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BACKGROUND. There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI).AIM. To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period.MATERIALS AND METHODS. AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected the data of hospitalized patients and included 3 visits. All subjects were divided into 3 groups: not overweight (n=2139), overweight (n=2931) and obese (n=2666).RESULTS. A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (pCONCLUSION. Overweight and/or obesity is a significant risk factor for severe course of the new coronavirus infection and the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Background/Introduction Empagliflozin was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for reducing cardiovascular mortality and heart failure (HF) hospitalization in both patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Purpose Limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and cost-effectiveness based on a nationwide prospective HF registry. Methods For the study, 3108 HFrEF and 2070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analysed. Eligibility was estimated by FDA and EMA label criteria and by inclusion and exclusion criteria of EMPEROR-Reduced and EMPEROR-Preserved trials. The cost-effectiveness analysis was performed using the decision tree model, where effectiveness was the avoidance of the first hospitalization. Results Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The main factor for exclusion in the clinical trial-based empagliflozin eligibility was low systolic blood pressure, including 18.7% of HFrEF and 11.0% of HFpEF patients. Other factors were acute ( Conclusion(s) There is a large discrepancy of real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. The cost-effectiveness benefit was more evident in patients with HFrEF than HFpEF. The efficacy and safety of empagliflozin in real-world patients should be further investigated for a broader range of clinical applications. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Minister of Science and Information and Communication Technologies (NRF-2021R1F1A1063430), by the Catholic Medical Center Research Foundation (2022), and by the Research of Korea Centers for Disease Control and Prevention (2010-E63003-00, 2011-E63002-00, 2012-E63005-00, 2013-E6300300, 2014-E63003-01, 2015-E63003-02, 2016-ER6303-00, and 2017-ER6303-01).

Background Difference in proteomic expression according to the etiology of cardiomyopathies is not well known. Purpose We aimed to identify proteome based pathogenesis in patients with biopsy proven cardiomyopathies. Methods Comparative proteomic analysis of biopsy specimens were performed from 9 patients with cardiomyopathy (3 dilated cardiomyopathy (DCM), 2 hypertrophic cardiomyopathy (HCM) and 4 myocarditis) as well as 5 controls (normal endomyocardial biopsy specimen from one-year surveillance of heart transplant recipients) by tandem mass tag combined with liquid chromatography-mass spectrometry. Differential expression protein analysis, gene ontology analysis and Ingenuity pathway analysis were done to discover molecular mechanism for the differentially expressed proteins in each cardiomyopathy compared to the control. Results Differential expression protein analysis showed higher proportion of significantly increased proteins (Log2 fold change ≥1) in HCM and myocarditis, whereas higher proportion of significantly decreased proteins (Log2 fold change ≤−1) in DCM compared to controls (Figure). According to the gene ontology analysis, upregulation of neutrophil degranulation, and down-regulation of mitochondrial translation protein was noted in patients with DCM. In patients with HCM, platelet degranulation protein was increased, and mitochondrial ATP synthesis coupled electron transport, was decreased. In patients with myocarditis, neutrophil related proteins and calcium ion binding protein was increased, but muscle cell development, protein was decreased. Ingenuity pathway analysis revealed downregulation of oxidative phosphorylation and upregulation of sirtuin signalling pathway both in DCM and HCM. In myocarditis, various pathways related to inflammation were upregulated with only RHO GDP dissociation inhibitors downregulated. Conclusions This study showed that each cardiomyopathy exhibited different proteomic expression compared to normal heart. Further large detailed study is needed to understand the association between proteomic expression and disease pathophysiology. Funding Acknowledgement Type of funding sources: None.

