Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Development of Clinically Validated Artificial Intelligence Model for Detecting ST-segment Elevation Myocardial Infarction.

STUDY OBJECTIVE: Although the importance of primary percutaneous coronary intervention has been emphasized for ST-segment elevation myocardial infarction (STEMI), the appropriateness of the cardiac catheterization laboratory activation remains suboptimal. This study aimed to develop a precise artificial intelligence (AI) model for the diagnosis of STEMI and accurate cardiac catheterization laboratory activation. METHODS: We used electrocardiography (ECG) waveform data from a prospective percutaneous coronary intervention registry in Korea in this study. Two independent board-certified cardiologists established a criterion standard (STEMI or Not STEMI) for each ECG based on corresponding coronary angiography data. We developed a deep ensemble model by combining 5 convolutional neural networks. In addition, we performed clinical validation based on a symptom-based ECG data set, comparisons with clinical physicians, and external validation. RESULTS: We used 18,697 ECGs for the model development data set, and 1,745 (9.3%) were STEMI. The AI model achieved an accuracy of 92.1%, sensitivity of 95.4%, and specificity of 91.8 %. The performances of the AI model were well balanced and outstanding in the clinical validation, comparison with clinical physicians, and the external validation. CONCLUSION: The deep ensemble AI model showed a well-balanced and outstanding performance. As visualized with gradient-weighted class activation mapping, the AI model has a reasonable explainability. Further studies with prospective validation regarding clinical benefit in a real-world setting should be warranted.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

Moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome and atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING trial.

AIM: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. MATERIALS AND METHODS: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. CONCLUSIONS: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes.

Comparison of Intracardiac Echocardiography Versus Transesophageal Echocardiography for Guidance During Transcatheter Aortic Valve Replacement.

BACKGROUND AND OBJECTIVES: Evidence regarding the efficacy and safety of intracardiac echocardiography (ICE) for guidance during transcatheter aortic valve replacement (TAVR) is limited. This study aimed to compare the clinical efficacy and safety of ICE versus transesophageal echocardiography (TEE) for guiding TAVR. METHODS: This prospective cohort study included patients who underwent TAVR from August 18, 2015, to June 31, 2021. Eligible patients were stratified by echocardiographic modality (ICE or TEE) and anesthesia mode (monitored anesthesia care [MAC] or general anesthesia [GA]). Primary outcome was the 1-year composite of all-cause mortality, rehospitalization for cardiovascular cause, or stroke, according to the Valve Academic Research Consortium-3 (VARC-3) definition. Propensity score matching was performed, and study outcomes were analyzed for the matched cohorts. RESULTS: Of the 359 eligible patients, 120 patients were matched for the ICE-MAC and TEE-GA groups, respectively. The incidence of primary outcome was similar between matched groups (18.3% vs. 20.0%; adjusted hazard ratio, 0.94; 95% confidence interval [CI], 0.53-1.68; p=0.843). ICE-MAC and TEE-GA also had similar incidences of moderate-to-severe paravalvular regurgitation (PVR) (4.2% vs. 5.0%; adjusted odds ratio, 0.83; 95% CI, 0.23-2.82; p=0.758), new permanent pacemaker implantation, and VARC-3 types 2-4 bleeding. CONCLUSIONS: ICE was comparable to TEE for guidance during TAVR for the composite clinical efficacy outcome, with similar incidences of moderate-to-severe PVR, new permanent pacemaker implantation, and major bleeding. These results suggest that ICE could be a safe and effective alternative echocardiographic modality to TEE for guiding TAVR.

Distribution of Neurofilament in Peeled Internal Limiting Membrane.

BACKGROUND AND OBJECTIVE: The aim was to study the distribution of neurofilament in peeled internal limiting membrane (ILM). PATIENTS AND METHODS: Prospective case study. Vitrectomy and ILM peeling were performed in patients with epiretinal membrane and macular hole. ILM flap specimens were obtained as one disc area size from five locations. Immunofluorescent staining was performed with an antineurofilament heavy antibody. Using a confocal microscope, retinal cell debris density was studied using the ImageJ program. RESULTS: Percent of stained neurofilament was 1.58 ± 1.14% in total (2.45 ± 1.37% in extranasal, 1.97 ± 0.75% in extratemporal, 1.93 ± 1.26% in juxta-nasal, 0.89 ± 0.69% in fovea, and 0.63 ± 0.46% in juxtatemporal). The Kruskal-Wallis test revealed significant differences among groups (P < 0.05). Bonferroni post hoc analysis only confirmed significant difference between juxtatemporal and extranasal groups (P < 0.05). CONCLUSIONS: In peeled ILM flap, neurofilaments are rarely detected in the juxtatemporal area. However, they are frequently detected in the extranasal area. [Ophthalmic Surg Lasers Imaging Retina 2023;54:643-648.].

