Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Gender Difference of Blood Pressure Control Rate and Clinical Prognosis in Patients With Resistant Hypertension: Real-World Observation Study.

BACKGROUND: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. METHODS: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. RESULTS: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men. During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. CONCLUSION: In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

Impact of a screening protocol for blood pressure level for hypertension in the Korean community health survey.

PURPOSE: A community program is an efficient model for improving the management of chronic diseases such as hypertension, diabetes, and dyslipidemia. A specific blood pressure (BP) measurement protocol was developed for community settings in which BP was measured by the interviewer at the interviewee's home. MATERIALS AND METHODS: In the 2018 Korean Community Health Survey, BP was measured twice at a five-minute interval after a five-minute resting period at the beginning of the survey. In 2019, BP was measured at the end of the survey after a two-minute rest and was obtained as three measurements at one-minute intervals. As factors related to BP level, stressful stimuli within 30 min before BP measurement such as smoking, caffeine, and/or exercise; duration of rest; and survey year were analysed. RESULTS: The mean age of participants was 55.2 years, and females accounted for 55.4% of the participants (n = 399,838). Stressful stimuli were observed in 21.9% of the participants in 2018 (n = 188,440) and 11.3% in 2019 (n = 211,398). Duration of rest was 0 min (2.1%), two minutes (55.0%), and five minutes (47.9%). When adjusted for age, sex, body mass index, antihypertensive medication, the arm of measurement, survey year (beta= -4.092), stressful stimuli (beta = 0.834), and resting time (beta = -1.296 per one minute of rest) were significant factors for mean systolic BP. A two-minute rest was not a significant factor in mean BP. The differences in adjusted mean systolic BPs were significant for rest times of five minutes vs. two minutes (3.1 mmHg, p < 0.0001), for stressful stimuli (0.8 mmHg, p < 0.0001), and for survey year (127.8 ± 0.2 mmHg vs. 122.2 ± 0.3 mmHg for 2018 vs. 2019, p < 0.0001). CONCLUSION: For the community-based home visit survey, avoidance of stressful stimuli, five-minute rest, and allocation of BP measurement in the last part of the survey was useful for obtaining a stable BP level.

Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation.

BACKGROUND: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). METHODS: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. RESULTS: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01-3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27-0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day re-hospitalization (wHR, 0.60; 95% CI, 0.37-0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48-0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59-0.99; P = 0.041). CONCLUSION: Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Beta-blocker Therapy at Discharge in Patients with Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: ß-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. METHODS: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. RESULTS: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34-0.82). CONCLUSION: In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis.

Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through apoptosis.

Prognostic Effect of Guideline-Directed Therapy Is More Noticeable Early in the Course of Heart Failure.

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), ß-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.95), mortality (HR, 0.41; 95% CI, 0.24-0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36-0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41-0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47-0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and ß-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.

Prognostic value of short-term follow-up BNP in hospitalized patients with heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) has prognostic significance in heart failure (HF), and reductions in BNP may predict clinical improvement. However, there are limited data regarding the prognostic value of BNP during short-term follow-up. The aim of this study was to evaluate the relationship between short-term follow-up BNP and mortality after discharge in patients with HF. METHODS: We analyzed 427 patients hospitalized with HF from the Wonju Severance Christian Hospital Heart Failure Registry from April 2011 to December 2013, with a planned follow-up period through February 2016. Of the 427 patients, 240 (mean age, 75 years; 102 males, 42.5%) had BNP measured on admission and within the short-term follow-up period (3 months). We compared all-cause mortality during the clinical follow-up period (median length of follow-up, 709.5 days) according to the median value of BNP on admission (as a baseline value) and over a short-term follow-up period after discharge. RESULTS: Median BNP at admission was 816.5 pg/ml, and median follow-up BNP was 369.7 pg/ml. Multivariate analysis revealed a positive association between risk of death and high BNP. High BNP during follow-up was significantly associated with a greater risk of all-cause mortality compared to low BNP (P < 0.001). Initial BNP was not significantly associated with all-cause mortality. A multivariate model showed that follow-up BNP and percent change in BNP were independently associated with all-cause mortality after adjustment for covariates. Of the 3 BNP measurement strategies, BNP after discharge (IDI of 0.072, P < .0001 and NRI of 0.707, P < .0001) and percent change in BNP (IDI of 0.113, P < .0001 and NRI of 0.782, P < .0001) demonstrated the greatest increase in discrimination and net reclassification for mortality. Unfortunately, we did not find any significant value with initial BNP. Kaplan-Meier survival analysis was performed to assess mortality stratified by BNP according to the median value, high median of follow-up BNP and percent change in BNP were associated with significantly higher mortality compared to the below median (log-rank, p < 0.001). CONCLUSIONS: Short-term follow-up BNP and percent change in BNP level are significant prognostic factors of all-cause mortality. These values will be clinically useful when evaluating prognosis in hospitalized patients with heart failure.

