Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: Mirabegron, the first-in-class beta-3 agonist, is the mainstay medication for overactive bladder (OAB). The aim of this study was to investigate the efficacy and safety of generic drugs of mirabegron (Mirabek® ) in adults diagnosed with OAB through a multicenter, prospective, non-interventional observational study. Materials and Methods: Adult patients with OAB prescribed Mirabek® SR Tab. 50 mg for the first time were recruited from hospitals between September 2021 and September 2022. Participants underwent baseline registration followed by two follow-ups at 4-and 8-week intervals. Data on demographics, medical history, OAB symptoms, vital signs, medication administration, and adverse events were collected. Results: Among 1,714 patients, Mirabek® SR Tab. 50 mg effectively improved OAB symptoms over an 8-week treatment period, with significant differences in symptom improvement between baseline and both 4- and 8-week time points as well as between 4 weeks and 8 weeks. The incidence rate of adverse events was 0.70%; most cases were mild with no severe reactions. Conclusions This study demonstrated that Mirabek® , a generic drug of betmiga, is an effective and safe treatment option for adults with OAB. Furthermore, the introduction of generic drug reduced the costs of prescription drugs and expanded the opportunity for many patients to access mirabegron.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Purpose: Temporomandibular joint osteoarthritis (TMJ-OA) can cause pain and functional limitations that are often resistant to conventional therapies. Polydeoxyribonucleotide (PDRN), known for its anti-inflammatory and regenerative effects via A2A adenosine receptor activation, has emerged as a potential alternative. This study evaluated the clinical efficacy of PDRN prolotherapy in TMJ-OA and compared outcomes between acute and chronic cases. Methods: A retrospective case series of 111 TMJ-OA patients treated with intra-articular PDRN injections was analyzed. Objective outcomes included maximum mouth opening (MMO) and numeric rating scale (NRS) scores before and after treatment. Subjective improvement was assessed using the Patient Global Impression of Change (PGIC). Subgroup analysis was conducted based on symptom duration: acute (<3 months) and chronic (≥3 months). Results: The acute group showed significantly greater improvements than the chronic group in ΔNRS (–3.74±2.13 vs. –2.64±2.16; p=0.012) and ΔMMO (6.97±7.25 mm vs.4.24±5.07 mm; p=0.045). Overall, 77.5% of patients reported improvement on PGIC, with a higher (but not statistically significant) proportion in the acute group (86.5% vs. 62.8%, p=0.250). Clicking improved more in acute cases (p=0.001). Conclusions PDRN injection therapy appears effective in reducing pain and improving function in TMJ-OA, with superior outcomes in acute cases. It may be a promising alternative for patients unsuitable for standard conservative treatments. Further prospective studies are needed to confirm these findings.

Purpose: Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC). Materials and Methods: This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests. Results: Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status. Conclusion Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.

Purpose: To evaluate the incidence and pattern of recurrence after surgery in patients with organ-confined renal cell carcinoma (RCC) to establish an appropriate follow-up plan. Materials and Methods: In this retrospective study, we evaluated data from 2960 patients who underwent radical or partial nephrectomy for stage 1 or 2 RCC. We investigated the location of first recurrence and recurrence-free survival (RFS) by plotting Kaplan–Meier curves and analyzed the associated variables using Cox regression analysis. Results: During a median follow-up of 59 months, the 10-year RFS rates were 94.5%, 75.0%, and 57.9%, for T1a, T1b, and T2 RCC, respectively. A total of 211 patients experienced recurrence: 67 after 5 years, and 14 after 10 years. The most common sites of the first recurrence were the lungs, bones, and contralateral kidneys. Male sex, older age, higher pathologic T stage, higher nuclear grade, clear-cell RCC, and presence of differentiation were associated with recurrence. Among patients followed up for more than 60 months, higher pathologic T stage and grade, as well as clear cell RCC were predictors of RFS. Conclusion Late recurrence after surgery is common in patients with organ-confined RCC, with recurrence occurring even after 10 years. Consequently, long-term follow-up, of perhaps 10 years or more, including imaging studies of the abdomen, lungs, and bone, should be considered for the early detection of recurrence.

Obstructive sleep apnea (OSA) is a disorder driven by a combination of anatomical and functional factors. A narrow upper airway, fatty deposits around the tongue, and enlarged soft tissues all contribute to airway collapse. Additionally, reduced neuromuscular activity during sleep and increased instability in respiratory control heighten the risk of airway obstruction. OSA is linked to serious health problems, including metabolic disorders, cardiovascular diseases, and excessive daytime sleepiness, underscoring the importance of early diagnosis and treatment. Diagnosis is typically made through polysomnography, and continuous positive airway pressure therapy remains the most effective treatment.For individuals with mild to moderate OSA, oral appliance therapy offers a viable alternative, while emerging treatments such as hypoglossal nerve stimulation and pharmacological interventions provide additional options. By identifying distinct OSA phenotypes, personalized treatment approaches can be developed, and future research should focus on optimizing these strategies to meet the specific needs of individual patients.

Purpose: The aims were to investigate potential differences in clinical assessments among acute pain-related temporomandibular disorder (TMD) with different concordance value (CV) between number of self-reported painful site (NSP) and number of painful sites on palpation (NPP), and if it makes sense to treat them differently. Methods: A total of 61 patients were divided into three groups according to CV: 10 patients (concordance poor [CP]), 19 patients (concordance moderate [CM]), and 32 patients (concordance high [CH]). Clinical assessments were conducted using a standardized method in diagnostic criteria for temporomandibular disorders (DC/TMD). We compared collected information including sex, diagnosis, numerical rating scale (NRS), NPP, NSP, sleep duration, DC/TMD Axis II questionnaire, and perceived stress scale among three groups. Results: Among the clinical assessment, NRS, sleep duration, NPP, NSP, total scores of Oral Behaviors Checklist, Patient Health Questionnaire (PHQ)-15, PHQ-9 showed significant differences among 3 groups. NRS, NPP, NSP, PHQ-15, and PHQ-9 were higher in the CP group than in the CM and CH groups. Sleep duration was positively and NPP, NRS were negatively correlated with CV. Conclusions While previous studies suggested differences between chronic and acute TMD in DC/TMD items, our findings propose the CV might be a key factor that could predict the severity and susceptibility of acute-TMD patients. However, Additional studies are required to determine whether their long-term prognosis was similar to that of chronic pain patients and what the response to treatment was among the three groups.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.