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Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16-/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16-/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury.

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We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance.

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BACKGROUND: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

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INTRODUCTION/AIMS: Hourglass-like constriction (HGC) may occur in several peripheral nerves. However, data on the prognosis of motor weakness in patients with HGC of the suprascapular nerve (SSN) are limited compared with other nerves. Here, we aimed to describe the clinical and imaging features of HGC of the SSN. METHODS: We retrospectively reviewed patients diagnosed with suprascapular neuropathy using magnetic resonance imaging (MRI) or electrodiagnostic studies over 16 years. After excluding extrinsic causes, patients with HGC of the SSN detected using MRI were included. RESULTS: Fourteen patients with HGC of the SSN were identified. MRI revealed that all HGCs were located between the origin of the SSN from the upper trunk of the brachial plexus and the suprascapular notch. Seven patients exhibited HGC precisely at the origin of the SSN from the brachial plexus. Four patients showed T2 hyperintensity of the SSN extending to the upper trunk of the brachial plexus or the extraforaminal cervical root. The initial treatments included observation (n = 1), steroid therapy (n = 12), suprascapular notch release (n = 1). Of the 12 patients with a sufficient follow-up period, nine fully recovered from motor weakness of the SSN with non-operative treatments. Six of the nine patients who recovered fully experienced their first clinical improvement more than 6 months after onset. DISCUSSION: Treatment strategies for HGC differ depending on the affected nerve. For HGC of the SSN, due to the high spontaneous recovery rate observed in our study, conservative management for at least 6 months should be initially considered.

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Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-ß (TGF-ß)-treated LX-2 cells. TGF-ß-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-ß-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-ß facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.

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Purpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan-Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes. Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively). Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.

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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.

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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.

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BACKGROUND: High-flow nasal oxygenation is reported to prolong duration of apnea while maintaining adequate oxygen saturation with the mouth closed. Also, buccal oxygenation is known to have similar effects in obese adults. We compared the effect of these two methods on prolongation of acceptable apnea time in pediatric patients with their mouth open. METHODS: Thirty-eight patients, aged 0-10 years were randomly allocated to either the high-flow nasal oxygenation group (n = 17) or the buccal oxygenation group (n = 21). After induction of anesthesia including neuromuscular blockade, manual ventilation was initiated until the expiratory oxygen concentration reached 90%. Subsequently, ventilation was paused, and the patient's head was extended, and mouth was opened. The HFNO group received 2 L·min-1·kg-1 of oxygen, and the BO group received 0.5 L·min-1·kg-1 of oxygen. We set a target apnea time according to previous literature. When the apnea time reached the target, we defined the case as "success" in prolongation of safe apnea time and resumed ventilation. When the pulse oximetry decreased to 92% before the target apnea time, it was recorded as "failure" and rescue ventilation was given. RESULTS: The success rate of safe apnea prolongation was 100% in the high-flow nasal oxygenation group compared to 76% in the buccal oxygenation group (p = .04). Oxygen reserve index, end-tidal or transcutaneous carbon dioxide partial pressure, and pulse oximetry did not differ between groups. CONCLUSION: High-flow nasal oxygenation is effective in maintaining appropriate arterial oxygen saturation during apnea even in children with their mouth open and is superior to buccal oxygenation. Buccal oxygenation may be a good alternative when high-flow nasal oxygenation is not available.

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This study aimed to elucidate the intramuscular distribution pattern of the medial plantar nerve and determine its motor nerve ending territories within the abductor hallucis muscle using modified Sihler's staining and external anatomical landmarks. The study included 40 specimens of the abductor hallucis muscle (13 men and seven women) from formalin-fixed (ten cadavers) and fresh cadavers (ten cadavers), with a mean age of 77.6 years. The entry point of the medial plantar nerve into the muscle was examined, followed by Sihler's staining to analyze the intramuscular distribution pattern and motor nerve ending location within the abductor hallucis muscle. Ultrasound- and palpation-guided injections were performed to verify the applicability of motor nerve ending location-based injections. The areas with the highest concentrations of nerve entry points and nerve endings were identified in the central portion of the muscle. Ultrasound- and palpation-guided injections were safely positioned near the densest nerve ending region of the muscle. These detailed anatomical data and injection methods would be beneficial for proceeding with safe and effective injection treatments using various analgesic agents to alleviate abductor hallucis muscle-associated pain disorders.

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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%.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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