Background This study aimed to investigate the adverse events (AEs) after SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) and to compare them with healthcare workers (HCWs). Methods We conducted a web-based survey on the local and systemic AEs experienced within 7 days of SARS-CoV-2 vaccination (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19) in IBD patients and HCWs between October 2021 and February 2022. The frequency of all AEs was compared between IBD patients and HCWs, and propensity score matching method was used to control confounding factors. Results A total of 336 IBD patients (139 Crohn’s disease [CD] and 197 ulcerative colitis [UC]) and 288 HCWs who completed the questionnaire had received the same type of vaccine for their first and second doses. Common local AEs in patients with IBD were injection site pain (78.9% and 70.8% after receiving first and second vaccine doses, respectively), swelling (35.4% and 31.5%), and induration (35.1% and 26.5%), and systemic AEs were fatigue (44.6% and 42.0%), myalgia (42.6% and 37.2%), and fever or febrile sense (29.5% and 32.1%). All severe AEs were rarely observed (0-3.9%). Hospital visits or hospitalizations associated with AEs were observed in 16 (4.8%) and 18 (5.4%) patients, respectively. A small number of patients reported deterioration of bowel frequency (CD: 10.1% and 12.2%, UC: 8.1% and 11.7%), abdominal pain (CD: 5.0% and 7.9%), and rectal bleeding (UC: 5.1% and 7.6%). About 30% of IBD patients reported a worsening of their sense of well-being. After propensity score matching, there was no significant increase in the frequency of AEs in IBD patients except for diarrhea (14.5% vs 4.8%, P = 0.005) and dyspepsia (15.2% vs 5.5%, P= 0.007) after first vaccination. Conclusion SARS-CoV-2 vaccination in patients with IBD was generally well-tolerated and severe AEs occurred rarely. Compared with HCWs, the frequency of AEs does not seem to increase except for diarrhea and dyspepsia.

Aim. To analyze newly diagnosed diseases and features of the post-COVID course in patients after a coronavirus disease 2019 (COVID-19) within 12-month follow-up.Material and methods. A total of 9364 consecutively hospitalized patients were included in the ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to the ACTIV registry, 18,1% of patients after COVID-19 had newly diagnosed diseases (NDDs) over the next 12 months. Hypertension (HTN), type 2 diabetes and coronary artery disease (CAD) prevailed in the NDD structure. Comparison of the age-standardized incidence of NDDs (HTN, CAD, diabetes) in the post-COVID period in the ACTIV registry with NDD incidence in 2019 according to Rosstat and the expected incidence of NDDs according to the EPOHA study revealed that HTN, diabetes, CAD in patients after COVID-19 were registered more often as follows: HTN by 7,0 and 4,4 times, diabetes by 7,3 and 8,8 times, CAD by 2,3 and 2,9 times, respectively. NDDs most often developed in patients aged 47 to 70 years. Comparison of the actual and expected number of cases of newly diagnosed HTN, CAD and diabetes depending on age showed that the actual number of cases in the population of patients in the ACTIV register is significantly higher than expected for patients aged 45-69 years and for patients with hypertension or diabetes and aged Conclusion. Available evidence suggests that a strategy for managing COVID-19 survivors should include mandatory screening for early detection of cardiovascular disease and diabetes, which will be key to reducing the risk of further COVID-19 consequences.

Patients with CTCL are at increased risk for bacteremia which is a leading cause of morbidity and mortality. We assessed risk factors for and the impact of bacteremia on survival in a retrospective cohort of 188 CTCL patients at a single US academic institution treated between 1990 and 2018. With a median follow up of 6.2 years, 20% of patients (n = 36) developed 79 bacteremia events. Risk factors for bacteremia included advanced stage, female gender, African American (AA) race, invasive lines, and chemotherapy. Bacteremia was associated with an increased risk of death on univariate and multivariable models. Bacteremia is associated with an increased risk of death in patients with CTCL. The greatest avoidable risk factors included chemotherapy treatment and presence of an invasive line.

Background Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Methods Mice were divided into three groups: control, colitis-induced, and SIRT7 inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. Results The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Conclusion Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.

