Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate- Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways in which inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that mice in which IPMK knockout is deleted, specifically in the skeletal muscle, displayed an increased body weight, disrupted glucose tolerance, and reduced exercise tolerance under the normal diet. Moreover, these changes were associated with an increased accumulation of triglyceride in skeletal muscle. Furthermore, we have confirmed that a loss of IPMK led to reduced beta-oxidation, increased triglyceride accumulation, and impaired insulin response in IPMK-deficient muscle cells. Thus, our results suggest that IPMK mediates the whole-body metabolism via regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes.

High level of gamma-glutamyltransferase is a possible risk factor for psoriasis: A nationwide population-based cohort study.

Background Gamma-glutamyl transferase (GGT) has been associated with coronary heart disease, diabetes mellitus, and hypertension, but its association with psoriasis has not yet been elucidated. Aims We conducted this study to determine the association between the risk of psoriasis and the serum GGT. Methods We conducted a nationwide population-based study. A total of 9,939,350 people met the enrolment criteria. The study population was classified into four groups based on GGT levels and the risk of psoriasis was calculated for each group. Results The incidence rates of psoriasis per 1,000 person-years were 2.96105 and 3.68577 in the lowest and highest GGT groups, respectively. After adjusting for age, sex, income, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol intake, exercise, and body mass index, the highest GGT group showed a significantly increased risk of developing psoriasis (hazard ratio: 1.057, 95% confidence interval: 1.044-1.07). This risk of psoriasis was significantly higher among the old age group (hazard ratio: 1.162, 95% confidence interval: 1.128-1.197) and women (hazard ratio: 1.14, 95% confidence interval: 1.117-1.164). Limitations The limitations of this study included the retrospective design, International Classification of Diseases code-based diagnosis, small hazard ratio, and non-availability of data on covariates. Conclusion The GGT level was found to be an independent risk factor for developing psoriasis.

A novel deep learning model for obstructive sleep apnea diagnosis: hybrid CNN-Transformer approach for radar-based detection of apnea-hypopnea events.

STUDY OBJECTIVES: The demand for cost-effective and accessible alternatives to polysomnography (PSG), the conventional diagnostic method for obstructive sleep apnea (OSA), has surged. In this study, we have developed and validated a deep learning model for detecting apnea-hypopnea events using radar data. METHODS: We conducted a single-center prospective cohort study, dividing participants with suspected sleep-disordered breathing into development and temporally independent test sets. Utilizing a hybrid CNN-Transformer architecture, we performed 5-fold cross-validation on the development set to develop and subsequently validate the model. Evaluation metrics included sensitivity for event detection, mean absolute error (MAE), intraclass correlation coefficient (ICC), and Pearson correlation coefficient (r) for apnea-hypopnea index (AHI) estimation. Linearly weighted kappa statistics (κ) assessed OSA severity. RESULTS: The development set comprised 54 participants (July 2021-May 2022), while the test set included 35 participants (June 2022-June 2023). In the test set, our model achieved an event detection sensitivity of 67.2% (95% CI: 65.8%, 68.5%) and demonstrated a MAE of 7.54 (95% CI: 5.36, 9.72), indicating good agreement (ICC = 0.889 [95% CI: 0.792, 0.942]) and a strong correlation (r = 0.892 [95% CI: 0.795, 0.945]) with the ground truth for AHI estimation. Furthermore, OSA severity estimation showed substantial agreement (κ = 0.780 [95% CI: 0.658, 0.903]). CONCLUSIONS: Our study highlights radar sensors and advanced AI models' potential to improve OSA diagnosis, paving the path for future radar-based diagnostic models in sleep medicine research.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

Artificial Intelligence-Based Electrocardiographic Biomarker for Outcome Prediction in Patients With Acute Heart Failure: Prospective Cohort Study.

