Background: As the global population ages, medical professionals are also aging. This study investigates the status of Korean anesthesiologists over the age of 60. Methods: Anesthesiologists aged 60 and older, residing and working in Korea, were invited to participate in this study via e-mail from February to March 2021 and by mail from June to August 2021. The survey consisted of 40 questions covering 10 topics, including health status, residence, work style, and economic status. Depending on the type of question, answers were ranked on a scale of 1, 2, and 3, with the most preferred response being selected. Results: A total of 63 responses were received, resulting in a response rate of 26.5%. Among the respondents, 56 were currently practicing as anesthesiologists and reported satisfaction with their clinical practice and life status. On average, they treated 24 patients per day without experiencing significant discomfort or inconvenience in their roles as senior physicians. Twenty-four respondents acknowledged physical discomfort related to aging, and nine expressed cautions regarding age-related changes. Fifty-two respondents indicated that reeducation for advanced medical practice as anesthesiologists was necessary. Conclusions Senior anesthesiologists in Korea are primarily working in secondary and tertiary hospitals and are satisfied with their current life status. A comprehensive evaluation of reeducation programs for advanced clinical practice and retirement strategies for senior anesthesiologists is needed to address the growing number of aging physicians in the workforce.

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease driven by autoantibodies against BP180 and BP230. While type 2 inflammation plays a key role, the precise immune cell alterations and transcriptomic changes remain unclear. Objective: To characterize immune cell composition and transcriptomic changes in BP patients using fluorescence-activated cell sorting (FACS)-based immunophenotyping and RNA sequencing. Methods: A case-control study was conducted on 10 newly diagnosed, treatment-naive BP patients and six healthy controls. Disease activity was assessed using the Bullous Pemphigoid Disease Area Index (BPDAI). Peripheral blood mononuclear cells were isolated for FACS analysis to determine immune cell subsets. RNA sequencing was performed to identify differentially expressed genes (DEGs) and enriched pathways. Statistical analyses included t-tests, Mann-Whitney U tests, and correlation analysis. Results: FACS analysis revealed a reduction in CD4 + T cells, T helper 2 (Th2), and B cells in BP patients (p<0.05), alongside an increase in M2a-like monocytes (p<0.001). RNA sequencing identified 262 DEGs, with secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237 being the most significantly upregulated. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) and SAM domain, SH3 domain, and nuclear localization signals 1 (SAMSN1) positively correlated with BPDAI (p<0.001). Gene ontology analysis highlighted enrichment in inflammatory responses and neutrophil degranulation pathways. Conclusion BP patients show distinct immune dysregulation, including decreased CD4 + T cells, Th2, and B cells, increased M2a-like monocytes, altered gene expression profiles, and correlations between PSTPIP2, SAMSN1 and disease activity. These findings provide insights into pathogenesis and potential therapeutic targets of BP.

Background: Circulating tumor DNA (ctDNA) profiling from peripheral blood allows relatively noninvasive monitoring of solid tumors; however, its utility post-surgery or chemotherapy in colorectal cancer remains underexplored. We evaluated the clinical implications of a ctDNA next-generation sequencing (NGS) panel post-surgery or chemotherapy in patients with colorectal cancer. Methods: We collected samples from 23 patients with colorectal cancer (17 men, median age 65 yrs) at baseline and post-surgery or chemotherapy at the National Cancer Center, Korea, between January 2021 and September 2023. ctDNA was analyzed using an NGS panel including 46 genes, and variant allele frequencies (VAFs) were determined. Followup samples were analyzed using the NGS panel or droplet digital PCR (ddPCR) when probes were available. Clinical status was compared with ctDNA results, and survival was analyzed using a time-dependent Cox model. Results: Mutations were identified in 13 out of 14 patients (92.8%) with stage II/III cancer and in all nine patients (100%) with stage IV cancer. Mutations were detected in KRAS (N = 15, 65%), APC (N = 8, 35%), TP53 (N = 7, 30%), PIK3CA (N = 5, 22%), and RET (N = 4, 17%). A 1% increase in KRAS and TP53 VAFs was associated with 48% and 32% increased mortality risk, respectively. Changes in VAF correlated well with clinical findings. Conclusions The detection of and an increase in KRAS and TP53 VAFs were associated with poor prognosis. ddPCR-based ctDNA monitoring results were comparable to those obtained with the NGS panel. ctDNA monitoring during treatment is clinically informative in managing colorectal cancer.

