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PURPOSE Despite decreased prevalence of tuberculosis, the incidence of the diseases associated with nontuberculous mycobacteria (NTM) has been increasing in South Korea and around the world. The present retrospective study was conducted to determine longitudinal changes in the epidemiology and distribution of NTM over 13 years at a tertiary care hospital in Korea. MATERIALS AND METHODS We retrospectively analyzed data on Mycobacterium species over 13 years (January 2007 to December 2019) by utilizing the laboratory information system. Mycobacterium species were identified using biochemical tests and PCR-restriction fragment length polymorphism and Mycobacteria GenoBlot assays. RESULTS After excluding duplicates from the initial pool of 17996 mycobacterial isolates, 7674 strains were analyzed and 2984 (38.9%) NTM were isolated. The proportion of NTM continuously increased over the 13-year period, from 17.0% in 2007 to 57.5% in 2019. Among the NTM isolates, the most common species were Mycobacterium intracellulare (50.6%), M. avium (18.3%), M. fortuitumcomplex (4.9%), M. abscessus (4.5%), M. gordonae (3.3%), M. kansasii (1.1%), M. chelonae (1.0%), and M. massiliense (0.9%). In patients over the age of 70 years, the proportion of NTM among the isolates increased from 26.6% in 2007 to 62.0% in 2019, and that of M. intracellulare isolates among the NTM increased from 13.9% (11/79) in 2007 to 37.4% (175/468) in 2019. CONCLUSION The number of NTM isolates continuously increased over the study period, and the increase in the proportion of M.intracellulare in patients aged over 70 years was notable.

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients’ blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.

Background A single‑lead implantable cardioverter-defibrillator (ICD) with a floating atrial dipole has been developed to enhance the diagnostic capability of atrial arrhythmias and to facilitate adjudication of arrhythmic events without the additional effort required for atrial lead insertion. However, there have been concerns about the long-term reliability of atrial sensing. Methods We enrolled patients with the single-chamber ICD with atrial-sensing electrodes from 4 tertiary university hospitals in Korea. Minimal, maximal, and mean P wave amplitudes were collected at 3–6 months, 6–12 months, and 12–24 months after implantation. The difference between the minimal and maximal sensing amplitudes was calculated as an indicator of the variability of atrial sensing, while the atrial sensing stability was assessed using the mean amplitude. Results A total of 86 patients were included for analysis. The variability of atrial sensing amplitudes significantly decreased at 12–24 months compared to 3–6 months (p = 0.01), while mean atrial amplitudes were stable throughout the mean follow-up duration of 17.4 months. Nine patients (10.5%) experienced inappropriate ICD therapy mostly due to misclassification of supraventricular tachycardia. Conclusions Under the hypothesis that sensing stability can be guaranteed as the variability decreases with time, we suggest that the concern about long-term sensing stability of a floating dipole can be abated with an ICD that has been implanted for over 2 years.

Background/Aims Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. Methods This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. Results A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. Conclusions This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Aims Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320.

Background Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. Methods This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. Results Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. Conclusions Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

This study aimed to analyze the effect of milk fermented with Lactobacillus curvatus SMFM2016-NK on periodontal diseases and gut health in a rat model. To improve the effect of Lb. curvatus SMFM2016-NK-fermented milk administration for relieving periodontitis, the periodontitis rat models were treated with the following for 4 wk: 10% skim milk (normal), periodontitis + 10% skim milk (negative control), periodontitis + Lactobacillus rhamnosus GG-fermented milk (positive control), and periodontitis + Lb. curvatus SMFM2016-NK-fermented milk (PD+LCFM). Transcriptional analysis of inflammatory cytokines [tumor necrosis factor α (TNF-α), IL-1β, IL-6, and IL-10] was performed via quantitative reverse-transcription PCR. The changes in the oral and gut microbiomes after administering Lb. curvatus SMFM2016-NK-fermented milk were analyzed with metagenomics sequencing using DNA extracted from the oral gingival tissues and feces from the cecum of the rat models. After treatment with Lb. curvatus SMFM2016-NK-fermented milk, the relative gene expression levels of TNFA and IL1B in the gingiva decreased in the PD+LCFM group compared with those in the negative control group. In the oral microbiome, the proportion of the phylum Proteobacteria in the PD+LCFM group was lower than that in the negative control after treatment with Lb. curvatus SMFM2016-NK-fermented milk. For the effect in the gut, the relative gene expression levels of inflammatory cytokines in the colon between the normal and negative control groups were not different; however, the expression levels of TNFA and IL1B in the PD+LCFM and positive control groups, respectively, were lower than those in the negative control group. The composition and diversity of the gut microbiome differed among normal, periodontitis, and Lb. curvatus SMFM2016-NK-fermented milk treatment groups. These results indicate that Lb. curvatus SMFM2016-NK-fermented milk could alleviate periodontal and gut inflammation and change oral and gut microbiota.

An isolated tibial component revision could be a treatment option for isolated tibial side loosening; however, few studies have proved its efficacy. This study aimed to compare the clinical and radiological outcomes between isolated (tibial component) and total (femoral and tibial component) revision total knee arthroplasty (TKA).Between January 2008 and February 2017, 31 patients underwent revision TKA for isolated tibial side loosening; 14 underwent an isolated tibial component revision (isolated group) and 17 underwent total (both femoral and tibial components) revision surgery (total group). The postoperative range of motion (ROM), Western Ontario and McMaster Universities osteoarthritis (WOMAC) index, Knee Society knee score (KSKS), Knee Society function score (KSFS), and mechanical axis (MA) were compared between the two groups. The intraoperative tourniquet time and amount of blood drainage were also compared.The mean follow-up durations in the isolated and total groups were 40.7 and 56.1 months, respectively. Both groups had similar postoperative ROM, WOMAC index, KSKS, KSFS, and MA; however, significantly shorter tourniquet time (105.2 vs. 154.6 min, P 0.001) and less blood drainage (417.2 vs. 968.1 ml, P 0.001) were noted in the isolated group than in the total group.Isolated tibial component revision TKA for tibial component loosening showed comparable clinical and radiological outcomes to those of total revision TKA. The advantages of the isolated tibial component revision surgery were short operation time and small blood loss.Level III, Retrospective comparative study.

