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Background: Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens., Method: A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1-18 years (median: 12 years; IQR: 9-14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods., Results: In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing., Conclusions: Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Darunavir is a potent HIV protease inhibitor with a high barrier to resistance. We conducted a nested pharmacokinetic sub-study within CHAPAS-4 to evaluate darunavir exposure in African children with HIV, taking once-daily darunavir/ritonavir for second-line treatment., Methods: We used data from the CHAPAS-4 pharmacokinetic sub-study treating children with once-daily darunavir/ritonavir (600/100 mg if 14-24.9 kg and 800/100 mg if ≥25 kg) with either tenofovir alafenamide fumarate (TAF)/emtricitabine (FTC), abacavir/lamivudine or zidovudine/lamivudine. Steady-state pharmacokinetic sampling was done at 0, 1, 2, 4, 6, 8, 12 and 24 hours after observed darunavir/ritonavir intake. Non-compartmental and population pharmacokinetic analyses were used to describe the data and identify significant covariates. Reference adult pharmacokinetic data were used for comparison. We simulated the World Health Organization (WHO) recommended 600/100 mg darunavir/ritonavir dose for the 25-34.9 kg weight band., Results: Data from 59 children with median age and weight 10.9 (range 3.8-14.7) years and 26.0 (14.5-47.0) kg, respectively, were available. A two-compartment disposition model with transit absorption compartments and weight-based allometric scaling of clearance and volume best described darunavir data. Our population achieved geometric mean (%CV) darunavir AUC0-24h, 94.3(50) mg·h/L and Cmax, 9.1(35) mg/L, above adult reference values and Ctrough, 1.5(111) mg/L, like adult values. The nucleoside reverse-transcriptase inhibitor backbone was not found to affect darunavir concentrations. Simulated WHO-recommended darunavir/ritonavir doses showed exposures equivalent to adults. Higher alpha-1-acid glycoprotein increased binding to darunavir and decreased apparent clearance of darunavir., Conclusions: Darunavir exposures achieved in our trial are within safe range. Darunavir/ritonavir can safely be co-administered with TAF/FTC. Both WHO-recommended 600/100 mg and CHAPAS-4 800/100 mg darunavir/ritonavir doses for the 25-34.9 kg weight band offer favourable exposures. The choice between them can depend on tablet availability., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: While both cellular and humoral immunity are important in immunologic protection against influenza, how the influenza-specific CD4 T cell response is established in response to early vaccination remains inadequately understood. In this study, we sought to understand how the CD4 T cell response to inactivated influenza vaccine (IIV) is established and develops throughout early childhood., Methods: Influenza-specific CD4 T cell responses were quantified following IIV over 2 influenza seasons in 47 vaccinated children between 6 months and 8 years of age who had no documented history of natural influenza infection during the study. Peripheral blood mononuclear cells were stimulated with peptide pools encompassing the translated regions of the pH1, H3, HAB, and NP proteins, and CD4 T cell responses were assessed via multiparameter flow cytometry., Results: There was boosting of H3- and HAB-specific CD4 T cells but not cells specific for the pH1 HA protein post-vaccination. A positive correlation between age and the magnitude of the influenza-specific CD4 T cell response was seen, with an overall greater magnitude of IFNγ-producing cells in subjects ≥3 years of age. Changes in CD4 T cell functionality were also noted in older compared to younger children, with increases in CD4 T cells producing IFNγ and TNF or IL-2 as well as IFNγ alone., Conclusions: Inactivated influenza vaccine elicits a CD4 T cell response to H3 and HAB, with increases in the magnitude of the CD4 T cell response and changes in cellular functionality throughout childhood. This suggests that repeated influenza vaccination contributes to the development of anti-influenza CD4 T cell memory in children., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD)., Methods: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients., Results: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts.We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a "positive" or "negative" result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining "indeterminate" patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity., Conclusions: Agreement of total serum copper and LBC fraction classification may constitute an effective "rule-in" and "rule-out" assessment for WD-TN patients., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A modified Vesikari severity score (MVSS) is a useful research tool for assessing severity of acute gastroenteritis. We present a MVSS for studies in which a follow-up assessment of symptoms cannot be obtained. The MVSS significantly correlated with other markers of severity, including illness duration and work and school absenteeism., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2024.)

