Effect of isoproterenol, a ß-adrenergic agonist, on the differentiation of insulin-producing pancreatic ß cells derived from human pluripotent stem cells.

Research on islet replacement through the differentiation of functionally matured insulin-producing ß-like cells for the treatment of diabetes presents a significant challenge. Neural signals in ß cell differentiation significantly impact the pancreatic microenvironment in glucose metabolism, but they are not fully understood. In this study, isoproterenol, a ß adrenoreceptor agonist, was introduced into pancreatic progenitor cells, derived from human pluripotent stem cells in vitro, undergoing endocrine differentiation, using 2-dimensional (2D) and 3-dimensional (3D) differentiation protocols. This resulted in increased insulin and C-peptide secretion, along with elevated expression of key pancreatic beta cell transcription factors, including PDX-1, NKX6.1, and MAFA, and improved function, demonstrated by increased responsiveness to glucose determined via a glucose-stimulated insulin secretion test. Moreover, RNA transcriptome analysis of isoproterenol-treated endocrine progenitors facilitated the identification of biological pathways and genes that contribute to mature beta cell differentiation efficiency correlated with neural signals, such as adrenoceptor beta 1, calcium/calmodulin dependent protein kinase II alpha, phospholipase C delta 4, and neurotrophic receptor tyrosine kinase 1. Among those genes, calcium/calmodulin dependent protein kinase II alpha was suggested as the most notable gene involved in the isoproterenol mechanism through inhibitor assays. This study illustrates that isoproterenol significantly enhances endocrine differentiation and underscores its effects on stem cell-derived beta cell maturation, emphasizing its therapeutic potential for the treatment of diabetes.

Validation of the Texas Hepatocellular Carcinoma Risk Index Predictive Model for Hepatocellular Carcinoma in Asian Cohort.

Hepatocellular carcinoma (HCC) represents a significant global health burden, with its incidence and mortality rates varying significantly across different geographic regions. This variance is largely attributed to differences in the prevalence of risk factors such as hepatitis B and C infections, and alcohol consumption, as well as genetic predispositions that are distinct between Eastern and Western populations. Moreover, the impact of racial and ethnic diversity on the disease's epidemiology further complicates the global understanding and prediction of HCC. Such disparities highlight the critical need to evaluate the applicability of predictive models across diverse populations, acknowledging that a model developed in one region may not necessarily translate with the same accuracy or effectiveness when applied to another, because of these underlying epidemiologic and genetic differences. In this study, we aimed to assess the cross-regional applicability and accuracy of an HCC prediction model (Texas hepatocellular carcinoma risk index [THCC-RI] predictive model) originally developed in Western populations, within an Eastern context.1,2.

Prediction of tumor recurrence after surgical resection of ampullary adenocarcinoma using magnetic resonance imaging.

OBJECTIVES: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. METHODS: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. RESULTS: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. CONCLUSIONS: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. CLINICAL RELEVANCE STATEMENT: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. KEY POINTS: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

Interobserver Variability and Diagnostic Performance in Predicting Malignancy of Pancreatic Intraductal Papillary Mucinous Neoplasm with MRI.