Objective To evaluate the effectiveness and safety of totally thoracoscopic ablation (TTA) in patients with left ventricular (LV) dysfunction for treatment of atrial fibrillation (AF) refractory to antiarrhythmic drug (AAD) therapy. Methods Between January 2012 and December 2018, 31 patients underwent TTA with drug-refractory AF and preoperative left ventricular ejection fraction (LVEF), Video Abstract

Background and Purpose: Unlike clinical atrial fibrillation (AF), the significance of subclinical AF (SCAF) burden in patients with permanent pacemakers has not been fully evaluated. Methods: We investigated whether the SCAF burden was associated with increased risks of composite adverse outcomes, including progression to clinical AF, ischemic stroke, myocardial infarction, heart failure-related hospitalization, or cardiac death, in patients without previous AF. To quantify the 6-month SCAF burden, the total cumulative time spent in SCAF during every 6-month follow-up was summed. Results: During the median 5.2-year follow-up, 496 consecutive permanent pacemaker patients were classified into the no SCAF (no SCAF episode in any device analysis; n=152), low-burden SCAF (6-month SCAF P P P P P Conclusions: In permanent pacemaker patients without preexisting AF, the presence of high-burden SCAF was closely associated with increased risks of composite adverse outcomes, particularly progression to clinical AF and ischemic stroke. Therefore, prospective studies deserve to be performed on the optimal anticoagulation therapy for permanent pacemaker patients with both high-burden SCAF and high stroke risk.

It has been known that ventricular conduction delays play a key role in the cardiac resynchronization therapy (CRT) response of patients with advanced heart failure (HF). However, no study to our knowledge has yet evaluated the serial changes in conduction times measured between different electrodes of CRT devices. The Reduction or Extension of Conduction Time with Ventricular Electromechanical Remodeling (RECOVER) study (NCT04397224) was designed to investigate serial changes in interelectrode conduction times and to elucidate their prognostic value. We plan to enroll 100 patients implanted with CRT systems with endocardial quadripolar left ventricular leads. Patients will be scheduled for follow-up every 3 months over a period of 2 years, where they will undergo measurement of interelectrode conduction times to evaluate their serial changes. The primary outcome of the RECOVER study is the correlation between the degree of conduction time changes and the CRT response as defined by echocardiography. The time course and prognostic value of the serial changes in conduction times will be investigated as well. The RECOVER study is investigating whether serial changes in interelectrode conduction times can be useful parameters in predicting the CRT response or detecting worsening HF at an early stage.

Background Cryoballoon ablation is a commonly used approach to treat patients with atrial fibrillation (AF). Objectives Report on the safety and efficacy of cryoballoon ablation for the treatment of AF in the largest global cohort of cryoablated patients prospectively studied within a single registry. Methods The Cryo AF Global Registry is a prospective, multi‐center registry. Patients with paroxysmal AF (PAF) or persistent AF (PsAF) were treated with the cryoballoon catheter according to routine practices at 93 sites across 36 countries. Primary efficacy endpoints included freedom from AF and freedom from AF/atrial flutter (AFL)/atrial tachycardia (AT) ≥30 seconds. The primary safety endpoint was serious device‐ or procedure‐related adverse events over 12 month follow‐up. Results During this evaluation window, 2922 subjects completed an index cryoballoon procedure, and 1440 completed 12 month follow‐up. The cohort was 61 ± 12 years of age, 36.3% female, and 78.7% PAF. Serious device‐ and procedure‐related adverse event rates were 1.5% and 3.4%, respectively. Freedom from AF/AFL/AT after the 90 day blanking period was 86.4% (95% CI: 84.3%‐88.3%) in patients with PAF and 70.9% (95% CI: 64.6%‐76.4%) in patients with PsAF. Freedom from AF/AFL/AT in first‐line PAF and PsAF was 90.0% (95% CI: 86.4%‐92.7%) and 72.9% (95% CI: 58.6%‐83.0%) at 12 months, respectively. Conclusions The Cryo Global AF Registry is the largest evaluation to demonstrate cryoablation is an efficient, safe, and effective treatment for patients with AF worldwide. Cryoablation was commonly used to treat patients prior to an AAD failure and may facilitate earlier therapy for patients on the AF disease continuum., Cryoballoon ablation was an efficient, safe, and effective treatment for 2,922 patients with paroxysmal and persistent atrial fibrillation treated according to standard‐of‐care techniques at 93 unique sites in 36 countries around the world.

Aims We sought to evaluate the effectiveness of cardiac resynchronization therapy (CRT) in far‐advanced heart failure (FA‐HF) patients with New York Heart Association (NYHA) class‐IV status and dependency on intravenous drugs (IVDs) and/or invasive supportive treatments (ISTs). Methods and results Among 305 patients who underwent CRT implantation between October 2005 to December 2019, we identified 17 FA‐HF patients with NYHA class‐IV status and dependency on IVDs (inotropes, diuretics, vasopressors, or vasodilators) and/or ISTs (extracorporeal membranous oxygenator or continuous renal replacement therapy). All patients (median age = 68.7 years, non‐ischaemic cardiomyopathy = 15) remained dependent on several IVDs (2.2 ± 1.3 per patient) and/or ISTs for 11.3 ± 7.8 days due to multiple tapering failure (4.3 ± 3.2 per patient) before CRT implantation. However, 14 (82%) patients were successfully weaned from IVDs/ISTs within 5.2 ± 5.3 days following CRT, and 12 (71%) stayed alive for more than 1 year free of ventricular assist device or heart transplantation with symptom improvement (≥1 NYHA class) and a reduced annual HF hospitalization rate (P = 0.002). Considerable improvements in ventricular systolic function (P = 0.004) and volumetric reverse remodelling (P = 0.007) were noticed during the long‐term follow‐up period (35 ± 15 months post‐CRT). The ventricular assist device/heart transplantation/death‐free survival rate post‐CRT was 71% and 65% at 1 and 3 years, respectively. Conclusions Cardiac resynchronization therapy implantation may be a feasible treatment that can offer short‐term and long‐term clinical benefits for NYHA class‐IV FA‐HF patients who are dependent on IVDs/ISTs. When considering treatment options, CRT should not be prematurely excluded solely based on a patient's dependency on IVDs/ISTs without first attempting to identify favourable CRT response factors.

Background: We investigated the impact of previous catheter ablation (CA) on the mid-term outcomes of totally thoracoscopic ablation in patients with lone atrial fibrillation (AF).Methods: Between February 2012 and July 2018, 332 patients underwent totally thora-coscopic ablation for the treatment of AF (persistent AF; n=264, 80%). The patients were stratified into CA (n=47, 14%) and non-CA (nCA; n=285, 86%) groups according to their CA history.Results: All the baseline clinical characteristics and risk factors were similar between the groups except for age, percentage of male patients, prevalence of paroxysmal AF, prior percutaneous coronary intervention, and left atrial volume index (LAVI). No significant in-tergroup differences were observed in the incidence of early and late complications. At late follow-up, normal sinus rhythm was observed in 92% (43 of 47) of the patients in the CA group and 85% (242 of 285) of the patients in the nCA group (p=0.268). The rate of free-dom from AF recurrence at 5 years was 55.3%±11.0% in the CA group, which was similar to that in the nCA group (55.7%±5.1%, p=0.690). In Cox regression analysis, preoperative brain natriuretic peptide levels and LAVI were associated with AF recurrence, but CA his-tory was not significant.Conclusion: Totally thoracoscopic ablation was safe and effective in treating AF irrespec-tive of CA history. A history of CA did not appear to affect the procedural complexity.