Decreased blood pressure associated with in-vehicle exposure to carbon monoxide in Korean volunteers.

BACKGROUND: Carbon monoxide (CO) is one of the primary components of emissions from light-duty vehicles, and reportedly comprises 77% of all pollutants emitted in terms of concentration. Exposure to CO aggravates cardiovascular disease and causes other health disorders. The study was aimed to assess the negative effects by injecting different amounts of CO concentration directly to human volunteers boarding in the car. METHODS: Human volunteers were exposed to CO concentrations of 0, 33.2, and 72.4 ppm, respectively during the first test and 0, 30.3, and 48.8 ppm respectively during the second test while seated in the car. The volunteers were exposed to each concentration for approximately 45 min. After exposure, blood pressure measurement, blood collection (carboxyhemoglobin [COHb] analysis), medical interview, echocardiography test, and cognitive reaction test were performed. RESULT: In patients who were exposed to a mean concentration of CO for 72.4 ± 1.4 ppm during the first exposure test and 48.8 ± 3.7 ppm during the second exposure test, the COHb level exceeded 2%. Moreover, the diastolic blood pressure was decreased while increasing in CO concentration after exposure. The medical interview findings showed that the degree of fatigue was increased and the degree of concentration was reduced when the exposed concentration of CO was increased. CONCLUSION: Although the study had a limited sample size, we found that even a low concentration of CO flowing into a car could have a negative influence on human health, such as change of blood pressure and degree of fatigue.

No association of the norepinephrine transporter gene (SLC6A2) and cognitive and behavioural phenotypes of patients with autism spectrum disorder.

We examined the association between the norepinephrine transporter (SLC6A2) gene and autism spectrum disorder (ASD) in a Korean population. In addition, we investigated which phenotypes of ASD are best attributed to the genotype of SLC6A2. A total of 184 subjects with ASD, their 156 unaffected siblings and both biological parents were recruited through university hospitals. We used the Autism Diagnostic Interview-Revised, the Aberrant Behaviour Checklist (ABC), the Child Behaviour Checklist (CBCL), the Stroop Colour-Word Interference Test and the Wisconsin Card Sorting Test (WCST) as quantitative measures of the ASD phenotypes. The associations between the quantitative measures and specific single-nucleotide polymorphisms (SNPs) were tested with linear regression analyses. We did not find any evidence of the over-transmission of either allele of the 10SLC6A2 SNPs in the DFAM test. At an empirical p value <0.05, findings that were consistent between the linear regression analyses and the QFAM tests were the positive associations between the A allele of rs36020 and attention problems on the CBCL and stereotypical behaviours on the ABC and between the C allele of rs1814270 and the number of trials required to complete the first WCST category. However, these associations did not remain after correction for multiple testing. The study results of this study do not support the association between the SLC6A2 and the diagnosis or phenotype of ASD. However, the study must be replicated in larger populations and with using more genetic markers.

Neural responses to various rewards and feedback in the brains of adolescent Internet addicts detected by functional magnetic resonance imaging.

