Broncho-Vaxom bacterial lysate prevents asthma via acetate enhancement in mouse model.

PURPOSE: Broncho-Vaxom (BV) is known to attenuate allergic airway inflammation and chronic bronchitis in humans, but the underlying mechanism of this gut-mediated immunity remains unclear. This study investigated the effects of an oral BV on gut and systemic short-chain fatty acids (SCFAs) and immune responses. METHODS: Oral BV was administered daily for 15 days prior to commencing the study in an asthma mouse model. Asthma was induced by ovalbumin (OVA) sensitization followed by a challenge with 1% OVA by inhalation. Asthmatic phenotypes, gut- and systemic- immune responses, and SCFAs in the cecum and blood were then investigated. RESULTS: Airway hyperresponsiveness, total immunoglobulin E production, and pulmonary inflammation were all significantly suppressed by BV. The interleukin-13 level was also suppressed, whereas TGF-ß expression was increased, in the lungs of the BV-treated mice. The regulatory T (Treg) cell numbers were increased in the small intestine, and the acetate level was increased in the cecum and serum after BV treatment. The levels of acetate in the cecum and serum were negatively correlated with airway hyperresponsiveness and with the eosinophil numbers in the BAL fluid of the OVA-induced mice. There was a positive correlation between the acetate levels in the feces and serum and the lung expression of TGF-ß in the asthma mice. CONCLUSIONS: Oral BV administration appears to prevent allergic inflammation by enhancing Treg cell proliferation and acetate production in an asthmatic mouse model.

The alternative bile acid pathway can predict food allergy persistence in early childhood.

BACKGROUND: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA. METHODS: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA. RESULTS: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid. CONCLUSION: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.

Machine learning-based prediction model for postoperative delirium in non-cardiac surgery.

BACKGROUND: Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium. METHODS: Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan-Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model. RESULTS: The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855-0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845-0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001). CONCLUSION: Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations. TRIAL REGISTRATION: KCT 0006363.

Indoor particulate matter induces epigenetic changes in companion atopic dogs.

The prevalence of atopic dermatitis (AD) is increasing and environmental factors are receiving attention as contributing causes. Indoor air pollutants (IAPs), especially particulate matter (PM) can alter epigenetic markers, DNA methylation (DNAm). Although DNAm-mediated epigenetic changes have been reported to modulate the pathogenesis of AD, their role at high risk of exposure to PM is still unclear. The study investigated the effects of exposure to IAPs in the development of AD and epigenetic changes through DNAm in companion atopic dogs that share indoor environment with their owners. Dogs were divided into two groups: AD (n = 47) and controls (n = 21). The IAPs concentration in each household was measured for 48 h, and a questionnaire on the residential environment was completed in all dogs. Eighteen dogs with AD and 12 healthy dogs were selected for DNAm analysis. In addition, clinical and immunological evaluations were conducted. The concentrations of PM2.5, PM10, and volatile organic compounds (VOCs) were significantly higher in the AD group. Moreover, there were more significant methylation differences in the LDLRAD4, KHSRP, and CTDSP2 genes in connection with PM10 in AD group compared to the controls. The degree of methylation of the LDLRAD4 and CTDSP2 genes was also correlated with related protein productions. The present study revealed that exposure to high indoor PM can cause epigenetic development of AD by methylation of the LDLRAD4, KHSRP, and CTDSP2 genes in dogs. Under the concept of "One Health," improving indoor environments should be considered to prevent the development of AD.

Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice.

BACKGROUND: Ruminococcus gnavus (R. gnavus) are mucin-degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment-induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD. METHODS: Four-week-old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated. RESULTS: Orally administered R. gnavus significantly reduced AD-associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA-specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2-related cytokine mRNA and upregulation of interleukin (IL)-10 and Foxp3 in the skin. The population of CD4+ FOXP3+ T cells in mesenteric- and skin-draining lymph nodes and butyrate levels in the cecum increased in R. gnavus-administered AD mice. CONCLUSIONS: Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T-cell counts and short-chain fatty acids production in AD mice.

Host-microbial interactions between PTGR2 and Bifidobacterium in the early life gut of atopic dermatitis children.

BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.

Accuracy of Cloud-Based Speech Recognition Open Application Programming Interface for Medical Terms of Korean.

BACKGROUND: There are limited data on the accuracy of cloud-based speech recognition (SR) open application programming interfaces (APIs) for medical terminology. This study aimed to evaluate the medical term recognition accuracy of current available cloud-based SR open APIs in Korean. METHODS: We analyzed the SR accuracy of currently available cloud-based SR open APIs using real doctor-patient conversation recordings collected from an outpatient clinic at a large tertiary medical center in Korea. For each original and SR transcription, we analyzed the accuracy rate of each cloud-based SR open API (i.e., the number of medical terms in the SR transcription per number of medical terms in the original transcription). RESULTS: A total of 112 doctor-patient conversation recordings were converted with three cloud-based SR open APIs (Naver Clova SR from Naver Corporation; Google Speech-to-Text from Alphabet Inc.; and Amazon Transcribe from Amazon), and each transcription was compared. Naver Clova SR (75.1%) showed the highest accuracy with the recognition of medical terms compared to the other open APIs (Google Speech-to-Text, 50.9%, P < 0.001; Amazon Transcribe, 57.9%, P < 0.001), and Amazon Transcribe demonstrated higher recognition accuracy compared to Google Speech-to-Text (P < 0.001). In the sub-analysis, Naver Clova SR showed the highest accuracy in all areas according to word classes, but the accuracy of words longer than five characters showed no statistical differences (Naver Clova SR, 52.6%; Google Speech-to-Text, 56.3%; Amazon Transcribe, 36.6%). CONCLUSION: Among three current cloud-based SR open APIs, Naver Clova SR which manufactured by Korean company showed highest accuracy of medical terms in Korean, compared to Google Speech-to-Text and Amazon Transcribe. Although limitations are existing in the recognition of medical terminology, there is a lot of rooms for improvement of this promising technology by combining strengths of each SR engines.

Sex difference in long-term clinical outcomes after percutaneous coronary intervention: A propensity-matched analysis of National Health Insurance data in Republic of Korea.

OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography.

OBJECTIVES: To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). METHODS: A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. RESULTS: No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p < 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p < 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p < 0.05). CONCLUSION: Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. KEY POINTS: • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5 mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

Medication Adherence and Clinical Outcome of Fixed-Dose Combination vs. Free Combination of Angiotensin Receptor Blocker and Statin.

BACKGROUND: Non-compliance with angiotensin receptor blockers (ARB) or statin is one of the major hurdles to optimal medical treatment. This study investigated whether fixed-dose combination (FDC) improved compliance to medication compared with traditional free combination (FC).Methods and Results:In this retrospective nationwide cohort study, medication persistency, medication adherence measured by proportion of days covered (PDC), and all-cause death of 123,992 patients who started ARB and stain were investigated for 540 days. Patients had a mean age of 63 years and 48% were male. Persistency, PDC, and proportion of PDC ≥80% of FDC (N=34,776) were higher than those for FC (N=89,216) in both unadjusted analysis (54.5% vs. 27.8%; 84.1% vs. 63.1%; 75.5% vs. 48.1%) and propensity-score matched analysis (P<0.001, all). Death risk for the investigation period (0-540 days) was lower in FDC in unadjusted (1.8% vs. 2.6%, P<0.001) and adjusted cohort (P<0.05). In landmark analyses at days 180 and 360, there was no significant difference of death risk between FDC and FC (P>0.05). CONCLUSIONS: In this real-world data analysis, patients taking FDC of ARB and statin showed higher medication persistence and adherence compared to patients taking FC of ARB and statin up to 540 days. The risk of all-cause death was not different between FDC and FC despite better medication compliance in the FDC patients.

Prognosis of Myocardial Injury After Non-Cardiac Surgery in Adults Aged Younger Than 45 Years.