Endocardial radiofrequency catheter ablation is considered to be a useful procedure for paroxysmal atrial fibrillation. However, catheter ablation has difficulties in achieving successful results in patients with persistent or long-standing persistent atrial fibrillation. Currently, the gold standard is surgical ablation (the Cox maze III procedure). However, because surgical ablation requires a sternotomy and extracorporeal cardiopulmonary bypass and has been associated with surgery-related complications, minimally invasive (totally thoracoscopic) and epicardial-endocardial (hybrid) ablation procedures have been developed. This article reviews the primary surgical and hybrid approaches used to treat persistent or long-standing persistent atrial fibrillation.

Background After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist. Objectives We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes. Methods Data were retrospectively collected from the hospital‐based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited. Results A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P

BACKGROUND Despite many studies on new tools and strategies for cavotricuspid isthmus (CTI) ablation, there is an unmet need to improve the CTI ablation procedure. Recently, high-power short-duration (HPSD) ablation has been widely used for pulmonary vein (PV) isolation in atrial fibrillation. We evaluated the effectiveness and safety of HPSD for CTI ablation in atrial flutter (AFL). METHODS Eighty-four patients who underwent CTI ablation with or without simultaneous PV isolation between January 2018 and February 2019 were enrolled in this prospective cohort study. We compared procedural characteristics, periprocedural complications, and recurrence of atrial tachyarrhythmia (ATa) between the HPSD group (50 W for 15 s) and conventional group (30 W for 60 s). RESULTS A total of 84 patients were divided into the HPSD (n = 42) and conventional (n = 42) groups. Bidirectional CTI block was achieved in all patients and 95% achieved bidirectional block after the first-line ablation in both groups. Although there was no difference in the total number of ablation lines between the two groups (1.17 ± 0.7 vs 1.38 ± 0.8, P = .067), HPSD ablation significantly reduced total ablation time compared to the conventional group (236.0 ± 85.6 vs 534.2 ± 235.2 s, P

The development of heat-generating magnetic nanostructures is critical for the effective management of tumors using magnetic hyperthermia. Herein, we demonstrate that polyethylene glycol (PEG)-coated iron oxide (magnetite, Fe3O4) multigranule nanoclusters (PEG-MGNCs) can enhance the efficiency of hyperthermia-based tumor suppression in vitro and in vivo. MGNCs consisting of granules (crystallites) measuring 22.9 nm in diameter were prepared via the hydrothermal polyol method, followed by the surface modification of MGNCs with PEG-dopamine. The freshly prepared PEG-MGNCs exhibit 145.9 ± 10.2 nm diameter on average under aqueous conditions. The three-dimensional structures of PEG-MGNCs enhance the hyperthermic efficacy compared with PEGylated single iron-oxide nanoparticles (NPs), resulting in severe heat damage to tumor cells in vitro. In the SCC7 tumor-bearing mice, near-infrared fluorescence dye (Cy5.5)-labeled PEG-MGNCs are successfully accumulated in the tumor tissues because of NP-derived enhanced permeation and retention effect. Finally, the tumor growth is significantly suppressed in PEG-MGNC-treated mice after two-times heat generation by using a longitudinal solenoid, which can generate an alternating magnetic field under high-frequency (19.5 kA/m, 389 kHz) induction. This study shows for the first time that the PEG-MGNCs greatly enhance the hyperthermic efficacy of tumor treatment both in vitro and in vivo.

Purpose With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. Materials and methods A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006-2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. Results Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. Conclusion Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

The growth arrest and DNA damage‐inducible beta (Gadd45β) protein have been associated with various cellular functions, but its role in progressive renal disease is currently unknown. Here, we examined the effect of Gadd45β deletion on cell proliferation and apoptosis, inflammation, and renal fibrosis in an early chronic kidney disease (CKD) mouse model following unilateral ureteral obstruction (UUO). Wild‐type (WT) and Gadd45β‐knockout (KO) mice underwent either a sham operation or UUO and the kidneys were sampled eight days later. A histological assay revealed that ablation of Gadd45β ameliorated UUO‐induced renal injury. Cell proliferation was higher in Gadd45β KO mouse kidneys, but apoptosis was similar in both genotypes after UUO. Expression of pro‐inflammatory cytokines after UUO was down‐regulated in the kidneys from Gadd45β KO mice, whereas UUO‐mediated immune cell infiltration remained unchanged. The expression of pro‐inflammatory cytokines in response to LPS stimulation decreased in bone marrow‐derived macrophages from Gadd45β KO mice compared with that in WT mice. Importantly, UUO‐induced renal fibrosis was ameliorated in Gadd45β KO mice unlike in WT mice. Gadd45β was involved in TGF‐β signalling pathway regulation in kidney fibroblasts. Our findings demonstrate that Gadd45β plays a crucial role in renal injury and may be a therapeutic target for the treatment of CKD.

Background Frequent ventricular premature depolarizations (VPDs) can cause reversible cardiomyopathy (CMP). However, many patients maintain a normal left ventricular (LV) function with a high VPD burden. The electrocardiographic characteristics of VPD‐induced CMP have not been elucidated. Methods One hundred and eighty (91 men, age; 51 ± 15 years) patients with frequent idiopathic VPDs (>10% VPDs/day or >10 000 VPDs/day) were studied. All patients underwent successful ablation and were then divided into two groups according to the echocardiographic findings before and after the ablation procedure. Results Group A (n = 139) had a normal LV function with VPD frequencies, and Group B (n = 41) had reversible LV dysfunction after ablation. The VPD QRS duration (QRSd) was wider in patients with CMP (Group A vs Group B; 137.2 ± 12.0 milliseconds vs 159.7 ± 5.3 milliseconds, P, Figure 1 Eletrocardiographic parameters. A, CI and post‐VPD CI; B, QR and RS interval and amplitude; C, r/R transition interval; D, Initial and terminal Angle of VPD. Abbreviations: CI, coupling interval; SCL, sinus cycle length; VPD, ventricular premature depolarization