The need for echocardiography in pediatric Staphylococcus aureus bacteremia (SAB) remains uncertain. We reviewed 331 pediatric SAB cases. Nine subjects, all with comorbidities, met the echocardiogram criteria for infective endocarditis (IE). IE was associated with congenital heart disease and prolonged bacteremia, suggesting that echocardiography is unnecessary in most children with SAB., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in paediatric Crohn disease [pCD]., Methods: In all, 56 pCD patients were included through a pre-planned sub-study of the multicentre, prospective, ImageKids cohort, designed to develop the Paediatric Inflammatory Crohn magnetic resonance enterography [MRE] Index [PICMI]. Children were included throughout their disease course when undergoing ileocolonoscopy and MRE and were followed for 18 months, when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score [SES], faecal calprotectin [FCP], and C-reactive protein [CRP], to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy [mRMR] feature selection with a j-fold cross-validation scheme identified the best subset of features and hyperparameter settings., Results: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve [AUC] > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in the citrate cycle [TCA cycle], aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism., Conclusions: We extend on recent studies, observing differences in serum metabolites between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assessment of disease severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: The head louse, Pediculus humanus capitis, is an obligate ectoparasite and its infestation remains a major public health issue worldwide. Determining the genetic characteristics of the existing clades is essential to identify the population structure and to develop head lice-control programs. Hence, we aimed to investigate the genetic diversity of head lice among infested individuals in northern Iran., Methods: Adult head lice were collected from 100 infested individuals referring to the health centers throughout five geographical regions in Mazandaran Province, Iran. Partial fragments of the mitochondrial cytb gene were amplified by PCR, then consequently sequenced., Results: The results of the phylogenetic tree of collected head lice confirmed the existence of two clades, A and B, in the studied areas. Thirteen haplotypes were detected in the studied populations, of which 11 were novel haplotypes. Clade A was the dominant form and accounted for 75% of samples, while clade B included the rest. Haplotype and nucleotide diversity were 0.999 and 0.0411, respectively., Conclusions: Clade A and B of Pediculus humanus capitis exist among the human populations of northern Iran. We observed high genotypic diversity of this head lice., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objectives: The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis., Methods: In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000. The pituitary gland was sagittally sliced from anterior to posterior into 6 to 8 sections. When H&E-stained sections revealed tumors, the tumors were immunohistochemically stained for 6 pituitary hormones., Results: Among 150 autopsy cases, 38 (25.3%) harbored microadenomas, including 4 cases with double tumors. Twenty-three (54.7%) cases were negative to all pituitary hormones. Of the remaining 19 tumors, 13 (30.9%) were lactotrophs, with 4 cases being concomitantly somatotrophs and gonadotrophs, and 2 cases were corticotropes. More than 85% of pituitary neuroendocrine tumors were adjacent to the capsule. Thirteen (8.7%) granular cell pituicytomas were found in the posterior lobe. There were pituicytes transforming into granular cell tumors., Conclusions: The incidence was 25.3% for pituitary neuroendocrine tumors and 8.7% for granular cell pituicytomas. Since most pituitary neuroendocrine tumors were adjacent to the pituitary capsule, the capsule appeared to be the germinal center. Both pituitary tumors belonged to the 2 different transcription factor lineages., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Post-artesunate delayed hemolysis (PADH) occurred in 6 of 24 children treated with artesunate for severe malaria in the United States; however, severe hemolysis requiring hospitalization or transfusion was rare. In children in the United States treated with artesunate, counseling, and symptom monitoring may be preferred to weekly laboratory surveillance for PADH., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Appropriate age- and sex-specific reference intervals for alkaline phosphatase (ALP) are essential to identify patients with hypophosphatasia (low ALP) and to avoid unnecessary ALP isoenzymes analysis (elevated ALP). This study used patient ALP historical data to statistically derive sex- and age-specific reference intervals., Methods: The ALP values reported as part of clinical management during an 18 month period (from July 2021 to March 2023) were obtained. Following logarithmic transformation of ALP data and repeated removal of outliers, cumulative frequency plots were generated using a modified Hoffmann approach to derive age- and sex-specific reference intervals., Results: Age-specific ALP reference intervals ranged from 110 to 250 and 120 to 295 U/L for males and females <15 days old, 80 to 400 and 90 to 380 U/L for males and females 15 days to 1 year old, 105 to 280 and 90 to 290 U/L for males and females 1 to 10 years old, 75 to 300 and 90 to 300 U/L for males and females 10 to 13 years old, 80 to 300 and 60 to 175 U/L for males and females 13 to 15 years old, 55 to 150 and 60 to 180 U/L for males and females 15 to 18 years old, and 55 to 140 and 60 to 147 U/L for male and female adults, respectively (>18 years old)., Conclusion: By applying derived ranges, a retrospective review of ALP isoenzymes would eliminate 24.5% of requests. Additionally, 9 neonates would have required investigation for possible hypophosphatasia., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Patatin-like phospholipase domain-containing lipase 8 (PNPLA8), one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological processes through the maintenance of membrane phospholipids. Biallelic variants in PNPLA8 have been associated with a range of paediatric neurodegenerative disorders. However, the phenotypic spectrum, genotype-phenotype correlations and the underlying mechanisms are poorly understood. Here, we newly identified 14 individuals from 12 unrelated families with biallelic ultra-rare variants in PNPLA8 presenting with a wide phenotypic spectrum of clinical features. Analysis of the clinical features of current and previously reported individuals (25 affected individuals across 20 families) showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. We found that complete loss of PNPLA8 was associated with the more profound end of the spectrum, with congenital microcephaly. Using cerebral organoids generated from human induced pluripotent stem cells, we found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Spatial transcriptomics revealed that loss of PNPLA8 altered the fate specification of apical radial glial cells, as reflected by the enrichment of gene sets related to the cell cycle, basal radial glial cells and neural differentiation. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. The reduced number of basal radial glial cells in patient-derived cerebral organoids was rescued, in part, by the addition of lysophosphatidic acid. Our data suggest that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims to give a comprehensive overview of clinical and molecular characteristics of pediatric FA MB patients., Methods: Clinical data including detailed information on the treatment and toxicities of 6 previously unreported FA MB patients were supplemented with data of 16 published cases., Results: We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n = 9), confirmed by methylation profiling in 5 patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n = 16) or FA-N (n = 3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT) ± chemotherapy (27%). Of 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI: 0.3-1.8). 1-year-progression-free-survival (PFS) was 26.3% ± 10.1% and 1-year-OS was 42.1% ± 11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3% ± 12.9%/33.3 ± 12.2% with adjuvant therapy, P = .006/P = .086)., Conclusions: MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy., Methods: We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models., Results: Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4)., Conclusion: Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome. With the increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable. This study focuses on exploring SMARCB1 germline alterations, notably mosaicism in blood samples of children with RT and in parents, using a custom NGS panel., Methods: A cohort of 280 children and 140 parents with germline analysis was studied. Germline DNA from 111 children with RT and 32 parents were reanalyzed with a custom NGS panel with 1500X average depth targeting the SMARCB1 gene to identify intragenic variants not detected with conventional low-sensitivity methods. Follow-up data was obtained for 77 patients., Results: Nine previously undetected mosaicism cases were identified, totaling 17/280 patients with a mosaic variant (6.1%) in the cohort, with variant allele frequencies between 0.9% and 33%, thus highlighting the prior underestimation of its prevalence. Follow-up data showed that 4 out of 7 survivors with mosaic variants developed distinct novel tumors, 2 sharing SMARCB1 alterations with the initial tumor, emphasizing the potential clinical impact of SMARCB1 mosaicism., Conclusions: The hitherto underestimated rate of SMARCB1 mosaicism in RT underscores the need for optimized genetic counseling and oncological monitoring. The findings have significant medical implications, considering the dire prognosis of RT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization, and biology in pediatric survivors of a posterior fossa tumor., Methods: Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic tool based on Cattell-Horn-Carroll's model for intelligence were analyzed., Results: Cognitive performance 5.14 years (mean; range = 1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had a strong impact on most subtests. pCMS was associated with psychomotor abilities (β = -0.25 to -0.16) and processing speed (β = -0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β = -0.20) and short-term memory (β = -0.15), age with crystallized intelligence (β = 0.15) and psychomotor abilities (β = -0.16 and β = -0.17). Scores for fluid intelligence (β = -0.23), short-term memory (β = -0.17) and visual processing (β = -0.25) declined, and scores for selective attention improved (β = 0.29) with time after diagnosis., Conclusions: The dose of CSI was strongly associated with neurocognitive outcomes. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI dose and toxicity caused by other treatment modalities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management., Methods: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression., Results: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13)., Conclusion: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of dengue fever with potentially life-threatening consequences and high mortality. Therefore, this study aims to investigate the prevalence, management and outcome of HLH in dengue fever., Methods: The major electronic databases, including PubMed, ScienceDirect and Ovid SP, were searched from inception until 31 January 2024 to identify relevant studies. Pooled prevalence and mortality were calculated using the random-effects generic inverse variance model with a 95% CI. All the statistical analysis was conducted using R programming., Results: A total of nine studies with 157 patients with HLH, 576 patients with severe dengue and 5081 patients with dengue fever were included in this meta-analysis. The prevalence of HLH in severe dengue (22.1%, 95% CI 8.07 to 48.0%) was significantly higher than the prevalence in dengue fever (3.12%, 95% CI 0.37 to 21.9%). The prevalence of HLH in severe dengue was higher in the paediatric population (22.8%, 95% CI 3.9 to 68.4%) compared with the adult population (19.0%, 95% CI 3.0 to 63.9%). The overall mortality rate was 20.2% (95% CI 9.7 to 37.2%)., Conclusion: The prevalence of dengue-associated HLH was low in patients with dengue fever but is significantly higher in patients with severe dengue and a high mortality rate., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD)., Methods: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults., Results: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02)., Conclusions: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence., Methods: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded., Results: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02)., Conclusion: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD., Methods: This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up., Results: Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegalovirus colitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively., Conclusion: While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Limited approval of second-line treatments in pediatric inflammatory bowel disease (pIBD) necessitates optimized use of infliximab (IFX) with proactive therapeutic drug monitoring (TDM). We investigated whether early combo-therapy with an immunomodulator (IMM) provides additional benefit., Methods: In the retrospectively reviewed medical records of all children treated with IFX and