Background There are insufficient studies on clinical outcome after surveillance of low grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD). We aimed to evaluate the clinical feature, frequency and risk factors of advanced neoplasia in IBD patients after diagnosis of LGD Methods From 2003 to 2020, medical records of 166 IBD patients from 6 university hospitals in Korea were reviewed retrospectively. All of the patients were diagnosed as LGD in surveillance. Patents’ baseline characteristics, disease status, polyp characteristics and treatment were evaluated. The frequency and risk factors of advanced neoplasia were also analyzed. Results Disease duration was 11.47 years (7.85-14.50), and follow-up duration was 3.74 years (1.95-7.58). Colitis associated LGD was noted in 56 cases (33.7%), Advanced neoplasia developed in 12 cases (6 large LGD, 3 tubulovillous adenoma, 3 high grade dysplasia) and all the cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo score and colitis-related dysplasia were more common than sporadic lesions (83.3% vs. 29.9%; P Conclusion Advanced neoplasia developed in 7.2% of IBD patients with LGD. Because most of advanced neoplasia developed from colitis-associated lesions, more careful examination is suggested in patients with colitis -associated LGD, especially with previous history, in surveillance colonoscopy.

Background Gut microbial dysbiosis has been suggested to contribute to pathogenesis of inflammatory bowel disease (IBD). Vedolizumab (VDZ), an α4β7 integrin blocker, has been used as an effective agent for patients with IBD. However, effect of VDZ on gut microbiome and its relationship with efficacy outcomes are still unclear. We investigated gut microbial change in patients with ulcerative colitis (UC) during VDZ treatment. Methods Patients with UC were prospectively enrolled and were given a 300 mg infusion of VDZ at weeks 0, 2, and 6 as an induction therapy and then every 8 weeks as a maintenance therapy. In cases of insufficient response, the interval of maintenance therapy was shortened to every 4 week infusion. Faecal samples were collected at weeks 0, 14, and 54 and 16S rRNA gene microbiome profiling analysis was performed. Clinical remission (CREM), clinical response (CRES), endoscopic mucosal healing (MH) and biochemical response (BioRES) were evaluated. Compositional differences in microbiome were analysed according to CREM, CRES, MH, and BioRES at weeks 0, 14, and 54. Results Faecal samples were collected from 27 patients and patients were classified according to their outcomes (Table 1). In the analyses regarding species richness (ACE, Chao1, Jackknife, The number of OTUs) and diversity indices (NPShannon, Shannon, Simpson, Phylogenetic Diversity), no significant difference was observed among groups at weeks 0, 14, and 54. There were no significant changes in microbial composition at week 14 and 54, respectively compared to basal level. However, compared to baseline, relative abundance of genus Prevotella showed significant differences between groups which achieved normalsation of C-reactive protein or not (p=0.0394) (Figure 1). In the linear discriminant analysis effect size (LEfSe) analysis, the genus Actinomyces and the species Actinomyces odontolyticus group increased in patients who had no response at efficacy outcomes (achievement of clinical remission, achievement of clinical response, achievement of endoscopic mucosal healing, normalisation of C-reactive protein, and normalisation of faecal calprotectin) at week 14, compared to week 0 (Fig 2A). The genus Clostridium_g24, the species Paraprevotella_uc and PAC001224_s were also significantly increased in the same patient group at week 54 (Fig 2B). Conclusion In UC patients treated with VDZ, microbial composition showed differences depending on the achievement of efficacy outcomes. Further studies regarding the causal relationship between microbial composition and outcomes are warranted with a larger number of patients.

Background A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD). Methods We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance. Results Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%). Conclusion Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.