Extent of late gadolinium enhancement (LGE) quantified by cardiac magnetic resonance was reportedly helpful for predicting the risk of ventricular tachyarrhythmias (VTA) in hypertrophic cardiomyopathy (HCM) patients. However, only a few data exist on the clinical implication of semi-quantitative assessment LGE extent in this patient population. The extent of left ventricular (LV) LGE was measured in 310 consecutive HCM patients using semi-quantitative (summing the LV segments with LGE, spatial extent) and quantitative (calculating the LGE volume percentage [vol% of LGE] against the total LV myocardial volume) methods, respectively. LV LGE was detected in 255 (82%) patients, most frequently in the mid-LV septum (n = 160, 52%). During the 49 ± 45 month follow-up, spontaneous VTA events were observed in 48 patients (16%) including aborted sudden cardiac death (SCD), appropriate defibrillator shock, and non-sustained VTA. The extent of LGE assessed by the two different methods showed a strong positive correlation (Spearman’s r = 0.63, P

Background Electrical cardioversion (ECV) is an effective method for restoring sinus rhythm after atrial fibrillation (AF). However, early recurrence of AF occurs in a significant number of patients after ECV. This study aimed to identify electrocardiographic (ECG) predictors of early AF recurrence after ECV. Methods A total of 272 patients with persistent AF undergoing successful ECV were consecutively enrolled in this study. We investigated clinical, echocardiographic, and ECG data. The 12‐lead ECG parameters were measured during sinus rhythm right after ECV using a digital caliper. The early AF recurrence was defined as recurrence within 2 months. Results Of the 272 patients, 165 patients (60.7%) experienced an early AF recurrence. Maximum P‐wave duration (PWD) in limb leads (OR: 1.086; 95% CI: 1.019–1.157; p = .012) and P‐terminal force (PTF) in V1 (OR: 1.019; 95% CI: 1.004–1.033; p = .011) were independent predictors of early AF recurrence after ECV. The optimal cutoff value of the maximum PWD in limb leads for predicting early AF recurrence was 134 ms, characterized by 90.3% sensitivity and 72.0% specificity. Likewise, the optimal cutoff value of PTF in V1 was 50 ms × mm, characterized by 80.0% sensitivity and 64.5% specificity. Conclusion A longer PWD (>134 ms) and a larger PTF (>50 ms × mm) were useful predictors of early recurrence of AF after successful ECV in clinical practice. A more effective rhythm control therapy such as catheter ablation or rate control strategy rather than a repeat ECV should be considered.

Background This study aims to investigate the current status of AF (atrial fibrillation) catheter ablation in Korea. Methods The patients who underwent AF catheter ablation from September 2017 to December 2019 were prospectively enrolled from 37 arrhythmia centers. Demographic data, procedural characteristics, the extent of catheter ablation, acute success of the ablation lesion set, rate and independent risk factor for recurrence of AF were analyzed. Results A total of 2402 AF patients [paroxysmal AF (PAF) 45.7%, persistent AF (PeAF) 43.1% and redo AF 11.2%] were included. Pulmonary vein isolation (PVI) was performed in 2378 patients (99%) and acute success rate was 97.9%. Additional non-PV ablation (NPVA) were performed in 1648 patients (68.6%). Post-procedural complication rate was 2.2%. One-year AF-free survival rate was 78.6% and the PeAF patients showed poorer survival rate than the ones with other types (PeAF 72.4%, PAF 84.2%, redo AF 80.0%). Additional NPVA did not influence the recurrence of AF in the PAF patients (PVI 17.0% vs. NPVA 14.6%, P value 0.302). However, it showed lower AF recurrence rate in the PeAF patients (PVI 34.9% vs. NPVA 24.4%, P value 0.001). Valvular heart disease, left atrial diameter, PeAF, PVI alone, need of NPVA for terminating AF, and failed ablation were independent predictors of AF recurrence. Conclusions Additional NPVA was associated better rhythm outcome in the patients with PeAF, not in the ones with PAF. The independent risk factors for AF recurrence in Korean population were similar to previous studies. Further research is needed to discover optimal AF ablation strategy.

Background Recent trials demonstrated the safety and efficacy of cryoballoon ablation prior to antiarrhythmic drug (AAD) usage in patients with paroxysmal atrial fibrillation (AF); however, global utilization and outcomes of first-line cryoablation in real-world AF patient management are unknown. Purpose To evaluate baseline characteristics and outcomes in patients selected for first-line cryoablation for treatment of AF. Methods The Cryo Global Registry (NCT02752737) is an ongoing, prospective, multicenter registry. In this analysis, AF patients with an index cryoballoon ablation performed according to local standards of care at 58 centers in 26 global countries were included. Subjects with no prior failed antiarrhythmic drug (AAD) usage and not taking an AAD at baseline were considered first-line and compared to drug-refractory patients who had failed an AAD prior to enrollment in the study and/or were taking an AAD at baseline. Baseline characteristics, serious procedure-related complication rates, and 12-month freedom from a ≥30sec AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence after a 90-day blanking period were compared between the groups. Results In total, 31% of the 1,394 patients (433 first-line, 961 drug-refractory) received a first-line cryoablation. The proportion of first-line enrollments by world region (3.7%-53.5%) and countries within region (i.e. EU: 0–59%) varied widely. Drug-refractory patients failed a mean of 1.2±0.5 AADs prior to cryoablation. First-line and drug-refractory patients were similar in age (60±13 vs 61±11), sex (35.1% vs 36.8% female), and CHA2DS2-VASC (2.0±1.6 vs 2.1±1.6). First-line was more often paroxysmal AF (87.3% vs 80.2%), with lower BMI (27±5 vs 28±5), diagnosed with AF fewer years (2.1±3.9 vs 3.7±5.0), and had smaller left atrial diameters (39±7 vs 42±8 mm; all p0.05). Serious adverse event rates were not statistically different between first-line and drug-refractory patients (2.3% vs 3.4%, respectively; p=0.32). Freedom from AF/AFL/AT after cryoablation in first-line vs drug-refractory PAF was 90.0% (95% CI: 86.4–92.7%) and 84.4% (95% CI: 81.5–86.8%) and in first-line vs drug-refractory persistent AF was 72.9% (95% CI: 58.6–83.0%) vs 70.2% (95% CI: 62.9–76.4%), respectively. First-line ablation resulted in higher rates of freedom from arrhythmia recurrence (p=0.02). Conclusion First-line cryoablation in a real-world setting resulted in improved efficacy without increasing the risk of a safety event. These data support cryoablation as an early intervention strategy for treatment of AF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic, Inc.

