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Background: The effects of the BRAF(V600E) mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta-analysis to assess the strength of associations between these conditions and the BRAF(V600E) mutation.Methods: The authors identified the clinical studies that examined the association of the BRAF(V600E) mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty-one relevant studies were hand-searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model.Results: The average prevalence rate of the BRAF(V600E) mutation was 49.4%. In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF(V600E) mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14-fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The associations were generally consistent across the different study populations.Conclusions: This meta-analysis demonstrates that the BRAF(V600E) mutation is closely related to the high-risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAF(V600E) mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Acidic mammalian chitinase (AMCase) has emerged as an important mediator of allergic asthma in both animal models and in humans. Recently, chitotriosidase has been suggested to play a role in innate immunity because of its phagocytic-specific expression. Thus, AMCase and chitotriosidase may play a role in the pathogenesis of allergic nasal mucosa. The expression and pattern of distribution of AMCase and chitotriosidase were, therefore, determined in normal and allergic nasal mucosa. Study Design: Controlled, prospective study. Methods: Normal inferior turbinate mucosa was obtained in patients who were admitted for augmentation rhinoplasty. Allergic turbinate mucosa was obtained from patients who had perennial allergic rhinitis during septo-turbinate surgery. Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blotting were applied to the normal and allergic nasal mucosa. Results: The expression of AMCase and chitotriosidase mRNAs and proteins analyzed by RT-PCR and Western blot were detected in all normal and allergic turbinate mucosa tested. The levels of expression of AMCase and chitotriosidase mRNAs and proteins were increased in allergic turbinate mucosa compared with normal turbinate mucosa. In both normal and allergic turbinate mucosa, AMCase and chitotriosidase were detected in the epithelium, inflammatory cells, and submucosal glands. The staining intensity for AMCase and chitotriosidase was stronger in allergic nasal mucosa than normal nasal mucosa. Conclusions: AMCase and chitotriosidase are constitutively expressed in normal turbinate mucosa, suggesting involvement in defense against chitin-containing pathogens. Upregulation of these chitinases in allergic condition suggests that they may play a role in the nasal allergic reaction like other inflammatory mediators in allergic rhinitis. Laryngoscope, 2010. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) have been shown to induce wound-healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound-healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound-healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O2) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up-regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound-healing function of ADSCs, at least partly, by up-regulating the secretion of VEGF and bFGF. [ABSTRACT FROM AUTHOR]

Background: Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF., Methods and Results: This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H 2 FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP-peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H 2 FPEF score subgroup (all P <0.05). LAP-peak increased with pacing (19.5 to 22.5 mm Hg) but decreased with isoproterenol (20.4 to 18.4 mm Hg). Under pacing, patients with PAF exhibited a significantly lower LAP-peak (90 bpm) than those with persistent AF (17.7±8.2 versus 21.1±9.3 mm Hg, P <0.001). However, there was no difference in LAP-peak (120 bpm) between the 2 groups (22.1±8.1 versus 22.9±8.4 mm Hg, P =0.056) because the LAP-peak significantly increased with heart rate in the group with PAF., Conclusions: Patients with PAF exhibited lower baseline LAP with greater increases during rapid pacing compared with individuals with persistent AF, indicating a need to revise the H 2 FPEF score for distinguishing PAF from persistent AF and emphasizing the importance of rate and rhythm control in PAF for symptom control., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02138695.

Aim: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D)., Materials and Methods: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104., Results: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT., Conclusions: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data., Materials and Methods: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC 025 regarding the association between GLP-1RA use and suicidality., Results: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC 025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC 025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC 025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC 025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC 025 0.01])., Conclusions: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population., (© 2024 John Wiley & Sons Ltd.)

Background: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores., Methods and Results: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals., Conclusions: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