proactive TDM between 2013 and 2022, IMMearly (IMM ≤3 months since IFX start) was evaluated against IMMother/no (late/short or no IMM) over follow-up of 3 to 60 months. Kaplan-Meier analysis was used to analyze time to loss of response (LOR) with IFX discontinuation or time to antibodies-to-IFX (ATI) development., Results: Three hundred fifteen patients with pIBD were reviewed; of those, 127 with 2855 visits were included (77 CD, 50 UC/IBD-unclassified). Sixty patients received IMMearly, 20 patients IMMother, and 47 had IFX monotherapy. Median follow-up time was 30 and 26 months for IMMearly and IMMother/no, respectively, with comparable proactive TDM. Infliximab treatment persistence was 68% after 60 months. Loss of response was observed in 7 IMMearly and 15 IMMother/no patients (P = .16). Early combo-therapy significantly delayed LOR with IFX discontinuation (median LOR free interval IMMearly 30 months vs IMMother/no 9 months, P = .01). Patients with IMMother/no were 10-, 3- and 2-times more likely to experience LOR with IFX discontinuation after 1, 3, and 5 years, respectively. There were no significant group differences regarding the presence of any positive (>10 arbitrary units per milliliter [AU/mL]) or high (>100 AU/mL) ATI, median ATI concentrations, and ATI-free interval., Conclusions: Early IMM combo-therapy in proactively monitored patients with pIBD significantly prolonged the median LOR free interval compared with late/short or no IMM treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the direct cytopathic effect is followed, under certain circumstances, by an antitumor immune response responsible for the partial or complete debulking of the tumor mass. OVs alone or combined with other therapeutic modalities have been primarily used in adult neuro-oncology. A surge in encouraging preclinical studies in pediatric brain tumor models recently led to the clinical translation of OVs with encouraging results in these tumors. In this review, we summarize the different virotherapy tested in preclinical and clinical studies in pediatric brain tumors, and we discuss the limitations and future avenues necessary to improve the response of these tumors to this type of therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit., Methods: Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance., Results: Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR-/FCI-. Of all discordant cases, 75 (6%) were STR+/FCI-, with only 5 (6.7%) cases best explained as identification of disease relapse. Eight cases were STR-/FCI+, representing relapsed/residual disease. Analysis of cases 1 year or more from transplant (54% of all cases) indicated only 9 (1.5%) were STR+/FCI-, and none uniquely identified relapse., Conclusions: These data suggest that STR analysis performed 1 year or more post-HSCT does not identify unknown cases of relapse. Furthermore, while STR testing is critical for identifying graft failure/rejection within the first year posttransplant, FCI appears superior to STR at detecting late relapses with low-level disease. Therefore, STR testing from patients 1 year or more post-HSCT may be unnecessary, as BM biopsy evaluation is sufficient to identify disease relapse., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: No previous reports have characterized national profiles of soft-tissue sarcoma overall. We examined the nationwide statistics for soft-tissue sarcoma in Japan using data from the population-based National Cancer Registry., Methods: We identified 23 522 soft-tissue-sarcoma patients who were entered in the National Cancer Registry during 2016-19 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient., Results: Soft-tissue sarcoma showed a slight male preponderance. Approximately 5500-6000 new cases were diagnosed as soft-tissue sarcoma per year, with the age-adjusted incidence of soft-tissue sarcoma being 3.22/100000/year. The age distribution showed a single peak in the 70-79 age range, and sex-stratified data showed it was higher in men. The most common histologic subtype was liposarcoma. The most frequent tumor locations were the soft tissue and skin, followed by the retroperitoneum. Extent of disease was categorized as: "localized" (31.3%), "regional" (38.9%), or "distant" (10.5%). We found significant associations between overall survival and sex, age, tumor location, facility type, hospital volume, reason for diagnosis, extent of disease, and surgical treatment., Conclusions: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of soft-tissue sarcoma in Japan using the National Cancer Registry. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences., Level of Evidence: Prognostic studies, Level III., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aobjective: The impact of fine motor impairment among adult survivors of childhood acute lymphoblastic leukemia (ALL) on life after treatment is unknown., Methods: This study evaluated prevalence and utilized multivariate logistic regression to identify risk factors for fine motor impairment among survivors of ALL, and associations with educational attainment and social independence. Latent class analysis defined social independence (independent, moderately independent, dependent), using employment, independent living, personal care assistance, routine need assistance, driver's license status, and marital status inputs., Results: Among 875 survivors who were ≥ 25 years old (age when most adults achieve independence) and ≥ 5 years from diagnosis (mean = 28.97 years), 33.6% had fine motor impairment, with scores at or below the 10th percentile of the scores of community controls (n = 460) on fine motor components of the physical performance test and the grooved peg-board test. Survivors exposed to cranial radiation had more fine motor impairment than those without (45.8% vs 20.2%). Male sex (exposed: odds ratio [OR] = 2.55, 95% confidence interval [CI] = 1.65-3.92; unexposed: OR = 3.02, 95% CI = 1.69-5.38) and lower scores on the Wechsler abbreviated scale of intelligence (exposed: OR = 0.46, 95% CI = 0.36-0.58; unexposed: OR = 0.43, 95% CI = 0.31-0.58) were risk factors for neuropathy. A 1-point-higher total neuropathy score was associated with 8% (95% CI = 1%-17%) increased odds of fine motor impairment. Fine motor impairment was associated with less than a college education (less than high school: OR = 2.23, 95% CI = 1.20-4.14; high school diploma/general equivalency diploma: OR = 2.66, 95% CI = 1.65-4.30; vocational education: OR = 2.07, 95% CI = 1.38-3.13) and less social independence (moderately independent: OR = 1.80, 95% CI = 1.15-2.83; dependent: OR = 2.65, 95% CI = 1.25-5.64)., Conclusion: Fine motor impairment in survivors of childhood ALL may interfere with optimal educational attainment and social independence., Impact: Early identification of survivors at risk for fine motor impairment, with timely intervention, may