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.

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: 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/Aims: Renal toxicity is a concern in patients with chronic hepatitis B taking nucleotide analogues, such as adefovir (ADV) and tenofovir disoproxil fumarate (TDF). We sought to determine the long-term renal effects of nucleotide analogue treatment versus entecavir (ETV) treatment. Methods: In this retrospective single-center study, we selected 87 patients who were treated with ADV and subsequently with TDF from June 2008 to December 2013. ETV-treated patients were matched by treatment duration. We analyzed the creatinine increase over 0.5 mg/dL, glomerular filtration rate (GFR) decrease over 25%, phosphorus decrease under 2.0 mg/dL, and dose reduction of antiviral agents. Results: The median follow-up period was 60.0 months for both groups. The incidence of liver cirrhosis was higher in the ADVTDF group than in the ETV group (32.2% vs 74.7%, p<0.01).Creatinine increased in both groups during follow-up, but the difference was not significant (5.7% and 2.3%, p=0.44). In addition, GFR decreased more often in the ADV-TDF group than in the ETV group (31.0% and 14.9%, p=0.01). After multivariate Cox regression analysis, ADV-TDF treatment was significantly associated with a GFR decrease over 25% (hazard ratio, 2.10; 95% confidence interval, 1.08 to 4.10; p=0.03) after adjusting for the baseline GFR decrease. Conclusions Patients taking nucleotide analogues had a significantly higher number of renal events than did those taking ETV. Clinicians should be aware of the development of renal toxicity in this patient population. Further long-term studies are warranted.

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.
Adult ; Animals ; Apoptosis ; Bone Marrow ; Cystitis ; Female ; Fibrosis ; Gene Expression ; Human Embryonic Stem Cells ; Humans ; Ketamine ; Mast Cells ; Mesenchymal Stromal Cells ; Multipotent Stem Cells ; Pelvic Pain ; Rats ; Urinary Bladder

OBJECTIVE: Epidural injection of hyaluronic acid may prevent adhesion formation after spine surgery, but the compounds used to stabilize hyaluronidase could interfere with its anti-adhesion effects. The present study was conducted as a clinical trial to evaluate the efficacy and safety of an experimental medical gel in preventing adhesion formation. METHODS: This study was designed as a multicenter, randomized, double-blind, and comparative controlled clinical trial with an observation period of 6 weeks. Subjects were randomly assigned into two groups: group A with sodium hyaluronate + 1,4-butanediol diglycidyl ether (BDDE) and group B with sodium hyaluronate + sodium carboxymethylcellulose (CMC). Visual analogue scale (VAS) of back and leg pain and the Oswestry disability index (ODI) and scar score ratings were assessed after surgery. RESULTS: Mean scar grade was 2.37+/-1.13 in group A and 2.75+/-0.97 in group B, a statistically significant difference (p=0.012). VAS of back and leg pain and ODI scores decreased significantly from baseline to 3 and 6 weeks postoperatively in both groups (p<0.001). However, VAS and ODI scores were not statistically different between groups A and B at baseline or at 3 and 6 weeks after operation (p>0.3). The number of adverse reactions related to the anti-adhesion gels was not statistically different (p=0.569), but subsequent analysis of nervous adverse reactions showed group B was superior with a statistically difference (p=0.027). CONCLUSION: Sodium hyaluronate with BDDE demonstrated similar anti-adhesion properties to sodium hyaluronate with CMC. But, care should be used to nervous adverse reactions by using sodium hyaluronate with BDDE.
Carboxymethylcellulose Sodium* ; Cicatrix ; Diskectomy* ; Ether* ; Gels ; Hyaluronic Acid* ; Hyaluronoglucosaminidase ; Injections, Epidural ; Leg ; Spine

PURPOSE: To report the occurrence of central vein occlusion in an Eales disease patient. CASE SUMMARY: A 23-year-old man presented with decreased left eye visual acuity and was diagnosed with bilateral Eales disease after ophthalmic evaluations. The patient received laser photocoagulation and visual acuity in his left eye improved 1 month after treatment. He was followed up regularly for 3 years and had no specific eye problems. Subsequently, the patient visited our clinic because of visual disturbance in his right eye. The patient's visual acuity was 0.6 in his right eye, and 1.0 in his left eye. On right eye fundus examination, there were multiple flame shape hemorrhages and retinal vascular tortuosity was observed. Arteriovenous transit time was extended on fluorescein angiography. Therefore, the patient was diagnosed with central retinal vein occlusion and underwent an internal medical examination to reveal a possible systemic cause of the central retinal vein occlusion; however, there were no systemic problems. Macular edema was observed on optical coherence tomography and the patient received an intravitreal bevacizumab injection. Six months after treatment, the right eye visual acuity and macular edema improved. CONCLUSIONS: Reports of branched retinal vein occlusion on the peripheral retina are common in Eales disease patients. However, the authors experienced and report a case of central retinal vein occlusion occurring in Eales disease.
Antibodies, Monoclonal, Humanized ; Eye ; Fluorescein Angiography ; Hemorrhage ; Humans ; Light Coagulation ; Macular Edema ; Neovascularization, Pathologic ; Retina ; Retinal Vasculitis ; Retinal Vein ; Retinal Vein Occlusion ; Retinaldehyde ; Tomography, Optical Coherence ; Veins ; Visual Acuity ; Young Adult ; Bevacizumab

PURPOSE: To report a case of bilateral optic neuropathy related with idiopathic hypertropic pachymeningitis. CASE SUMMARY: A 66-year old woman presented with acute visual loss that developed 6 days previously in the right eye and 3 days prior in the left eye. During the initial evaluation, her visual acuity was light perception in the right eye and counting fingers at 30 cm in the left eye. A relative afferent papillary defect (RAPD) was noted in the patient's right eye. On brain MRI, the duramater was thickened and enhanced by contrast. The erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) level were increased and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) as positive. Other neurological and medical abnormalities were not found. Under the suspicion of bilateral optic neuropathy due to idiopathic hypertrophic pachymeningitis, the patient was treated with methylprednisolone pulse therapy. Two days after the treatment, the visual acuity was hand movements at 20 cm in the right eye and 0.6 in the left eye. Three months after the treatment, the visual acuity was counting fingers at 20 cm in the right eye, and 0.7 in the left eye. The right eye showed optic disc pallor and diffuse retinal nerve fiber layer (RNFL) defect. The left eye showed a suspicious RNFL defect, and was otherwise normal. CONCLUSIONS: The authors report a rare case of optic neuropathy related with idiopathic hypertrophic pachymeningitis. Idiopathic hypertrophic pachymeningitis should be considered as one of the various causes of optic neuropathy.
Blood Sedimentation ; Brain ; C-Reactive Protein ; Cytoplasm ; Eye ; Female ; Fingers ; Hand ; Humans ; Light ; Meningitis ; Methylprednisolone ; Nerve Fibers ; Optic Nerve Diseases ; Pallor ; Patient Rights ; Retinaldehyde ; Visual Acuity