Background Although high and low volume polyethylene glycol(PEG) bowel preparations are recommended for patients with inflammatory bowel disease(IBD) before colonoscopy, sometime it is limited due to poor compliance. So, studies regarding novel low volume preparations in IBD are need, but, there is limited data. We aimed to evaluated the safety, tolerability and efficacy of oral sulfate tablet (OST) by comparison with 2L PEG and ascorbate (PEG/Asc) in patients with IBD. Methods One hundred ten patients with IBD were enrolled in this single-blind, multicenter, non-inferiority study. Patients were assigned either 2L PEG/Asc or OST to be administered in a split-dose regimen. OST patients were administered 14 tablets with more than 1L of free water in the evening, and the following morning. Colonoscopies were performed by blinded investigators. The primary efficacy endpoint was successful bowel cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded endoscopist in each hospital. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Flare up of IBD symptoms and mucosa change associated with preparation were also evaluated. Tolerability, in terms of taste and degree of resistance to drink was assessed with VAS score by interview before colnoscopy. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. Results The cleansing score at all the segment was significantly higher in OST group. A high rate of cleansing success was seen with OST (98.1%), which was noninferior to 2L PEG/Asc (98.1%). Proportion of patients with bubble score 0 was significantly higher in OST than 2L PEPG/Asc group (94.5% vs. 50.0%, p Conclusion Oral sulfate tablets achieved a high level of cleansing comparable with 2L PEG/Asc in patients with IBD. The risk of mucosal change or symptom relapse were not higher, on the other hand the degree of satisfaction was higher than 2L PEG/Asc. OST split method could be considered as one of the preparation method for patients with inactive IBD.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of Conclusion. A decrease in LDL-C in the acute period is significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. Determination of LDL-C can be included in the examination program for patients with COVID-19. However, the predictive value of this parameter requires further study in prospective clinical studies.

Aim To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients’ privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).ResultsThe analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

Background Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC. Methods A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms. Results Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively. Conclusion Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.

One of the most serious complications of modern anesthesia is malignant hyperthermia, which is a pharmacogenetic disease phenotype manifested by skeletal muscle hypermetabolism and rhabdomyolysis during or after general anesthe- sia with the use of inhaled anesthetics and succinylcholine. In Russia, the problem of malignant hyperthermia remains unresolved. This is mainly due to the fact that the only specific drug dantrolene created for the effective treatment of malignant hyperthermia is still not legalized and thus formally prohibited to import, disseminate and apply on the domestic pharmaceutical market. This article deals with the regulatory framework of specific treatment of malignant hyperthermia in Russia, allowing the possibility to legally import to the territory of the Russian Federation dantrolene as an unregistered drug, if it is a question of rendering medical assistance on vital indications to a particular patient, or its unauthorized use for vital indications in a situation of extreme necessity. The article presents the recommendations of domestic experts on the treatment of malignant hyperthermia. In this case, as a possible alternative to dantrolene, magnesium preparations are considered, whose role in the treatment of the crisis of malignant hyperthermia continues to be specified. Thus, given the increasing use of inhalation anesthesia by Russian anesthetists, to ensure the safety of patients with regard to the development of malignant hyperthermia, it is possible only in the case of official registration in the do- mestic dantrolene market. Also, in the territory of Russia, a network of relevant consultative and diagnostic centers should be established. These measures will undoubtedly increase the effectiveness of treatment and prevention of severe consequences of this disease in our country.

The work is dedicated to the topic of parallelizing programs in especially difficult cases - when the used algorithm is purely sequential, there are no parallel alternatives to the algorithm used, and its execution time is unacceptably high. Various parallelization methods for software implementations of such algorithms and resulting computational load balancing are considered, allowing to obtain significant performance acceleration for application programs using purely sequential algorithms. The above methods are illustrated by the practice of their application to two algorithms used in a dynamic binary code analysis toolset. The main goal of this paper is to show that the use of a purely sequential algorithm in a software implementation does not necessarily imply inevitability of its sequential execution. The proposed methods of parallelizing implementations of such algorithms and balancing the resulting computational load can help to develop efficient parallel program that fully utilize the hardware capabilities of modern computing systems.

Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes. Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose. Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.

