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/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Purpose: To evaluate the relationship between distal fusion level in correction and fusion surgery for adolescent idiopathic scoliosis (AIS) and radiologic changes in the sacroiliac (SI) joint. Materials and Methods: This retrospective cohort study evaluated patients who underwent correction and fusion for AIS between 2005 and 2017 with at least 5 years of follow-up. We categorized patients into two groups: Group 1 (distal fusion above L2, 74 patients) and Group 2 (distal fusion at L3 and below, 52 patients). Radiologic parameters and SI joint changes were evaluated on plain radiographs obtained from preoperative to 5 years postoperatively. We also investigated other risk factors for SI joint change. Results: Analysis of demographic factors revealed no significant difference between the two groups. There was a significant difference in the incidence of SI joint change between Group 1 (5 patients, 6.75%) and Group 2 (18 patients, 34.61%), with Group 2 showing a faster increase in incidence according to the Kaplan-Meier method (p<0.0001). Preoperative lumbar lordosis (LL) and ΔLL had a significant relationship with SI joint changes [preoperative LL, hazard ratio (HR)=0.77, 95% confidence interval (CI)=0.64– 0.93, p=0.008; ΔLL, HR=0.79, 95% CI=0.67–0.95, p=0.01). Conclusion After AIS surgery, patients who had fusion to the lower lumbar vertebrae (L3 or L4) experienced a higher incidence and faster progression of degenerative changes in the SI joint. Low preoperative LL and inadequate correction of LL during the operation were also risk factors for SI joint degeneration.

Background/Aims: Despite of the coronavirus disease 2019 (COVID-19) pandemic, there is little data regarding its impact on colorectal cancer (CRC)-related clinical practice. This study aimed to assess the changes in its impact during the COVID-19 pandemic. Methods: This was a retrospective national population-based study using the Health Insurance Review and Assessment database from January 2019 to December 2021. The number of patients in 2020 and 2021 was compared with those in 2019 for the diagnostic and therapeutic colonoscopy, CRC-related operation, and any treatment for CRC. Results: The annual number of patients undergoing diagnostic colonoscopies decreased by 6.9% in 2020 but increased 8.1% in 2021, compared to those in 2019; number of patients undergoing therapeutic colonoscopies increased by 6.0% and 37.7% in 2020 and 2021, respectively; number of patients operated for CRC decreased by 4.2% in 2020 and increased by 2.3% in 2021. The number of patients treated for CRC decreased by 2.8% in 2020 and increased by 4.4% in 2021. Diagnostic and therapeutic colonoscopies and any CRC-related treatment decreased by 43.8%, 37.5%, and 11.3% in March 2020, during the first surge of COVID-19, but increased by 26.0%, 58.1%, and 9.5% in June 2021, respectively. CRC-related operations decreased by 24.1% in April 2020 and increased by 12.6% in August 2021. Conclusions Negative impact of the COVID-19 pandemic on clinical practices related to CRC completely recovered within second year. It could be considered for the development of an optimal strategy on CRC management in response to the pandemic-driven crisis.

Background: To identify the optimal surgical technique for single-level anterior cervical discectomy and fusion (ACDF), this study compared surgical outcomes and incidence of adjacent segment degeneration (ASD) in patients undergoing single-level ACDF using cage alone single-level fusion and plate fixation techniques. Methods: This single-center retrospective study (2003–2018) included patients who underwent single-level ACDF with either plate fixation (PLATE) or cage (CAGE) alone. The radiologic and clinical outcomes between the 2 surgical groups were compared over a 4-year follow-up period. Outcomes of interest included parameters related to range of motion, sagittal alignment, as well as fusion, subsidence, and ASD rates. Clinical outcomes were evaluated using the Neck Disability Index (NDI) and visual analog scale (VAS) for pain. Dysphagia and hoarseness rates were estimated based on medical records. Results: Forty-seven patients were included (n=17 in CAGE group). In the CAGE group, 94.1% of the patients had Bridwell grade 1 or 2, compared to 83.3% in the PLATE group (p = 0.396). Subsidence occurred in 12.5% and 3.6% of the CAGE and PLATE cases, respectively (p = 0.543). Segmental kyphosis progressed in the CAGE group compared to the PLATE group at 12, 24, and 48 months (p < 0.001). Radiographic ASD was observed in 41.2% and 30.0% of patients in the CAGE and PLATE groups, respectively, with a higher incidence in the upper segments for both groups. Preoperative NDI scores were similar between the groups; however, postoperatively, the CAGE group had significantly lower NDI scores (3.50 ± 2.74 vs. 8.00 ± 5.81) at 4 years (p = 0.020). Neck pain VAS scores also showed significant improvement in the CAGE group (2.33 ± 2.94) compared with that in the PLATE group (3.07 ± 2.31) at 4 years (p = 0.045). Both groups showed comparable arm pain VAS scores at 2 and 4 years postoperatively. Postoperative dysphagia occurred in 1 patient in the PLATE group, resolving almost completely by 1 year. Conclusions Single-level ACDF using a cage alone technique demonstrated favorable radiologic and clinical outcomes overall compared to plate-augmented ACDF. However, plate augmentation is recommended for patients with severe cervical kyphosis or those at high risk of subsidence.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group. Methods: This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated. Results: Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures. Conclusion In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

Background: Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations. Methods: This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID. Results: Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001). Conclusion Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.