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: To investigate the clinicopathologic pattern of prostate cancer (PCa) in elderly patients compared with their younger counterparts with a prostate-specific antigen (PSA) level below the low-risk threshold (< 10 ng/mL), which is often a deciding factor for biopsy. Methods: A nationwide database of PCa at the time of biopsy from 2010 to 2020 was constructed from 39 hospitals. Patients were categorized into age groups of < 64 years, 65–69 years, 70–74 years, and ≥ 75 years considering guidelines that recommend PSA testing only for those aged 55–69 years during the study period, the average age of Korean PCa registrants of 70.3 years (2010–2020), and the average life expectancy of Korean males of 80.3 years (2020). Results: The mean ± standard deviation age was 70.3 ± 8.2 years, which was normally distributed (kurtosis = 0.095). Among 14,548 subjects, 54.1%, 39.5%, and 6.4% of them had high-risk disease, intermediate-risk disease, and low-risk disease, respectively. Based on three risk parameters, a marked increase in high-risk cancer was observed in the oldest age group (linear combination, P < 0.001). The same pattern was observed among patients with low-risk disease (PSA < 10 ng/mL), who were divided into PSA tiers as follows: 4–5 ng/mL (P < 0.001), 5–6 ng/mL (P < 0.001), 6–7 ng/mL (P < 0.001), 7–8 ng/mL (P < 0.001), 8–9 ng/mL (P = 0.009), and 9–10 ng/mL (P < 0.001). In all PSA tiers between 4 and 10 ng/mL, multivariate analysis demonstrated a significantly higher prevalence of high-risk cancer in the oldest age group than in the youngest age group. In the lowest tier (4–5 ng/mL), 35.2% of those aged over 75 years had high-risk PCa. Conclusion The older the patient, the more aggressive the PCa. Moreover, there was an increase in high-risk PCa in older males compared with younger males even with a PSA level below the low-risk threshold of 10 ng/mL, suggesting the need to strengthen cancer screening policies in the older population.

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.

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: To investigate the clinicopathologic pattern of prostate cancer (PCa) in elderly patients compared with their younger counterparts with a prostate-specific antigen (PSA) level below the low-risk threshold (< 10 ng/mL), which is often a deciding factor for biopsy. Methods: A nationwide database of PCa at the time of biopsy from 2010 to 2020 was constructed from 39 hospitals. Patients were categorized into age groups of < 64 years, 65–69 years, 70–74 years, and ≥ 75 years considering guidelines that recommend PSA testing only for those aged 55–69 years during the study period, the average age of Korean PCa registrants of 70.3 years (2010–2020), and the average life expectancy of Korean males of 80.3 years (2020). Results: The mean ± standard deviation age was 70.3 ± 8.2 years, which was normally distributed (kurtosis = 0.095). Among 14,548 subjects, 54.1%, 39.5%, and 6.4% of them had high-risk disease, intermediate-risk disease, and low-risk disease, respectively. Based on three risk parameters, a marked increase in high-risk cancer was observed in the oldest age group (linear combination, P < 0.001). The same pattern was observed among patients with low-risk disease (PSA < 10 ng/mL), who were divided into PSA tiers as follows: 4–5 ng/mL (P < 0.001), 5–6 ng/mL (P < 0.001), 6–7 ng/mL (P < 0.001), 7–8 ng/mL (P < 0.001), 8–9 ng/mL (P = 0.009), and 9–10 ng/mL (P < 0.001). In all PSA tiers between 4 and 10 ng/mL, multivariate analysis demonstrated a significantly higher prevalence of high-risk cancer in the oldest age group than in the youngest age group. In the lowest tier (4–5 ng/mL), 35.2% of those aged over 75 years had high-risk PCa. Conclusion The older the patient, the more aggressive the PCa. Moreover, there was an increase in high-risk PCa in older males compared with younger males even with a PSA level below the low-risk threshold of 10 ng/mL, suggesting the need to strengthen cancer screening policies in the older population.

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.

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.