Background & Aims: Although non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC), HCC risk in non-cirrhotic NAFLD received little attention. We aimed to develop and validate an HCC risk prediction model for non-cirrhotic NAFLD., Methods: A nationwide cohort of non-cirrhotic NAFLD patients in Korea was recruited to develop a risk prediction model and validate it internally (n = 409 088). A model using a simplified point system was developed by Cox proportional hazard model. K-fold cross-validation assessed the accuracy, discrimination and calibration. The model was validated externally using a hospital cohort from Asan Medical Center (n = 8721)., Results: An 11-point HCC risk prediction model for non-cirrhotic NAFLD was developed using six independent factors of age, sex, diabetes, obesity, serum alanine aminotransferase level and gamma-glutamyl transferase level (c-index 0.75). The average area under receiver operating curves (AUROCs) of the model was 0.72 at 5 years and 0.75 at 10 years. In the external validation cohort, the AUROCs were 0.79 [95% confidence interval [CI], 0.59-0.95] at 5 years and 0.84 (95% CI, 0.73-0.94) at 10 years. The calibration plots showed the expected risks corresponded well with the observed risks. Risk stratification categorized patients into the low (score 0-6), moderate (7, 8) and high (9-11; estimated incidence rate >0.2%/year) risk groups., Conclusions: A novel HCC risk prediction model for non-cirrhotic NAFLD patients was developed and validated with fair performance. The model is expected to serve as a simple and reliable tool to assess HCC risk and assist precision screening of HCC., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although successful atrial fibrillation (AF) ablation can maintain sinus rhythm and reduce the left atrial (LA) dimension, blunted LA reverse remodeling can be observed in patients with atrial myopathy. We explored the potential mechanisms and long-term outcomes in patients with blunted LA reverse remodeling after successful AF catheter ablation., Methods and Results: We included 1685 patients who underwent baseline and 1-year follow-up echocardiograms, had a baseline LA dimension ≥40 mm, and did not have a recurrence of AF within a year. The patients were divided into tertile groups according to the delta value of the change in LA dimension on the preprocedure and 1-year postprocedure echocardiography. After propensity score matching for age, sex, AF type, and LA dimension, 1272 patients were finally included in the analyses (424 in each group; the least/blunted, moderate, and the most reverse remodeling group). The patients in the T1 group (blunted LA reverse remodeling) were independently associated with higher left ventricular mass index (odds ratio [OR], 1.014 [95% CI, 1.005-1.022], P =0.001), change in ΔH 2 FPEF score (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder, filling pressure) score (OR, 1.445 [95% CI, 1.121-1.861], P =0.004), ventricular epicardial adipose tissue volume (OR, 1.010 [95% CI, 1.003-1.017], P =0.003), thinner LA wall thickness (OR, 0.461 [95% CI, 0.271-0.785], P =0.004), lower LA voltage (OR, 0.670 [95% CI, 0.499-0.899], P =0.008), and showed higher long-term AF recurrence (log-rank P <0.001) than other groups., Conclusions: Blunted LA reverse remodeling after AF catheter ablation, which is suggestive of atrial myopathy, was independently associated with a larger ventricular epicardial adipose tissue volume and worsening of H 2 FPEF score. Blunted LA reverse remodeling after AF catheter ablation was also an independent predictor for higher recurrences of AF post-1-year AF catheter ablation.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P =0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P =0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

Polydeoxyribonucleotide (PDRN) is a DNA-derived drug extracted from the sperm cells of Oncorhynchus mykiss or O. keta. PDRN exhibits wound healing and anti-inflammatory activities by activating adenosine A 2A receptor and salvage pathways. However, commercial PDRN products (e.g., Placentex, Rejuvenex, and HiDr) have limitations as they are exclusively extracted O. mykiss and O. keta, which are expensive and can only be used as extraction sources during a specific period when their sperm cells are activated. Therefore, this study aimed to extract PDRN from Porphyra sp. (Ps-PDRN) and investigate whether it has anti-inflammatory activity through a comparative study with commercial product. The results indicated that Ps-PDRN had an anti-inflammatory effect on Escherichia coli lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. It inhibited nitric oxide production and inducible nitric oxygen synthase protein expression by suppressing phosphorylation of p38 and ERK, without cytotoxicity. Furthermore, Ps-PDRN promoted cell proliferation and collagen production in human dermal fibroblast. In conclusion, our study confirms that Ps-PDRN exhibits both anti-inflammatory and cell proliferative effects. These results indicated that Ps-PDRN has the potential as a bioactive drug for tissue engineering., (© 2023 John Wiley & Sons Ltd.)

Background: Bismuth-based quadruple therapy (BQT) is recommended as the first-line empirical therapy for Helicobacter pylori eradication as it is not associated with resistance. However, few studies have investigated the use of potassium-competitive acid blockers for BQT., Aim: To investigate the efficacy and safety profiles of tegoprazan-based BQT (TBMT) versus lansoprazole-based BQT (LBMT) for H. pylori eradication., Methods: We included patients older than 18 with an H. pylori infection without a history of H. pylori eradication who visited four university-affiliated hospitals between March 2020 and December 2021. H. pylori infection was diagnosed using a rapid urease test or Giemsa staining. Patients were randomly assigned to the TBMT or LBMT group., Results: 217 subjects were randomly allocated to receive either TBMT (n = 108) or LBMT (n = 109) therapy. Intention-to-treat (ITT) eradication rates of TBMT and LBMT were 80.0% and 77.4% (95% confidence interval [CI]: -8.4 to 13.7, p = 0.0124), respectively. Corresponding modified ITT rates were 90.3% and 84.5% (95% CI: -3.6 to 15.2, p = 0.0005), respectively. Per-protocol (PP) eradication rates of TBMT and LBMT were 90.2% and 82.4% (95% CI: -2.5 to 18.2, p = 0.0003), respectively. There was no significant difference in the rate of adverse events between the TBMT and LBMT groups (39.1% vs. 43.4%, p = 0.5211). TBMT showed higher eradication rates than that of LBMT in ITT, m-ITT, and PP analysis., Conclusion: TBMT showed a noninferior eradication rate and similar adverse events to LBMT as a first-line eradication regimen. Our results suggest that tegoprazan might be substituted for proton pump inhibitors in H. pylori eradication regimens., (© 2023 John Wiley & Sons Ltd.)

