Han Seong Kim

A V-set Ig domain-containing 4 (VSIG4), known for complement receptor, has been involved in the profibrotic pathway in chronic kidney disease including diabetic kidney disease. However, its relationship with renal aging has not been examined longitudinally. This study aims to elucidate the role of VSIG4 in the aging process of kidneys, particularly in diabetes. Male db/m and db/db mice were followed from 8 to 38 weeks. Urinary albumin and VSIG4 levels were assessed using 6 h timed urine collections and ELISA. The intrarenal expression of VSIG4 and klotho were analyzed through immunohistochemical stating. In db/db mice, urinary albumin levels were significantly higher from 8 weeks onward compared to db/m mice. These levels increased progressively with age, peaking at 38 weeks. Similarly, urinary VSIG4 levels showed a significant initial increase in db/db mice, followed by a consistent rise with age. Interestingly, both urinary albumin and VSIG4 levels in db/m mice showed a sudden surge at 38 weeks. Urinary VSIG4 levels showed a strong correlation with urinary albumin levels (r = 0.867, p < 0.001). Intrarenal VSIG4 expression increased with age, appearing earlier and more predominantly in diabetic mice, and was predominantly localized to distal tubular segments, while klotho expression progressively declined. These findings indicate that VSIG4 expression changes with renal aging and that diabetes is associated with earlier activation of this process. Urinary VSIG4 reflects aging-related kidney changes rather than diabetic injury alone.

Background: We previously developed a benchmarking strategy using mixtures of homozygote and heterozygote DNAs as reference standards to simultaneously assess sensitivity and false positive (FP) error rates in targeted next-generation sequencing (T-NGS) and whole-exome sequencing (WES), revealing substantial variability across commercial platforms. However, optimal analytic conditions for clinical application remain undefined. Methods: We systematically evaluated multiple sequencing kits and bioinformatics pipelines across various variant allele fraction (VAF) thresholds to identify conditions that maximize both sensitivity and specificity. Recurrent error-prone alleles were defined and filtered to enhance specificity. Results: Optimal performance was achieved using the DRAGEN pipeline with recurrent FP allele filtering. For T-NGS, a 1% VAF cutoff yielded a 95% detection threshold of 2.99% and 1.21 FPs per megabase (FP/Mb); for WES, a 2% cutoff yielded a 95% threshold of 5.02% and 1.15 FP/Mb. These settings improved sensitivity >3-fold and reduced FP rates >96% versus suboptimal pipelines. Notably, VAF thresholds flattened sensitivity differences across platforms, obscuring key performance disparities—challenging assumptions that T-NGS is inherently more sensitive than WES. In-house and conventional pipelines undercalled up to 10% of true variants. Restricting reporting of 1–4% VAF variants to ∼1,000 predefined actionable sites enabled recovery of clinically relevant mutations while reducing FP risk >99%. Conclusions: This study provides a quantitative framework for optimizing NGS performance. Our findings support actionable strategies to improve diagnostic accuracy in clinical genomics through tailored pipeline selection, VAF thresholding, and artifact filtering.

Background: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Methods: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19–related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Results: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. Conclusion: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19’s impact on GN.

Radiation therapy results in radiation-induced vasculopathy, characterized by alterations in the vascular architecture stemming from radiation exposure. The exact molecular pathways and associated pathologies of this condition have yet to be comprehensively understood. This study aimed to identify specific markers’ roles in cerebral vascular endothelial injury pathogenesis after radiosurgery and explore their unique expression patterns in diverse pathologies post-stereotactic radiosurgery. A retrospective cohort study was conducted to assess the expression profiles of endothelial markers via immunohistochemical analysis in 25 adult patients (13 males and 12 females) who had undergone neurosurgical resection for various central nervous system pathologies following stereotactic radiosurgery or radiotherapy from 2001 to 2015. Our findings revealed strong immunohistochemical expression of ICAM-1 and E-selectin across various disease states, while MMP-9, PAI-1, and eNOS exhibited moderate expression levels. In contrast, VCAM-1 and P-Selectin had the weakest expression across all groups. Notably, while individual markers showed significant variations in expression levels when comparing different diseases (P < .001), no substantial differences were found in the overall immunohistochemical expression patterns across the 5 distinct pathologies studied (P = .407, via 2-way ANOVA). Despite the varied long-term effects of radiotherapy on the vascular endothelium, a common thread of inflammation runs through the pathology of these conditions. The distinct patterns of marker expression identified in our study suggest that different markers play unique roles in the development of radiation-induced vasculopathy. These findings offer insights that could lead to the development of novel preventive strategies and treatments.