Background The 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas are widely used. Purpose To evaluate the interobserver agreement and diagnostic performance of MRI assessment in predicting the malignant potential of IPMN according to radiologists' experience. Materials and Methods This multicenter retrospective study included 100 patients with pathologically proven pancreatic IPMN (77 patients with surgery, 23 patients with biopsy) who underwent contrast-enhanced MRI between 2016 and 2021. Eight post-fellowship radiologists (four more-experienced [8-20 years] and four less-experienced [1-4 years] reviewers) evaluated MRI for high-risk stigmata and worrisome features identified by the most recent 2017 guidelines. Interobserver agreement was determined using Fleiss κ statistics according to radiologist experience. The diagnostic performance for malignant IPMN was assessed using receiver operating characteristic curve analysis. Results Among 100 patients (mean age, 66 years ± 10 [SD]; 57 men), 52 (52%) had malignant IPMN. For high-risk stigmata, interobserver agreement was substantial for main pancreatic duct size of at least 10 mm (κ = 0.78; 95% CI: 0.75, 0.82), enhancing mural nodule of at least 5 mm (κ = 0.70: 95% CI: 0.66, 0.74), and at least one high-risk stigmata (κ = 0.73: 95% CI: 0.69, 0.76). The worrisome features showed fair to substantial interobserver agreement (κ range, 0.22-0.80). More-experienced reviewers demonstrated better agreement in the assessment of at least one high-risk stigmata than less-experienced reviewers (κ = 0.77 vs κ = 0.69, P < .001). The overall diagnostic performance of each reviewer was good for the prediction of malignant pancreatic IPMN (area under the receiver operating characteristic curve [AUC] range, 0.77-0.84; median AUC, 0.82), with substantial agreement (κ = 0.76). Conclusion The 2017 international consensus guidelines enabled good diagnostic performance and substantial interobserver agreement for high-risk stigmata but not worrisome features on the evaluation of the malignant pancreatic IPMN using MRI. Agreement tended to be better among more-experienced reviewers than among less-experienced reviewers. © RSNA, 2023 Supplemental material is available for this article.

Validation of MELD 3.0 scoring system in East Asian patients with cirrhosis awaiting liver transplantation.

Recently, a new predictive model that jointly considers the Model of End-stage Liver Disease (MELD) 3.0 and albumin has been proposed. This study investigated the performance of the MELD 3.0 score in predicting the 3-month survival of East Asian patients with cirrhosis compared with the other MELD-based scores. Validation was performed with the retrospective data of 2153 patients in South Korea who were listed for liver transplantation (LT). Discrimination and calibration analyses were performed using the MELD-based scores as an independent variable. On average, patients had the original MELD score of 18.70 ± 9.65. Alcohol (39.99%) and chronic HBV (38.55%) were the 2 main etiologies. The MELD 3.0 with albumin showed slightly better discrimination [c-index = 0.738, incremental AUC (iAUC) = 0.719] compared with the MELD 3.0 without albumin (c-index = 0.737, iAUC = 0.715), MELD-Na (c-index = 0.730, iAUC = 0.707), or the original MELD (c-index = 0.718, iAUC = 0.687) for predicting 3-month survival but not significantly different compared with prior models. Likewise, in the stratified analysis according to the strata of MELD, although the performance of MELD 3.0 was better throughout all the MELD strata than MELD original, there was no statistical difference in performance. The MELD 3.0 with albumin reclassified 22.61% of cases classified by the original MELD to higher MELD score categories, and there was no significant difference in the reclassification rate between males and females. The predictive power of the MELD-based system is lower in Asian populations than in western countries. Nonetheless, the MELD 3.0 score with albumin was significantly better in predicting the short-term prognosis of East Asian patients on the LT waitlist than the current allocation system, original MELD.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers.

BACKGROUND: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. METHODS: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. RESULTS: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.

Objective predictors of delayed neurological sequelae in patients with altered mental status after carbon monoxide poisoning.

BACKGROUND AND PURPOSE: Following carbon monoxide (CO) poisoning, altered mental status is an important predictor of poor neurological prognosis, including delayed neurological sequelae (DNS). However, it is difficult to interview CO-poisoned patients accurately about exposure intervals and loss of consciousness (LOC). Thus, we investigated whether DNS can be predicted using objective factors such as laboratory results and brain imaging in patients suffering CO poisoning with altered mental status. METHODS: This was a prospective observational study involving all CO-poisoned patients who visited the university hospital emergency department (ED) in Bucheon, South Korea, between January 2019 and April 2020. All were registered in the CO registry. We excluded patients who were under 18 years of age, had no change in mental status, were lost to follow-up, had neurological deficits persisting at discharge from the ED, and/or were transferred from another hospital 24 hours after exposure. RESULTS: A total of 21 (25.3%) of 82 patients had DNS with a median onset of 21 (12 to 30) days. Creatinine kinase (CK) (odds ratio 1.0002, 95% confidence interval 2.734-105.231) and brain imaging (odds ratio 3.206, 95% confidence interval 1.008-10.199) were independent prognostic factors of DNS. CONCLUSION: A high level of serum CK and abnormal brain-imaging results were significant predictors of the occurrence of DNS in CO-poisoned patients with altered mental status. Critically, these are objective rather than subjective factors such as CO exposure interval.