Effects of Subcutaneous Methotrexate in Patients with Refractory Uveitis and Chorioretinitis.

PURPOSE: Methotrexate (MTX) is an immunosuppressive agent used to treat noninfectious inflammatory eye conditions and is generally administered orally for ocular inflammatory diseases. When used in rheumatological diseases, subcutaneous administration has been reported to show higher efficacy than oral administration. Therefore, this study aimed to evaluate the effect of subcutaneous MTX in patients with refractory uveitis or choroiditis who did not respond to other immunosuppressive agents. METHODS: A retrospective case series study was performed between January and December 2018. Patients with uveitis or chorioretinitis who showed little to no treatment response for 6 months or more with conventional immunosuppressive agents were treated with MTX, administered subcutaneously. After 6 months of treatment, patients were evaluated to determine whether complete suppression of inflammation sustained for ≥28 days was achieved in both eyes and whether improvement can be confirmed by fluorescein angiography (FAG). RESULTS: Subcutaneous MTX treatment was performed on 18 patients: 11 had intermediate uveitis and seven had posterior uveitis. In the intermediate uveitis patient group, five patients (50% of the group excluding one patient who dropped out) showed improvement in FAG and three patients (30%) showed complete suppression of inflammation. In the posterior uveitis group, two out of seven patients (excluding two patients who dropped out) showed an improvement, two patients in the group showed little change, and one patient showed aggravation of FAG findings. CONCLUSIONS: The study confirmed that in patients with uveitis or chorioretinitis who had a refractory response to treatment with other immunosuppressive agents, subcutaneous MTX showed improved treatment efficacy.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis.

BACKGROUND: The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. OBJECTIVES: We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. RESULTS: Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). CONCLUSIONS: Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665).

Adult-onset MELAS syndrome in a 51-year-old woman without typical clinical manifestations: a case report.

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a multi-organ disorder resulting from mitochondrial DNA (mtDNA) mutations. We report a case of suspected MELAS syndrome that progressed to left ventricular dysfunction 24 years after an initial diagnosis of atrioventricular block (AVB). Case summary: A 51-year-old woman was referred to heart failure clinic because of dyspnoea on exertion and progressive cardiomegaly. She had a dual-chamber pacemaker implanted for 24 years because of a high-degree AVB. She was treated for diabetes mellitus for 23 years and used hearing aids for 12 years because of sensorineural hearing loss. Transthoracic echocardiography revealed reduced left ventricular ejection fraction (26%), with increased thickness and unusual texture of the myocardium. The absence of abnormal findings on serum and urine protein electrophoresis suggested that light-chain amyloidosis was unlikely. In addition, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy revealed no definite uptake in the myocardium. Endomyocardial biopsy revealed a hypertrophy of myocytes in haematoxylin-eosin staining, and electron microscopy revealed a disarrangement of mitochondrial cristae, which were suggestive of mitochondrial cardiomyopathy. A mtDNA test detected the m.3243A > G mutation in the MT-TL1 gene. According to these findings, MELAS syndrome was the most probable diagnosis despite the absence of common symptoms such as stroke-like episodes or lactic acidosis. Discussion: The patient had progressed to heart failure with reduced ejection fraction 24 years after the first cardiac manifestation. An identification of the mutation in the MT-TL1 gene, indicative of MELAS syndrome, enabled the diagnosis of MELAS syndrome without typical manifestations.

Pharmacopuncture Effects on Insomnia Disorder: Protocol for a Multi-Site, Randomized, Acupuncture-Controlled, Clinical Trial.