BACKGROUND: Although several biomarkers exist for patients with heart failure (HF), their use in routine clinical practice is often constrained by high costs and limited availability. OBJECTIVE: We examined the utility of an artificial intelligence (AI) algorithm that analyzes printed electrocardiograms (ECGs) for outcome prediction in patients with acute HF. METHODS: We retrospectively analyzed prospectively collected data of patients with acute HF at two tertiary centers in Korea. Baseline ECGs were analyzed using a deep-learning system called Quantitative ECG (QCG), which was trained to detect several urgent clinical conditions, including shock, cardiac arrest, and reduced left ventricular ejection fraction (LVEF). RESULTS: Among the 1254 patients enrolled, in-hospital cardiac death occurred in 53 (4.2%) patients, and the QCG score for critical events (QCG-Critical) was significantly higher in these patients than in survivors (mean 0.57, SD 0.23 vs mean 0.29, SD 0.20; P<.001). The QCG-Critical score was an independent predictor of in-hospital cardiac death after adjustment for age, sex, comorbidities, HF etiology/type, atrial fibrillation, and QRS widening (adjusted odds ratio [OR] 1.68, 95% CI 1.47-1.92 per 0.1 increase; P<.001), and remained a significant predictor after additional adjustments for echocardiographic LVEF and N-terminal prohormone of brain natriuretic peptide level (adjusted OR 1.59, 95% CI 1.36-1.87 per 0.1 increase; P<.001). During long-term follow-up, patients with higher QCG-Critical scores (>0.5) had higher mortality rates than those with low QCG-Critical scores (<0.25) (adjusted hazard ratio 2.69, 95% CI 2.14-3.38; P<.001). CONCLUSIONS: Predicting outcomes in patients with acute HF using the QCG-Critical score is feasible, indicating that this AI-based ECG score may be a novel biomarker for these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01389843; https://clinicaltrials.gov/study/NCT01389843.

High Mobility Transistors and Flexible Optical Synapses Enabled by Wafer-Scale Chemical Transformation of Pt-Based 2D Layers.

Electronic devices employing two-dimensional (2D) van der Waals (vdW) transition-metal dichalcogenide (TMD) layers as semiconducting channels often exhibit limited performance (e.g., low carrier mobility), in part, due to their high contact resistances caused by interfacing non-vdW three-dimensional (3D) metal electrodes. Herein, we report that this intrinsic contact issue can be efficiently mitigated by forming the 2D/2D in-plane junctions of 2D semiconductor channels seamlessly interfaced with 2D metal electrodes. For this, we demonstrated the selectively patterned conversion of semiconducting 2D PtSe2 (channels) to metallic 2D PtTe2 (electrodes) layers by employing a wafer-scale low-temperature chemical vapor deposition (CVD) process. We investigated a variety of field-effect transistors (FETs) employing wafer-scale CVD-2D PtSe2/2D PtTe2 heterolayers and identified that silicon dioxide (SiO2) top-gated FETs exhibited an extremely high hole mobility of ∼120 cm2 V-1 s-1 at room temperature, significantly surpassing performances with previous wafer-scale 2D PtSe2-based FETs. The low-temperature nature of the CVD method further allowed for the direct fabrication of wafer-scale arrays of 2D PtSe2/2D PtTe2 heterolayers on polyamide (PI) substrates, which intrinsically displayed optical pulse-induced artificial synaptic behaviors. This study is believed to vastly broaden the applicability of 2D TMD layers for next-generation, high-performance electronic devices with unconventional functionalities.

North American Cancer Center Clinical Research Capacity and Benchmarking in the Postpandemic Era.

PURPOSE: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here. METHODS: The 28 question 2023 survey was sent to directors of AACI's clinical member cancer centers. Survey participation was voluntary, no compensation was provided, and data requested covered operations during 2022. Definitions were consistent with National Cancer Institute (NCI) CCTO reporting requirements and AACI staff anonymously compiled results for descriptive statistical reporting. RESULTS: The survey response rate was 61% (60/99). The median annual CCTO budget was $11.5 million (M) US dollars (USD) versus $8.2M USD in 2018. These budgets support a median of 150 FTEs versus 104 previously, and a median total of 384 versus 280 interventional treatment trials and a median of 479 versus 531 interventional treatment accruals. Sources of support for CCTO annual budgets were primarily from industry revenue (45.3%) or institutional support (31.7%). Nearly 60% of centers reported activating NCI-sponsored studies within 90 days but only 9% reported meeting a 90-day activation timeline for industry sponsored studies. CONCLUSION: Contemporary benchmarks for CCTO operations through this survey demonstrate larger staff sizes, larger budgets, more trials supported, but fewer patients enrolled to interventional treatment trials in comparison with 2018. These data shine a critical light on the increasing complexity of cancer clinical trials, the importance of external funding sources, and necessary operational efficiency upgrades to provide cutting-edge cancer research and care.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Epidemiologic relationship between alcohol flushing and smoking in the Korean population: the Korea National Health and Nutrition Examination Survey.