Protein phosphatase magnesium-dependent 1A (PPM1A), serine/threonine protein phosphatase, in sera level was increased in patients with ankylosing spondylitis (AS). Preosteoblasts were differentiated actively to matured osteoblasts by intracellular PPM1A overexpression. However, it was unclear whether extracellular PPM1A contributes to the excessive bone-forming activity in AS. Here, we confirmed that PPM1A and runt-related transcription factor 2 (RUNX2) were increased in facet joints of AS. During osteoblasts differentiation, exogenous PPM1A treatment showed increased matrix mineralization in AS-osteoprogenitor cells accompanied by induction of RUNX2 and factor forkhead box O1A (FOXO1A) protein expressions. Moreover, upon growth condition, exogenous PPM1A treatment showed an increase in RUNX2 and FOXO1A protein expression and a decrease in phosphorylation at ser256 of FOXO1A protein in AS-osteoprogenitor cells, and positively regulated promoter activity of RUNX2 protein-binding motif. Mechanically, exogenous PPM1A treatment induced the dephosphorylation of transcription factor FOXO1A protein and translocation of FOXO1A protein into the nucleus for RUNX2 upregulation. Taken together, our results suggest that high PPM1A concentration promotes matrix mineralization in AS via the FOXO1A-RUNX2 pathway., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank P =0.006), and the events were not significantly different regarding right ventricular LGE (log-rank P >0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank P =0.002), and higher T2 (versus lower T2, log-rank P =0.002), higher extracellular volume (versus lower extracellular volume, log-rank P =0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers. Conclusions LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.

Background The purpose of the RAFAS (Risk and Benefits of Urgent Rhythm Control of Atrial Fibrillation in Patients With Acute Stroke) trial was to explore the risks and benefits of early rhythm control in patients with newly documented atrial fibrillation (AF) during an acute ischemic stroke (IS). Method and Results An open-label, randomized, multicenter trial design was used. If AF was diagnosed, the patients in the early rhythm control group started rhythm control within 2 months after the occurrence of an IS, unlikely the usual care. The primary end points were recurrent IS within 3 and 12 months. The secondary end points were a composite of all deaths, unplanned hospitalizations from any cause, and adverse arrhythmia events. Patients (n=300) with AF and an acute IS (63.0% men, aged 69.6±8.5 years; 51.2% with paroxysmal AF) were randomized 2:1 to early rhythm control (n=194) or usual care (n=106). A total of 273 patients excluding those lost to follow-up (n=27) were analyzed. The IS recurrences did not differ between the groups within 3 months of the index stroke (2 [1.1%] versus 4 [4.2%]; hazard ratio [HR], 0.257 [log-rank P =0.091]) but were significantly lower in the early rhythm control group at 12 months (3 [1.7%] versus 6 [6.3%]; HR, 0.251 [log-rank P =0.034]). Although the rates of overall mortality, any cause of hospitalizations (25 [14.0%] versus 16 [16.8%]; HR, 0.808 [log-rank P =0.504]), and arrhythmia-related adverse events (5 [2.8%] versus 1 [1.1%]; HR, 2.565 [log-rank P =0.372]) did not differ, the proportion of sustained AF was lower in the early rhythm control group than the usual care group (60 [34.1%] versus 59 [62.8%], P <0.001) in 12 months. Conclusions The early rhythm control strategy of an acute IS decreased the sustained AF and recurrent IS within 12 months without an increase in the composite adverse outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02285387.

