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 AND OBJECTIVES: The intracoronary injection of acetylcholine (Ach) has been shown to induce coronary spasms in patients with variant angina. Clinical significance and angiographic characteristics of patients with a significant response to lower Ach dosages are as-yet non-clarified compared with patients responding to higher Ach doses. SUBJECTS AND METHODS: A total of 3034 consecutive patients underwent coronary angiography with Ach provocation tests from January 2004 to August 2010. Ach was injected in incremental doses of 20, 50, 100 microg into the left coronary artery. Significant coronary artery spasm was defined as focal or diffuse severe transient luminal narrowing (>70%) with/without chest pain or ST-T change on the electrocardiogram (ECG). We compared the clinical and angiographic characteristics of patients who responded to a lower Ach dose (20 or 50 microg, n=556) to those that responded to a higher Ach dose (100 microg, n=860). RESULTS: The baseline clinical and procedural characteristics are well balanced between the two groups, except diabetes was higher in the lower Ach dose group and there were differences in medication history. After adjusting for confounding factors, the lower Ach dose group showed more frequent temporary ST elevation and atrioventricular block on the ECG. Furthermore, the group of patients who responded to the lower Ach dose was associated with a higher incidence of baseline and severe spasm than those who responded to a higher Ach dose. CONCLUSION: Patients with a significant response to a lower Ach dose were associated with more frequent ST elevation, baseline spasm, and more severe spasm compared with those who responded to a higher Ach dose, suggesting more intensive medical therapy with close clinical follow-up is required for those patients.
Acetylcholine ; Angina Pectoris, Variant ; Atrioventricular Block ; Chest Pain ; Coronary Angiography ; Coronary Vessels ; Electrocardiography ; Humans ; Incidence ; Phenobarbital ; Spasm

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

Salmonella infection occurs in 5 different clinical forms; gasteroenteritis, enteric fever, bacteremia, chronic carried state and localization at one or more sites. Extraintestinal pyogenic infections caused by salmonella species include soft tissue abscesses, bone and joint infections, cholecystitis, liver abscess and splenic abscess etc. Pancreatic abscess due to Salmonella typhi is a very rare extraintestinal manifestation of salmonellosis. Infection pathways may be considered as reflux of infected bile through the pancreatic duct, hematogenous spread from a distant site or lymphatic spread from the intestinal tract. Treatment of pancreatic abscess needs surgical intervention and antibiotics therapy. We have experienced a case of a 40-years-old female with pancreatic abscess due to Salmonella typhi. She was treated with ultrasonography-guided catheter drainage and intravenous ceftriaxone for 18 days. After 14 days, the sonographic examination revealed the abscess cavity in pancreas almost disappeared. We report this case with review of literatures.
Abscess* ; Anti-Bacterial Agents ; Bacteremia ; Bile ; Catheters ; Ceftriaxone ; Cholecystitis ; Drainage ; Female ; Humans ; Joints ; Liver Abscess ; Pancreas ; Pancreatic Ducts ; Salmonella Infections ; Salmonella typhi* ; Salmonella* ; Typhoid Fever ; Ultrasonography

BACKGROUND AND OBJECTIVES: Coronary flow reserve (CFR) is considered an important index of the functional significance of coronary artery stenosis, but is influenced by several factors, such as left ventricle hypertrophy (LVH), diabetes mellitus (DM), hyperlipidemia and smoking. Measurement of the coronary flow velocity of the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) is feasible, and provides reliable information. The purpose of this study was to investigate the relationship between CFR and LVH, DM, hyperlipidemia and hypertension in patients with or without coronary artery disease, and to assess the prominent factors influencing CFR. SUBJECTS AND METHODS: Coronary angiographies were performed in 38 patients to evaluate chest pain. The distal LAD flow velocity was measured by TTDE, and the CFR calculated as a ratio of the hyperemic and baseline mean diastolic velocities. The CFR was compared with clinical, echocardiographic and angiographic parameters. RESULTS: The CFR was similar in patients both with and without hypertension, DM, high LDL-cholesterol levels and low ejection fraction(<40%). The mean CFR was lower in patients with (50% LAD stenosis than in patients with no significant stenosis. The CFR of patients with a left ventricle wall thickness of (12mm was lower than in those without LVH. The multivariate analysis of the aforementioned factors showed that LVH was the factor most influencing to the CFR (p<0.05). CONCLUSION: When using CFR as a functional parameter of LAD stenosis, one should consider LVH as one of the factors attributed to CFR modification.
Chest Pain ; Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease ; Coronary Circulation ; Coronary Stenosis ; Coronary Vessels ; Diabetes Mellitus ; Echocardiography ; Echocardiography, Doppler* ; Heart Ventricles ; Humans ; Hyperlipidemias ; Hypertension ; Hypertrophy ; Multivariate Analysis ; Smoke ; Smoking

The anal canal is the most distal part of the gastrointestinal tract, and it is developed and formed during the embryonic period. Infection is the most common disease process that occurs around the anorectum, yet tumors or cysts are occasionally encountered. The abnormal development of these parts of the gastrointestinal track during the embryonic period can result in congenital lesions that are discovered in young children or adults. A 72-year-old woman presented to us with postprandial lower abdominal discomfort and fecal incontinence. An anorectal mass was felt on the rectal examination. The colonoscopy demonstrated a submucosal tumor that was closely located to the anorectal junction. The tumor was excised with a snare and it was diagnosed as an analgland cyst due to the histologic features. It is necessary to differentiate anal gland cyst from the other diseases that have submucosal characters, such as carcinoid tumor.
Child ; Adult ; Male ; Female ; Humans ; Cysts