Background: The Xpert MTB/RIF Ultra (Xpert Ultra) was introduced to enhance the sensitivity of tuberculosis detection, particularly in smear-negative cases, compared with its predecessor, Xpert MTB/RIF (Xpert). However, its performance in high-resource, intermediateburden settings remains unassessed. We prospectively compared the diagnostic accuracy of Xpert Ultra and Xpert for detecting Mycobacterium tuberculosis (MTB) and rifampin resistance in Korea. Methods: In total, 309 respiratory specimens were analyzed using both assays. We used two reference standards: mycobacterial culture and a composite reference standard based on clinical diagnosis and treatment decisions. Diagnostic performance, including sensitivity, specificity, and agreement between the two assays, was assessed. Spiking experiments using 13 MTB isolates with known rpoB mutations were performed to evaluate rifampin resistance detection. Results: Xpert Ultra showed increased, albeit not significantly, sensitivity (73.7% vs. 65.8% with culture; 63.8% vs. 53.2% with the composite reference standard) over Xpert. Its specificity was comparable to that of Xpert; however, a few false-positive results were observed among trace- and very low-positives. Among six culture-negative but Xpert Ultra-positive cases, two were clinically diagnosed as tuberculosis. Of the 13 rpoB mutant strains, Xpert correctly detected all mutations in the rifampin resistance-determining region, whereas Xpert Ultra yielded indeterminate results for Q432P and Q429H/L430P/H445Q. Conclusions Xpert Ultra tends to have increased sensitivity; however, it shows potential diagnostic ambiguity associated with trace- or very low-positive results. These findings highlight the importance of clinical correlation, particularly in culture-negative cases. Indeterminate results in certain rpoB mutations require cautious interpretation.

Background: An international reference measurement laboratory network for creatinine (Cr) is lacking; therefore, Korea developed an independent evaluation and certification system. The in vitro diagnostics (IVD) certification program, launched in 2017, formed part of a broader Cr standardization initiative intended to enhance accuracy at the manufacturing stage. Methods: The program was designed to evaluate analytical systems, including all reagent lots, calibrators, and instrument models, twice annually. Bias, imprecision, total error (TE), and linearity were evaluated based on established acceptance criteria. A post-certification process allows submission for a second challenge and validation of corrective actions. Results: Between 2017 and 2023, 489 analytical systems were evaluated. Average acceptance rates for bias, imprecision, TE, and linearity were 70.8%, 95.9%, 87.7%, and 87.8%, respectively. The lowest acceptance rate for bias evaluation was 8.7% for the kinetic Jaffe method without compensation in 2018. Over the 7-year period, the mean absolute percentage bias (absBias%), coefficient of variation (CV), and TE were 4.62%, 1.37%,and 7.29%, respectively. The highest absBias% (7.94%) was observed in the 0.0 ≤ Cr < 1.0target value range. Since 2019, a consistent reduction in absBias% has been observed. Conclusions This program is a pioneering response to the absence of a global certification program for Cr assays. It offers significant advantages, including comprehensive evaluations, fee-free participation, and a robust post-certification process. Continuous participation and improvement efforts by manufacturers have contributed to enhanced accuracy in Cr assays.

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: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

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: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Background: This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules. Methods: This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images. Results: Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity. Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Background: This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules. Methods: This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images. Results: Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity. Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.