We developed a high-resolution and comprehensive typing method for swine leukocyte antigen 3 (SLA-3), an MHC class I gene, employing locus-specific genomic PCR followed by subsequent direct sequencing. A total of 292 individuals from nine pure, one cross-breed and six cell lines were successfully typed. A total of 21 SLA-3 alleles were identified, of which four were found to be novel alleles. However, the allelic diversity of SLA-3 was lower than that of previously reported class I genes, SLA-1 and -2. More SLA-3 alleles were observed in the Landrace and Yorkshire breeds than the other breeds. SLA-3*04:01 was identified in seven out of nine breeds and was the most widely distributed allele across all breeds. Therefore, the typing method reported in this study completes our efforts to develop high-resolution typing methods for major SLA molecules, facilitating the combined analysis of major SLA genes from field samples, which is important to understand the relationship between the adaptive immune responses against pathogens and the immunogenetic makeup of an individual., (© 2021 Stichting International Foundation for Animal Genetics.)

Background: Despite antiviral therapy, liver function often fails to recover in patients with hepatitis B virus (HBV)-related decompensated cirrhosis., Aim: To establish a prognostic model to predict re-compensation in patients starting potent nucleos(t)ide analogue (NUC) therapy METHODS: We analysed 311 consecutive patients with HBV-related decompensated cirrhosis treated with entecavir or tenofovir. The primary outcome was re-compensation, defined as recovery to a Child-Pugh score of 5. The BC2AID score was developed from a cohort of 152 subjects based on competing risk models and validated in another cohort of 159 subjects., Results: Re-compensation occurred in 57.2% and 66.7% of the subjects in the derivation and validation cohorts, respectively. Six independent predictors for re-compensation were identified in the derivation cohort and these comprised the BC2AID score: bilirubin ≤5 mg/dL (adjusted sub-distribution hazard ratio [aSHR] 2.18), absence of severe complications (aSHR 2.78), alpha-fetoprotein (AFP) ≥50 ng/mL (aSHR 2.54), alanine aminotransferase ≥200 IU/L (aSHR 2.62), international normalised ratio ≤1.5 (aSHR 2.37) and ≤6 months from initial decompensation until initiation of NUCs (aSHR 4.79). In the validation cohort, the area under the receiver operating characteristic curve of the BC2AID score for re-compensation within 1 year of NUC therapy was significantly higher than that of the Child-Pugh, MELD, MELDNa and BE3A scores (0.813 vs 0.691, 0.638, 0.645 and 0.624, respectively; all P < 0.05)., Conclusions: Six clinical parameters, including AFP and the timing of antiviral therapy, were combined into a scoring system to accurately predict early re-compensation in patients with HBV-related decompensated cirrhosis., (© 2021 John Wiley & Sons Ltd.)

Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients with recently diagnosed atrial fibrillation (AF). This study investigated the effects of rhythm control compared with rate control on the incidence of stroke, heart failure, myocardial infarction, and cardiovascular death stratified by timing of treatment initiation. Methods and Results We conducted a retrospective population-based cohort study including 22 635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011 to 2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Compared with rate control, rhythm control initiated within 1 year of AF diagnosis decreased the risk of stroke. The point estimates for rhythm control initiated at selected time points after AF diagnosis are as follows: 6 months (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87), 1 year (HR, 0.78; 95% CI, 0.66-0.93), and 5 years (HR, 1.00; 95% CI, 0.45-2.24). The initiation of rhythm control within 6 months of AF diagnosis reduced the risk of hospitalization for heart failure: 6 months (HR, 0.84; 95% CI, 0.74-0.95), 1 year (HR, 0.96; 95% CI, 0.82-1.13), and 5 years (HR, 2.88; 95% CI, 1.34-6.17). The risks of myocardial infarction and cardiovascular death did not differ between rhythm and rate control regardless of treatment timing. Conclusions Early initiation of rhythm control was associated with a lower risk of stroke and heart failure-related admission than rate control in patients with recently diagnosed AF. The effects were attenuated as initiating the rhythm control treatment later.

Background: The transaortic approach is the most common method of septal myectomy. However, difficulties arise due to a limited view of the surgical field. Here, we report our experience with videoscope-assisted transaortic myectomy., Methods: We reviewed myectomy operations that were performed between July 2015 and June 2019 at Chung-Ang University Hospital, Seoul, South Korea. Patients who previously had cardiac surgery, alcohol septal ablation, or concomitant disease which required combined surgery, were excluded. Among the 21 patients included, 10 patients underwent videoscope-assisted transaortic myectomy (VA group), and 11 patients underwent myectomy in a conventional manner (CO group). The preoperative data, echocardiographic images, operative records, and postoperative outcomes of these patients were reviewed., Results: There were no differences in baseline characteristics between groups VA and CO. The main indications for videoscope-assisted transaortic myectomy in group VA were midventricular septal muscle resection (70%), abnormal papillary muscle resection (40%), and abnormal chordal connection resection (30%). Eight (80%) patients had multiple indications for videoscope-assisted transaortic myectomy. There was no surgical mortality in either group. Postoperative patients showed less than moderate mitral regurgitation and a New York Heart Association class either III or IV. There were no differences in hospital days (9.5 vs. 12.0 days; p = .383), nor postoperative pressure gradient (14 vs. 15 mmHg; p > .99)., Conclusions: Videoscope-assisted transaortic myectomy is an effective surgical technique in selective hypertrophic cardiomyopathy patients with complex intraventricular anatomy, diffuse hypertrophy, and midventricular obstruction., (© 2021 Wiley Periodicals LLC.)