Validation Study on Automated Sleep Stage Scoring Using a Deep Learning Algorithm.

Background and Objectives: Polysomnography is manually scored by sleep experts. However, manual scoring is a time-consuming and labor-intensive task. The goal of this study was to verify the accuracy of automated sleep-stage scoring based on a deep learning algorithm compared to manual sleep-stage scoring. Materials and Methods: A total of 602 polysomnography datasets from subjects (Male:Female = 397:205) aged 19 to 65 years (mean age, 43.8, standard deviation = 12.2) were included in the study. The performance of the proposed model was evaluated based on kappa value and bootstrapped point-estimate of median percent agreement with a 95% bootstrap confidence interval and R = 1000. The proposed model was trained using 482 datasets and validated using 48 datasets. For testing, 72 datasets were selected randomly. Results: The proposed model exhibited good concordance rates with manual scoring for stages W (94%), N1 (83.9%), N2 (89%), N3 (92%), and R (93%). The average kappa value was 0.84. For the bootstrap method, high overall agreement between the automated deep learning algorithm and manual scoring was observed in stages W (98%), N1 (94%), N2 (92%), N3 (99%), and R (98%) and total (96%). Conclusions: Automated sleep-stage scoring using the proposed model may be a reliable method for sleep-stage classification.

Association between lower urinary tract symptoms and cardiovascular risk scores in ostensibly healthy women.

OBJECTIVES: To investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk in women, as severe LUTS are known to be associated with CVD risk in men but few studies have focused on this issue in women. SUBJECTS AND METHODS: A total of 1014 ostensibly healthy women, who participated in a voluntary health check in a health promotion centre from November 2013 to October 2015, were enrolled. LUTS were assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). CVD risk scores were calculated using the Framingham risk score and the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) score. Correlation, partial correlation, and multiple logistic regression analyses were conducted. RESULTS: The mean age and body mass index (BMI) of the women were 51 years and 22.6 kg/m2 , respectively. The ASCVD score showed significant positive correlations with IPSS items Question 2 (Q2), Q3, Q5, and Q7 (all P < 0.05), total IPSS (P = 0.001), IPSS storage (P = 0.006) and IPSS voiding symptoms scores (P = 0.001) based on partial correlation analysis after adjustment for BMI. For the OABSS, the ASCVD score showed significant positive correlations with OABSS items Q2, Q3, and Q4 (P < 0.001, P = 0.017, and P < 0.001, respectively) and total OABSS (P < 0.001). Multiple logistic regression analysis showed that the moderate-severe risk groups of the OABSS and IPSS were associated with the ASCVD risk score in adjusted models (P < 0.001) compared to the none-mild OABSS and mild IPSS groups. After adjustment for age and BMI, IPSS storage score was significantly related with the ASCVD risk score (B = 0.855, P = 0.016) CONCLUSIONS: LUTS, especially storage symptoms, might be risk factors for predicting future CVD risk in women. Further prospective or cohort studies are needed to validate this possibility.

Diagnostic performance of the current risk-stratified approach with computed tomography for suspected choledocholithiasis and its options when negative finding.

