02 ± 1.00, p = 0.35) despite a greater improvement in OSA in the ES group. However, a reduction in nighttime diastolic BP z-score correlated with improvements in OSA severity indexes (r = 0.21-0.22, p < 0.05), and a significant improvement in nighttime diastolic BP z-score [-0.43 ± 1.01, p = 0.027] following surgery was observed in participants with severe preoperative OSA (OAHI ≥10/h). The ES group had a significant increase in body mass index z-score after surgery [+0.27 ± 0.57, p < 0.001], which correlated with the increase in daytime systolic BP z-score (r = 0.2, p < 0.05). CONCLUSION: Surgical treatment did not lead to significant improvements in ABP in OSA children except in those with more severe disease. The improvement in BP was partially masked by the weight gain following surgery. CLINICAL TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn. REGISTRATION NUMBER: ChiCTR-TRC-14004131).

Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload.

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.

PHGDH-mediated endothelial metabolism drives glioblastoma resistance to chimeric antigen receptor T cell immunotherapy.

The efficacy of immunotherapy is limited by the paucity of T cells delivered and infiltrated into the tumors through aberrant tumor vasculature. Here, we report that phosphoglycerate dehydrogenase (PHGDH)-mediated endothelial cell (EC) metabolism fuels the formation of a hypoxic and immune-hostile vascular microenvironment, driving glioblastoma (GBM) resistance to chimeric antigen receptor (CAR)-T cell immunotherapy. Our metabolome and transcriptome analyses of human and mouse GBM tumors identify that PHGDH expression and serine metabolism are preferentially altered in tumor ECs. Tumor microenvironmental cues induce ATF4-mediated PHGDH expression in ECs, triggering a redox-dependent mechanism that regulates endothelial glycolysis and leads to EC overgrowth. Genetic PHGDH ablation in ECs prunes over-sprouting vasculature, abrogates intratumoral hypoxia, and improves T cell infiltration into the tumors. PHGDH inhibition activates anti-tumor T cell immunity and sensitizes GBM to CAR T therapy. Thus, reprogramming endothelial metabolism by targeting PHGDH may offer a unique opportunity to improve T cell-based immunotherapy.

Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.

The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer. In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), to activate mitochondrial respiration, which induced neural differentiation in neuroblastoma cells. NEN treatment increased the NAD+/NADH and pyruvate/lactate ratios and also the α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, NEN treatment induced promoter CpG island demethylation and epigenetic landscape remodeling, activating the neural differentiation program. In addition, NEN treatment upregulated p53 but downregulated N-Myc and ß-catenin signaling in neuroblastoma cells. Importantly, even under hypoxia, NEN treatment remained effective in inhibiting 2-HG generation, promoting DNA demethylation, and suppressing hypoxia-inducible factor signaling. Dietary NEN intervention reduced tumor growth rate, 2-HG levels, and expression of N-Myc and ß-catenin in tumors in an orthotopic neuroblastoma mouse model. Integrative analysis indicated that NEN treatment upregulated favorable prognosis genes and downregulated unfavorable prognosis genes, which were defined using multiple neuroblastoma patient datasets. Altogether, these results suggest that mitochondrial uncoupling is an effective metabolic and epigenetic therapy for reversing the Warburg effect and inducing differentiation in neuroblastoma. SIGNIFICANCE: Targeting cancer metabolism using the mitochondrial uncoupler niclosamide ethanolamine leads to methylome reprogramming and differentiation in neuroblastoma, providing a therapeutic opportunity to reverse the Warburg effect and suppress tumor growth. See related commentary by Byrne and Bell, p.167.

Association of growth patterns during infancy and puberty with lung function, wheezing and asthma in adolescents aged 17.5 years: evidence from 'Children of 1997' Hong Kong Chinese Birth Cohort.

BACKGROUND: Rapid growth is related to adverse respiratory outcomes although possibly confounded or limited by growth modelling methods. We investigated the association of infant and pubertal growth with lung function, wheezing and asthma in a non-Western setting. METHODS: In Hong Kong's 'Children of 1997' Chinese birth cohort (n = 8327), weight during infancy and weight, height and body mass index (BMI) during puberty were modelled using a super-imposition by translation and rotation model to identify (larger or smaller) size, (earlier or later) tempo and (slower or faster) velocity. Sex-specific associations with forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC (Global Lung function Initiative z-score) and self-reported wheezing and asthma at ∼17.5 years were assessed. RESULTS: For each fraction higher than average weight growth velocity during infancy, FVC was higher in boys (0.90 SD, 95% CI 0.35; 1.44) and girls (0.77 SD, 95% CI 0.24; 1.30), FEV1/FVC was lower (-0.74 SD, 95% CI -1.38; -0.10) and wheezing was higher (odds ratio 6.92, 95% CI 1.60; 29.99) in boys and an inverse association with FVC was observed for tempo but not for size. Associations for weight growth velocity in puberty were similar but weaker. Greater size and higher velocity of BMI growth was associated with higher FVC, lower FEV1/FVC and higher asthma and wheezing risk. CONCLUSION: Accelerated infant and pubertal weight growth were associated with disproportionate lung size and airway growth, and higher risk of asthma; optimizing early-life growth patterns could be important.

The magic bullet: Niclosamide.