Background This study examines changes in the ideal cardiovascular health (CVH) status and whether these changes are associated with incident cardiovascular disease (CVD) and mortality in the elderly Asian population. Methods and Results In the Korea National Health Insurance Service-Senior cohort aged ≥60 years, 208 673 participants without prior CVD, including 109 431 who showed changes in CVH status, were assessed. The association of the changes in cardiovascular risk factors with incident CVD was assessed from 2004 to 2014 in the elderly (aged 60-74 years) and very elderly (≥75 years) groups. During the follow-up period (7.1 years for CVD and 7.2 years for mortality), 19 429 incident CVD events and 24 225 deaths occurred. In both the elderly and very elderly participants, higher CVH status resulted in a lower risk of CVD and mortality. In the very elderly participants, compared with consistently low CVH, consistently high CVH (subhazard ratio, 0.41; 95% CI, 0.23-0.73) was associated with a lower risk of CVD. This trend was consistently observed in the elderly population. In the very elderly participants, total cholesterol level was not informative enough for the prediction of CVD events. In both the elderly and very elderly groups, body mass index and total cholesterol were not informative enough for the prediction of all-cause mortality. Conclusions In both the elderly and very elderly Asian populations without CVD, a consistent relationship was observed between the improvement of a composite metric of CVH and the reduced risk of CVD. Body mass index and total cholesterol were not informative enough for the prediction of all-cause mortality in both the elderly and very elderly groups.

Purpose: A retrospective study to analyze the clinical performance of 3D printed complete dentures in edentulous patients compared with conventional complete dentures regarding postinsertion visits and patient reported outcomes., Material and Methods: Electronic charts were reviewed to analyze 420 (maxilla 270, mandible 150) heat-polymerized conventional complete dentures (CCD) inserted between July 1, 2015 and June 30, 2016 and 217 (maxilla 130, mandible 86) 3D printed complete dentures (PCD) inserted between July 1, 2017 and June 30, 2018. Number of remakes, number of postinsertion adjustments, type and number of repairs, and patient reported complications were compared between two types of complete dentures. The frequency of denture repair and patient reported complications were analyzed using chi-square of independence test., Results: The frequency of pain and visible ulcer lesions in the maxilla was determined to be 46.67% with CCD and 36.15% in PCD (p = 0.047). There was no statistical significance in other items. The majority of esthetic concerns was dissatisfaction with the shape of dentures with CCD (4.67%) and they had statistically significant, less frequent, esthetic problems than PCD (11.63%) (p = 0.047)., Conclusions: Similar clinical performance was recorded between the two groups, but the overall pain and visible ulcer lesions were less in the printed complete dentures then the conventionally processed dentures. However, the esthetic aspect was better in conventionally processed complete dentures., (© 2021 by the American College of Prosthodontists.)