AIM: This study aimed to examine differences in brain activation for various types of reward and feedback in adolescent Internet addicts (AIA) and normal adolescents (NA) using functional magnetic resonance imaging (fMRI). METHODS: AIA (n = 15) and NA (n = 15) underwent fMRI while performing easy tasks for which performance feedback (PF), social reward (SR) (such as compliments), or monetary reward (MR) was given. Using the no reward (NR) condition, three types of contrasts (PF-NR, SR-NR, and MR-NR) were analyzed. RESULTS: In NA, we observed activation in the reward-related subcortical system, self-related brain region, and other brain areas for the three contrasts, but these brain areas showed almost no activation in AIA. Instead, AIA showed significant activation in the dorsolateral prefrontal cortex for the PF-NR contrast and the negative correlation was found between the level of activation in the left superior temporal gyrus (BA 22) and the duration of Internet game use per day in AIA. CONCLUSION: These findings suggest that AIA show reduced levels of self-related brain activation and decreased reward sensitivity irrespective of the type of reward and feedback. AIA may be only sensitive to error monitoring regardless of positive feelings, such as sense of satisfaction or achievement.

The Last Rise and Fall Shown to us by the Man Who Chose "Swollen Foot": The Film The Whale.

The film The Whale goes beyond just depicting one aspect of the life of a morbidly obese man. As the audience watches Charlie, the main character who helplessly chose to live a morbidly obese life, we are compelled to reflect on what it means for ourselves to rise from the ground as we live in a gravitational field. Ultimately, this film is in line with director Darren Arnofsky's previous masterpiece, Black Swan. While the Oedipus complex runs through both films, this film goes one step further than Black Swan to face head-on the theme of "swollen foot," which is the original meaning of Oedipus. Through this move, we realize the essence of the Oedipus complex-something more fundamental than castration anxiety-something that we have been missing.

Basic Management Strategies by Life Cycle for Treatment of the Persons With Autism Spectrum Disorder.

Interventions for targeted symptoms are important when setting treatment strategies for individuals with autism spectrum disorder (ASD) and developmental disabilities. Especially, the goal should be to achieve individual "niche construction" by allowing them to select and adjust an environment where they can demonstrate their special characteristics and strengths. In addition, these choices should vary depending on the stage of development of each person with ASD and developmental disabilities. It is necessary to establish a detailed and systematic plan for diagnosis and treatment necessary for infants and toddlers, school placement in school age, and employment or self-reliance in adult transition period to establish customized treatment strategies that fit the individual level of people with ASD and developmental disabilities.

Clinical Midterm Results of Surgical Aortic Valve Replacement with Sutureless Valves.

Background: Sutureless aortic valves may enable shorter procedure times, which benefits patients with elevated surgical risk. We describe the outcomes of patients with aortic stenosis who underwent aortic valve replacement (AVR) using the sutureless Perceval aortic bioprosthesis. Methods: Data from a retrospective cohort were obtained from a clinical database. The study enrolled patients with symptomatic severe aortic stenosis who underwent surgical AVR with a sutureless bioprosthesis between August 2015 and December 2020. In total, 113 patients were included (mean age, 75.3±8.4 years; 57.5% women; median Society of Thoracic Surgeons score, 9.7%; mean follow-up period, 51.19±20.6 months). Of these patients, 41 were octogenarians (36.2%) and 3 were nonagenarians (2.6%). Transthoracic echocardiography was employed to assess changes in ejection fraction (EF), left ventricular mass index (LVMI), and mean pressure gradient (MPG). Results: The in-hospital mortality rate was 2.6%, and 13 patients developed new-onset atrial fibrillation. A permanent pacemaker was implanted in 3 patients (2.6%). The median intensive care unit stay was 1 day (interquartile range [IQR], 1-2 days), and the median hospital stay was 12 days (IQR, 9.5-15 days). The overall survival rate at 5 years was 95.9%. LVMI and MPG were reduced postoperatively, while EF increased over the follow-up period. No structural valve deterioration was observed, and no meaningful paravalvular leakage developed during follow-up. Conclusion: The use of a sutureless valve in the aortic position is safe and feasible, even for high-risk elderly patients requiring surgical AVR. LVMI and MPG decreased postoperatively, while EF increased over the follow-up period.

Practical Recommendations for the Evaluation and Management of Cardiac Injury Due to Carbon Monoxide Poisoning.