The term 'magic bullet' is a scientific concept proposed by the German Nobel laureate Paul Ehrlich in 1907, describing a medicine that could specifically and efficiently target a disease without harming the body. Oncologists have been looking for a magic bullet for cancer therapy ever since. However, the current therapies for cancers-including chemotherapy, radiation therapy, hormone therapy, and targeted therapy-pose either pan-cytotoxicity or only single-target efficacy, precluding their ability to function as a magic bullet. Intriguingly, niclosamide, an FDA-approved drug for treating tapeworm infections with an excellent safety profile, displays broad anti-cancer activity in a variety of contexts. In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/ß-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK. Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1. We recently discovered that niclosamide ethanolamine (NEN) reprograms cellular metabolism through its uncoupler function, consequently remodeling the cellular epigenetic landscape to promote differentiation. Inspired by the promising results from the pre-clinical studies, several clinical trials are ongoing to assess the therapeutic effect of niclosamide in cancer patients. This current review summarizes the functions, mechanism of action, and potential applications of niclosamide in cancer therapy as a magic bullet.

Level of urinary catecholamine in children with Sleep Disordered Breathing: A systematic review and meta-analysis.

OBJECTIVE: To compare the levels of different urinary catecholamines amongst paediatric patients with and without sleep-disordered breathing (SDB). METHODS: Literature searches were conducted on PubMed and EMBASE until 25/06/2022. Inclusion criteria were original human studies, English language, paediatric subjects diagnosed with SDB/obstructive sleep apnoea (OSA). The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The registered number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42022332939. The main outcome measured was standardised mean difference (SMD) of urinary catecholamine between subjects with and without SDB, between those with and without OSA, and also between subjects with mild OSA and those with moderate/ severe OSA. Sensitivity analyses were performed to avoid bias. RESULTS: 9 studies (8 cross-sectional and 1 cohort study) with a total of 838 subjects, were included in the quantitative analysis. Urine level of noradrenaline was higher in patients with SDB, which included primary snoring (PS), when compared to controls: SMD = 0.86 (95%CI=0.32-1.41; I2=85%, P=0.002). The levels of urinary noradrenaline and adrenaline were higher in children with OSA when compared to controls: SMD = 1.45 (95%CI=0.91-2.00; I2=75%, P < 0.001); SMD = 1.84 (0.00-3.67; I2=97%, P=0.05). Urine level of noradrenaline was higher in subjects with moderate/severe OSA compared to the mild OSA: SMD = 0.55 (95%CI=0.10-1.00; I2=0%, P=0.02). Urinary dopamine was not associated with SDB regardless of severity. CONCLUSIONS: Urinary noradrenaline was higher in all patients with SDB. Subjects with OSA, a more severe form of SDB, had higher urine levels of noradrenaline and adrenaline. Hence, noradrenaline and adrenaline may be markers of sympathetic overtone in patients with SDB and could potentially act as surrogate markers for SDB complications. Further studies are needed to assess this association.

Inferior endothelial function improved following optimisation of asthma control in children.

Association between asthma control and cardiovascular disease (CVD) remains highly plausible as the two are related to chronic systemic inflammation. Children with physician-diagnosed asthma and matched healthy controls underwent endothelial function assessment. Repeat measurements were performed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS), compared to those with well-controlled asthma without ICS therapy. We found that children with uncontrolled asthma had inferior endothelial function compared to matched healthy controls. Enhancement in endothelial function, lung function and symptom control was observed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS). These results provided further evidence of a likely relationship between asthma control and cardiovascular health.

Validation of the Sonographic Measurement of Lateral Parapharyngeal Wall Thickness in Childhood Obstructive Sleep Apnea.

Background: Lateral parapharyngeal wall (LPW) thickness is a potentially useful anatomical marker of childhood obstructive sleep apnea (OSA). Measuring LPW thickness by ultrasonography (USG) is technically feasible but its use in children has not been validated. Therefore, this study aimed to assess the intra- and inter-operator reliability of the sonographic measurements of LPW thickness in children and to assess its validity against magnetic resonance imaging (MRI) measurements. Methods: Prepubertal children aged 6-11 years suspected to suffer from OSA were recruited. Repeated measurements of LPW thickness by USG were conducted to evaluate the intra- and inter-operator reliability, examined by intraclass correlation coefficient (ICC). LPW thickness was measured as the distance between the internal carotid artery and the echogenic surface of the pharynx in an oblique coronal plane by USG. LPW thickness was measured by MRI at the retropalatal level. The agreement between the LPW thickness measured by USG and MRI was assessed by ICC and Bland-Altman plot. Results: Thirty-four children (mean age: 8.66 ± 1.61, 26 male) were recruited. The intra- and inter-operator reliability of the LPW thickness by USG was good (ICC = 0.84 and 0.82, respectively). The agreement between the USG-measured and MRI-measured LPW thickness was moderate (ICC = 0.72). he Bland-Altman plot demonstrated a mean difference of 0.061 cm and a 95% limit of agreement from 0.91 to 1.12 cm. Conclusion: In this study, we demonstrated that ultrasonography is a valid and reliable method to assess LPW thickness in children. This study was supported by the Direct Grant for Research from the Research Committee of the Chinese University of Hong Kong (Project no. 2020.073).