The development of high throughput genotyping techniques has facilitated the identification of selection signatures of pigs. The detection of genomic selection signals in a population subjected to differential selection pressures may provide insights into the genes associated with economically and biologically important traits. To identify genomic regions under selection, we genotyped 488 Duroc (D) pigs and 155 D × Korean native pigs (DKNPs) using the Porcine SNP70K BeadChip. By applying the FST and extended haplotype homozygosity (EHH-Rsb) methods, we detected genes under directional selection associated with growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG, COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159 and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly near or at fixation. These results could be a basis for investigating the underlying mutations associated with observed phenotypic variation. Validation using genome-wide association analysis would also facilitate the inclusion of some of these markers in genetic evaluation programs.

Background Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pre-treatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments. Methods We performed a multicentre, prospective study of patients with IBD at 5 tertiary medical centres in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2–2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/μL, levels of haemoglobin 10 g/dl, or platelet counts below 100 K/μl. Results Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (p = .005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22–0.81; p = 0.009), pre-treatment genotype analysis (HR, 0.37; 95% CI, 0.18–0.77; p = 0.008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19–0.59; p < 0.001) independently decreased risk of myelosuppression. Pre-treatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions. Conclusion In a randomised controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leucopoenia significantly reduced the proportion of patients with myelosuppression during treatment.

A deep draft semi-submersible hull has been developed by SHI (Samsung Heavy Industries) and Williams as a standardization concept which can support the topside structures up to the facility weight for the specific level of daily oil production in GOM (Gulf of Mexico). The designed hull has the optimized dimensions of pontoon and column which secure the sufficient level of GM for the stability and ballast capacity for coping with the weight change of topside structures. The hull form also has the good global motion in waves to be able to use the SCR (Steel Catenary Riser) as a deep draft semi-submersible concept. Two hull forms are designed to have 4 columns with two different cross sections and the conventional ring pontoon. The compartmentation and basic hydrodynamic analysis are performed at the hull sizing stage to achieve the sufficient stability and the motion performance as well. The mooring systems are also designed for two different water depths of 1000m and 3000m as a standard design concept of hull including mooring lines. To verify the feasibility of the proposed hull concept with regard to the hydrostatic/hydrodynamic characteristics and mooring line design, the numerical global performance analyses are carried out. Hydrostatic stability is investigated for intact and damage condition of operational loading condition and the proper tank compartments are verified under the given topside weight and the environment condition in GOM. The global motion is validated for all the possible combinations of wave, wind, current for a site in central GOM. Through the frequency-domain analysis and quasi-static time-domain analysis as well, the essential items such as the maximum offset, mooring line tension/fatigue, air-gap and the extreme acceleration at topside are examined and confirms that the certain design criteria of Semi FPU (Floating Production Unit) operation are satisfied. The possibility of SCR usage is also investigated with the fully coupled time domain analysis using the preliminary design of risers and confirms that the designed hull form has the suitable hydrodynamic characteristics to permit the minimum motion performance for SCR in the sense of extreme load and fatigue life.

This letter presents a high-selectivity compact microstrip bandpass filter (BPF) with a flexibly controllable bandwidth, based on multi-path source-load couplings and a square-type split-ring resonator (STSRR). An STSRR, which is enclosed between the capacitively coupled source and load transmission feed lines, forms the structure of the proposed BPF. The main advantages of the proposed BPF lie in its simple structure and high selectivity due to multiple transmission zeros generated by multipath source-load couplings based on STSRR-enabled magnetic coupling between the feed lines with dual capacitive couplings. In addition, the bandwidth of the proposed BPF can be flexibly controlled by varying the magnetic coupling gap between the STSRR and the feed lines. The measured pass-band insertion and return loss of 0.83 and 27.23 dB, respectively, for a prototype BPF with a central frequency of 3.83 GHz and corresponding bandwidth of 12.98%, demonstrates the validity of the proposed method.

