Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA). However, clinical evidence for its use in AA is limited. Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA. Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12). Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug’s effects on inflammatory pathways. Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively). Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common. In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege. Conclusion Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies. Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.

Background: A novel botulinum toxin type A (Protoxin; Protox Inc.) has been developed. Objective: To evaluate the efficacy and safety of the newly developed Protoxin compared to the approved drug onabotulinumtoxinA (OBoNT) in moderate to severe glabellar lines. Methods: Adults with a glabellar line Facial Wrinkle Scale (FWS) score of 2 (moderate) or 3 (severe) were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive either Protoxin or OBoNT. A total of 20 units of botulinum toxin was injected at five sites in the glabellar region (4 units at each site). FWS scores were assessed at baseline and at weeks 4, 8, 12, and 16 post-injection. The primary endpoint was the proportion of subjects at week 4 who had a reduction of 2 or more points in FWS and a final score of 0 (none) or 1 (mild). Results: A total of 274 subjects were randomized, of whom 78.1% were female. At week 4 post-treatment, the improvement rate of glabellar lines was 62.22% in the Protoxin group and 62.96% in the OBoNT group. The lower limit of the two-sided 95% confidence interval (−12.24%) exceeded the −15% margin, confirming the non-inferiority of the new drug. Safety profiles were comparable between the two groups. Conclusion Protoxin demonstrated efficacy and safety profiles comparable to those of OBoNT in the treatment of moderate to severe glabellar lines.

BACKGROUND/OBJECTIVES: Dietary supplement use is common among breast cancer survivors, but studies on Asian populations remain limited. This study investigated dietary supplement use among Korean breast cancer survivors, distinguishing between vitamin/ mineral (VM) and non-vitaminon-mineral (NVNM) supplements. SUBJECTS/METHODS: This cross-sectional study included 1,136 stage I–III breast cancer survivors from 12 Korean hospitals, who survived more than 6 mon post-surgery. The participants completed a questionnaire on post-diagnostic dietary supplement use. Stepwise logistic regression was applied, calculating odds ratios (ORs) and 95% confidence intervals (CIs) to identify the demographic and clinical factors associated with VM and NVNM use. RESULTS: Seventy percent of survivors reported supplement use, with 25% using a single product. The most common VM supplements were multivitamins/minerals, vitamin D, and vitamin C, while the most common NVNM supplements included omega-3 fatty acids, probiotics, and ginseng. Survivors with higher education and greater physical activity were more likely to use VM supplements (ORs [95% CIs], 2.74 [1.76–4.25] for college graduates or above vs. middle school or below; 1.38 [1.02–1.88] for the most active group vs. the least active group). NVNM use was associated with higher education, greater physical activity levels, and a history of smoking (ORs [95% CIs], 2.29 [1.46–3.58] for college graduates or above vs. middle school or below; 1.52 [1.13–2.06] for the most active group vs. the least active group; 2.00 [1.23–3.25] for ever smokers vs. never smokers). Survivors who had undergone chemotherapy were also more likely to use NVNM supplements than those who had not (OR [95% CI], 1.37 [1.02–1.84]). CONCLUSION Seventy percent of Korean breast cancer survivors used dietary supplements in this study. VM use was associated with higher education and physical activity, while higher NVNM use was associated with higher education, greater physical activity, a history of smoking, and chemotherapy.

Background: The existing clinical subtype classification of basal cell carcinoma (BCC) does not adequately reflect tumor invasiveness or its relationship with histologic patterns. Objective: To suggest the upgrading classification of clinical subtype of BCC and evaluate its correlation with histologic subtypes and tumor invasiveness. Methods: This study enrolled 422 patients with 425 biopsy-proven BCC lesions. All of the patients were treated by Mohs micrographic surgery (MMS) at our hospital from January 2018 to October 2021. All BCCs were categorized according to upgrading clinical subtype classification we suggest: Basic subtypes (including nodular [N], papular [P], superficial-elevated [SE]/-flat [SF]/-depressed [SD] and infiltrative [I] subtype) and combined subtype. We conducted a retrospective study through medical record, clinical photographs, pathologic slide and MMS sheets. Results: The most common in basic subtypes was SE (23.1%), followed by N (22.1%) and I (12.0%) subtype. Nodulo-infiltrative (N-I) (8.7%) was the most common in combined subtype.In N, P, SE and SF subtype (non-aggressive group), the rate of tumor with pigmentation (63.1%) was high, non-aggressive pattern (91.4%) in histologic subtype was observed much more. In SD, I and combined subtype (aggressive group), pigmentation (24.0%) was relatively rare, aggressive and mixed pattern (74.4%) in histologic subtype was observed more. More wider surgical margin and more MMS stage number were required in aggressive group than non-aggressive group. Conclusion The upgrading classification of BCC clinical subtype can be not only described briefly and concretely for clinical appearance of BCCs but also highly correlated with histologic subtypes and tumor invasiveness.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

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.

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: Periprosthetic fracture (PPF) is a troublesome complication as it utilizes substantial healthcare resources. Recent studies about the epidemiology of PPF after total knee arthroplasty (TKA) are still lacking, and there is limited national-level analysis focusing on the comorbid chronic conditions as risk factors of PPF. This study used national registry data from South Korea and aimed to investigate the epidemiology of PPF following TKA between 2010 and 2020 and identify which comorbidities contributed to the risk of PPF. Methods: Using Health Insurance Review and Assessment (HIRA) service data in South Korea, the incidence of PPF after TKA between 2010 and 2020 was evaluated and stratified by age and sex. Medical comorbidities were evaluated as possible risk factors for PPF using Cox regression analysis. Results: PPF occurred in 14,429 patients, accounting for 2.37% of total TKA patients. The prevalence of PPF by sex was 2.50% in women and 1.64% in men. The PPF rate was 2.82% in under 60 years, 2.25% in 60 to 69 years, 2.42% in 70 to 79 years, 2.29% in 80 to 89 years, and 2.12% in over 90 years. Among 17 analyzed comorbidities, 11 were found to be associated with PPF after TKA. Severe liver disease (hazard ratio [HR], 1.303), hemiplegia (HR, 1.244), and dementia (HR, 1.206) were the top 3 risk factors.Although osteoporosis, pulmonary disease, peptic ulcer, and diabetes showed relatively low HRs than these top 3 factors, the incidence rates were higher. Conclusions PPF occurred in 2.37% of TKA patients in South Korea from 2010 to 2020. PPF rate was higher in women. To prevent PPF after TKA, proper patient management and education should be emphasized, particularly in patients with severe liver disease, hemiplegia, and dementia.