Insomnia is a common health problem that can lead to various diseases and negatively impact quality of life. Pharmacopuncture is a new type of acupuncture that involves applying herbal medicine extracts to acupoints. Korean medicine doctors frequently use it to treat insomnia disorder. However, there is insufficient evidence to support the effectiveness and safety of pharmacopuncture for insomnia disorder. We designed a pragmatic randomized controlled trial to compare the effectiveness of pharmacopuncture and acupuncture for insomnia disorder. This multi-site, randomized, acupuncture-controlled trial will enroll 138 insomnia patients. The subjects will be randomly assigned to one of two groups, pharmacopuncture or acupuncture, at a 2:1 ratio. For 4 weeks, the participants will receive ten sessions of pharmacopuncture or acupuncture treatment and will be followed up for 4 weeks after the treatment ends. The Pittsburgh Sleep Quality Index score is the primary outcome measure. Insomnia severity index score, sleep parameters recorded using actigraphy and sleep diaries, physical symptoms associated with insomnia, emotions, quality of life, medical costs, and safety are the secondary outcome measures. The findings of this trial willprovide evidence that will be useful in clinical decision-making for insomnia treatment strategies.

Association of Artificial Intelligence-Aided Chest Radiograph Interpretation With Reader Performance and Efficiency.

Importance: The efficient and accurate interpretation of radiologic images is paramount. Objective: To evaluate whether a deep learning-based artificial intelligence (AI) engine used concurrently can improve reader performance and efficiency in interpreting chest radiograph abnormalities. Design, Setting, and Participants: This multicenter cohort study was conducted from April to November 2021 and involved radiologists, including attending radiologists, thoracic radiology fellows, and residents, who independently participated in 2 observer performance test sessions. The sessions included a reading session with AI and a session without AI, in a randomized crossover manner with a 4-week washout period in between. The AI produced a heat map and the image-level probability of the presence of the referrable lesion. The data used were collected at 2 quaternary academic hospitals in Boston, Massachusetts: Beth Israel Deaconess Medical Center (The Medical Information Mart for Intensive Care Chest X-Ray [MIMIC-CXR]) and Massachusetts General Hospital (MGH). Main Outcomes and Measures: The ground truths for the labels were created via consensual reading by 2 thoracic radiologists. Each reader documented their findings in a customized report template, in which the 4 target chest radiograph findings and the reader confidence of the presence of each finding was recorded. The time taken for reporting each chest radiograph was also recorded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated for each target finding. Results: A total of 6 radiologists (2 attending radiologists, 2 thoracic radiology fellows, and 2 residents) participated in the study. The study involved a total of 497 frontal chest radiographs-247 from the MIMIC-CXR data set (demographic data for patients were not available) and 250 chest radiographs from MGH (mean [SD] age, 63 [16] years; 133 men [53.2%])-from adult patients with and without 4 target findings (pneumonia, nodule, pneumothorax, and pleural effusion). The target findings were found in 351 of 497 chest radiographs. The AI was associated with higher sensitivity for all findings compared with the readers (nodule, 0.816 [95% CI, 0.732-0.882] vs 0.567 [95% CI, 0.524-0.611]; pneumonia, 0.887 [95% CI, 0.834-0.928] vs 0.673 [95% CI, 0.632-0.714]; pleural effusion, 0.872 [95% CI, 0.808-0.921] vs 0.889 [95% CI, 0.862-0.917]; pneumothorax, 0.988 [95% CI, 0.932-1.000] vs 0.792 [95% CI, 0.756-0.827]). AI-aided interpretation was associated with significantly improved reader sensitivities for all target findings, without negative impacts on the specificity. Overall, the AUROCs of readers improved for all 4 target findings, with significant improvements in detection of pneumothorax and nodule. The reporting time with AI was 10% lower than without AI (40.8 vs 36.9 seconds; difference, 3.9 seconds; 95% CI, 2.9-5.2 seconds; P < .001). Conclusions and Relevance: These findings suggest that AI-aided interpretation was associated with improved reader performance and efficiency for identifying major thoracic findings on a chest radiograph.

Clinical evidence of initiating a very low dose of sacubitril/valsartan: a prospective observational analysis.

Sacubitril/valsartan is superior to enalapril in reducing the risks of cardiovascular death and preventing hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). However, patients often do not receive sacubitril/valsartan because of concerns about hypotension. We examined the feasibility of initiating sacubitril/valsartan at a very low dose (VLD) in potentially intolerant patients with HFrEF and subsequent dose up-titration, treatment persistence and outcomes. We analyzed 206 patients with HFrEF grouped according to starting sacubitril/valsartan dose. The VLD group (n = 106) commenced 25 mg twice daily, and the standard-dose (SD) group (n = 100) started on ≥ 50 mg twice daily. Baseline systolic blood pressure was 103 ± 12 mmHg vs. 119 ± 14 mmHg in the SD group (P < 0.001). The maximal target dose achievement rate was higher in the SD group (27.0% vs 9.4%, p = 0.001) and the VLD group experienced more dose up-titrations and fewer down-titrations than the SD group. The VLD group had a decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) similar to the SD group and a similar increase in left ventricular ejection fraction. There were no significant differences in symptomatic hypotension, worsening renal function, hyperkalemia, cardiovascular mortality, and rehospitalization due to HF between the two groups during follow-up period. In patients considered by the treating physician likely to be intolerant of sacubitril/valsartan, initiation with 25 mg twice daily was generally possible and patients remained in therapy, with similar decreases in NT-proBNP and increases in left ventricular ejection fraction to those observed in patients receiving SD sacubitril/valsartan.