Background Totally thoracoscopic ablation (TTA) is a minimally invasive and safe alternative to radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF). It has evolved over the last decades, but data are limited. The aim of this study was to report the long-term efficacy and safety of TTA through a single center experience. Methods We retrospectively analyzed all consecutive patients who underwent TTA for AF from February 2012 to December 2018. All patients were followed every 3 months after operation with 12-lead ECG and 24-hour Holter ECG monitoring. The late recurrence of AF was defined as any atrial tachyarrhythmia (ATa) sustained more than 30 s from 3 months after surgery. Results Of the total 408 patients undergoing TTA, 265 were analyzed in this study (17% paroxysmal, persistent or long standing persistent 83%, mean age 56 ± 9 years). During the mean follow-up duration 23 ± 18 months, ATa-free survival rate was 74%, 64%, 58%, 51% and 51% at 1,2,3,4 and 5 years, respectively. At the last follow-up, 75% of patients had sinus rhythm with or without additional intervention. The overall complication rate was 4.5% (12 events) and four patients (1.5%) had a stroke during follow-up. Conclusions TTA could be effective treatment option for AF. It had a very low risk of complication and could reduce stroke incidence. Further studies are needed to improve treatment strategy.

Background and Objectives: Cryoballoon ablation (CBA) and totally thoracoscopic surgical ablation (TTA) have emerged as alternatives to radiofrequency catheter ablation (RFCA) for atrial fibrillation. In this study, we describe our experience comparing patient characteristics and outcomes of RFCA, CBA, and TTA. Materials and Methods: We retrospectively analyzed data from patients who underwent RFCA, CBA, or TTA. Both atrial fibrillation (AF)- and atrial tachyarrhythmia (ATa)-free survival rates were compared using time to recurrence after a 3-month blanking period (defined by a duration of more than 30 s). All patients were regularly followed using 12-lead ECGs or Holter ECG monitoring. Results: Of 354 patients in this study, 125 underwent RFCA, 97 underwent CBA and 131 underwent TTA. The TTA group had more patients with persistent AF, a larger LA diameter, and a history of stroke. The CBA group showed the shortest procedure time (p &lt, 0.001). The CBA group showed significantly lower AF-free survival at 12 months than the RFCA and TTA groups (RFCA 84%, CBA 74% and TTA 85%, p = 0.071, p = 0.859 for TTA vs. RFCA, p = 0.038 for RFCA vs. CBA and p = 0.046 for TTA vs. CBA). There were no significant differences in ATa-free survival among the three groups (p = 0.270). There were no procedure-related adverse events in the RFCA group, but some complications occurred in the CBA group and the TTA group (6% and 5%, respectively). Conclusions: RFCA and CBA are effective and safe as first-line treatments for paroxysmal and persistent AF. In some high-risk stroke patients, TTA may be a viable option. It is important to consider patient characteristics when selecting an ablation method for AF.

Reduced-dose nonvitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed to Asian patients with nonvalvular atrial fibrillation (NVAF). We aimed to compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between patients treated with reduced-dose NOACs and those treated with warfarin, using the claims database in Korea. Patients with NVAF newly initiated on oral anticoagulants (OACs, apixaban, dabigatran, rivaroxaban, and warfarin) between 1 July 2015 and 30 November 2016 were included. Among all patients with NVAF treated with OACs, 5249, 6033, 7602, and 8648 patients were treated with reduced-dose apixaban, dabigatran, rivaroxaban, and warfarin, respectively. Patients treated with reduced-dose NOACs were older and had higher CHA2DS2-VASc and HAS-BLED scores than those treated with warfarin. Compared to warfarin, all reduced-dose NOACs showed significantly lower risk of S/SE (hazard ratios (95% confidence interval), 0.63 (0.52–0.75) for apixaban, 0.51 (0.42–0.61) for dabigatran, and 0.67 (0.57–0.79) for rivaroxaban) and MB (0.54 (0.45–0.65) for apixaban, 0.58 (0.49–0.69) for dabigatran, 0.73 (0.63–0.85) for rivaroxaban). In the real-world practice among Asians with NVAF, all reduced-dose NOACs were associated with a significantly lower risk of S/SE and MB compared to those of warfarin.

Background Annually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results. Methods During the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention. Results During the first A/H3N2-dominant season in 2012–2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15–77). In the latter two seasons (2013–2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only. Conclusion During consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate.

Background and objectives The association between thyroid dysfunction and supraventricular tachyarrhythmia (SVT) other than atrial fibrillation (AF) is not well elucidated. We hypothesized that patients with suspected or documented SVT have undetected thyroid dysfunction more frequently than general population. Subjects and methods Patients with symptoms suggestive of SVT other than AF who were planned to undergo an EP study at our center were eligible for this study. Patients with known thyroid disease, medications affecting thyroid function test (TFT) or atrial fibrillation were excluded. The primary outcome was prevalence of TFT abnormalities in the study population. The secondary outcome was prevalence of clinically significant arrhythmia during the EP study. Results A total of 533 patients were analyzed. Patients were divided into the two groups according to TFT results. Fifty-six (10.5%) patients had abnormal TFT results (thyroid dysfunction group), while 477 (89.5%) had normal thyroid function (euthyroidism group). The overall prevalence of thyroid dysfunction was 10.5%. The thyroid dysfunction group showed a tendency for higher induction of clinically significant SVT than the euthyroidism group. However, thyroid dysfunction was not an independent predictor of clinically significant SVT during EP study. Conclusion In this study, patients with suspected SVT who were planned for EP study had a relatively high incidence of thyroid dysfunction. Clinically significant arrhythmia tended to be induced more frequently in the thyroid dysfunction group than in the euthyroidism group. Further investigations are needed to verify the clinical implications of TFT in patients with SVT other than AF.

The aim of this study was to identify associations between the smoothness index of central SBP (CSBP) and changes of ambulatory carotid femoral pulse wave velocity in response to 20-week treatments with losartan and amlodipine vs. losartan and hydrochlorthiazide combinations.For 142 (losartan and hydrochlorthiazide: 72, losartan and hydrochlorthiazide: 70) patients examined with ambulatory central blood pressure (BP) monitoring device, we calculated smoothness indices and trough-to-peak ratios of brachial SBP, CSBP, ambulatory pulse pressure amplification (APPA), ambulatory augmentation index at heart rate 75 beats per minute (AAIx75) and ambulatory carotid femoral pulse wave velocity (AcfPWV).Mean age was 58.9 ± 12.3 years, and women accounted for 25.9%. Changes in office SBP/DBP were not different between groups (losartan and hydrochlorthiazide: -15.2 ± 15.0/-7.8 ± 8.0 vs. losartan and amlodipine: -14.9 ± 13.7/-9.2 ± 7.5 mmHg). Reduction of 24-h CSBP was not significantly different (losartan and hydrochlorthiazide: 6.4 ± 1.1 vs. losartan and amlodipine: 9.2 ± 1.1 mmHg, P = 0.074). Reduction in nocturnal AcfPWV was greater in the losartan and amlodipine group (losartan and hydrochlorthiazide: 0.09 ± 0.05 vs. losartan and amlodipine: 0.26 ± 0.05 m/s, P = 0.0216). Intraindividual SIs for CSBP were higher in the losartan and amlodipine group (0.40 ± 0.57 vs. 0.65 ± 0.74, P = 0.022). In multivariable regression analysis, smoothness index of CSBP was independently associated with the losartan and amlodipine group. In model additionally considering the changes in arterial stiffness, decrease in AcfPWV instead of the treatment group was independently associated with smoothness indices. In mediation analysis, smoothness index was fully mediated by reduction in night-time AcfPWV.Losartan and amlodipine combination was superior to the losartan and hydrochlorthiazide combination in terms of achieving higher smoothness index for CSBP after 20-week treatments. The effect of losartan and amlodipine on smoothness index was fully mediated by reduction of night-time AcfPWV.