improve long-term outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters?, Summary Answer: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility., What Is Known Already: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years., Study Design, Size, Duration: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021., Participants/materials, Setting, Methods: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21)., Main Results and the Role of Chance: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy., Limitations, Reasons for Caution: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited., Wider Implications of the Findings: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment., Study Funding/competing Interest(s): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: This study experimentally evaluated how well lay individuals could interpret and use 4 types of electronic health record (EHR) patient-facing immunization visualizations., Materials and Methods: Participants (n = 69) completed the study using a secure online survey platform. Participants viewed the same immunization information in 1 of 4 EHR-based immunization visualizations: 2 different patient portals (Epic MyChart and eClinicWorks), a downloadable EHR record, and a clinic-generated electronic letter (eLetter). Participants completed a common task, created a standard vaccine schedule form, and answered questions about their perceived workload, subjective numeracy and health literacy, demographic variables, and familiarity with the task., Results: The design of the immunization visualization significantly affected both task performance measures (time taken to complete the task and number of correct dates). In particular, those using Epic MyChart took significantly longer to complete the task than those using eLetter or eClinicWorks. Those using Epic MyChart entered fewer correct dates than those using the eLetter or eClinicWorks. There were no systematic statistically significant differences in task performance measures based on the numeracy, health literacy, demographic, and experience-related questions we asked., Discussion: The 4 immunization visualizations had unique design elements that likely contributed to these performance differences., Conclusion: Based on our findings, we provide practical guidance for the design of immunization visualizations, and future studies. Future research should focus on understanding the contexts of use and design elements that make tables an effective type of health data visualization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Context: Ramadan fasting (RF) is associated with various physiological and metabolic changes among fasting Muslims. However, it remains unclear whether these effects are attributable to changes in meal timing or changes in dietary energy and macronutrient intakes. Furthermore, the literature on the associations between RF, meal timing, and energy and macronutrient intakes is inconclusive., Objectives: This systematic review aimed to estimate the effect sizes of RF on energy and macronutrient intakes (carbohydrates, protein, fats, dietary fiber, and water) and determine the effect of different moderators on the examined outcomes., Data Sources: The Cochrane, CINAHL, EMBASE, EBSCOhost, Google Scholar, PubMed/MEDLINE, ProQuest Medical, Scopus, ScienceDirect, and Web of Science databases were searched from inception to January 31, 2022., Data Extraction: The studies that assessed energy, carbohydrate, protein, fat, fiber, and water intakes pre- and post-fasting were extracted., Data Analysis: Of the 4776 identified studies, 85 relevant studies (n = 4594 participants aged 9-85 y) were selected. The effect sizes for the studied variables were as follows: energy (number of studies [K] = 80, n = 3343 participants; mean difference [MD]: -142.45; 95% confidence interval [CI]: -215.19, -69.71), carbohydrates (K = 75, n = 3111; MD: -23.90; 95% CI: -36.42, -11.38), protein (K = 74, n = 3108; MD: -4.21; 95% CI: -7.34, -1.07), fats (K = 73, n = 3058; MD: -2.03; 95% CI: -5.73, 1.67), fiber (K = 16, n = 1198; MD: 0.47; 95% CI: -1.44, 2.39), and water (K = 17, n = 772; MD: -350.80; 95% CI: -618.09, 83.50). Subgroup analyses showed age significantly moderated the 6 dietary outcomes, and physical activity significantly moderated water intake. There were significant reductions in energy, carbohydrate, and protein intakes during RF., Conclusions: The change in meal timing rather than quantitative dietary intake may explain various physiological and health effects associated with RF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Patients with chronic illnesses, including kidney disease, consider their sense of normalcy when evaluating their health. Although this concept is a key indicator of their self-determined well-being, they struggle to understand if their experience is typical. To address this challenge, we set out to explore how to design personal health visualizations that aid participants in better understanding their experiences post-transplant, identifying barriers to normalcy, and achieving their desired medical outcomes., Materials and Methods: Pediatric kidney transplant patients and their caregivers participated in three asynchronous design sessions involving sharing experiences, presenting symbolic objects, and providing feedback on visualizations to understand their perceptions of normalcy post-transplant. Data analysis of design session 1 and 2 comprised deductive and inductive analysis. We used affinity diagramming to identify thematic areas about participants' transplant experiences. Comprehension of design session three normalcy visualizations was also evaluated., Results: Participants effectively engaged in the design sessions, revealing diverse perspectives on their experiences. We found there is a significant need for visualizations that depict normalcy to better inform patients and caregivers about their health., Discussion: Normalcy Visualizations should incorporate three key design principles: personal values, facilitating peer and self-comparison, and seamlessly communicating abstract concepts to help youth kidney transplant recipients comprehend and contextualize if their transplant experience is normal and what normalcy means to them., Conclusion: By incorporating holistic aspects of patients' and caregivers' lives into personal health visualizations, they can be cognizant of their progress to normalcy and empowered to make decisions that help them feel normal., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: The impact of unhealthy foods and beverages, namely those high in sugar, salt, and saturated or trans fats, has been studied extensively in relation to weight, body composition, and noncommunicable diseases, but less so in relation to the risk of dental caries. Few previous reviews have examined the evidence from all countries globally., Objective: A systematic review was conducted to assess the impact of unhealthy food and beverage consumption on the risk of dental caries in children aged ≤10 years, commissioned by the World Health Organization to inform updated complementary feeding recommendations., Data Sources: Systematic searches were conducted in the PubMed, Cochrane, and Embase databases for articles meeting the inclusion criteria dating from January 1971 to March 2022; supplementary searches were undertaken for articles from that period to June 2022., Data Extraction: Unhealthy foods and beverages were identified using nutrient- and food-based approaches. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I)., Data Analysis: A total of 30 023 unique citations were screened, yielding 37 studies for inclusion. Studies were conducted in high-income (n = 23 [62.2%]) or middle-income countries (n = 14 [37.8%]). Evidence synthesis was performed narratively, stratified by age (0 years to <2 years, 2 years to <5 years, and 5 years to ≤10 years) and exposure (unhealthy foods and unhealthy beverages). The heterogeneity of the exposures and comparators across studies was high. Almost all studies (n = 34) reported positive associations between the consumption of sugar-sweetened beverages or foods high in free sugars and dental caries. However, 67.6% of studies were assessed as having serious risk of bias., Conclusion: The evidence indicates that the consumption of unhealthy food and beverages in children ≤10 years appears to increase the risk of dental caries. Further longitudinal studies with high-quality dietary assessments, including studies in low-income countries and children aged >5 years at baseline, are recommended in order to build a more robust evidence base for use in the development of policy recommendations., Systematic Review Registration: PROSPERO registration no. CRD42020218109., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

The incidence of inflammatory bowel disease [IBD] is rising most rapidly among children and adolescents. Paediatric-onset IBD is associated with a more extensive and severe disease course compared to adult-onset IBD. At a young age, screening for underlying genetic and immunological disorders is important and may impact treatment management. Early and effective treatment is crucial to reach disease remission and prevent complications of ongoing active disease. In children with Crohn's disease, exclusive enteral nutrition is an effective induction therapy. Other promising dietary therapies, such as the Crohn's disease exclusion diet, are emerging. Within paediatric IBD, anti-tumour necrosis factor therapy is the only approved biological thus far and additional treatment options are crucially needed. Other biological therapies, such as vedolizumab and ustekinumab, are currently prescribed off-label in this population. A specific challenge in paediatric IBD is the unacceptable and major delay in approval of drugs for children with IBD. A guided transfer period of paediatric patients to adult care is associated with improved disease outcomes and is required. Major knowledge gaps and challenges within paediatric IBD include the aetiology, diagnostics, and monitoring of disease, tailoring of treatment, and both understanding and coping with the physical and psychological consequences of living with IBD. Challenges and research gaps in paediatrics should be addressed without any delay in comparison with the adult field, in order to ensure a high quality of care for all patients with IBD, irrespective of the age of onset., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: The incidence of inflammatory bowel diseases [IBD] has risen over the past decade to become a global issue. The objectives of this review were to describe the incidence and/or prevalence of IBD in the era of advanced therapies, and to describe the association between environmental risk factors and both pathogenesis and disease course across the ages., Methods: We performed a search of English language publications listed in PubMed regarding the epidemiology of IBD and key environmental factors implicated in IBD from January 2000 to December 2023., Results: Annual incidence rates varied by geographical region with IBD estimates ranging from 10.5 to 46.14 per 100 000 in Europe, 1.37 to 1.5 per 100 000 in Asia and the Middle East, 23.67 to 39.8 per 100 000 in Oceania, 0.21 to 3.67 per 100 000 in South America, and 7.3 to 30.2 per 100 000 in North America. The burden of IBD among children and adolescents, and older people is rising globally. Key environmental factors implicated in IBD pathogenesis include exposure to tobacco smoking, antibiotics, non-steroidal anti-inflammatory drugs, oral contraceptives, infections, and ultra-high processed foods. Breastfeeding and a high-quality diet rich in fruit, vegetables, fish, and other fibre sources are important protective factors. Smoking has consistently been shown to negatively impact disease outcomes for Crohn's disease., Conclusion: The epidemiology of IBD has undergone considerable change in recent decades, with an increase in the burden of disease worldwide. Optimally studying and targeting environmental triggers in IBD may offer future opportunities for disease modification., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Over the last 20 years, there has been a significant increase in fentanyl-related deaths in Ontario, Canada. This report examines toxicological findings in a series of death investigations in which fentanyl was quantitated to identify the prevalence, trends, and demographic data associated with fentanyl in Ontario, Canada, and to highlight the changes in these trends since fentanyl began appearing in casework in Ontario in the early 2000s. A retrospective study of all cases in which fentanyl was quantitated in blood, using liquid chromatography (LC)-tandem mass spectrometry (MS-MS), was conducted for the time period between 1 January 2020 and 31 December 2022. A total of 4395 cases were included; 77% of the decedents were male, and 23% was female with ages ranging from 0 to 95 years. The most frequently classified cause of death was mixed drug toxicity (69%) followed by fentanyl intoxication at 19%. Less than 10% of cases where fentanyl was quantitated were classified as nondrug-related deaths. Fentanyl concentrations in all cases ranged from 1.3 to >2000 ng/mL. Other drugs were frequently detected with fentanyl. In mixed drug toxicity cases, stimulants were the most frequently encountered class of drugs: cocaine was identified in 51.8%, and methamphetamine was observed in 43.0% of cases. Detailed reports for select cases were included to provide additional insight into the different case types and to show the difficulty in interpreting blood concentrations without additional detailed case histories. This study provides valuable information for the scientific and medical community regarding the continued use of fentanyl and how patterns of fentanyl use have evolved since it began to appear in forensic casework., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: The goal of the present study was to examine teachers' perceptions of neuropsychological reports broadly and their preparedness to support the educational needs of students with chronic health conditions., Method: Teachers were selected from across the United States using stratified random sampling. 