Although facial flushing after drinking alcohol (alcohol flushing response) is common in Asian populations, the epidemiological features in a large sample have been investigated in only a few studies. This study assessed the epidemiologic characteristics and associated factors for alcohol flushing in a Korean population. This study was based on data collected during the 2019 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5572 Korean adults was included in the general population group, and the alcohol flushing group consisted of 2257 participants. Smoking and physical activity were evaluated as possible associated factors for alcohol flushing. The overall prevalence of alcohol flushing was estimated at 40.56% of the general population (43.74% in males and 37.4% in females), and the prevalence was highest at 60-69 years of age and lowest in individuals older than 80 years. Occasional, frequent, and persistent alcohol flushing was reported by 11.9%, 3.7% and 15.0% of current flushers, among whom persistent flushers consumed the least amount of alcohol. Subjects who currently smoke had a higher propensity of alcohol flushing (adjusted OR 1.525, 95% CI 1.2-1.938), and subjects with smoking history of 20-29 pack-years (PYs) showed the highest association (adjusted OR 1.725, 95% CI 1.266-2.349) with alcohol flushing after adjustment for confounders. In contrast, significant association was not found between physical activity and alcohol flushing. The results demonstrated that current smoking status is shown to be significantly associated with alcohol flushing, and that current smokers with a history of smoking ≥ 20 PYs had a higher likelihood of alcohol flushing than non-smokers or ex-smokers.

Sihler's staining of the anterior belly of digastric muscle for botulinum toxin injection.

PURPOSE: The anterior belly of the digastric muscle (ABDM) is the target of botulinum toxin injection; however, anatomical considerations related to the injection point are absent. This study used Sihler's staining to analyze the intramuscular nerve distribution of ABDM to identify the most effective botulinum toxin injection points. METHODS: We used 12 specimens from 6 embalmed cadavers in this study. The specimens were manually dissected to preserve the mylohyoid nerve and subjected to Sihler's staining. From the gnathion to and hyoid bone, the ABDM was divided into three equal parts, distinguishing the anterior, middle, and posterior thirds. RESULTS: Only a branch of the mylohyoid nerve entered the ABDM, and its entry point was located in the middle-third region in all cases. The nerve endings were concentrated in the middle third (100%), followed by the anterior third (58.3%) and were not observed in the posterior third. CONCLUSION: The landmarks used in this study (gnathion and hyoid bone) are easily palpable on the skin surface, allowing clinicians to target the most effective injection site (middle third of ABDM). These results provide scientific and anatomic evidence for injection points, and will aid in the management of ABDM injection procedures in clinical practice.

Effect of positive end expiratory pressure on non-hypoxic apnea time and atelectasis during induction of anesthesia in infant: A randomized controlled trial.