BACKGROUND: Several studies evaluated the current guideline of the American Society for Gastrointestinal Endoscopy (ASGE) and reported only suboptimal accuracy. This study evaluated the diagnostic performance of the ASGE guideline based on computed tomography (CT) and role of endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) in patients with suspected choledocholithiasis but negative CT finding. METHODS: Patients with suspected choledocholithiasis undergoing ERCP between January 2016 and January 2017 were retrospectively analyzed. All patients underwent CT to detect choledocholithiasis. EUS or MRCP was performed when the CT scan showed negative findings. Patients were classified into the high and intermediate-risk groups, based on predictors from the ASGE criteria. RESULTS: Of 583 patients with suspected choledocholithiasis, 340 (58.3%) had stones on ERCP (65.9% in the high-risk group and 40.6% in the intermediate-risk group). The accuracy of ASGE guideline for CT was 63.98% (79.12% sensitivity, 42.80% specificity) and 36.02% (20.88% sensitivity, 57.20% specificity) in the high-risk and intermediate-risk groups, respectively. In 103 patients in the high-risk group underwent both CT and US, the accuracy of CT was higher than that of US for detecting choledocholithiasis (78.64% vs. 53.40%), with a significant difference in area under the curve (AUC) (0.78 vs. 0.59, P < 0.001). Of 339 with negative CT finding, the accuracy of EUS was higher than that of MRCP (90.91% vs. 82.76%), but with no significant difference in AUC (0.91 vs. 0.83, P = 0.347). CONCLUSIONS: CT-based ASGE guideline showed superior diagnostic performance than US for predicting choledocholithiasis. The diagnostic options, EUS or MRCP, with negative CT finding showed comparable performance. Therefore, the diagnostic modality should be selected based on availability, experience, cost, and contraindications.

Preoperative MRI-based nomogram to predict survival after curative resection in patients with gallbladder cancer: a retrospective multicenter analysis.

PURPOSE: To use preoperative MRI data to construct a nomogram to predict survival in patients who have undergone R0 resection for gallbladder cancer. METHODS: The present retrospective study included 143 patients (M:F, 76:67; 67.15 years) with gallbladder cancer who underwent preoperative MRI and subsequent R0 resection between 2013 and 2021 at two tertiary institutions. Clinical and radiological features were analyzed using univariate and multivariate Cox regression analysis to identify independent prognostic factors. Based on the multivariate analysis, we developed an MRI-based nomogram for determining prognoses after curative resections of gallbladder cancer. We also obtained calibration curves for 1-,3-, and 5-year survival probabilities. RESULTS: The multivariate model consisted of the following independent predictors of poor overall survival (OS), which were used for constructing the nomogram: age (years; hazard ratio [HR] = 1.04; 95% confidence interval [CI], 1.04-1.07; p = 0.033); tumor size (cm; HR = 1.40; 95% CI, 1.09-1.79; p = 0.008); bile duct invasion (HR = 3.54; 95% CI, 1.66-7.58; p = 0.001); regional lymph node metastasis (HR = 2.47; 95% CI, 1.10-5.57; p = 0.029); and hepatic artery invasion (HR = 2.66; 95% CI, 1.04-6.83; p = 0.042). The nomogram showed good probabilities of survival on the calibration curves, and the concordance index of the model for predicting overall survival (OS) was 0.779. CONCLUSION: Preoperative MRI findings could be used to determine the prognosis of gallbladder cancer, and the MRI-based nomogram accurately predicted OS in patients with gallbladder cancer who underwent curative resection.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. RESULTS: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). CONCLUSION: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

Can Over Six Months of Teriparatide Treatment Prevent the Progression of Osteoporotic Thoracolumbar Compression Fracture?

Objective: Osteoporosis is one of the most common causes of thoracolumbar compression fractures. Teriparatide is an anabolic agent used to treat osteoporosis. This study aimed to determine whether teriparatide treatment for over 6 months could be effective in patients with osteoporotic thoracolumbar compression fractures. Methods: Between July 2012 and June 2020, we reviewed 50 patients with thoracolumbar osteoporotic compression fractures who could be followed up for more than 1 year. Patients were divided into 3 groups: 11 patients who did not receive teriparatide (Group 0), 19 patients who received teriparatide for less than 5 months (Group 1), and 20 patients who received teriparatide for over 6 months (Group 2). Demographic data, visual analog scale (VAS) scores, and medical histories were reviewed. Radiographs were reviewed to evaluate the vertebral body compression ratio and kyphotic angles. Results: VAS scores improved in all groups at each time point after injury. Score improvements at 6 months and 1 year between Group 0 and Groups 1 or 2 were significantly different. The compression ratio in all groups increased at each time point after injury, but the differences between Groups 0, 1, and 2 were statistically significant at 3 weeks and 6 months. While the kyphotic angle significantly increased at 1 year in all groups, the differences between the groups at each time point did not reach statistical significance. Conclusion: Over 6 months of teriparatide treatment had some effects on pain in patients with osteoporotic thoracolumbar compression fractures, but did not prevent the progression of vertebral collapse.

Relationship between Handgrip Strength and Incident Diabetes in Korean Adults According to Gender: A Population-Based Prospective Cohort Study.

(1) Background: Diabetes mellitus (DM) is a well-known disease that causes comorbidities such as chronic kidney disease (CKD) and cardiovascular disease. Therefore, it is necessary to develop diagnostic tools to prevent DM. Handgrip strength, a known diagnostic tool for sarcopenia, is a predictor of several diseases. However, the value of handgrip strength as an indicator of incident DM in Asian populations remains unknown. This study aimed to identify the relationship between handgrip strength and incidence of DM in Korean adults according to sex. (2) Methods: A total of 173,195 participants registered in a nationwide cohort were included in this study. After applying the exclusion criteria, 33,326 participants remained. DM occurred in 1473 individuals during the follow-up period (mean follow-up period, 4.1 years). To reduce the impact of body size, the study population was subdivided into quartiles of relative handgrip strength, defined as absolute handgrip strength divided by body mass index. Multivariate Cox regression analysis revealed that the relative handgrip strength was inversely associated with new-onset DM. (3) Results: Compared with the lowest quartile (Q1), the hazard ratios (HRs) [95% confidence intervals (CIs)] for new-onset DM for the highest quartiles (Q4) was 0.60 (0.43-0.84) in men and 0.72 (0.52-0.99) in women after adjusting for confounding factors. The incidence of DM decreased with the increase in the relative handgrip strength. These inverse relationships were statistically more significant in men than in women. (4) Conclusions: This novel study revealed that relative handgrip strength is related to incident DM in both men and women. Relative handgrip strength can be used as a practical tool to prevent DM. Regular measurement of handgrip strength can be used to detect DM.

Initial and 5-day positivity rate of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) in exposed inpatients within shared rooms during the omicron-variant dominant period.

In this observational study conducted in 2022, 12.3% of patients who shared a room with a patient positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) also had a positive polymerase chain reaction (PCR) test, either at initial screening or during a 5-day quarantine. Therefore, screening and quarantine are still necessary within hospitals for close-contact inpatients during the SARS-CoV-2 omicron-variant dominant period.

Accuracy of visual estimation of ejection fraction in patients with heart failure using augmented reality glasses.

OBJECTIVE: Left ventricular ejection fraction (LVEF) is measured to assess haemodynamic status and cardiac function. It may be difficult to accurately measure in patients with heart failure (HF) as they are often poorly echogenic. The augmented reality (AR) technology is expected to provide real-time guidance that will enable more accurate measurements. METHODS: A prospective, randomised, case-crossover simulation study was conducted to confirm the effect of AR glasses on echocardiographic interpretation in patients with HF. 22 emergency physicians participated. The participants were randomly assigned to two groups. Group A estimated the visual ejection fraction of echocardiographic video clips without the AR glasses, while group B estimated them with glasses. After a washout period, the two groups crossed over. The estimates were then compared with the ejection fraction measurements obtained by echocardiologists; intraclass correlation coefficient (ICC) was calculated. RESULTS: The ICC with glasses (0.969, 95% CI 0.966 to 0.971) was higher than without glasses (0.705, 95% CI 0.681 to 0.727) among all participants. In the subgroup analysis, the first-year and second-year residents showed the most significant difference, with an ICC of 0.568 (95% CI 0.508 to 0.621) without glasses compared with 0.963 (95% CI 0.958 to 0.968) with glasses. For the third-year and fourth-year residents group, the ICC was 0.754 (95% CI 0.720 to 0.784) without glasses and 0.972 (95% CI 0.958 to 0.968) with glasses. Among the group of attending physicians, the ICC was 0.807 (95% CI 0.775 to 0.834) without glasses and 0.973 (95% CI 0.969 to 0.977) with glasses. CONCLUSIONS: AR glasses could be helpful in measuring LVEF and could be more helpful to those with little visual estimation experience.