Objectives/hypothesis: To evaluate the efficacy and safety of a slow-release form of bepotastine salicylate (HL151, Belion CR) in patients with perennial allergic rhinitis (PAR)., Study Design: Double-blind, placebo-controlled multicenter comparative study., Methods: Two hundred seventy-two PAR patients (aged 19-65 years) were studied to determine the efficacy and safety of HL151 (20 mg once daily administration) relative to those of a placebo in terms of improvements in total and nasal symptom scores. The subjects were randomized to the placebo (n = 138) or HL151 group (n = 134, 20 mg orally once daily for 4 weeks), and reflective and instantaneous total nasal symptom scores (TNSS) were measured daily in comparison with baseline. Among 272 subjects, 229 subjects (119 in the placebo group, 110 in the HL151 group) who completed the study were included for efficacy analysis., Results: Instantaneous and reflective TNSS and nasal symptoms such as rhinorrhea, nasal itching, and sneezing at 2 and 4 weeks showed that HL151 was superior to the placebo (all P < .05). There were no significant differences in terms of adverse events and adverse drug reactions between the two groups. Regarding serious adverse events, there was only one case of acute hepatitis B, which was reported not to be associated with HL151., Conclusions: This multicenter trial showed that once-daily use of HL151 is efficacious and safe in adult patients with PAR and could improve compliance due to its convenience., Level of Evidence: 1b Laryngoscope, 131:E702-E709, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Aims: This prospective observational study aimed to evaluate the best serum and urine markers to assess predictability for the prognosis of patients with decompensated cirrhosis., Methods: Serum creatinine and cystatin C (CysC), and urinary N-acetyl-beta-D glucosaminidase (uNAG) and neutrophil gelatinase-associated lipocalin (uNGAL) levels were measured from hospitalized patients with decompensated cirrhosis., Results: In total, 328 patients (mean age, 57.2 ± 12.0 years; 237 men) with decompensated cirrhosis were included. Alcoholic liver disease was the most frequent underlying liver disease (68.0%). Acute kidney injury (AKI) was concomitantly present in 41 patients (12.5%) at baseline. INR, serum creatinine and CysC levels, and uNAG and uNGAL levels were significantly higher in patients with AKI. During hospitalization, AKI had progressed in 37 patients (11.3%). In 287 patients without AKI, the incidence of AKI at 3, 6, 9 and 12 months was 15.4%, 22.2%, 28.6% and 32.5% respectively. On multivariate analysis, serum CysC and uNAG levels were independent predictors of AKI, and their optimal cut-off values were 1.055 mg/L and 23.1 U/g urinary Cr respectively. When patients were classified into three groups with these cut-off values of serum CysC and uNAG levels (group 1, both low; group 2, one of two high; and group 3, both high), progression of AKI during hospitalization (P = .001), incidence of AKI in patients without AKI at baseline (P = .001) and mortality rate (P < .001) differed significantly according to serum CysC and uNAG levels., Conclusion: Serum CysC and uNAG levels are useful prognostic markers for renal outcomes and mortality in patients with decompensated cirrhosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes., Materials and Methods: In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92)., Results: After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks., Conclusion: In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes. Methods and Results We evaluated 53 649 AF patients treated with an NOAC using Korean National Health Insurance Service database during the period from 2013 to 2016. NOAC doses were classified as either underdosed or overdosed, consistent with Korea Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Overall, 16 757 NOAC-treated patients (31.2%) were underdosed, 4492 were overdosed (8.4%), and 32 400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (aged 71±8 and 75±7 years versus 70±9 years, respectively; P <0.001) and had higher CHA 2 DS 2 -VASc scores (4.6±1.7 and 5.3±1.7 versus 4.5±1.8, respectively; P <0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 versus 4.03 events/100 patient-years, P <0.001), major bleeding (4.77 versus 2.94 events/100 patient-years, P <0.001), and all-cause mortality (5.43 versus 3.05 events/100 patient-years, P <0.001) compared with label-adherent use. Conclusions In real-world practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with worse clinical outcomes in Asian AF patients.

Background It is still controversial whether catheter ablation for atrial fibrillation (AF) improves survival and other outcomes in patients with AF. This study evaluated whether ablation reduces death and other events in nationwide real-world Asian patients with AF. Methods and Results From the Korean National Health Insurance Service database, 194 928 adult patients (aged ≥18 years) with newly diagnosed AF were treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between January 1, 2005, and December 1, 2015. Among these patients, this study included 9185 with ablation and 18 770 with medical therapy. The time at risk was counted from the first medical therapy, and ablation was analyzed as a time-varying covariate. Inverse probability of treatment weighting was used to correct for differences between the groups. After weighting, the 2 cohorts had similar background characteristics. During a median (25th, 75th percentiles) follow-up of 43 (19, 81) months, ablation of AF was associated with lower incidence and risk of composite outcome, including death, heart failure admission, and stroke/systemic embolism (2.5 and 6.4 per 100 person-years, respectively; hazard ratio [HR], 0.47; 95% CI, 0.43-0.52; P <0.001), all-cause death (1.0 and 3.6 per 100 person-years; HR, 0.41; 95% CI, 0.36-0.47; P <0.001), heart failure admission (0.7 and 1.9 per 100 person-years; HR, 0.43; 95% CI, 0.37-0.50), and ischemic stroke/systemic embolism (1.1 and 2.8 per 100 person-years; HR, 0.39; 95% CI, 0.34-0.44) than medical therapy. Conclusions Ablation may be associated with lower risk of death, heart failure admission, and ischemic stroke/systemic embolism in real-world Asian patients with AF.

Background We previously reported the benefit of linear ablation from the superior vena cava to the right atrial septum (SVC-L) within a year after circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (AF). We explored the long-term effects of SVC-L and its potential related mechanisms. Methods and Results Among 2140 consecutive patients with AF ablation, we included 614 patients (73.3% male, aged 57.8±10.7 years, 13.7% with persistent AF) who did not undergo an extra-pulmonary vein left atrial ablation after propensity score matching; of those, 307 had additional SVC-L and 307 had CPVI alone. We evaluated the heart rate variability and computational modeling study to explore mechanisms. Although the procedure time was longer in the SVC-L group than the CPVI group ( P <0.001), the complication rates did not differ ( P =0.560). During 40.5±24.4 months of follow-up, the rhythm outcome was significantly better in the SVC-L group than the CPVI group (log rank, P <0.001). At 2-year follow-up of heart rate variability, a significantly higher mean heart rate ( P =0.018) and a lower ratio of low/high-frequency components ( P =0.011) were found with SVC-L than CPVI alone. In realistic in silico biatrial modeling, which reflected the electroanatomies of 10 patients, SVC-L significantly reduced biatrial dominant frequency compared with CPVI alone ( P <0.001) and increased AF termination and defragmentation rates ( P =0.033). Conclusions SVC-L ablation in addition to CPVI significantly improved the long-term rhythm outcome over 2 years after AF catheter ablation by mechanisms involving autonomic modulation and AF organization.

Background: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea., Materials and Methods: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons., Results: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication., Conclusion: There was no relationship between the eradication rate and antibiotic use density in Korea., (© 2019 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Background Although it has been reported that renal function can improve after catheter ablation of atrial fibrillation (AF), long-term changes in renal function and its relationship to rhythm outcomes have not yet been evaluated. We explored the 5-year change in estimated glomerular filtration rate (eGFR) in AF patients depending on medical therapy and catheter ablation. Methods and Results Among 1963 patients who underwent AF catheter ablation and 14 056 with AF under medical therapy in the National Health Insurance Service database, we compared 571 with AF catheter ablation (59±10 years old, 72.3% male, and 66.5% paroxysmal AF) and 1713 with medical therapy after 1:3 propensity-score matching. All participants had 5 years of serial eGFR data (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] method). Catheter ablation improved eGFR 5 yrs (P<0.001), but medical therapy did not. In 2284 matched patients, age (adjusted odds ratio [OR], 0.98 [0.97-0.99]; P<0.001) and AF catheter ablation (adjusted OR, 2.02 [1.67-2.46]; P<0.001) were independently associated with an improved eGFR 5 yrs . Among 571 patients who underwent AF ablation, freedom from AF/atrial tachycardia recurrence after the last AF ablation procedure was independently associated with an improved eGFR 5 yrs (adjusted OR, 1.44 [1.01-2.04]; P=0.043), especially in patients without diabetes mellitus (adjusted OR, 1.78 [1.21-2.63]; P=0.003, P for interaction=0.012). Although underlying renal dysfunction (<60 mL/min/1.73m 2 ) was associated with atrial structural remodeling (adjusted OR, 1.05 [1.00-1.11]; P=0.046), it did not affect the AF ablation rhythm outcome. Conclusions AF catheter ablation significantly improved renal function over a 5-year follow-up, especially in patients maintaining sinus rhythm without preexisting diabetes mellitus.

