An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs and tissues and is used for evaluating the safety and effectiveness of drugs and the toxicity of industrial chemicals. Organoid technology is a new methodology that could replace testing on animals testing and accelerate development of precision and regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility of the production process and no internationally agreed standards for quality evaluation factors at endpoints. To overcome these barriers that hinder the regulatory acceptance and commercialization of organoids, Korea established the Organoid Standards Initiative in September 2023 with various stakeholders, including industry, academia, regulatory agencies, and standard development experts, through public and private partnerships. This developed general guidelines for organoid manufacturing and quality evaluation and for quality evaluation guidelines for organoid-specific manufacturing for the liver, intestines, and heart through extensive evidence analysis and consensus among experts. This report is based on the common standard guideline v1.0, which is a general organoid manufacturing and quality evaluation to promote the practical use of organoids. This guideline does not focus on specific organoids or specific contexts of use but provides guidance to organoid makers and users on materials, procedures, and essential quality assessment methods at end points that are essential for organoid production applicable at the current technology level.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare locally aggressive cutaneous neuroendocrine carcinoma with a high incidence of local recurrence, regional lymph node metastasis, followed by distant metastasis. Because of shortage of the retrospective study, standard treatment has not been established. The purpose of this study was to present the surgical treatment and outcome of 8 patients with MCC. METHODS: We report our experiences with 8 patients who underwent treatment for MCC at our institution from 2000 through 2012. Two men and 6 women received treatment for MCC. The mean age was 76.4 years (range, 53 to 93 years). RESULTS: The follow-up period ranged from 7 to 26 months (mean, 22.9). During the follow-up period, three of 8 patients had a relapse (mean time before recurrence, 10 months; 1 month, 7 months, and 22 months). After primary surgery, 3 patients underwent radiotherapy, and 1 patient received chemotherapy. CONCLUSION: MCC is an aggressive skin cancer with a high rate of local recurrence. Complete surgical excision is the mainstay of local treatment, but adjuvant radiotherapy should be considered for better local control.
Carcinoma, Merkel Cell ; Carcinoma, Neuroendocrine ; Disease Management ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Skin Neoplasms

OBJECTIVES: We studied the circadian rhythm of nonlinear heart rate dynamics in healthy subjects. BACKGROUND: The frequency of sudden cardiac death increases in the morning. The relationship between decreased complexity of heart rate dynamics and sudden cardiac death has been documented. An understanding of the circadian variation in the complexity of cardiac dynamics may be important and to predict and prevent this sudden cardiac death. METHODS: Dynamic 24-hour electrocardiographic recordings were obtained from 30 healthy ambulant subjects aged 41 to 50 years and the digitized data was partitioned into sections of 30 minutes' duration. For each section, four indexes obtained from separate algorithms of nonlinear dynamics of RR interval - correlation dimension, Lyapunov exponent, approximate entropy, and fractal dimension - were calculated. Normalized low- (0.04-0.1 hertz) and high-frequency (>0.15 hertz) components were also calculated. RESULTS: All the four indexes of nonlinear dynamics showed a remarkably similar circadian rhythm: a prominent morning dip preceded by a steep decline during the late night, a recovery during the evening and a peak around midnight. In the morning, the low frequency component rose rapidly with concomitant withdrawal of the high frequency component. CONCLUSION: The complexity of cardiac dynamics decreases significantly in the morning, and this may contribute to the ominously increased rate of cardiac death in the morning hours.
Circadian Rhythm* ; Death ; Death, Sudden, Cardiac ; Electrocardiography ; Entropy ; Fractals ; Heart Rate ; Nonlinear Dynamics