Carbon monoxide (CO) is a relatively frequent cause of poisoning evaluated in emergency departments. The risk of neurologic injuries, such as cognitive, psychological, vestibular, and motor deficits, is 25% to 50%. However, the risk of cardiac injuries should also be considered. Among patients with CO poisoning, the mortality in patients with myocardial injury is approximately 3 times greater than that in patients without myocardial injury. In large-scale studies, up to 69.2% of patients with acute CO poisoning exhibiting elevated troponin I levels and no underlying cardiovascular illnesses had late gadolinium enhancement on cardiac magnetic resonance, suggesting covert CO-induced myocardial fibrosis. Myocardial damage can be evaluated using electrocardiography, echocardiography, computed tomography, and cardiac magnetic resonance. This paper offers recommendations for cardiac evaluations based on our collective experience of managing >2,000 cases of acute CO poisoning with supporting information taken from peer-reviewed published reports on CO poisoning.

Angiotensin receptor-neprilysin inhibitor adherence and outcomes in heart failure with reduced ejection fraction.

AIMS: Whether medication adherence to angiotensin receptor-neprilysin inhibitor (ARNI) in real-world practice is associated with the reduced risk of all-cause mortality or hospitalization relative to that with traditional renin-angiotensin system (RAS) blockade remains unclear. This study investigated the influence of medication adherence of ARNI and traditional RAS blockade in heart failure with reduced ejection fraction (HFrEF). METHOD: We conducted a nationwide longitudinal cohort study with patients with HFrEF using data from the Korean National Health Insurance Service data (2017-2021) covering the entire population. A total of 13 483 patients with HFrEF who received ARNI were matched 1:1 with 13 483 patients who received traditional RAS blockade using propensity score matching. The primary outcome was a composite of all-cause mortality or any hospitalization within one year. Medication adherence was assessed by calculating the proportion of days covered (PDC) relative to total medication prescribed. ARNI and traditional RAS blockade adherence rates were directly compared to analyse their respective associations with the primary outcome. RESULTS: Patients in the ARNI group had a lower rate of the primary outcome than those in the traditional RAS blockade group [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.75-0.81; P < 0.001]. Mean PDC values spanning 1 year were 92.6 ± 14.5% and 90.9 ± 17.7% in the ARNI and RAS blockade groups, respectively (P < 0.001). Among patients with PDC ≥ 80%, the risk of primary outcome was significantly lower in the ARNI group than in the RAS blockade group (HR 0.75; 95% CI 0.72-0.78; P < 0.001) while a risk reduction with ARNI was not observed among patients with PDC < 80% (HR 0.95; 95% CI 0.85-1.05; P = 0.313). The beneficial effect was more pronounced among patients with PDC ≥ 80% than that among patients with PDC < 80% (P for interaction <0.001). CONCLUSIONS: In a real-world cohort with HFrEF, ARNI was superior to traditional RAS blockade in reducing the risk of all-cause mortality and hospitalization. The benefit of ARNI was pronounced among patients with high medication adherence but not among those with low medication adherence, highlighting the importance of adherence to ARNI treatment for HFrEF. TRIAL REGISTRATION: PARADE-HF ClinicalTrials.gov number, NCT05329727.

Prognostic Impact of Non-Predominant Lepidic Components in Pathologic Stage I Invasive Nonmucinous Adenocarcinoma.

INTRODUCTION: This study investigated the prognostic impact of non-predominant lepidic components in invasive nonmucinous adenocarcinoma. METHODS: Patients who underwent lobectomy and were diagnosed with stage I nonmucinous, non-lepidic-predominant invasive adenocarcinoma based on pathologic findings were included. Tumors were staged according to the eighth edition of TNM classification and categorized on the basis of the presence of lepidic components in the final pathologic findings. Overall survival (OS) and recurrence-free survival (RFS) were analyzed before and after applying inverse probability of treatment weighting. Competing risk analyses for recurrence were also compared in the two groups. RESULTS: Of the 1270 patients, 858 (67.6%) had lepidic components (+). The pathologic stage and histologic grade were higher in the lepidic (-) group (p < 0.001, respectively). The 5-year OS and RFS were significantly worse in the lepidic (-) group than in the lepidic (+) group (OS: 88.2% versus 94.9%, p < 0.001; RFS: 79.4% versus 91.9%, p < 0.001). These trends were consistent after weighted analysis (OS: 92.4% versus 96.4%, p = 0.029; RFS: 85.6% versus 92.3%, p = 0.007). The 5-year cumulative incidence of any recurrence was 14.0% in the lepidic (-) group and 4.1% in the lepidic (+) group (p < 0.001). Multivariable Fine-Gray regression analysis found that the lepidic (+) group exhibited a lower risk of recurrence than did the lepidic (-) group (hazard ratio = 0.52, 95% confidence interval: 0.29-0.93, p = 0.031). CONCLUSIONS: In pathologic stage I invasive nonmucinous adenocarcinoma, the presence of histologically diagnosed non-predominant lepidic components might be associated with a better prognosis after curative surgery.