Objective: The aim of this study was to identify the difference of gain value in the video head impulse test (vHIT) according to the age of the patient and the direction of the impulse., Method: All participants were subjected to vHIT with horizontal semicircular canal (HSCC). vHIT with vertical canal (posterior and anterior semicircular canal [PSCC and ASCC]) additionally was performed in 434 participants., Results: The mean vestibulo-ocular reflex (VOR) gain was maintained in patients in the HSCC at below 70 years (1.025 ± 0.08) and in the vertical canal at below 80 years (PSCC: 0.965 ± 0.12, ASCC: 0.975 ± 0.14). However, the decrease of VOR gain was significant in patients over 70 years in the HSCC (0.978 ± 0.35, P < .001) and in patients over 80 years in the vertical canal (PSCC: 0.828 ± 0.16, ASCC: 0.851 ± 0.13, P < .001). In addition, a VOR gain of rightward impulse was higher than the leftward impulse, but there was no difference based on the direction of impulse in the vertical impulse test., Conclusion: VOR gain declines with increasing age, over 70 years on the horizontal canal, and over 80 years on the vertical canal. Additionally, horizontal VOR gain of rightward impulse was higher than the leftward impulse in right-eye recordings only, but the vertical canal showed no difference of gain according to the direction of impulse., Level of Evidence: 2b. Laryngoscope, 128:E228-E233, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Increasing evidence has suggested that epilepsy is a network disease. Graph theory is a mathematical tool that allows for the analysis and quantification of the brain network. We aimed to evaluate the influences of duration of epilepsy on the topological organization of brain network in focal epilepsy patients with normal MRI using the graph theoretical analysis based on diffusion tenor imaging., Methods: We prospectively enrolled 66 patients with focal epilepsy (18/66 patients were newly diagnosed) and 84 healthy subjects. All of the patients with epilepsy had normal MRI on visual inspection. All of the subjects underwent diffusion tensor imaging that was analyzed using graph theory to obtain network measures., Results: The measures of characteristic path length and small-worldness in the patients with focal epilepsy were significantly decreased, even after multiple corrections (P < .01). Moreover, the measures including mean clustering coefficient and global efficiency in the patients with epilepsy had strong tendency to decrease compared to those in healthy subjects (P = .0153 and P = .0138, respectively). When comparing the measures among the patients with newly diagnosed/chronic epilepsy and healthy subjects using ANOVA, the characteristic path length (P = .006), small-worldness (P = .032), and global efficiency (P = .004) were significantly different. In addition, the duration of epilepsy was negatively correlated with global efficiency (r = -.249, P = .0454)., Conclusions: We newly found a progressive topological disorganization of the brain network in focal epilepsy. In addition, we demonstrated disrupted topological organization in focal epilepsy, shifting toward a more random state., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Relief of the intaglio surface of a denture base is conventionally performed using thin wax and soft metal foil attached to the master cast. The following report highlights a new relief procedure for the mental foramen using a CT double scan technique on the CAD/CAM dentures fabricated for the patient with paresthesia of the left lower lip and chin during mastication., (© 2016 by the American College of Prosthodontists.)

Objective: Laryngopharyngeal reflux disease (LPRD) is one of potential factors in recalcitrant chronic rhinosinusitis with or without polyps. An increase in junctional permeability in the nasal mucosa in LPRD may be due to disrupted protein bridge formation with cell-to-cell adhesion molecules such as E-cadherin. Despite the relationship between nasal mucosal inflammation and LPRD, the clear mechanism by which acid reflux affects the nasal epithelium remains unclear., Methods: The expression levels and distribution patterns of E-cadherin in primary culture of nasal epithelial cells after acid exposure with or without dexamethasone and matrix metalloproteinase (MMP) inhibitor were determined using Western blot and immunocytochemistry. The functional roles of MMP inhibitor in maintaining junctional permeability in the nasal epithelium were elucidated by transepithelial permeability test., Results: By acid exposure to nasal epithelial cells, mature E-cadherin was decreased and cleaved E-cadherin was increased. This was thought to be caused by cleavage of mature E-cadherin between cells and was confirmed by the increment of E-cadherin inside a cell in immunocytochemical evaluation. Whereas disruption of E-cadherin was not recovered by steroid medication with various treatments of dexamethasone, disrupted E-cadherin was restored to normal by inhibition of MMPs with actinonin, a broad MMP inhibitor. This recovery was functionally demonstrated by transepithelial permeability test., Conclusion: Our results suggest that altered expression of E-cadherin in the nasal epithelium by acid exposure may be a possible mechanism for nasal tissue injury in chronic nasal inflammation with LPRD, and that MMP inhibition is a potential treatment., Level of Evidence: NA. Laryngoscope, 128:E1-E7, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

A significant relationship between arsenic exposure and non-melanoma skin cancer (NMSC) is well known. The toxicity of arsenics which develop NMSC is dependent on their species. Accordingly, total arsenic levels are unreliable for risk assessment of NMSC. However, there are few studies on quantitative exposure assessment of arsenic species in NMSC patients. To validate the contribution of each arsenic species to NMSC, we compared the creatinine-adjusted urinary concentration of arsenic species in NMSC patients and community controls. A total of 124 biopsy-proven NMSC cases and 125 age- and sex-matched community controls, drinking tap water with low-level arsenic concentration (<5 μg/L), were included in the study. High-performance liquid chromatography and inductively coupled plasma mass spectrometry were used for the measurement. The NMSC group was found to have significantly higher levels of total inorganic arsenic, trivalent and pentavalent arsenic and monomethylarsonic acid than the control group. Total arsenic, organic arsenic and dimethylarsonic acid levels were lower in the NMSC group. We suggest that inorganic arsenic species, trivalent arsenic and pentavalent arsenic may influence the prevalence of NMSC, in spite of these levels being lower than the Agency for Toxic Substances and Disease Registry-recommended standard or the levels reported by other highly contaminated areas and neighboring countries in East Asia. Furthermore, it also suggests that total arsenic level cannot represent the risk of NMSC., (© 2017 Japanese Dermatological Association.)