Complicated epidermoid cysts (ECs) occur commonly on the back, but few reports have described their management. We present our experience in managing patients with ECs on the back using a keystone-design perforator island flap (KDPIF) reconstruction, thereby focusing on reduction and redistribution of wound tension. Altogether, 15 patients (average age, 48.067 ± 14.868 years) underwent KDPIF reconstructions after complete excision of complicated ECs on the back. We retrospectively reviewed the medical records and clinical photographs of all patients. Final scar appearance was evaluated using the Patient and Observer Scar Assessment Scale (POSAS). All patients had ruptured ECs, while 6 patients also had cellulitis of the surrounding tissues. All defects, after complete excision of ECs and debridement of surrounding unhealthy tissues, were successfully covered with KDPIF. The mean ‘tension-change’ at the defect and donor sites was −4.73 ± 0.21 N and −4.88 ± 0.25 N, respectively (p

Background/Aims Although cardiovascular (CV) risk factors are well established, some patients experience acute myocardial infarction (AMI) even without any risk factors. Methods We analyzed total 11,390 patients (63.6 ± 12.6 years old, 8,401 males) with AMI enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health from November, 2011 to December, 2015. Patients were divided into two groups according to the presence of any CV risk factors (group I, without risk factors, n = 1,420 [12.5%]; group II, with risk factors, n = 9,970 [87.5%]). In-hospital outcomes were defined as in-hospital mortality and complications. One-year clinical outcomes were defined as the composite of major adverse cardiac events (MACE). Results Group I was older (67.3 ± 11.6 years old vs. 63.0 ± 12.7 years old, p < 0.001) and had higher prevalence of female gender (36.2% vs. 24.8%, p < 0.001) than the group II. Group I experienced less previous history of angina pectoris (7.0% vs. 9.4%, p = 0.003) and the previous history of cerebrovascular accidents (3.4% vs. 6.9%, p < 0.001). In-hospital mortality (2.6% vs. 3.0%, p = 0.450) and complications (20.6% vs. 20.0%, p = 0.647) were no differences between the groups. And 1 year clinical outcomes (5.7% vs. 5.1%, p = 0.337) were no differences between the groups. In multivariate logistic regression analysis, serum creatinine level (hazard ratio, 1.35; 95% confidence interval, 1.05 to 1.75; p = 0.021) were independent predictors of 1 year MACE in patients without any CV risk factors. Conclusions Elderly female patients were prone to develop AMI even without any modifiable CV risk factors. We suggest that more intensive care is needed in AMI patients without any CV risk factors who have high serum creatinine levels.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly and double right coronary artery (RCA) is a very rare coronary anomaly. Because patients with ALCAPA usually die within 1 year of being born due to myocardial infarction (MI) and heart failure, ALPACA is very rarely seen in adults. Here, we report an extremely rare asymptomatic case of MI, presumably caused by ALCAPA and double RCA, and provide a review of the literature. This is the first reported case of coronary artery anomaly that had both ALCAPA and double RCA. (Korean J Med 2019;94:215-220)

Background Few studies have investigated the prognostic value of cardiac implantable electronic device (CIED)-detection of sleep-disordered breathing (SDB) for risk stratification of cardiovascular events. In the Device-Detected CArdiac Tachyarrhythmic events and Sleep-disordered breathing (DEDiCATES) study, we aim to determine whether device-detected SDB events are associated with increased risk of cardiac arrhythmias or other cardiovascular outcomes. Methods and design Six-hundred patients (300 patients with low-voltage pacing devices and 300 with high-voltage defibrillator devices) who have dual chamber CIEDs with AP Scan™ function (Boston Scientific Inc., Marlborough, MA, USA) are planned to be enrolled in this study. AP Scan reports the average number of sleep disturbance events per hour per night in the form of a Respiratory Disturbance Index (RDI). The daily RDI values are to be used for quantitative measurement of the severity and burden of SDB. CIED-detected atrial high rate episodes (AHREs) and clinical atrial tachyarrhythmia will be assessed as the primary outcomes over a follow-up period of 2 years. Correlations between CIED-detected SDB and AHRE burdens will be analyzed. The secondary outcomes are CIED-detected or clinical ventricular arrhythmic events, stroke, heart failure hospitalization, mortality, and quality of life. Conclusion This study will determine the prognostic value of automated diagnostic function of CIED for SDB, which will help to improve the cardiovascular prognoses of CIED patients by enabling convenient and accurate assessments of SDB events.

Background Atrial fibrillation (AF) often progresses to more sustained forms and increases the risk of ischemic stroke or sinus node dysfunction. However, there have been no data on the clinical outcomes of patients who developed AF during head-up tilt testing (HUT). Objective The purpose of this study was to evaluate the clinical significance of AF detected during HUT performed for syncope evaluation. Methods We analyzed incidence, short- and long-term prognosis, and predictors of adverse outcomes of AF detected during HUT, which was performed in 6780 consecutive patients without AF history. Results Of the 6780 patients, 52 (0.8%) developed AF during passive tilting (n = 5), isoproterenol infusion (n = 32), and recovery phase (n = 15) of HUT, respectively. There was no short-term adverse event: spontaneous sinus conversion occurred in 43 patients (83%) within 48 hours. Over a median follow-up of 34.8 months, 24 patients (46%) had AF recurrence with initial presentation as ischemic stroke (n = 2), sinus node dysfunction requiring pacemaker (n = 10), and AF alone (n = 12). In addition, 19 of 24 recurred AF cases (79.2%) progressed to persistent/permanent forms. The index AF duration was identified as an independent predictor of AF recurrence. Patients with longer AF duration (≥1.0 hour) showed worse prognosis than did those with shorter AF duration ( Conclusion The incidence of AF during HUT was ∼0.8%, and short-term prognosis was favorable. However, about half of the cases were complicated by long-term adverse outcomes. Therefore, regular follow-up might be warranted for patients with HUT-induced AF, particularly when AF duration is long.