BACKGROUND: This study compared myocardial injury after non-cardiac surgery (MINS) and mortalities between patients under and over the age of 45 years.Methods and Results:From January 2010 and June 2019, patients with cardiac troponin measurement within 30 days after non-cardiac surgery were enrolled and divided into groups according to age: >45 (≥45 years) and <45 (<45 years). Further analyses were conducted only in patients who were diagnosed with MINS. The outcomes were MINS and 30-day mortality. Of the 35,223 patients, 31,161 (88.5%) patients were in the >45-year group and 4,062 (11.5%) were in the <45-year group. After adjustment with inverse probability of weighting, the <45-years group showed a lower incidence of MINS and cardiovascular mortality (16.6% vs. 11.7%; odds ratio, 0.77; 95% confidence interval [CI], 0.69-0.84; P<0.001 and 0.4% vs. 0.2%; hazard ratio [HR], 0.41; 95% CI, 0.19-0.88; P=0.02, respectively). In a comparison of only the <45-years group, MINS was associated with increased 30-day mortality (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18-17.78; P<0.001), but the mortalities of patients with MINS did not differ according to age. CONCLUSIONS: MINS has a comparable prognostic impact in patients aged under and over 45 years; therefore, future studies need to also consider patients aged <45 years regarding risk factors of MINS and screening of perioperative troponin elevation.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Association Between High Body Mass Index and Mortality Following Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Despite an association between obesity and increased risks for various diseases, obesity has been paradoxically reported to correlate with improved mortality in patients with established cardiovascular disease. However, its effect has not been evaluated to date in patients with myocardial injury after noncardiac surgery (MINS). METHODS: From January 2010 to June 2019, of a total of 35,269 adult patients with postoperative cardiac troponin level data, 5633 (16.0%) patients had MINS as diagnosed by postoperative cardiac troponin I above the 99th-percentile upper reference of 40 ng·L-1 using the TnI-Ultra immunoassay. Patients with MINS were divided into 3 groups according to body mass index (BMI), with 3246 (57.6%) were in the normal (18.5-25 kg·m-2), 425 (7.5%) in the low BMI (<18.5 kg·m-2), and 1962 (34.8%) in the high BMI (≥25 kg·m-2) groups, respectively. The primary outcome was mortality during the first year after surgery, and the mortality during 30 days was also compared. RESULTS: Following adjustment for confounding with inverse probability of treatment weighting, mortality within the first year appeared to be significantly lower in the high BMI group compared with the normal (14.8% vs 20.9%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.66-0.85; P < .001) and the low BMI (14.8% vs 25.6%; HR: 0.56; 95% CI, 0.48-0.66; P < .001) groups. CONCLUSIONS: High BMI may be associated with decreased mortality following MINS. Further investigations are needed to support this finding.

Elevated high-sensitivity C-reactive protein concentrations may be associated with increased postdischarge mortality in patients with myocardial injury after noncardiac surgery: A retrospective observational study.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is one of the most common cardiovascular complications associated with mortality and morbidity during the first 2 years after surgery. However, the relevant variables associated with mortality after discharge in patients with MINS have not been fully investigated. OBJECTIVES: This study aimed to evaluate the association between persistent inflammation detected by high-sensitivity C-reactive protein (hsCRP) at discharge and postdischarge mortality after MINS. DESIGN: Retrospective observational analysis of acquired data from Samsung Medical Center Troponin in Noncardiac Operation (SMC-TINCO) registry. SETTING: A tertiary hospital from January 2010 to June 2019. PATIENTS: Patients who were discharged alive after a diagnosis of MINS. MAIN OUTCOME MEASURES: The primary endpoint was postdischarge 1-year mortality, and 30-day mortality and the mortality from 30 days to 1 year was also compared. RESULTS: Data from a total of 4545 adult patients were divided into two groups according to hsCRP concentration at discharge. There were 757 (16.7%) patients in the normal hsCRP group and 3788 (83.3%) patients in the elevated hsCRP group. After inverse probability weighting, 1-year mortality was significantly higher in the elevated group than the normal group (hazard ratio 1.93, 95% CI 1.45 to 2.57, P  < 0.001). Thirty-day mortality and the mortality from 30 days to 1 year were also increased in the elevated group. CONCLUSION: In patients with MINS, an elevated hsCRP concentration at discharge appeared to be associated with increased mortality. Further research is needed to determine whether controlling inflammation can be helpful in reducing mortality.