280 teachers (76.2% female; 58.4% public school; 53.9% rural setting) completed an anonymous electronic survey via Qualtrics., Results: Half of the teachers were familiar with neuropsychology and previously read a neuropsychological report, which the majority found useful with a preference toward shorter reports. Most found listed recommendations to be appropriate, but half of teachers identified limited resources as a barrier to implementation. Teachers reported limited education, training, and comfort for providing accommodations to children with chronic health conditions, which was significantly lower for cancer, congenital heart disease, and sickle cell disease. Older teachers, more years of experience, and special education teachers demonstrated significantly higher levels of education, training, and comfort. Frequency of implementing accommodations was significantly negatively correlated with perceived burden and positively correlated with perceived benefit across most accommodations. Teachers reported a preference for single-page handouts and speaking directly to neuropsychologists about the specific learning needs of students with chronic health conditions., Conclusions: Results highlight areas for future research and intervention regarding teacher's preparedness for working with children with chronic health groups and opportunities to improve communication between neuropsychologists and teachers to ultimately improve access to educational supports and overall quality of life of students with chronic health conditions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Exposure to secondhand smoke (SHS) risks children's health. However, biomarkers are rarely used to study SHS exposure among children in low- and middle-income countries., Aims and Methods: We analyzed cross-sectional data collected between March and November 2022 for a cluster-randomized controlled trial investigating a Smoke-Free Intervention in 2769 children aged 9-15 in 74 schools (34 in Dhaka, Bangladesh, and 40 in Karachi, Pakistan). Children's saliva was tested for the concentration of cotinine-a highly sensitive and specific biomarker for SHS exposure. Based on their reports, children's homes were categorized as Nonsmoking Homes (NSH) when residents were nonsmokers; Smoke-free Homes (SFH) when residents and visitors smoked outdoors only; and Smoke-permitted Homes (SPH) when either residents or visitors smoked indoors. We compared cotinine concentrations across these home types and the two cities using a proportional odds model., Results: Overall, 95.7% of children (92% in Dhaka; and 99.4% in Karachi) had cotinine levels between 0.1 and 12 ng/mL, indicating SHS exposure. Median cotinine levels were higher in Karachi (0.58 ng/mL, IQR 0.37 to 0.93) than in Dhaka (0.27 ng/mL, IQR 0.16 to 0.49). Median cotinine concentration was also higher among children living in SPH than those in either NSH or SFH; with absolute differences of approximately 0.1-0.3 and 0.05 ng/mL, respectively., Conclusions: The level of SHS exposure in Dhaka and Karachi indicates widespread and unrestricted smoking. Smoking restrictions in households and enforcement of smoking bans are urgently needed., Implications: The high levels of SHS exposure in children living in SFH suggest parental behavior to hide their smoking and/or exposure in private vehicles or public spaces. It is important to advocate for SFH and cars to protect children from SHS exposure. However, these initiatives alone may not be enough. There is a need to enforce smoking bans in enclosed public places and transportation, as well as extend these bans to playgrounds, parks, fairgrounds, and other public spaces that children frequently visit. It is essential to complement smoking restrictions with tobacco cessation advice and support in these settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Introduction: The prevalence of daily secondhand smoke (SHS) exposure among pregnant nonsmoking women and children in Egypt is estimated to be about 50% and 55%, respectively. This study aimed to explore barriers to preventing SHS exposure among pregnant women/children and smoking in the home in Egypt., Aims and Methods: Six focus group discussions with pregnant women or mothers of children residing in urban-rural areas (n = 61) were conducted. Data were managed and analyzed using the Framework Method., Results: Sixty-one participants aged 18-49 were recruited. They reported being never smokers and SHS exposure for themselves and their children was mainly at home. Pregnant women or mothers had some general knowledge of the dangers of SHS, but their knowledge appeared incomplete. The most commonly reported barriers to preventing SHS exposure/adopting a smoke-free home or workplace were social acceptance of smoking and SHS exposure, masculinity and gender norms of accepting smoking among men as a normative behavior, fear among women of damaging a relationship with family or even divorce, women resigning themselves to SHS exposure, and doctors not being supportive of smoking cessation. The majority of interviewees' families were reported to allow smoking anywhere in the home. Others implemented some measures to prevent SHS; however, these tended to be inconsistently implemented., Conclusions: Changing the norm of accepting smoking among men as a normative behavior within Egyptian society and better enforcement of smoke-free policies, will help to protect pregnant women and children from SHS., Implications: This study suggests promising approaches to support the promotion of smoke-free homes and the prevention of SHS exposure among pregnant women and children in public places in Egypt. Better enforcement of smoke-free policies is needed. Healthcare professionals should support smoking cessation services in primary health centers. SHS policy, practice, and research should focus on husbands/fathers as they are the main source of SHS. There is a need for denormalization of SHS exposure in Egyptian society., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue., Methods: We specified the protocol of a two-arm cluster-randomized test-negative controlled trial (cRCT) and emulated it using a nationally representative test-negative/positive database of individuals reporting for febrile illness to any public hospital, general practitioner or polyclinic. We retrospectively built a cohort of individuals who reside in Wolbachia locations vs a comparator control group who do not reside in Wolbachia locations, using a nationally representative database of all individuals whom report for febrile illness and were tested for dengue at the Environmental Health Institute/hospital laboratories/commercial diagnostic laboratories, through general practitioner clinic, polyclinic or public/private hospital from epidemiological week (EW) 1 2019 to EW26 2022. We emulated a constrained randomization protocol used in cRCTs to balance dengue risk between intervention and control arms in the pre-intervention period. We used the inverse probability weighting approach to further balance the intervention and control groups using a battery of algorithmically selected sociodemographic, environmental and anthropogenic variables. Intention-to-treat analyses were conducted to estimate the risk reduction of dengue given Wolbachia exposure., Results: Intention-to-treat analyses revealed that, compared with controls, Wolbachia releases for 3, 6 and ≥12 months was associated to 47% (95% confidence interval: 25-69%), 44% (33-77%) and 61% (38-78%) protective efficacy against dengue, respectively. When exposed to ≥12 months of Wolbachia releases, protective efficacies ranged from 49% (13-72%) to 77% (60-94%) across years. The proportion of virologically confirmed dengue cases was lower overall in the intervention arm. Protective efficacies were found across all years, age and sex subgroups, with higher durations of Wolbachia exposure associated to greater risk reductions of dengue., Conclusion: Results demonstrated that Wolbachia-mediated sterility can strengthen dengue control in tropical cities, where dengue burden is the greatest., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

Background: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007 to 2022., Methods: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive dengue virus (DENV)-specific reverse-transcriptase polymerase chain reaction, positive NS-1 antigen and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high-titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 World Health Organization guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive., Results: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: <1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%) and business (11.0%). The most frequent regions of acquisition were South East Asia (50.4%), South Central Asia (14.9%), the Caribbean (10.9%) and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019., Conclusions: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pre-travel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long dengue) due to travel-related dengue., (Published by Oxford University Press on behalf of International Society of Travel Medicine 2024.)

Background: Systemic glucocorticosteroids (SGCs) are used in the short-term treatment of atopic dermatitis (AD), but are not recommended for long-term use because they are associated with severe side-effects., Objectives: This study aimed to characterize the utilization and potentially negative effects of SGC use for AD in German statutory health insurance (SHI) claims data., Methods: Cross-sectional and longitudinal analysis of a large nationwide SHI dataset. SGC drug prescriptions and incidences of predefined comorbidities after drug initiation that were known to be potentially harmful side-effects were analysed. SGC use was quantified by (-definition 1) the number of quarters with at least one SGC prescription and (definition 2) the defined daily doses (DDD). Comparisons were adjusted for age, sex and morbidity., Results: The AD prevalence was 4.07% in 2020 (4.12% women, 3.42% men). During this period 9.91% of people with AD were prescribed SGCs compared with 5.54% in people without AD (P < 0.01). Prescribing of SGCs was significantly higher in women (10.20% vs. 9.42% in men, P < 0.01) and in the elderly. AD and SGC prevalence varied regionally. In a 3-year follow-up period, 58% of people with AD receiving a SGC were prescribed SGCs in > one quarter and 15% in > six quarters. The odds of developing osteoporosis [odds ratio (OR) 3.90 -(definition 1) and 1.80 (definition 2)] and diabetes [OR 1.90 (definition 1) and 1.38 (definition 2)] were significantly higher in people with AD on SGCs, especially in the frequently prescribed group compared with the rarely prescribed group, regardless of quantified use., Conclusions: A considerable number of people with AD in Germany are prescribed long-term SGCs. The onset of medical conditions known to be harmful effects of steroids was significantly more frequent in those who were frequently prescribed SGCs, indicating the need for optimized healthcare., Competing Interests: Conflicts of interest K.H., T.K., K.M. and C.W. declare no conflicts of interest. M.A. has served as a consultant, lecturer or researcher and/or has received institutional research grants from companies manufacturing drugs for atopic dermatitis, including AbbVie, Almirall, Beiersdorf, Eli Lilly, Galderma, LEO, Novartis, Pfizer and Sanofi-Genzyme., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Very few studies have evaluated the global prevalence of pruritus., Objectives: To assess its prevalence according to age, sex, ethnicity and geographic region., Methods: An international cross-sectional study was conducted in 20 countries from January to April 2023. Participants were asked to complete a questionnaire on sociodemographics, and to confirm the presence or absence of a skin disease in the last 12 months and the presence or absence of pruritus in the last 7 days., Results: The studied sample included 50 552 individuals. The worldwide prevalence of pruritus was 39.8%. The age group ≥ 65 years had the highest prevalence (43.3%). The prevalence was 40.7% among women and 38.9% among men (P < 0.001). There was no significant difference between ethnicities (P = 0.14). Compared with North America (41.2%), the prevalence of pruritus was significantly lower in Europe (35.9%, P < 0.001), Australia (38.4%, P = 0.017), East Asia (40.2%, P = 0.04) and Latin America (36.5%, P < 0.001), and higher in Africa (45.7%, P = 0.007). No significant difference was found with the Middle East (40.2%, P = 0.36). The prevalence of pruritus in BRICS countries (40.3%) was significantly higher than that in developed countries (38.7%) (P < 10-3)., Conclusions: Out analysis is limited because there is no information about the severity or type (acute, chronic) of pruritus. The global prevalence of pruritus revealed age, sex and geographic region differences, with no ethnic differences., Competing Interests: Conflicts of interest M.S.A., N.P.C. and C.B. are employed by the Pierre Fabre Laboratory. G.Y., C.S., C.T., M.I., Y.B.H., B.H., M.A.R. and L.M. have no conflicts of interest in this study., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)