Contrast-enhanced MRI T1 Mapping for Quantitative Evaluation of Putative Dynamic Glymphatic Activity in the Human Brain in Sleep-Wake States.

Background Evaluation of the glymphatic system with intrathecal contrast material injection has limited clinical use. Purpose To investigate the feasibility of using serial intravenous contrast-enhanced T1 mapping in the quantitative evaluation of putative dynamic glymphatic activity in various brain regions and to demonstrate the effect of sleep on glymphatic activity in humans. Materials and Methods In this prospective study from May 2019 to February 2020, 25 healthy participants (mean age, 25 years ± 2 [standard deviation]; 15 men) underwent two cycles of MRI (day and night cycles). For each cycle, T1 maps were acquired at baseline and 0.5, 1, 1.5, 2, and 12 hours after intravenous contrast material injection. For the night cycle, participants had a normal night of sleep between 2 and 12 hours. The time (tmin) to reach the minimum T1 value (T1min), the absolute difference between baseline T1 and T1min (peak ΔT1), and the slope between two measurements at 2 and 12 hours (slope[2h-12h]) were determined from T1 value-time curves in cerebral gray matter (GM), cerebral white matter (WM), cerebellar GM, cerebellar WM, and putamen. Mixed-model analysis of variance (ANOVA), Friedman test, and repeated-measures ANOVA were used to assess the effect of sleep on slope(2h-12h) and to compare tmin and peak ΔT1 among different regions. Results The slope(2h-12h) increased from the day to night cycles in cerebral GM, cerebellar GM, and putamen (geometric mean ratio [night/day] = 1.4 [95% CI: 1.2, 1.7], 1.3 [95% CI: 1.1, 1.4], and 2.4 [95% CI: 1.6, 3.6], respectively; P = .001, P < .001, and P < .001, respectively). Median tmin values were 0.5 hour in cerebral and cerebellar GM and putamen for both cycles. Cerebellar GM had the highest mean peak ΔT1, followed by cerebral GM and putamen in both day (159 msec ± 6, 99 msec ± 4, and 62 msec ± 5, respectively) and night (152 msec ± 6, 104 msec ± 6, and 58 msec ± 4, respectively) cycles. Conclusion Clearance of a gadolinium-based contrast agent was greater after sleep compared with daytime wakefulness. These results suggest that sleep was associated with greater glymphatic clearance compared with wakefulness. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Anzai and Minoshima in this issue.

Effectiveness of radiologist training in improving reader agreement for Lung-RADS 4X categorization.

OBJECTIVES: To identify the agreement on Lung CT Screening Reporting and Data System 4X categorization between radiologists and an expert-adjudicated reference standard and to investigate whether training led to improvement of the agreement measures and diagnostic potential for lung cancer. METHODS: Category 4 nodules in the Korean Lung Cancer Screening Project were identified retrospectively, and each 4X nodule was matched with one 4A or 4B nodule. An expert panel re-evaluated the categories and determined the reference standard. Nineteen radiologists were asked to determine the presence of CT features of malignancy and 4X categorization for each nodule. A review was performed in two sessions, and training material was given after session 1. Agreement on 4X categorization between radiologists and the expert-adjudicated reference standard and agreement between radiologist-assessed 4X categorization and lung cancer diagnosis were evaluated. RESULTS: The 48 expert-adjudicated 4X nodules and 64 non-4X nodules were evenly distributed in each session. The proportion of category 4X decreased after training (56.4% ± 16.9% vs. 33.4% ± 8.0%; p < 0.001). Cohen's κ indicated poor agreement (0.39 ± 0.16) in session 1, but agreement improved in session 2 (0.47 ± 0.09; p = 0.03). The increase in agreement in session 2 was observed among inexperienced radiologists (p < 0.05), and experienced and inexperienced reviewers exhibited comparable agreement performance in session 2 (p > 0.05). All agreement measures between radiologist-assessed 4X categorization and lung cancer diagnosis increased in session 2 (p < 0.05). CONCLUSION: Radiologist training can improve reader agreement on 4X categorization, leading to enhanced diagnostic performance for lung cancer. KEY POINTS: • Agreement on 4X categorization between radiologists and an expert-adjudicated reference standard was initially poor, but improved significantly after training. • The mean proportion of 4X categorization by 19 radiologists decreased from 56.4% ± 16.9% in session 1 to 33.4% ± 8.0% in session 2. • All agreement measures between the 4X categorization and lung cancer diagnosis increased significantly in session 2, implying that appropriate training and guidance increased the diagnostic potential of category 4X.