Pre-operative anaemia and myocardial injury after noncardiac surgery: A retrospective study.

BACKGROUND: Pre-operative anaemia is associated with adverse outcomes of noncardiac surgery, but its association with myocardial injury after noncardiac surgery (MINS) has not been fully investigated. OBJECTIVE: The association between pre-operative anaemia and MINS. DESIGN: A single-centre retrospective cohort study. SETTING: Tertiary care referral centre. PATIENTS: Patients with measured cardiac troponin (cTn) I levels after noncardiac surgery. INTERVENTIONS: Patients were separated according to pre-operative anaemia (haemoglobin <13 g dl-1 in men and <12 g dl-1 in women). Anaemia was further stratified into mild and moderate-to-severe at a haemoglobin level threshold of 11 g dl-1. MAIN OUTCOME MEASURES: The primary outcome was MINS, defined as a peak cTn I level more than 99th percentile of the upper reference limit within 30 postoperative days. RESULTS: Data from a total of 35 170 patients were collected, including 22 062 (62.7%) patients in the normal group and 13 108 (37.3%) in the anaemia group. After propensity score matching, 11919 sets of patients were generated, and the incidence of MINS was significantly associated with anaemia [14.5 vs. 21.0%, odds ratio (OR) 1.57, 95% confidence interval (CI) 1.47 to 1.68, P < 0.001]. For the entire population, multivariable analysis showed a graded association between anaemia severity and MINS (OR 1.32, 95% CI 1.22 to 1.43, P < 0.001 for mild anaemia and OR 1.80, 95% CI 1.66 to 1.94, P < 0.001 for moderate-to-severe anaemia compared with the normal group) and a significantly higher incidence of MINS for moderate-to-severe anaemia than mild anaemia (18.6 vs. 28.6%, OR 1.37, 95% CI 1.25 to 1.50, P < 0.001). The estimated threshold for pre-operative haemoglobin associated with MINS was 12.2 g dl-1, with an area under the curve of 0.622. CONCLUSIONS: Pre-operative anaemia was independently associated with MINS, suggesting that MINS may be related to the association between anaemia and postoperative mortality. TRIAL REGISTRATION: SMC 2019-08-048.

Feasibility of Changing Intra-Arterial Flow Direction by Temporary Occlusion Using Retrievable Coils: Study with a Normal Pig Model.

PURPOSE: To evaluate feasibility of changing intra-arterial flow direction by temporary occlusion using retrievable coils. MATERIALS AND METHODS: In 2 healthy pig livers, injection of a lipiodol mixture (lipiodol:saline = 2:1) was performed at the segmental arteries after occluding 1 of the subsegmental arteries. This was accomplished using a retrievable coil in 5 different segmental arteries (3 in pig A and 2 in pig B). Injection of the lipiodol mixture was performed through a 3-way system using a hemostatic valve, whereas the retrievable coil delivery system was in the lumen of a microcatheter. Successful coil deployment, occlusion of the vessel, and coil retrieval were evaluated. Redistribution of flow after placement of the coil and vessel patency after coil removal were angiographically evaluated. The distribution of lipiodol mixture was evaluated using cone beam computed tomography. RESULTS: All 5 of the retrievable coils were successfully deployed and removed. Angiography revealed successful occlusion of subsegmental artery after coil placement with flow redistribution followed by restoration of flow after coil retrieval in all cases. On cone beam computed tomography, lipiodol tagging was abundant in hepatic parenchyma supplied by the hepatic artery without coils compared with that supplied by the branch with coils. CONCLUSIONS: Temporary arterial flow redistribution using a retrievable coil was feasible in the healthy pig model and could be applicable for endovascular procedures in which superselection is difficult or unavailable.

Prenatal PM2.5 exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

BACKGROUND: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 µm to 2.5 µm (PM2.5) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM2.5 exposure and AD in an offspring. OBJECTIVE: To determine the critical windows of prenatal PM2.5 exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring. METHODS: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM2.5 was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta. RESULTS: PM2.5 exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM2.5 exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM2.5 and low CB vitamin D. CONCLUSION: Higher PM2.5 during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.

Factors related to paradoxical reactions during propofol-induced sedated endoscopy.