INTRODUCTION: This study aimed to assess the impact of positive-end-expiratory pressure (PEEP) on the non-hypoxic apnea time in infants during anesthesia induction with an inspired oxygen fraction of 0.8. METHODS: This age stratified randomized controlled trial included patients under 1 year of age. Preoxygenation was performed using an inspired oxygen fraction of 0.8 for 2 min. Inspired oxygen fraction of 0.8 was administered via a face mask with volume-controlled ventilation at a tidal volume of 6 mL.kg-1, with or without 7 cmH2O of PEEP. Tracheal intubation was performed after 3 min of ventilation; however, it was disconnected from the breathing circuit. Ventilation was resumed once the pulse oximetry readings reached 95%. The primary outcome was the non-hypoxic apnea time, defined as the time from the cessation of ventilation to achieving a pulse oximeter reading of 95%. The secondary outcome measures included the degree of atelectasis assessed by ultrasonography and the presence of gastric air insufflation. RESULTS: Eighty-four patients were included in the final analysis. In the positive end-expiratory pressure group, the atelectasis score decreased (17.0 vs. 31.5, p < .001; mean difference and 95% CI of 11.6, 7.5-15.6), while the non-hypoxic apnea time increased (80.1 s vs. 70.6 s, p = .005; mean difference and 95% CI of -9.4, -16.0 to -2.9), compared to the zero end-expiratory pressure group, among infants who are 6 months old or younger, not in those aged older than 6 months. DISCUSSION: The application of positive end-expiratory pressure reduced the incidence of atelectasis and extended the non-hypoxic apnea time in infants who are 6 months old or younger. However, it did not affect the incidence of atelectasis nor the non-hypoxic apnea time in patients aged older than 6 months.

Ultrasound-Guided Botulinum Neurotoxin Injection for Alleviating Cricopharyngeus Muscle Spasticity: A Cadaveric Feasibility Study with Nerve Ending Analysis.

Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler's staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases.

A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia.

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed.This trial was registered at www.clinicaltrials.gov as #NCT02773732.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Simultaneous Detection Method of 11 Respiratory Drug Substances Including Theobromine, Oxymetazoline, etc. in Adulterated Dietary Supplements Using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Analysis.

Recently, the demand for respiratory disease-related products has surged due to the influence of coronavirus disease 2019, prompting warnings about illegal dietary supplements containing unauthorized substances. Additionally, adulterated dietary supplements are continuously detected in open markets, posing significant public health safety problem. In this study, we developed and validated an analytical method for 11 respiratory drug substances using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and proposed optimal conditions for LC-quadrupole time-of-flight MS (LC-QTOF-MS) to determine the fragmentation patterns of each substance. This method underwent thorough validation considering specificity, linearity, limits of detection and quantification, accuracy, precision, matrix effect, stability, etc. All results met international guidelines. These validated methods were applied to 52 dietary supplements advertised for treating respiratory diseases and enhancing respiratory function, among which one sample was found to contain 313.7 mg/g of theobromine. This determination was made by comparing the product ion ratios with the standards and subsequent quantification. To re-confirm the detected substances, their fragmentation patterns were compared with those of the standards using LC-QTOF-MS. In conclusion, the mass-based information, coupled with the LC-ESI-MS/MS method development, can be successfully applied to rapidly identify 11 respiratory drug substances in illegal dietary supplements used for respiratory disease treatment. The developed simultaneous detection method contributes to public health and safety improvements.

Triglyceride-Catabolizing Lactiplantibacillus plantarum GBCC_F0227 Shows an Anti-Obesity Effect in a High-Fat-Diet-Induced C57BL/6 Mouse Obesity Model.

Given the recognized involvement of the gut microbiome in the development of obesity, considerable efforts are being made to discover probiotics capable of preventing and managing obesity. In this study, we report the discovery of Lactiplantibacillus plantarum GBCC_F0227, isolated from fermented food, which exhibited superior triglyceride catabolism efficacy compared to L. plantarum WCSF1. Molecular analysis showed elevated expression levels of α/ß hydrolases with lipase activity (abH04, abH08_1, abH08_2, abH11_1, and abH11_2) in L. plantarum GBCC_F0227 compared to L. plantarum WCFS1, demonstrating its enhanced lipolytic activity. In a high-fat-diet (HFD)-induced mouse obesity model, the administration of L. plantarum GBCC_F0227 mitigated weight gain, reduced blood triglycerides, and diminished fat mass. Furthermore, L. plantarum GBCC_F0227 upregulated adiponectin gene expression in adipose tissue, indicative of favorable metabolic modulation, and showed robust growth and low cytotoxicity, underscoring its industrial viability. Therefore, our findings encourage the further investigation of L. plantarum GBCC_F0227's therapeutic applications for the prevention and treatment of obesity and associated metabolic diseases.