The added value of MRI in distinguishing malignant and benign ampullary strictures: a multicenter retrospective study.

PURPOSE: To investigate the added value of using contrast-enhanced magnetic resonance imaging (MRI) in conjunction with contrast-enhanced computed tomography (CT) for differentiating malignant and benign ampullary strictures. MATERIALS AND METHODS: The present retrospective study included 90 patients with ampullary strictures who underwent preoperative contrast-enhanced CT and contrast-enhanced MRI at two tertiary institutions. The image sets (i.e., CT alone vs. combined CT and MRI) were evaluated by three abdominal radiologists, who used a five-point Likert scale to score their confidence for diagnosing malignancy in patients with ampullary strictures. Diagnostic accuracy was calculated using receiver-operating characteristic (ROC) curve analysis, sensitivity, specificity, and accuracy. Additionally, interobserver agreement regarding the scoring of potential malignancies of the ampullary strictures was assessed. RESULTS: The addition of contrast-enhanced MRI to contrast-enhanced CT showed a significant improvement in predicting malignant ampullary strictures in all three observers (p = 0.007, 0.001, and 0.002) using ROC curve analysis, and a significant improvement was observed in diagnostic sensitivity and accuracy for predicting malignancy (p = 0.016 and 0.029 for observer 1; p = 0.023 and 0.010 for observer 2; and p = 0.010 and 0.011 for observer 3). The interobserver agreement for the five-point scale in determining malignancies of the ampullary strictures was 0.86 for CT alone and 0.93 for the combined set of CT and MRI. CONCLUSION: The addition of contrast-enhanced MRI to CT provided added value for differentiating malignant from benign ampullary strictures.

Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis.

BACKGROUND: For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis. METHODS: In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs. RESULTS: DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001). CONCLUSION: Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.

Enhancing differentiation and functionality of insulin-producing cells derived from iPSCs using esterified collagen hydrogel for cell therapy in diabetes mellitus.

BACKGROUND: Islet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for ß-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels. METHODS: iPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques. RESULTS: Esterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups. CONCLUSION: Esterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic ß-cells, advancing cell therapy in diabetes cell therapy.

Differentiation of malignant from benign ampullary strictures: A prediction nomogram based on MR imaging and clinical findings.

PURPOSE: To construct a predictive nomogram based on contrast-enhanced magnetic resonance imaging (MRI) and clinical findings for differentiating malignant from benign ampullary strictures. METHOD: In this retrospective study, 76 patients with ampullary strictures (51 benign and 25 malignant) who underwent contrast-enhanced MRI were enrolled. Imaging findings were evaluated independently by two abdominal radiologists who reached consensus. Clinical findings were also collected. Significant findings for malignant ampullary strictures were assessed by univariable and multivariable logistic regression analyses. Based on the results of multivariable analysis, a nomogram to differentiate malignant from benign ampullary strictures was developed and internally validated. RESULTS: In multivariable analysis, presence of an ampullary mass (odds ratio [OR]: 8.42, p = 0.047), bulging ampulla (OR: 8.32, p = 0.033), diffusion restriction of the ampulla (OR: 42.76, p = 0.004) on MRI, and jaundice (OR: 12.41, p = 0.019) were significant predictors of malignant ampullary strictures. A predictive nomogram was constructed using these findings. Among them, diffusion restriction of the ampulla showed the highest OR and predictor score on the nomogram. The calibration plots for internal validation achieved strong agreement between the predicted probabilities and the actual rates of malignant ampullary strictures. CONCLUSION: A combination of significant contrast-enhanced MRI and clinical findings of ampullary mass, bulging ampulla, diffusion restriction of the ampulla, and jaundice may be useful in the prediction of malignant ampullary stricture.