Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disorder caused by a biallelic expansion of pentanucleotide repeats in the RFC1 gene. Previous studies have reported up to 22% of patients with late-onset ataxia harbor this pathogenic repeat expansion. Despite its relatively high prevalence, CANVAS is often underdiagnosed because the disease is not well recognized and genetic testing is not performed in clinical practice. Here, we present a patient with characteristic clinical features, confirmed by genetic testing.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disorder caused by a biallelic expansion of pentanucleotide repeats in the RFC1 gene. Previous studies have reported up to 22% of patients with late-onset ataxia harbor this pathogenic repeat expansion. Despite its relatively high prevalence, CANVAS is often underdiagnosed because the disease is not well recognized and genetic testing is not performed in clinical practice. Here, we present a patient with characteristic clinical features, confirmed by genetic testing.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disorder caused by a biallelic expansion of pentanucleotide repeats in the RFC1 gene. Previous studies have reported up to 22% of patients with late-onset ataxia harbor this pathogenic repeat expansion. Despite its relatively high prevalence, CANVAS is often underdiagnosed because the disease is not well recognized and genetic testing is not performed in clinical practice. Here, we present a patient with characteristic clinical features, confirmed by genetic testing.

CD8+ T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8+ T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8+ T cells have been found to express activating or inhibitory NK receptors. CD8+ T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8+ T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8+ T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.

Objective: To develop and evaluate a deep learning-based artificial intelligence (AI) model for detecting skull fractures on plain radiographs in children. Materials and Methods: This retrospective multi-center study consisted of a development dataset acquired from two hospitals (n = 149 and 264) and an external test set (n = 95) from a third hospital. Datasets included children with head trauma who underwent both skull radiography and cranial computed tomography (CT). The development dataset was split into training, tuning, and internal test sets in a ratio of 7:1:2. The reference standard for skull fracture was cranial CT. Two radiology residents, a pediatric radiologist, and two emergency physicians participated in a two-session observer study on an external test set with and without AI assistance. We obtained the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity along with their 95% confidence intervals (CIs). Results: The AI model showed an AUROC of 0.922 (95% CI, 0.842–0.969) in the internal test set and 0.870 (95% CI, 0.785–0.930) in the external test set. The model had a sensitivity of 81.1% (95% CI, 64.8%–92.0%) and specificity of 91.3% (95% CI, 79.2%–97.6%) for the internal test set and 78.9% (95% CI, 54.4%–93.9%) and 88.2% (95% CI, 78.7%– 94.4%), respectively, for the external test set. With the model’s assistance, significant AUROC improvement was observed in radiology residents (pooled results) and emergency physicians (pooled results) with the difference from reading without AI assistance of 0.094 (95% CI, 0.020–0.168; p = 0.012) and 0.069 (95% CI, 0.002–0.136; p = 0.043), respectively, but not in the pediatric radiologist with the difference of 0.008 (95% CI, -0.074–0.090; p = 0.850). Conclusion A deep learning-based AI model improved the performance of inexperienced radiologists and emergency physicians in diagnosing pediatric skull fractures on plain radiographs.