Background Despite its increasing incidence, large-scale data regarding the demographics and characteristics of paediatric inflammatory bowel disease (IBD) at diagnosis in Korea is scarce. We aimed to compare the differences of paediatric Crohn’s disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. Methods This analysis was conducted using data from a multicentre, registry-based, retrospective cohort study conducted at five centres in Korea between 2013 and 2018. Baseline demographics, clinical characteristics, results from laboratory, endoscopic, radiologic examinations were compared between paediatric CD and UC patients who were Results A total 307 patients were included in this analysis. Among them 227 patients were diagnosed with CD (73.9%), and 80 patients (26.1%) with UC. The male to female ratio was 2.49:1 for CD, and 1.29:1 for UC (p = 0.019). Median age at diagnosis was 14.4 years (IQR 12.4–16.2) for CD, and 14.4 (11.7–16.5) for UC (p = 0.962). Symptoms at presentation that were dominant in CD patients compared with UC patients were abdominal pain (76.2% vs. 51.2%, p < 0.001), weight loss (51.5% vs. 22.5%, p < 0.001), perianal fistulas (18.9% vs. 0%, p < 0.001), perianal skin tags (15.9% vs. 1.2%, p < 0.001), fever (20.3% vs. 6.2%, p = 0.007), and oral ulcers (13.7% vs. 3.8%, p = 0.026), while hematochezia was the only dominant symptom in UC patients compared with CD patients (86.2% vs. 30.8%, p < 0.001). White blood cell counts, platelet counts, ESR, CRP were significantly higher, and serum albumin level was significantly lower in CD patients. ASCA was positive in 44.5% and 16.2% of CD and UC patients, respectively (p < 0.001), and ANCA was positive in 15.0% and 58.8% of CD and UC patients, respectively (p < 0.001). Terminal ileal involvement on endoscopy was prominent in CD (62.1% vs. 16.2%, p < 0.001), while rectal involvement was more prominent in UC (52.4% vs. 83.8%, p < 0.001). Small bowel involvement and perianal perforating diseases on radiologic exams were also more prominent in CD. Conclusion Clinical symptoms, laboratory test results, radiologic findings, endoscopic findings were significantly different between paediatric Crohn’s disease and ulcerative colitis at diagnosis in Korea. A large-scale study on a nationwide basis is expected to better clarify this difference in the future.

Background Recent researches reported that inflammatory bowel disease (IBD) in Asia has become more prevalent. Since IBD is chronic inflammation disorder and its relapse is frequent, obtaining and maintaining remission is important. As our knowledge on the pathogenesis of IBD deepened, many immunosuppressants and biological agents were introduced and confirmed to be both safe and effective. However, biologics known as anti-tumour necrosis factor (anti-TNF) agents was reported to lose response over time in 23–46% of patients. Therefore, combination therapy adding immunomodulator drug such as azathioprine was introduced and showed better outcome by optimising biologic pharmacokinetics and minimising immunogenicity. Adversely, rates of tuberculosis are increased, but there is no large population data estimating and comparing these risk in combination therapy. Methods We used 2008–2016 data of the South Korean Health Insurance and Review Agency (HIRA), and odd ratio (OR) for tuberculosis in IBD patients who underwent anti-tumour necrosis factor (TNF) agent, azathioprine, or combination therapy. Results Between 2008 and 2016, 47,760 patients were newly diagnosed as IBD, 29,440 as UC and 15,320 as CD. We compared the risk of tuberculosis according to the medication divided into 5 groups; infliximab only, azathioprine only, combination of azathioprine and infliximab, azathioprine monotherapy and infliximab monotherapy, and azathioprine and infliximab whether simultaneously or separately. We also compared the risk between male and female. Hazard ratio of tuberculosis in infliximab monotherapy, azathioprine, and combination therapy in IBD patients were 1.132, 1.256, and 2.118, respectively. Conclusion Our study shows that Korean IBD patients are at risk for tuberculosis, and this results may highlight the importance of screening for tuberculosis in IBD patients.

