Background: Acute deterioration of patients in general wards often leads to major adverse events (MAEs), including unplanned intensive care unit transfers, cardiac arrest, or death. Traditional early warning scores (EWSs) have shown limited predictive accuracy, with frequent false positives. We conducted a prospective observational external validation study of an artificial intelligence (AI)-based EWS, the VitalCare - Major Adverse Event Score (VC-MAES), at a tertiary medical center in the Republic of Korea. Methods: Adult patients from general wards, including internal medicine (IM) and obstetrics and gynecology (OBGYN)—the latter were rarely investigated in prior AI-based EWS studies—were included. The VC-MAES predictions were compared with National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) predictions using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and logistic regression for baseline EWS values. False-positives per true positive (FPpTP) were assessed based on the power threshold. Results: Of 6,039 encounters, 217 (3.6%) had MAEs (IM: 9.5%, OBGYN: 0.26%). Six hours prior to MAEs, the VC-MAES achieved an AUROC of 0.918 and an AUPRC of 0.352, including the OBGYN subgroup (AUROC, 0.964; AUPRC, 0.388), outperforming the NEWS (0.797 and 0.124) and MEWS (0.722 and 0.079). The FPpTP was reduced by up to 71%. Baseline VC-MAES was strongly associated with MAEs (P<0.001). Conclusions The VC-MAES significantly outperformed traditional EWSs in predicting adverse events in general ward patients. The robust performance and lower FPpTP suggest that broader adoption of the VC-MAES may improve clinical efficiency and resource allocation in general wards.

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

Purpose: This study was conducted to update the practice guidelines for intravenous infusion therapy published in 2017, focusing on the most recent evidence for peripheral intravenous infusion therapy. Methods: The guideline update was conducted using the 22-step methodology. Results: The updated guidelines consist of 17 domains and 235 recommendations (including 284 sub-recommendations). The domains are as follows: general instructions (5 items), peripheral catheter selection (7), catheter insertion site selection (11), management during peripheral catheter insertion (10), post-insertion management (30), perfusion and locking (17), blood sampling via peripheral catheters(6), exchange and removal of peripheral catheters (6), infusion set management (14), add-on devices (32), complications (25), chemotherapy infusions (10), PCA infusions (7), parenteral nutrition (20), transfusion therapy (23), education (5), and documentation and reporting (7). The evidence levels for these recommendations are as follows: 27(9.5%) at level I, 3 (1.1%) at level I A/P, 118 (41.5%) at level II, and 136 (47.9%) at level III.Recommendation grades are categorized as follows: 30 (10.6%) at level A, 118 (41.5%) at level B, and 136(47.9%) at level C. Of these, 73 (25.7%) recommendations were newly developed, 49 (17.3%) underwent major revisions, and 147 (51.7%) underwent minor revisions. Conclusion The updated practice guideline, based on the latest evidence, is anticipated to enhance nursing practice related to peripheral intravenous infusion therapy.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP. Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns. Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, USH2A was the most common causative gene (14/60, 23.3%), followed by EYS (13/60, 21.7%) and RP1 (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in CHM, and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and RDH12 and RPGRIP1 were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti’s crystalline dystrophy, with CYP4V2 identified as the causative gene. In another patient (1/60, 1.7%), ABCA4 variants were detected with clinical findings suggestive of cone-rod dystrophy. Conclusion This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.

Purpose: This study was conducted to update the practice guidelines for intravenous infusion therapy published in 2017, focusing on the most recent evidence for peripheral intravenous infusion therapy. Methods: The guideline update was conducted using the 22-step methodology. Results: The updated guidelines consist of 17 domains and 235 recommendations (including 284 sub-recommendations). The domains are as follows: general instructions (5 items), peripheral catheter selection (7), catheter insertion site selection (11), management during peripheral catheter insertion (10), post-insertion management (30), perfusion and locking (17), blood sampling via peripheral catheters(6), exchange and removal of peripheral catheters (6), infusion set management (14), add-on devices (32), complications (25), chemotherapy infusions (10), PCA infusions (7), parenteral nutrition (20), transfusion therapy (23), education (5), and documentation and reporting (7). The evidence levels for these recommendations are as follows: 27(9.5%) at level I, 3 (1.1%) at level I A/P, 118 (41.5%) at level II, and 136 (47.9%) at level III.Recommendation grades are categorized as follows: 30 (10.6%) at level A, 118 (41.5%) at level B, and 136(47.9%) at level C. Of these, 73 (25.7%) recommendations were newly developed, 49 (17.3%) underwent major revisions, and 147 (51.7%) underwent minor revisions. Conclusion The updated practice guideline, based on the latest evidence, is anticipated to enhance nursing practice related to peripheral intravenous infusion therapy.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP. Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns. Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, USH2A was the most common causative gene (14/60, 23.3%), followed by EYS (13/60, 21.7%) and RP1 (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in CHM, and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and RDH12 and RPGRIP1 were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti’s crystalline dystrophy, with CYP4V2 identified as the causative gene. In another patient (1/60, 1.7%), ABCA4 variants were detected with clinical findings suggestive of cone-rod dystrophy. Conclusion This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.

Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.

Background: Postoperative pain management is challenging in patients with oral cancer, especially those undergoing reconstructive surgery. Patient-controlled analgesia (PCA) is widely used, and fentanyl (FTN) concentration adjustments may improve pain control. This study aimed to evaluate the effects of FTN PCA concentration and reconstructive surgery on postoperative pain in patients with oral cancer. Methods: This retrospective observational study analyzed 140 patients with oral cancer who underwent surgery under general anesthesia. Patients were categorized based on FTN PCA dosage (FTN 700 mcg and ketorolac 150 mg vs. FTN 1400 mcg and ketorolac 150 mg). Pain was assessed using the visual analog scale (VAS) at multiple time points postoperatively (0, 12, 24, 36, 48, 60, and 72 h). PCA usage patterns, including demand count, delivery count, and delivery/demand ratios, were compared across subgroups. Missing data were imputed using linear interpolation. Results: PCA usage and pain control were evaluated between the FTN 700 mcg (N = 40) and 1400 mcg (N = 100) groups, stratified by reconstruction status. Demographic characteristics showed no significant difference.In the reconstructive surgery subgroup, patients in the FTN 1400 mcg group showed lower PCA refill counts (1.45 ± 0.69 vs. 1.61 ± 0.58) and fewer delivery counts (17.1 ± 21.3 vs. 25.1 ± 28.5) compared to those in the FTN 700 mcg group, achieving similar or superior pain control with fewer interventions. Similarly, patients without reconstructive surgery in the FTN 1400 mcg group demonstrated lower PCA refill counts, shorter PCA usage times, and fewer delivery counts. VAS scores decreased consistently over time across all groups but remained higher in the reconstruction groups. Logistic regression analysis revealed that patients with reconstructive surgery in the FTN 1400 mcg group were more likely to achieve a VAS score of ≤ 3.0 at 72 h postoperatively (P = 0.022). These findings indicate FTN 1400 mcg’s superiority in managing postoperative pain. Conclusion Comparing FTN PCA dosages, 1400 mcg demonstrated superior pain control to 700 mcg in patients undergoing oral cancer surgery, particularly those who underwent reconstructive surgery. This finding underscores the importance of optimizing FTN dosages to enhance postoperative pain management, reduce PCA-related demands, and achieve better patient outcomes.