Objective: The factors related to paradoxical excitement during propofol-induced sedation remain unclear. We aimed to investigate this issue during sedated upper endoscopy. Material and methods: Among the health examinees scheduled for sedated upper endoscopy from June 2017 to December 2017, 421 participated in the study. Endoscopists were blinded to the information about the examinees and evaluated the development of paradoxical reactions. Propofol was exclusively used as the sedative agent via intermittent bolus injection. A multiple logistic regression analysis was performed to investigate the factors associated with paradoxical reactions. Results: The incidence of paradoxical reactions was 16.1%. Anxiety (adjusted odds ratio: 2.76; 95% confidence interval: 1.46 - 5.27; p = .002) and age (odds ratio: 0.92; 95% confidence interval: 0.89 - 0.96; p < .001) were significantly associated with paradoxical reactions. Of the nine items of the anxiety questionnaire, four had independent and significant associations with paradoxical reactions (i.e., excess worry, sleeping problems, somatic symptoms, and health concerns; odds ratios: 2.38, 2.71, 2.27 and 2.39, respectively). Conclusion: Propofol-induced paradoxical reactions tend to occur when an individual has anxiety and is of a young age. Further large population-based studies should be performed to confirm this phenomenon.

Predictive Value of Intraoperative Pulmonary Vascular Resistance in Liver Transplantation.

We aimed to evaluate the association between intraoperative pulmonary vascular resistance (PVR) and clinical outcome of liver transplantation (LT). Cardiovascular involvement of end-stage liver disease is relatively common, and hemodynamic instability during LT can be fatal to recipients. However, the clinical impact of intraoperative PVR in LT remains undetermined. A total of 363 adult recipients with intraoperative right heart catheterization from January 2011 to May 2016 were analyzed. Patients were divided into 2 groups according to PVR. Two separate analyses were performed according to the time point of measurement: at the beginning and at the end of LT. The primary outcome was all-cause death or graft failure during the follow-up period. Increased PVR was observed in 11.8% (43/363) of recipients at the beginning and 12.7% (46/363) of recipients at the end of LT. PVR at the beginning of LT had no significant effect on the rate of death or graft failure in the multivariate analysis (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.64-2.38; P = 0.52). In contrast, PVR at the end of LT was significantly associated with death or graft failure during the overall follow-up period (HR, 2.00; 95% CI, 1.13-3.54; P = 0.02). In conclusion, PVR at the end of LT, rather than the beginning, is associated with clinical outcome. Larger trials are needed to support this finding.

Effect of Side Branch Predilation in Coronary Bifurcation Stenting With the Provisional Approach　- Results From the COBIS (Coronary Bifurcation Stenting) II Registry.

BACKGROUND: Whether side branch (SB) predilation before main vessel (MV) stenting is beneficial is uncertain, so we investigated the effects of SB predilation on procedural and long-term outcomes in coronary bifurcation lesions treated using the provisional approach.Methods and Results:A total of 1,083 patients with true bifurcation lesions undergoing percutaneous coronary intervention were evaluated. The primary outcome was a major adverse cardiovascular event (MACE): cardiac death, myocardial infarction, or target lesion revascularization. SB predilation was performed in 437 (40.4%) patients. Abrupt (10.5% vs. 11.3%; P=0.76) or final SB occlusion (2.7% vs. 3.9%; P=0.41) showed no differences between the predilation and non-predilation groups. The rates of angiographic success (69.1% vs. 52.9%, P<0.001) and SB stent implantation (69.1% vs. 52.9%, P<0.001) were significantly higher in the predilation group. During a median follow-up of 36 months, we found no significant difference between the groups in the rate of MACE (9.4% vs. 11.5%; P=0.67) in a propensity score-matched population. In subgroup analysis, patients with minimal luminal diameter of the parent vessel ≤1 mm benefited from SB predilation in terms of preventing abrupt SB occlusion (P for interaction=0.04). CONCLUSIONS: For the treatment of true bifurcation lesions, SB predilation improved acute angiographic and procedural outcomes, but could not improve long-term clinical outcomes. It may benefit patients with severe stenosis in the parent vessel.