Background The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC). Methods We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method. Results A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis. Conclusion Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.

Supplementary_material for Identification of aldo-keto reductase (AKR7A1) and glutathione S-transferase pi (GSTP1) as novel renal damage biomarkers following exposure to mercury by Y-J Shin, K-A Kim, E-S Kim, J-H Kim, H-S Kim, M Ha, and O-N Bae in Human & Experimental Toxicology

A beam position monitor (BPM) with the nanometer-scale position resolution and the decay time of approximately 20 ns is developed as an interaction point BPM, to verify the nanometer stabilization of the International Linear Collider beam trains at the Accelerator Test Facility (ATF), High Energy Accelerator Research Organization (KEK). The developed low- $Q$ cavity BPM consists of a one-cell sensor cavity and a one-cell reference cavity. An electronic system is developed, based on the beam test results, to process the signals from the BPM. The beam position resolution of the low- $Q$ cavity BPM with the electronics system is measured at the ATF2 beam line of KEK, and the results of the beam tests conducted on the developed low- $Q$ cavity-type BPM are described.

The RAON is the name of the heavy ion accelerator facility under construction in Korea that includes the In-flight Fragment (IF) and Isotope Separation On-Line (ISOL) facilities to support cutting-edge research in various science fields. The superconducting linac is the driver for the IF facility that can accelerate beams from proton to uranium with 200 MeV/u, 400 kW (for uranium beam). A 70-MeV, 1-mA H− cyclotron is the driver for the ISOL facility and is followed by a post-accelerator consisting of s superconducting linac that can accelerate rare-isotope (RI) beams and deliver them to experimental halls. These facilities provide high-intensity stable ion and rare isotope (RI) beams for domestic and international users. In this paper, design and prototyping efforts for the RAON accelerator systems are presented.

Lactic acid bacteria (LAB) are major components of the microbial flora of packaged and cured meats and can contribute to spoilage. Bacteriological analyses of the pork meat and pork meat product samples were carried out to know the diversity of LAB across the samples. Thirty-one samples of raw pork meat, semi-processed pork meat and pork meat products were collected from four meat factories in Korea. A total of 216 LAB were isolated and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 16S rRNA gene sequencing followed by confirmation of results using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Lactobacillus (Lb.) sakei was the most dominant LAB associated with all samples, regardless of the origin or packaging. The next predominant LAB were Lactococcus (Lc.) lactis and Pediococcus pentosaceus in raw samples, Lb. plantarum and Lb. brevis in semi-processed samples, and Weissella viridescens and Lc. lactis in product samples. Lb. plantarum, Lc. lactis and Lb. brevis were LAB found in all sample groups. Practical Applications Identification of lactic acid bacteria (LAB) in pork meat and pork meat products is fundamental to understanding the onset of spoilage. The results will reveal the prevalence of different species in different processing conditions and be helpful in order to analyze spoilage by LAB rapidly and accurately. The high LAB loads detected on pork meat indicated that strategies to reduce microbial load and improve food safety are needed.

Introduction: Patients (pts) with CTCL have disruption in their skin barrier and are at increased risk for cutaneous infections. In particular, staphylococcal infections are common in pts with CTCL and are associated with pathogenesis of the lymphoma. Previous studies have identified extra-cutaneous involvement of lymphoma as the most important independent risk factor for recurrent skin infection, bacteremia, and death from infection. However, the risk of mortality with bacteremia and risk factors for developing bacteremia in CTCL have not been fully elucidated. We aimed to explore risk factors for bacteremia and subsequent mortality in pts with CTCL at Emory University. Methods: We conducted a single center retrospective analysis at the Winship Cancer Institute of Emory University analyzing CTCL pts from 01/01/1990 - 06/01/2019. We selected pts from an existing cutaneous lymphoma database and separated them by presence or absence of bacteremia at any point following diagnosis. Bacteremia was defined as identification of at least one microbe in the bloodstream on culture. The primary objective was to assess 90-day mortality among pts with CTCL with bacteremia. Secondary objectives included assessing patterns of care in bacteremic pts, identifying risk factors for bacteremia incidence and for poor outcomes following bacteremia (defined as a composite outcome of intensive care unit stay, mortality at 90 days, or re-current hospitalization within 90 days). Additionally, we explored patterns of oral antibiotic use in the outpatient setting and their association with bacteremia incidence and outcomes. Prophylactic skin antibiotics were defined in the notes as "prophylactic" i.e. not being used to treat active cellulitis or other infections. Categorical variables were analyzed with chi-squared tests. Results: 184 of 549 pts identified from our cutaneous lymphoma database were included in our analysis. Patients were excluded for lack of follow up or missing data. The median age was 57. Most pts had mycosis fungoides (n=137), followed by Sézary syndrome (n=20), CTCL, NOS (n=12), and CD30+ variants (n=6). 85 pts were early stage, and 87 were advanced stage (stage 2B n=41; 3 n=16; 4 n= 30) at diagnosis. 37 of 184 pts (20.1%) developed bacteremia. 95 pts used intermittent skin prophylactic antibiotics in the outpatient setting, 84 did not, and 5 were unknown. A total of 101 bacteremic episodes were noted (range of 1-10 per pt). The most common organisms were Staphylococcus species (sp) (MRSA n=21, MSSA n=10, other staph n=10). Other organisms included Corynebacterium sp., Enterococcus sp., Acinetobacter sp., Pseudomonas sp., and Escherichia-coli. Polymicrobial bacteremias were noted in 23 pts (28.8%). 42 (40%) had concurrent positive skin/wound . 69 pts (86.3%) were taking oral at the time of bacteremia. 71 pts were hospitalized for bacteremia (88.8%), and 41 pts (51.3%) had a recurrent admission within 90 days of discharge. 45 pts (56.3%) had invasive lines prior to bacteremia, and 44 of these had them removed following bacteremia. 71 (88.8%) cases were treated with appropriate antibiotic coverage. 56 pts were receiving active disease therapy at the time of bacteremia (70%), including 33 who were receiving systemic therapy. Intermittent prophylactic antibiotic use was highly associated with development of bacteremia (p < 0.001, table 1), as was advanced stage (12.8% early stage patients developed bacteremia compared to 29.9% of advanced stage, p=0.005). Prior systemic therapy, and in particular chemotherapy was associated with increased incidence of bacteremia (31 of 106 (29.2%) patients treated with chemotherapy developed bacteremia, p=0.0003) Extra-cutaneous disease was not associated with bacteremia in our analysis. The 90-day mortality among CTCL pts developing bacteremia was 11.25%. Conclusions This is the largest study assessing outcomes and risk factors for bacteremia in CTCL in the modern era. We confirmed that bacteremia is associated with high rates of re-admission, recurrent infection, and 90-day mortality, and identified advanced stage and use of chemotherapy as risk factors associated with bacteremia. The positive association of prophylactic antibiotics with bacteremia likely represents increased prescribing of skin prophylaxis among those at higher risk for bacteremia. Uni-variate, multivariate, and survival analyses will be updated at the time of the presentation. Disclosures Lechowicz: Kyowa: Consultancy.

4-1BB, a member of the TNF receptor superfamily, has a role in various inflammatory pathologies through its interaction with 4-1BB ligand. We previously demonstrated that it participates in initiating and promoting obesity-induced adipose inflammation in a rodent model. In this study, we examined whether 4-1BB is related to obesity-induced adipose inflammation and metabolic parameters in humans. A total of 50 subjects, 25 obese (body mass index (BMI)⩾25 kg m−2) and 25 lean (BMI