PURPOSE: It is very important to correct renal anemia by erythropoiesis stimulating agents (ESA) because anemia is associated with poor outcomes in chronic kidney disease (CKD) patients. We investigated whether once-biweekly (Q2W) treatment with epoetin-alpha (EPO-alpha) is as effective as Q2W darbepoetin-alpha (DA-alpha) in CKD patients who are not on dialysis. METHODS: Fifteen CKD patients not receiving dialysis with renal anemia (M:F 6:9, age 60.1+/-7.2 years, eGFR-MDRD 15.7+/-6.4 mL/min/1.73m2, DM 46.7%) were enrolled. All patients received Q2W subcutaneous DA-alpha (40 microgram) for 10 weeks. After 6 weeks of wash-out period, patients were switched to Q2W subcutaneous EPO-alpha (10,000 IU) for 10 weeks. RESULTS: There were no significant differences in baseline parameters, such as hemoglobin (Hb), serum ferritin, and transferrin saturation, between before DA-alpha therapy and before EPO-alpha therapy. Hb levels significantly increased after completion of ESA therapy (DA-alpha, 9.8+/-0.4 vs. 10.4+/-0.6 g/dL, p=0.001; EPO-alpha, 9.6+/-0.7 vs. 10.2+/-0.4 g/dL, p=0.003). After completion of ESA therapy, Hb levels did not reveal significant differences between two groups (p=0.123). Erythropoietin resistance index (8.2+/-1.6 vs. 8.4+/- 1.5 IU/kg weight/g hemoglobin/week, p=0.136) and % increase of Hb (106.7+/-5.5 vs. 106.8+/-6.4%, p=0.776) were not significantly different between DA-alpha therapy and EPO-alpha therapy. There were no significant adverse effects observed during study periods. CONCLUSION: These findings indicate that Q2W high dose (10,000 IU) of EPO-alpha therapy in CKD patients who are not on dialysis may be effective in maintaining Hb levels as Q2W DA-alpha therapy.
Anemia ; Dialysis ; Erythropoietin ; Ferritins ; Hematinics ; Hemoglobins ; Humans ; Kidney Failure, Chronic ; Renal Insufficiency, Chronic ; Transferrin

This report presents guidelines for the systematic management of packaging, storage, transportation, and traceability of source cells used for organoid research. Given the important role of source cells in organoid studies, it is important to ensure the preservation of their quality and integrity throughout transportation and distribution processes. The proposed guidelines, therefore, call for a cohesive strategy through these stages to minimize the risks of contamination, deterioration, and loss–threats that significantly compromise the safety, efficacy, and efficiency of source cells. Central to these guidelines is the quality control measures that include roles and responsibilities across the entire supply chain, with recommendations specific to packaging materials, transportation facilities, and storage management. Furthermore, the need for an integrated management system is emphasized, spanning from source cell collection to the final application. This system is crucial for maintaining the traceability and accountability of source cells, facilitating the sharing, distribution, and utilization on a global scale, and supporting to advance organoid research and development.

BACKGROUND/AIMS: There have been reports that interatrial septal (IAS) thickness is increased in patients with atrial fibrillation (AF). This study was performed to investigate whether IAS thickness determined by transthoracic echocardiography (TTE) represents the amount of left atrium (LA) structural and functional remodeling. METHODS: The study population consisted of 104 consecutive patients who underwent catheter ablation (CA) for AF (paroxysmal atrial fibrillation [PAF], 82; persistent atrial fibrillation [PeAF], 22). IAS thickness and left atrium volume (LAV) using TTE, and LA voltage (LAVOL) using 3-dimensional electroanatomical mapping system were assessed during sinus rhythm. RESULTS: IAS thickness was significantly correlated with maximal LAV (LAVmax) (r = 0.288, p = 0.003), mean LAVOL (r = -0.537, p < 0.001), total left atrium emptying fraction (LAEFtotal; r = -0.213, p = 0.030), and active LAEF (LAEFactive; r = -0.249, p = 0.014). IAS thickness was greater in the high-risk group (> or = 2) compared to other groups according to CHA2DS2-VASc score (p = 0.019). During a follow-up of 19.6 months, 23 subjects (22.1%; PAF, 17; PeAF, 6) had recurrence of arrhythmia. Univariate analysis showed that LAVmax, minimal LAV, mean LAVOL, LVEFtotal, LVEFactive, and IAS thickness were associated with recurrence of arrhythmia. However, on multivariate analysis, only mean LAVOL and LAEFactive were independent risk factors for recurrence. CONCLUSIONS: Although IAS thickness showed significant correlations with parameters for LA structural and functional remodeling, this parameter alone could not independently predict recurrence of arrhythmia after CA for AF.
Action Potentials ; Adult ; Aged ; Area Under Curve ; Atrial Fibrillation/physiopathology/*radiography/surgery/*ultrasonography ; *Atrial Function, Left ; *Atrial Remodeling ; Atrial Septum/physiopathology/*radiography/*ultrasonography ; Catheter Ablation ; Chi-Square Distribution ; *Echocardiography, Doppler ; Electrophysiologic Techniques, Cardiac ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; *Multidetector Computed Tomography ; Multivariate Analysis ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Recurrence ; Risk Factors ; Time Factors ; Treatment Outcome