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

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

Background and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions The study’s results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270).Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.

Objectives: . The recent expansion of eligibility for cochlear implantation (CI) by the U.S. Food and Drug Administration (FDA) to include infants as young as 9 months has reignited debates concerning the clinically appropriate cut-off age for pediatric CI. Our study compared the early postoperative trajectories of receptive and expressive language development in children who received CI before 9 months of age with those who received it between 9 and 12 months. This study involved a unique pediatric cohort with documented etiology, where the timing of CI was based on objective criteria and efforts were made to minimize the influence of parental socioeconomic status. Methods: . A retrospective review of 98 pediatric implantees recruited at a tertiary referral center was conducted. The timing of CI was based on auditory and language criteria focused on the extent of delay corresponding to the bottom 1st percentile of language development among age-matched controls, with patients categorized into very early (CI at <9 months), early (CI at 9–12 months) and delayed (CI at 12–18 months) CI groups. Postoperative receptive/expressive language development was assessed using the Sequenced Language Scale for Infants receptive and expressive standardized scores and percentiles. Results: . Only the very early CI group showed significant improvements in receptive language starting at 3 months post-CI, aligning with normal-hearing peers by 9 months and maintaining this level until age 2 years. During this period (<2 years), all improvements were more pronounced in receptive language than in expressive language. Conclusion . CI before 9 months of age significantly improved receptive language development compared to later CI, with improvements sustained at least up to the age of 2. This study supports the consideration of earlier CI, beyond pediatric Food and Drug Administration labeling criteria (>9 months), in children with profound deafness who have a clear deafness etiology and language development delays (<1st percentile).

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.