Investigating Microcystin-LR adsorption mechanisms on mesoporous carbon, mesoporous silica, and their amino-functionalized form: Surface chemistry, pore structures, and molecular characteristics.

Microcystin-LR (MC-LR) is the most common cyanotoxin released from algal-blooms. The study investigated the MC-LR adsorption mechanisms by comparing adsorption performance of protonated mesoporous carbon/silica (MC-H, MS-H) and their amino-functionalized forms (MC-NH2 and MS-NH2) considering surface chemistry and pore characteristics. The maximum MC-LR adsorption capacity (Langmuir model) of MC-H (37.87 mg/g) was the highest followed by MC-NH2 (29.25 mg/g) and MS-NH2 (23.03 mg/g), because pore structure is partly damaged during amino-functionalization. However, MC-NH2 (k2 = 0.042 g/mg/min) reacted faster with MC-LR than MC-H during early-stage adsorption due to enhancing electrostatic interactions. Intra-particle diffusion model fit indicated Kp,1 of MC-H (2.11 mg/g/min1/2) was greater than MC-NH2 due to its greater surface area and pore volume. Also, large mesopore diameters are favorable to MC-LR adsorption by pore diffusion. The effect of adsorbate molecular size on adsorption trend against MC-H, MC-NH2 and MS-NH2 was determined by kinetic experiments using two dyes, reactive blue and acid orange: MS-NH2 achieved the highest adsorption for both dyes due to the large number of amino groups on its surface (41.2 NH2/nm2). Overall, it was demonstrated that adsorption of MC-LR on mesoporous materials is governed by (meso-)pore diffusion and π - π (and hydrophobic) interactions induced by carbon materials; in addition, positively-charged grafted amino groups enhance initial MC-LR adsorption rate.

Oxidation of tetracycline and oxytetracycline for the photo-Fenton process: Their transformation products and toxicity assessment.

Advanced oxidation processes have gained significant attention for treating tetracycline (TC) and oxytetracycline (OTC), however, their oxidation using the photo-Fenton process has not been sufficiently studied. Although degradations of TC and OTC were enhanced by increasing H2O2 and Fe2+ within the ranges investigated (H2O2 = 20-50 mg/L and Fe = 1-10 mg/L) under UV irradiation, further experiments for the photo-Fenton process were conducted with 20 mg/L of H2O2 and 5 mg/L of Fe2+ to balance efficiency and cost. The photo-Fenton process (UV/H2O2/Fe2+) was shown to be more effective to remove TC and OTC than H2O2, ultraviolet (UV), and UV/H2O2 at the same doses of oxidants. Inorganic anions and cations were shown to inhibit the degradation of TC and OTC during the photo-Fenton process, in the following order: HPO42- > HCO3- â‰« SO42- > Cl- and Cu2+ ≫ Ca2+ > Na+. The TC and OTC degradation are generally improved by increasing pH, which is opposite to the kpCBA,obs values, caused by increasing the deprotonation degree of TC and OTC. Four and nine transformation products of TC and OTC, respectively, were detected over the treatment period. Among the transformation products, m/z 443.14 (C22H22N2O8) formed during TC degradation, and m/z 433.16 (C20H20N2O9) and m/z 415.15 (C20H18N2O8) formed during OTC degradation, were reported for the first time. Vibrio fischeri toxicity assessment indicated that the inhibition ratio was decreased with a decreasing TC concentration, while, OTC transformation lead to higher toxicity. The product (m/z 477.15b) was determined to be the compound causing toxicity during degradation of OTC by using the quantitative structure activity relationship (QSAR). This toxic transformation product caused higher inhibition ratios than its parental compound (OTC), but its further oxidization resulted in decreasing the inhibition ratios.