Purpose: Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles. Materials and Methods: Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer. Results: The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity. Conclusions Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: This study compared the efficacy of different irrigation methods for the removal of Ca(OH)2 paste from the root canal. Materials and Methods: The root canals of 75 human mandibular premolars with standardized 15-mm canal lengths were prepared using nickel-titanium rotary files. After drying, the canals were filled with Ca(OH)2 paste. The teeth were divided into five groups: Control group (Group C), conventional irrigation; Group EA, sonic activation (EndoActivator); Groups EQA and EQB, sonic activation (EQ-S with metal tips A and B, respectively); and Group EU, ultrasonic activation (EndoUltra).The Ca(OH)2 paste volume before and after irrigation was measured using micro-computed tomography (CT) images. One specimen from each group was bisected along the long axis, and the canal walls were evaluated at 100× magnification using a scanning electron microscope. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U tests. Results: Overall, Ca(OH)2 paste removal was higher in Group EQA than in Group C. In the coronal third, removal rate was higher in Group EQA than in Group C. In the middle third, Groups EQB and EU outperformed Group C. Removal from the apical third was higher in Group EQA than in Group C. All groups showed greater removal from the coronal and middle thirds than from the apical third. Conclusion Sonic and ultrasonic irrigation methods demonstrated higher efficacy than conventional irrigation method for the removal of Ca(OH)2 paste from the root canal. All groups demonstrated better effectiveness in removal from the coronal and middle thirds than from the apical third.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Background: and Purpose Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. Methods: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. Results: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. Conclusions Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19×11×15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.