The Relationship Between Brain Activation for Taking Others' Perspective and Interoceptive Abilities in Autism Spectrum Disorder: An fMRI Study.

Objectives: In this functional magnetic resonance imaging study, we aimed to investigate the differences in brain activation between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals during perspective taking. We also examined the association between brain activation and empathic and interoceptive abilities. Methods: During scanning, participants from the ASD (n=17) and TD (n=22) groups were shown pain stimuli and asked to rate the level of the observed pain from both self- and other-perspectives. Empathic abilities, including perspective taking, were measured using an empathic questionnaire, and three dimensions of interoception were assessed: interoceptive accuracy, interoceptive sensibility, and interoceptive trait prediction errors. Results: During self-perspective taking, the ASD group exhibited greater activation in the left precuneus than the TD group. During other-perspective taking, relative hyperactivation extended to areas including the right precuneus, right superior frontal gyrus, left caudate nucleus, and left amygdala. Brain activation levels in the right superior frontal gyrus while taking other-perspective were negatively correlated with interoceptive accuracy, and those in the left caudate were negatively correlated with perspective taking ability in the ASD group. Conclusion: Individuals with ASD show atypical brain activation during perspective taking. Notably, their brain regions associated with stress reactions and escape responses are overactivated when taking other-perspective. This overactivity is related to poor interoceptive accuracy, suggesting that individuals with ASD may experience difficulties with the self-other distinction or atypical embodiment when considering another person's perspective.

Differences in the Effects of Beta-Blockers Depending on Heart Rate at Discharge in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

Background and Objectives: Beta-blockers (BBs) improve prognosis in heart failure (HF), which is mediated by lowering heart rate (HR). However, HR has no prognostic implication in atrial fibrillation (AF) and also BBs have not been shown to improve prognosis in heart failure with preserved ejection fraction (HFpEF) with AF. This study assessed the prognostic implication of BB in HFpEF with AF according to discharge HR. Methods: From the Korean Acute Heart Failure Registry, 687 patients with HFpEF and AF were selected. Study subjects were divided into 4 groups based on 75 beats per minute (bpm) of HR at discharge and whether or not they were treated with BB at discharge. Results: Of the 687 patients with HFpEF and AF, 128 (36.1%) were in low HR group and 121 (36.4%) were in high HR group among those treated with BB at discharge. In high HR group, HR at discharge was significantly faster in BB non-users (85.5±9.1 bpm vs. 89.2±12.5 bpm, p=0.005). In the Cox model, BB did not improve 60-day rehospitalization (hazard ratio, 0.93; 95% confidence interval [95% CI], 0.35-2.47) or mortality (hazard ratio, 0.77; 95% CI, 0.22-2.74) in low HR group. However, in high HR group, BB treatment at discharge was associated with 82% reduced 60-day HF rehospitalization (hazard ratio, 0.18; 95% CI, 0.04-0.81), but not with mortality (hazard ratio, 0.77; 95% CI, 0.20-2.98). Conclusions: In HFpEF with AF, in patients with HR over 75 bpm at discharge, BB treatment at discharge was associated with a reduced 60-day rehospitalization rate.

Failed Thrombus Aspiration and Reduced Myocardial Perfusion in Patients With STEMI and Large Thrombus Burden.

BACKGROUND: Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization. OBJECTIVES: The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB. METHODS: In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group. RESULTS: The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure. CONCLUSIONS: TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non-left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127).