We investigated the clinical features, predictors, and long-term prognosis of pacing-induced cardiomyopathy (PiCM).From a retrospective analysis of 1418 consecutive pacemaker patients, 618 were found to have a preserved baseline left ventricular ejection fraction (LVEF), follow-up echocardiographic data, and no history of heart failure (HF). PiCM was defined as a reduction in LVEF ( 50%) along with either (i) a ≥ 10% decrease in LVEF, or (ii) new-onset regional wall motion abnormality unrelated to coronary artery disease. PiCM occurred in 87 of 618 patients (14.1%), with a decrease in mean LVEF from 60.5% to 40.1%. The median time to PiCM was 4.7 years. Baseline left bundle branch block, wider paced QRS duration (≥ 155 ms), and higher ventricular pacing percentage (≥ 86%) were identified as independent predictors of PiCM in multivariate logistic regression analysis. The risk of PiCM increased gradually with the number of identified predictors, becoming more significant in the presence of two or more predictors (P 0.001). During the entire follow-up (median 7.2 years), the risk of all-cause death or HF admission was significantly higher in patients with PiCM compared to those without PiCM (38.3% vs. 54.0%, adjusted hazard ratio 2.93; 95% confidence interval 1.82-4.72; P 0.001).Pacing-induced cardiomyopathy patients showed a worse long-term prognosis than those without PiCM. Therefore, patients with multiple risk factors of PiCM should be monitored carefully even if their left ventricular systolic function is preserved initially. A timely upgrade to a biventricular or His-bundle pacing device needs to be considered in patients with PiCM.

Background Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Asian 3 countries, China, Japan and Korea, which are scrub typhus endemic areas, and its incidence is increasing. As the two infections overlap epidemiologically and clinically and the accessibility or sensitivity of diagnostic tests is limited, early clinical prediction may be useful for diagnostic and therapeutic purposes. Methods Patients aged ≥16 years who were clinically suspected and laboratory-confirmed to be infected with Orientia tsutsugamushi or the SFTS virus in South Korea were enrolled. Clinical and laboratory parameters were compared. Scrub typhus was further subclassified according to the status of eschar and skin rash. An SFTS prediction scoring tool was generated based on a logistic regression analysis of SFTS compared with scrub typhus. Results The analysis was performed on 255 patients with scrub typhus and 107 patients with SFTS. At initial presentation, subjective symptoms except for gastrointestinal symptoms, were more prominent in scrub typhus patients. In addition to the characteristic eschar and skin rash, headache was significantly more prominent in scrub typhus, while laboratory abnormalities were more prominent in SFTS. Leukopenia (white blood cell count

Background The efficacy of catheter ablation for persistent atrial fibrillation (AF) remains suboptimal. A hybrid approach of catheter ablation combined with totally thoracoscopic surgical ablation can improve outcomes. In this study, we evaluated the efficacy of the early staged hybrid procedure in hospital stay after totally thoracoscopic ablation compared to the stand-alone totally thoracoscopic ablation. Methods Patients who underwent totally thoracoscopic ablation from February 2012 to December 2018 were included in this study. We compared the outcomes of the totally thoracoscopic ablation only group versus the early staged hybrid procedure group. The primary outcome was recurrence of atrial tachyarrhythmia after three months of blanking period. The secondary outcome was repeated unplanned additional electrophysiology study and catheter ablation due to atrial tachyarrhythmia recurrence. Results A total of 306 patients (mean age, 56.8 ± 8.5 years; 278 [90.8%] males) was included in the study, with 81 patients in the early staged hybrid group and 225 patients in the stand-alone totally thoracoscopic ablation only group. The mean follow-up duration was 30.0 months. Overall arrhythmia-free survival showed no significant difference between the two groups (log-rank P = 0.402). There was no significant difference in the rate of repeat procedure between the two groups (log-rank = 0.11). Conclusion The early staged hybrid procedure after thoracoscopic ablation could not improve the outcome of recurrence of atrial tachyarrhythmia. The second stage of electrophysiology study could be deferred to patients with recurrence of atrial tachyarrhythmia during follow up after totally thoracoscopic ablation., Graphical Abstract

We examined antithrombotic treatment patterns with clinical characteristics and therapy changes over time in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Using the Health Insurance Review and Assessment service claims database (01JAN2007-30NOV2016) in Korea, we included adult patients with AF and PCI: (1) who underwent PCI with stenting between 01JAN2008 and 30NOV2016, (2) with ≥1 claim for AF (ICD code: I48) (3) with antithrombotics 1 day prior to or at the date of PCI, and (4) with CHADS2-VASc of ≥2. In this study, 7749 patients with AF who underwent PCI, triple therapy, dual therapy, dual antiplatelet therapy (DAPT), and single antiplatelet therapy were prescribed to 24.6%, 3.4%, 60.8%, and 11.0%, respectively. In the triple therapy group, 23.1% persisted with triple therapy for 12 months, whereas the remaining patients switched to a different therapy. In the entire cohort and several subgroups, the median treatment duration of triple therapy was 55–87 days. DAPT use for 12 months was the most common treatment pattern (62.6%) in the DAPT group (median treatment duration, 324–345 days). A significant discrepancy exists between the current guidelines and real-world practice regarding antithrombotic treatment with PCI for patients with AF. Appropriate use of anticoagulants should be emphasized.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed. ispartof: EUROPEAN CARDIOLOGY REVIEW vol:16 ispartof: location:England status: published

The dopamine precursor 3,4-dihydroxyphenyl- l-alanine (L-DOPA) is the most widely used symptomatic treatment for Parkinson's disease (PD); however, its prolonged use is associated with L-DOPA-induced dyskinesia in more than half of patients after 10 years of treatment. The present study investigated whether co-treatment with β-Lapachone, a natural compound, and L-DOPA has protective effects in a 6-hydroxydopamine (6-OHDA)-induced mouse model of PD. Unilateral 6-OHDA-lesioned mice were treated with vehicle or β-Lapachone (10 mg/kg/day) and L-DOPA for 11 days. Abnormal involuntary movements (AIMs) were scored on days 5 and 10. β-Lapachone (10 mg/kg) co-treatment with L-DOPA decreased the AIMs score on both days 5 and 10. β-Lapachone was demonstrated to have a beneficial effect on the axial and limb AIMs scores on day 10. There was no significant suppression in dopamine D1 receptor-related and ERK1/2 signaling in the DA-denervated striatum by β-Lapachone-cotreatment with L-DOPA. Notably, β-Lapachone-cotreatment with L-DOPA increased phosphorylation at the Ser9 site of glycogen synthase kinase 3β (GSK-3β), indicating suppression of GSK-3β activity in both the unlesioned and 6-OHDA-lesioned striata. In addition, astrocyte activation was markedly suppressed by β-Lapachone-cotreatment with L-DOPA in the striatum and substantia nigra of the unilateral 6-OHDA model. These findings suggest that β-Lapachone cotreatment with L-DOPA therapy may have therapeutic potential for the suppression or management of the development of L-DOPA-induced dyskinesia in patients with PD.

OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION ClinicalTrials.gov NCT01090362.

Background To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between non‐vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF), this retrospective study was conducted using the Korean Health Insurance Review & Assessment Service (HIRA) claims database. Methods Patients with AF who initiated NOACs (apixaban, dabigatran, and rivaroxaban) from July 1, 2015 to November 30, 2016 were included. We applied inverse probability of treatment weighting (IPTW) method using propensity score to make weighted populations having similar characteristics between groups. Hazard ratio (HR) of S/SE and MB were estimated by Cox proportional hazard model. Results Of the 39 783 patients with AF, 10 564; 11 418; and 17 801 used apixaban, dabigatran, and rivaroxaban, respectively. The mean CHA2DS2‐VASc and HAS‐BLED scores were 4.59 ~ 4.69 and 3.58 ~ 3.62, respectively, among all patients after applying IPTW. For S/SE, there were no significant differences between NOACs (HR [95% confidence interval (CI)]): apixaban vs dabigatran (0.99 [0.87‐1.13]), apixaban vs rivaroxaban (0.95 [0.84‐1.07]), and dabigatran vs rivaroxaban (0.96 [0.85‐1.08]). For MB (HR [95% CI]), both apixaban (0.77 [0.68‐0.86]) and dabigatran (0.88 [0.79‐0.98]) had a significantly lower risk compared with rivaroxaban. Apixaban also had a significantly lower risk of MB compared with dabigatran (0.87 [0.76‐0.99]). Conclusions In real‐world practice among Korean AF patients with relatively high risk of stroke and bleeding, there were no significant differences in the risk of S/SE between all NOAC comparisons. Apixaban was associated with lower risk of MB than dabigatran and rivaroxaban., In real‐world practice among Koreans with AF, there were no significant differences in the risk of S/SE between all NOAC comparisons. Apixaban was associated with lower risk of MB than dabigatran and rivaroxaban.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. Methods A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. Results Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score 5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). Conclusions After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score, Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. In patients with SFTS, steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score

The extent to which cognitive function differs between patients who receive implantable cardioverter-defibrillator (ICD) therapy and patients with heart failure (HF) who do not receive ICD therapy remains to be elucidated.The aim of this study was to compare the cognitive function between patients with primary or secondary ICDs and patients with HF without an ICD.This descriptive, comparative study included 116 patients who received ICDs and 74 patients with HF who did not receive ICDs. Patients underwent neuropsychological assessment for general cognition, memory, and executive function.Immediate recall memory loss (18.9%) occurred more often in patients with HF without an ICD than in patients with primary (3.1%) and secondary (7.1%) ICDs (P = .018). After adjusting for age and education, delayed recall memory of patients with HF without ICDs was significantly worse than that of patients with primary ICDs (4.0 vs 6.5; P.001), whereas delayed recall memory of patients with primary ICDs was better than that of patients with secondary ICDs (6.0 vs 6.5; P = .006). Executive function of patients with HF without ICDs was significantly worse than that of patients with primary (35 vs 58 seconds; P.001) and secondary (28 vs 58 seconds; P = .0012) ICDs.Patients with ICDs, regardless of primary or secondary indication, had less impairment of memory and executive function than patients with HF without ICDs, implying that ICD therapy did not interfere with cognitive performance. Cognitive screening as a part of routine care could be helpful for identifying impairment and implementing early cognitive training, especially in patients with HF.

Background: Little is known about electrical remodeling of the native conduction systems,particularly how the PR interval changes, after cardiac resynchronization therapy (CRT). Weinvestigated the effects of CRT on the intrinsic PR interval (i-PRi) and QRS duration (i-QRSd).Methods and results: In 100 consecutive CRT recipients with sinus rhythm and long-term followup(&gt, 1 year), the i-PRi and i-QRSd were measured at baseline and at the last echocardiographicfollow-up (33.4 &plusmn, 17.9 months) with biventricular pacing temporarily withdrawn. The relativedecrease in the left ventricular end-systolic volume (LVESV) was measured to define CRTresponders(&ge, 15%) and super-responders (&ge, 30%). Following CRT, the left ventricular (LV) ejectionfraction increased significantly (p &lt, 0.001). In CRT-responders (n = 71), the LVESV and i-QRSddecreased markedly (170 &plusmn, 39 to 159 &plusmn, 24 ms, p = 0.012). However, the i-PRi was not shortened withCRT response and was actually likely to increase, even in the super-responder group (n = 33).Moreover, lengthening of the i-PRi was observed consistently irrespective of the CRT responsestatus, beta-blocker use, or amiodarone use. CRT non-responders were associated with a remarkablePR prolongation (p = 0.005) and QRS widening (p = 0.001), along with positive ventricularremodeling. Conclusion: LV volume and i-QRSd decreased markedly with CRT response.However, the i-PRi was not shortened, but rather increased regardless of the degree of CRTresponse. CRT non-response was associated with a considerable increase in the i-PRi and i-QRSd,along with positive ventricular remodeling. CRT-induced electrical reverse remodeling might occurpreferentially in the intraventricular, but not the atrioventricular, conduction system.

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)-induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

Background: The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectrum of genetic variants and genotype&ndash, phenotype relationships within a Korean HCM population. Methods: Eighty-nine consecutive unrelated HCM patients were included. All patients underwent genotypic analysis for 23 HCM-associated genes. Clinical parameters including echocardiographic and cardiac magnetic resonance (CMR) parameters were evaluated. A composite of major adverse cardiac and cerebrovascular events was assessed. Results: Genetic variants were detected in 55 of 89 subjects. Pathogenic variants or likely pathogenic variants were identified in 27 of HCM patients in MYBPC3, TNNI3, MYH7, and MYL7. Variants of uncertain significance were identified in 28 patients. There were significant differences in the presence of non-sustained ventricular tachycardia (p = 0.030) and myocardial fibrosis on CMR (p = 0.029) in the detected compared to the not-detected groups. Event-free survival was superior in the not-detected group (p = 0.006). Conclusion: Genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR. Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients.