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There have been few studies comparing the clinical characteristics and outcomes of SARS-CoV-2 pneumonia in individuals with and without moderately to severely immunocompromised conditions. We reviewed adult patients with SARS-CoV-2 infection who had radiologic evidence of pneumonia at a tertiary hospital in Seoul, South Korea, from February 2020 to April 2022. Moderately to severely immunocompromised status was defined as medical conditions or treatments that resulted in increased risk of severe COVID-19 and weakened immune response to COVID-19 vaccine as recommended by Centers for Disease Control and Prevention. The time to pneumonia development was defined as the time from symptom onset to the time when radiologic evidence of pneumonia was obtained. Viral clearance was defined as a Ct value > 30. COVID-19-related death was defined as 90-day death following imaging-confirmed pneumonia without any other plausible cause of death. A total of 467 patients with SARS-CoV-2 pneumonia were analyzed. Of these, 102 (22%) were moderately to severely immunocompromised. The median (IQR) time to pneumonia development was significantly longer in moderately to severely immunocompromised patients (9.5 [6-14] days) than the comparator (6 [3-8] days), p < 0.001), as was the median time to viral clearance (21 versus 12 days, p < 0.001). Moderately to severely immunocompromised status (aOR, 18.39; 95% CI, 5.80-58.30; p < 0.001) was independently associated with COVID-19-related death. Patients with moderately to severely immunocompromised conditions are likely to experience a more protracted course of SARS-CoV-2 pneumonia and a worse outcome than those without these conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Prognostic effect of discontinuing renin-angiotensin-aldosterone-system-inhibitor (RAASi) for patients with heart failure (HF) after acute myocardial infarction (AMI) whose left ventricular (LV) systolic function was restored during follow-up is unknown. To investigate the outcome after discontinuing RAASi in post-AMI HF patients with restored LV ejection fraction (EF). Of 13,104 consecutive patients from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry, HF patients with baseline LVEF < 50% that was restored to ≥ 50% at 12-month follow-up were selected. Primary outcome was a composite of all-cause death, spontaneous MI, or rehospitalization for HF at 36-month after index procedure. Of 726 post-AMI HF patients with restored LVEF, 544 maintained RAASi (Maintain-RAASi) beyond 12-month, 108 stopped RAASi (Stop-RAASi), and 74 did not use RAASi (RAASi-Not-Used) at baseline and follow-up. Systemic hemodynamics and cardiac workloads were similar among groups at baseline and during follow-up. Stop-RAASi group showed elevated NT-proBNP than Maintain-RAASi group at 36-month. Stop-RAASi group showed significantly higher risk of primary outcome than Maintain-RAASi group (11.4% vs. 5.4%; adjusted hazard ratio [HR adjust ] 2.20, 95% confidence interval [CI] 1.09-4.46, P = 0.028), mainly driven by increased risk of all-cause death. The rate of primary outcome was similar between Stop-RAASi and RAASi-Not-Used group (11.4% vs. 12.1%; HR adjust 1.18 [0.47-2.99], P = 0.725). In post-AMI HF patients with restored LV systolic function, RAASi discontinuation was associated with significantly increased risk of all-cause death, MI, or rehospitalization for HF. Maintaining RAASi will be necessary for post-AMI HF patients, even after LVEF is restored., (© 2023. The Author(s).)

Background: The Centers for Disease Control and Prevention (CDC) recommends 5-10 days of isolation for patients with COVID-19, depending on symptom duration and severity. However, in clinical practice, an individualized approach is required. We thus developed a clinical scoring system to predict viable viral shedding., Methods: We prospectively enrolled adult patients with SARS-CoV-2 infection admitted to a hospital or community isolation facility between February 2020 and January 2022. Daily dense respiratory samples were obtained, and genomic RNA viral load assessment and viral culture were performed. Clinical predictors of negative viral culture results were identified using survival analysis and multivariable analysis., Results: Among 612 samples from 121 patients including 11 immunocompromised patients (5 organ transplant recipients, 5 with hematologic malignancy, and 1 receiving immunosuppressive agents) with varying severity, 154 (25%) revealed positive viral culture results. Multivariable analysis identified symptom onset day, viral copy number, disease severity, organ transplant recipient, and vaccination status as independent predictors of culture-negative rate. We developed a 4-factor predictive model based on viral copy number (-3 to 3 points), disease severity (1 point for moderate to critical disease), organ transplant recipient (2 points), and vaccination status (-2 points for fully vaccinated). Predicted culture-negative rates were calculated through the symptom onset day and the score of the day the sample was collected., Conclusions: Our clinical scoring system can provide the objective probability of a culture-negative state in a patient with COVID-19 and is potentially useful for implementing personalized de-isolation policies beyond the simple symptom-based isolation strategy., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Due to their powerful immune surveillance activity and ability to kill and clear cancer cells, natural killer (NK) cells are an emerging anticancer immunotherapeutic agent. Therefore, there is much interest in developing efficient technologies that further enhance the therapeutic antitumor efficacy of NK cells., Methods: To produce chemically primed NK cells, we screened polymers with various electric charges and examined their ability to enhance the cytotoxicity of NK cells. The effect of primary amine and electric charges of 25 kDa branched polyethylenimine (25KbPEI) was investigated by fluorination of the chemical. The role of 25KbPEI in determining the major priming mechanism was investigated in terms of calcium influx into NK cells. In vivo therapeutic efficacy of chemically primed NK cells was evaluated against solid tumor mouse model of triple negative breast and ovarian cancers., Results: Chem&#95;NK that was produced by the priming activity of 25KbPEI showed potent antitumor activity to various cancer cells. Chem&#95;NK showed an activated phenotype, which manifests as increased expression of activating/adhesion/chemokine receptors and perforin accumulation, leading to enhanced migration ability and antitumor activity. Chem&#95;NK display potent therapeutic efficacy against in vivo mouse model of triple negative breast and ovarian cancers. Fluorination of the primary amine group reduces the activity of 25KbPEI to prime NK cells, indicating that the cationic charge on the chemical plays a critical role in NK cell activation. A major priming mechanism was 25KbPEI-mediated calcium influx into NK cells, which occurred mainly via the Ca2 + -permeable non-selective cation channel transient receptor potential melastatin 2., Conclusions: NK cells can be chemically primed with 25KbPEI to express potent antitumor activity as well as enhanced migration ability. Because PEI is a biocompatible and Food and Drug Administration-approved chemical for biomedical use, these results suggest a cost-effective and simple method of producing therapeutic NK cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We developed a dual-diffusing optical fiber probe (DDOFP), capable of uniformly illuminating the anatomical structure of pancreatic duct for photodynamic therapy (PDT) of pancreatic cancer in clinical settings. Background: Optical fiber presents a unique route for pancreatic PDT by enabling access to the pancreatic duct. For effective pancreatic PDT, the optical fiber should produce a uniform illumination covering of the pancreatic duct, while maintaining its transmission property under thermomechanical stresses in surgical environments. Methods: The transmission profiles of DDOFP were measured using a charge-coupled device (CCD) camera at two directions: front-spherical and side-cylindrical areas of the optical fiber. We simulated the change in transmission property by curved tube structures using optically transparent phantom. DDOFP was integrated with 19-gauge needle catheter that is commercially used as an optical guide to treat pancreatic cancer. The temperature of DDOFP was measured at the end face using a thermistor probe in the bovine tissue, while delivering laser energy of over 200 and 500 J. Results: DDOFP was customized to secure the inner diameter of the 19-gauge needle catheter of 686 μm to be integrated as a clinical device. The round ball lens fiber tip minimized the back-burn effect caused by blood carbonization during surgery and induced front-spherical diffusion. DDOFP produced uniform light illumination with intensity difference of <10%. When DDOFP was bent with a small curvature <15 mm, the transmission intensity was consistent. Under high-power laser transmission, DDOFP was found to be robust to cracking or deformation. Conclusions: DDOFP was customized for pancreatic PDT with superior thermomechanical property and uniform light illumination at both the front-spherical and side-cylindrical areas. This is the smallest clinically available optical fiber per our knowledge and officially approved by the Korea Food and Drug Administration (item approval number: 17-516). DDOFP can contribute immensely toward the efficient delivery of pancreatic PDT and photothermal therapy.

Background: Tramadol is known to cause fewer adverse events (AEs) than other opioids. However, recent research has raised concerns about various safety issues., Objective: We aimed to explore these new AEs related to tramadol using social media and conventional pharmacovigilance data., Methods: This study used 2 data sets, 1 from patients' drug reviews on WebMD (January 2007 to January 2021) and 1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS; January 2016 to December 2020). We analyzed 2062 and 29,350 patient reports from WebMD and FAERS, respectively. Patient posts on WebMD were manually assigned the preferred terms of the Medical Dictionary for Regulatory Activities. To analyze AEs from FAERS, a disproportionality analysis was performed with 3 measures: proportional reporting ratio, reporting odds ratio, and information component., Results: From the 869 AEs reported, we identified 125 new signals related to tramadol use not listed on the drug label that satisfied all 3 signal detection criteria. In addition, 20 serious AEs were selected from new signals. Among new serious AEs, vascular disorders had the largest signal detection criteria value. Based on the disproportionality analysis and patients' symptom descriptions, tramadol-induced pain might also be an unexpected AE., Conclusions: This study detected several novel signals related to tramadol use, suggesting newly identified possible AEs. Additionally, this study indicates that unexpected AEs can be detected using social media analysis alongside traditional pharmacovigilance data., (©Susan Park, So Hyun Choi, Yun-Kyoung Song, Jin-Won Kwon. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 04.01.2022.)

Four common health risk behaviors have the greatest impact on all-cause mortality risk, but studies are needed with larger samples and the appropriate age range for cigarette smokers. We examined the impact of smoking in the context of multiple health behaviors on all-cause mortality using a nationally representative sample of adults aged 30 and older in the United States. National Health Interview Survey data from 1997 to 2005 were linked to the National Death Index with a follow-up to December 2015. The primary dependent variable was all-cause mortality, and the primary predictors were smoking, heavy drinking, physical inactivity, and unhealthy weight (underweight or obesity). The sample contained 189,087 individuals (≥ age 30; population estimate = 140.7 million). Our primary statistical analysis tool involved fitting Cox proportional hazards models. Our findings demonstrated that smoking led to the highest mortality risk among the four risk behaviors examined, but more than half of smokers engaged in at least one additional health risk behavior. Smokers who engaged in multiple health behaviors experienced higher increased mortality risks: smoking combined with one other health risk behavior increased mortality risk by 32% and by 82% when combined with two behaviors. Engaging in all four risk behaviors more than doubled the mortality risk of smokers. Smoking cessation interventions that address multiple risk behaviors-physical inactivity, heavy drinking, and unhealthy weight-will likely prevent premature death better than interventions that address only smoking.

Poly (lactic-co-glycolic acid) (PLGA) has been used in many long-acting drug formulations which have been approved by the US Food and Drug Administration (FDA). However, generic counterparts for PLGA products have yet to gain FDA approval due to many complexities in formulation, characterization, and evaluation of test products. To address the challenges of generic development of PLGA-based products, the FDA has established an extensive research program to investigate novel methods and tools to aid both product development and regulatory review. The research focus have been: (1) analytical tools for characterization of PLGA polymers; (2) impacts of PLGA characteristics and manufacturing conditions on product performance; (3) in vitro drug release testing and in vitro-in vivo correlation of PLGA-based products, and (4) modeling tools to facilitate formulation design and bioequivalence study design of PLGA-based drugs. This article provides an overview of FDA's PLGA research program and highlights scientific accomplishments as well as regulatory outcomes that have resulted from successful research investigations.

Aims: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk., Methods and Results: Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable., Conclusion: The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes) 1 . In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

Objectives: To determine the accuracies of the American College of Radiology (ACR)-thyroid imaging reporting and data systems (TIRADS), Korean (K)-TIRADS, and European (EU)-TIRADS for diagnosing malignancy in thyroid nodules., Methods: Original studies reporting the diagnostic accuracy of TIRADS for determining malignancy on ultrasound were identified in MEDLINE and EMBASE up to June 23, 2019. The meta-analytic summary sensitivity and specificity were obtained for TIRADS category 5 (TR-5) and category 4 or 5 (TR-4/5), using a bivariate random effects model. To explore study heterogeneity, meta-regression analyses were performed., Results: Of the 34 eligible articles (37,585 nodules), 25 used ACR-TIRADS, 12 used K-TIRADS, and seven used EU-TIRADS. For TR-5, the meta-analytic sensitivity was highest for EU-TIRADS (78% [95% confidence interval, 64-88%]), followed by ACR-TIRADS (70% [61-79%]) and K-TIRADS (64% [58-70%]), although the differences were not significant. K-TIRADS showed the highest meta-analytic specificity (93% [91-95%]), which was similar to ACR-TIRADS (89% [85-92%]) and EU-TIRADS (89% [77-95%]). For TR-4/5, all three TIRADS systems had sensitivities higher than 90%. K-TIRADS had the highest specificity (61% [50-72%]), followed by ACR-TIRADS (49% [43-56%]) and EU-TIRADS (48% [35-62%]), although the differences were not significant. Considerable threshold effects were noted with ACR- and K-TIRADS (p ≤ 0.01), with subject enrollment, country of origin, experience level of reviewer, number of patients, and clarity of blinding in review being the main causes of heterogeneity (p ≤ 0.05)., Conclusions: There was no significant difference among these three international TIRADS, but the trend toward higher sensitivity with EU-TIRADS and higher specificity with K-TIRADS., Key Points: • For TIRADS category 5, the meta-analytic sensitivity was highest for the EU-TIRADS, followed by the ACR-TIRADS and the K-TIRADS, although the differences were not significant. • For TIRADS category 5, K-TIRADS showed the highest meta-analytic specificity, which was similar to ACR-TIRADS and EU-TIRADS. • Considerable threshold effects were noted with ACR- and K-TIRADS, with subject enrollment, country of origin, experience level of reviewer, number of patients, and clarity of blinding in review being the main causes of heterogeneity.

Background: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection., Methods: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted., Results: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic., Conclusion: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Atrial fibrillation (AF) may occur after an acute precipitant and subsequently resolve. Management guidelines for AF in these settings are unclear as the risk of recurrent AF and related morbidity is poorly understood. We examined the relations between acute precipitants of AF and long-term recurrence of AF in a clinical setting., Methods: From a multi-institutional longitudinal electronic medical record database, we identified patients with newly diagnosed AF between 2000 and 2014. We developed algorithms to identify acute AF precipitants (surgery, sepsis, pneumonia, pneumothorax, respiratory failure, myocardial infarction, thyrotoxicosis, alcohol, pericarditis, pulmonary embolism, and myocarditis). We assessed risks of AF recurrence in individuals with and without a precipitant and the relations between AF recurrence and heart failure, stroke, and mortality., Results: Among 10 723 patients with newly diagnosed AF (67.9±9.9 years, 41% women), 19% had an acute AF precipitant, the most common of which were cardiac surgery (22%), pneumonia (20%), and noncardiothoracic surgery (15%). The cumulative incidence of AF recurrence at 5 years was 41% among individuals with a precipitant compared with 52% in those without a precipitant (adjusted hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]; P <0.001). The lowest risk of recurrence among those with precipitants occurred with postoperative AF (5-year incidence 32% in cardiac surgery and 39% in noncardiothoracic surgery). Regardless of the presence of an initial precipitant, recurrent AF was associated with increased adjusted risks of heart failure (hazard ratio, 2.74 [95% CI, 2.39-3.15]; P <0.001), stroke (hazard ratio, 1.57 [95% CI, 1.30-1.90]; P <0.001), and mortality (hazard ratio, 2.96 [95% CI, 2.70-3.24]; P <0.001)., Conclusions: AF after an acute precipitant frequently recurs, although the risk of recurrence is lower than among individuals without an acute precipitant. Recurrence is associated with substantial long-term morbidity and mortality. Future studies should address surveillance and management after newly diagnosed AF in the setting of an acute precipitant.

Petunia plants are used for urban landscaping in many parts of the world, including South Korea. In this study, we aimed to investigate the occurrence of petunia vein clearing virus (PVCV) infection in petunia plants in Seoul, South Korea. PVCV was detected from 23 of 79 petunia samples collected from Seoul. We obtained the complete genome sequences of the Korean isolates in this study (called PVCV-Kr, Kr2, and Kr3), which were compared with the genome sequence of the USA isolate of the virus (PVCV-USA). The genomic DNA of the three PVCV isolates was found to comprise 7210-7267 nucleotides (nts), which is 4-15 nts longer than the PVCV-USA genome. The genomes of the Kr and Kr2 isolates encode a large polyprotein of 252 kDa (2180 amino acids (aa)). The genome of the Kr3 isolate encodes a large polyprotein of 255 kDa (2203 aa). The polyprotein has six protein domains: a movement protein (MP; 72 aa), a coiled-coil domain (CC; 33 aa), an RNA-binding domain (RB; 18 aa), a protease (PR; 21 aa), a reverse transcriptase (RT; 196 aa), and an RNase H (RH; 121 aa). The large polyprotein and six domains of the three isolates showed 93.9-100.0% sequence homology with those of PVCV-USA. Furthermore, the polymerase polyprotein gene (PR, RT, and RH) of the four PVCV isolates containing the USA isolate grouped with those of Rice tungro bacilliform virus and Soybean chlorotic mottle virus, which belong to the same family (Caulimoviridae). Our findings suggested that the Korean isolates represent a new isolate of PVCV. To our knowledge, this is the first report of PVCV detection in South Korea.

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count <10 (including singletons) in the imputation target samples, average information content rescued was >86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations., Competing Interests: Edwin K Silverman and Michael H Cho have received grant support from GSK, MHC has received consulting fees from Genentech. Scott T. Weiss and Kathleen C. Barnes received royalties from UpToDate. Patrick T. Ellinor is supported by a grant from Bayer AG to the Broad Institute focused on the genetics and therapeutics of cardiovascular diseases, and has also served on advisory boards or consulted for Bayer AG, Quest Diagnostics and Novartis. Steven A Lubitz receives sponsored research support from Bristol Myers Squibb / Pfizer, Bayer HealthCare, and Boehringer Ingelheim, and has consulted for Abbott, Quest Diagnostics, Bristol Myers Squibb / Pfizer. Other authors declared no conflicts of interest.

Background: The differential prognostic impact of β-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to β-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no β-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no β-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363-0.521, P<0.001; HR, 0.519; 95% CI: 0.350-0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789-1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same., Conclusions: The use of β-blockers in post-AMI patients had significant survival benefit compared with no use of β-blockers. There was no significant additional benefit of high-dose β-blockers compared with low-dose β-blockers, however, in terms of 1-year risk of cardiac death.

Background: The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown., Methods: We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk., Results: Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition ( P <0.001)., Conclusions: In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk., (© 2018 American Heart Association, Inc.)

Background and Objectives: Diagnostic tests for influenza infection commonly use nasopharyngeal swabs (NPS) even though these are invasive to obtain. As an alternative specimen, we evaluated the diagnostic usefulness of saliva samples with rapid influenza diagnostic tests (RIDTs)., Study Design: Both NPS and saliva samples were collected from 385 influenza suspected patients and analyzed using Sofia Influenza A+B Fluorescence Immunoassay (Quidel Corporation, San Diego, CA, USA), ichroma TRIAS Influenza A+B (Boditech, Chuncheon, Korea), SD Bioline Influenza Ag (Standard Diagnostic, Yonggin, Korea), BinaxNOW Influenza A/B antigen kit (Alere Inc., Waltham, MA, USA), and real-time reverse transcriptase PCR (RT-PCR)., Results: Of the 385 patients, 31.2% (120/385) were positive for influenza A, and 7.5% (29/385) were positive for influenza B virus with saliva or NPS by RT-PCR. The diagnostic sensitivity was slightly higher in NPS than in saliva samples for both influenza A and B by all of the four RIDTs. The diagnostic sensitivities of Sofia and ichroma TRIAS were significantly superior to those of the other conventional influenza RIDTs with both types of sample. The sensitivities of Sofia and ichroma TRIAS with saliva specimens were comparable to the sensitivities of the other two conventional RIDTs with NPS specimens. The simultaneous use of saliva and NPS samples exhibited improved sensitivity from 10.0% to 13.3% for influenza A and from 10.3% to 17.2% for influenza B compared to using NPS alone., Conclusions: This study demonstrates that saliva is a useful specimen for influenza detection, and that the combination of saliva and NPS could improve the sensitivities of influenza RIDTs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: We evaluated the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project's recommended criteria for sarcopenia's association with mortality among older Korean adults., Methods: We conducted a community-based prospective cohort study which included 560 (285 men and 275 women) older Korean adults aged ≥65 years. Muscle mass (appendicular skeletal muscle mass-to-body mass index ratio (ASM/BMI)), handgrip strength, and walking velocity were evaluated in association with all-cause mortality during 6-year follow-up. Both the lowest quintile for each parameter (ethnic-specific cutoff) and FNIH-recommended values were used as cutoffs., Results: Forty men (14.0%) and 21 women (7.6%) died during 6-year follow-up. The deceased subjects were older and had lower ASM, handgrip strength, and walking velocity. Sarcopenia defined by both low lean mass and weakness had a 4.13 (95% CI, 1.69-10.11) times higher risk of death, and sarcopenia defined by a combination of low lean mass, weakness, and slowness had a 9.56 (3.16-28.90) times higher risk of death after adjusting for covariates in men. However, these significant associations were not observed in women. In terms of cutoffs of each parameter, using the lowest quintile showed better predictive values in mortality than using the FNIH-recommended values. Moreover, new muscle mass index, ASM/BMI, provided better prognostic values than ASM/height2 in all associations., Conclusions: New sarcopenia definition by FNIH was better able to predict 6-year mortality among Korean men. Moreover, ethnic-specific cutoffs, the lowest quintile for each parameter, predicted the higher risk of mortality than the FNIH-recommended values., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to determine the relationship between occupational exposures and cigarette smoking among operating engineers. A cross-sectional survey was conducted with operating engineers (N = 412) from a midwestern state in the United States. The survey included validated questions on cigarette smoking, occupational exposures, demographics, comorbidities, and health behaviors. About 35% were current smokers. Those exposed to asphalt fumes, heat stress, concrete dust, and welding fumes were less likely to smoke (odds ratio [OR] = .79, 95% confidence interval [CI]: .64-.98). Other factors associated with smoking included younger age (OR = .97, 95% CI: .94-.99), problem drinking (OR = 1.07, 95% CI: 1.03-1.12), lower Body Mass Index (OR = .95, 95% CI: .90-.99), and being separated/widowed/divorced (OR = 2.24, 95% CI: 1.19-4.20). Further investigation is needed for better understanding about job-specific exposure patterns and their impact on cigarette smoking among operating engineers.

Objective: This study tested a healthy immigrant effect (HIE) and postimmigration health status changes among late life immigrants., Methods: Using three waves of the Second Longitudinal Study of Aging (1994-2000) and the linked mortality file through 2006, this study compared (a) chronic health conditions, (b) longitudinal trajectories of self-rated health, (c) longitudinal trajectories of functional impairments, and (d) mortality between three groups (age 70+): (i) late life immigrants with less than 15 years in the United States (n = 133), (ii) longer term immigrants (n = 672), and (iii) U.S.-born individuals (n = 8,642). Logistic and Poisson regression, hierarchical generalized linear modeling, and survival analyses were conducted., Results: Late life immigrants were less likely to suffer from cancer, had lower numbers of chronic conditions at baseline, and displayed lower hazards of mortality during the 12-year follow-up. However, their self-rated health and functional status were worse than those of their counterparts over time., Conclusion: A HIE was only partially supported among older adults.