We report a case of primary bilateral tuberculous otitis media in a patient who underwent kidney transplantation. This case presents unusual clinical features and histopathology from those of classical tuberculous otitis media. A 75-year-old woman presented at the clinic with purulent ear discharge and hearing loss in both ears. She had undergone kidney transplantation 6 years prior and had been taking immunosuppressant medications. Otoscopic examination and imaging studies suggested acute otitis media, which was irresponsive to antibiotics. The patient underwent surgery to eradicate the disease, and histopathologic examination revealed multifocal granulomas with Langhans giant cells without caseous changes. Ziehl–Neelsen staining and polymerase chain reaction confirmed the diagnosis of tuberculous otitis media. While tuberculous otitis media is a very rare manifestation of extrapulmonary tuberculosis, this case is more noteworthy in that it occurred as a primary infection rather than as a reactivation of a prior infection. In addition, it did not show the classical triad of clinical manifestations, which occurred bilaterally, and its histopathology was different from those of classical tuberculous otitis media. This case presents a new clinical variation in tuberculous otitis media. Cite this article as: Lee JM, Jung K-W, Kim K-W, Lee G, Kim HS. Primary bilateral tuberculous otitis media after kidney transplantation: A case report. J Int Adv Otol. 2023;19(5):440-443.

Oh Jun Yu, Jin Soo Suh, Han Sung Kim, Jun Young Choi. JKFAS 2023;27:75-8. https://doi.org/10.14193/jkfas.2023.27.2.75

V-set Ig domain-containing 4 (VSIG4) regulates an inflammatory response and is involved in various diseases. However, the role of VSIG4 in kidney diseases is still unclear. Here, we investigated VSIG4 expression in unilateral ureteral obstruction (UUO), doxorubicin-induced kidney injury mouse, and doxorubicin-induced podocyte injury models. The levels of urinary VSIG4 protein significantly increased in the UUO mice compared with that in the control. The expression of VSIG4 mRNA and protein in the UUO mice was significantly upregulated compared with that in the control. In the doxorubicin-induced kidney injury model, the levels of urinary albumin and VSIG4 for 24 h were significantly higher than those in the control mice. Notably, a significant correlation was observed between urinary levels of VSIG4 and albumin (r = 0.912, p < 0.001). Intrarenal VSIG4 mRNA and protein expression were also significantly higher in the doxorubicin-induced mice than in the control. In cultured podocytes, VSIG4 mRNA and protein expressions were significantly higher in the doxorubicin-treated groups (1.0 and 3.0 μg/mL) than in the controls at 12 and 24 h. In conclusion, VSIG4 expression was upregulated in the UUO and doxorubicin-induced kidney injury models. VSIG4 may be involved in pathogenesis and disease progression in chronic kidney disease models.

Fibrosis is the final common finding in patients with advanced diabetic kidney disease. V-set Ig domain containing 4 (VSIG4) is related to fibrosis in several diseases. It also contributes to fibrosis under high-glucose conditions in renal tubule cells. To determine the role of VSIG4 in type 2 diabetes, we examined VSIG4 expression in a type 2 diabetic animal model and podocyte. Urinary excretion of albumin and VSIG4 was significantly higher in db/db mice than in the control group. Urine VSIGs levels for 6 h were about three-fold higher in db/db mice than in db/m mice at 20 weeks of age: 55.2 ± 37.8 vs. 153.1 ± 74.3 ng, p = 0.04. Furthermore, urinary VSIG4 levels were significantly correlated with urinary albumin levels (r = 0.77, p < 0.01). Intrarenal VSIG4 mRNA expression was significantly higher in db/db mice than in control mice (1.00 ± 0.35 vs. 1.69 ± 0.77, p = 0.04). Further, VSIG4 expression was almost twice as high in db/db mice at 20 weeks of age. Intrarenal VSIG immunoreactivity in db/db mice was also significantly higher than that in control mice. In cultured podocytes, both high glucose and angiotensin II significantly upregulated the expression of VSIG4 mRNA and protein. In conclusion, VSIG4 was upregulated in an animal model of type 2 diabetes and was related to albuminuria and pro-fibrotic markers. Considering these relationships, VSIG4 may be an important mediator of diabetic nephropathy progression.

Kim BC, et al. J Korean Med Sci. 2022 Jun;37(26):e204. https://doi.org/10.3346/jkms.2022.37.e204

Esophageal cancer is one of the lethal malignant tumors because it is often diagnosed in the advanced stage with lymph node or distant metastasis. The recurrence rate of esophageal cancer is known to be about 40% to 50% even in the patients who underwent curative esophageal resection. Most frequent sites of metastases are known to be the liver. Furthermore, other distant metastases also could be developed in lung, bone, brain, kidney, adrenal, abdominal cavity, and skin. However, ampulla of Vater (AoV) metastasis rarely occurs from esophageal cancer. Therefore, we report herein a case of AoV metastasis from squamous cell carcinoma of the esophagus. Copyright (C) 2021, Society of Gastrointestinal Intervention.