Comparative Effectiveness of a Second Tumor Necrosis Factor Inhibitor Versus a Non-Tumor Necrosis Factor Biologic in the Treatment of Patients With Polyarticular-Course Juvenile Idiopathic Arthritis.

OBJECTIVE: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic following discontinuation of a TNFi for patients with polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: Using the Childhood Arthritis and Rheumatology Research Alliance Registry, patients with pJIA who started receiving a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on the index date and a visit six months after the index date. Outcome measures included Clinical Juvenile Arthritis Disease Activity Score with a maximum of 10 active joints (cJADAS10), cJADAS10 inactive disease (ID; ≤2.5) and cJADAS10 minimal disease activity (MiDA; ≤5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aORs) were calculated using propensity score quintiles to compare outcomes at six months following second biologic initiation. RESULTS: There were 216 patients included, 84% initially received etanercept, and most patients stopped receiving it because of its ineffectiveness (74%). A total of 183 (85%) started receiving a second TNFi, and 33 (15%) started receiving a non-TNFi. Adalimumab was the most common second biologic received (71% overall, 84% of second TNFi), and tocilizumab was the most common non-TNFi second biologic received (9% overall, 58% of non-TNFi). There was no difference between receiving TNFi versus non-TNFi in cJADAS10 ID (29% vs 25%; aOR 1.23, 95% confidence interval [CI] 0.47-3.20) or at least MiDA (43% vs 39%; aOR 1.11, 95% CI 0.47-2.62) at six months. CONCLUSION: Most patients with pJIA started receiving TNFi rather than non-TNFi as their second biologic, and there were no differences in disease activity at six months.

Repurposing a Cyclin-Dependent Kinase 1 (CDK1) Mitotic Regulatory Network to Complete Terminal Differentiation in Lens Fiber Cells.

Purpose: During lens fiber cell differentiation, organelles are removed in an ordered manner to ensure lens clarity. A critical step in this process is removal of the cell nucleus, but the mechanisms by which this occurs are unclear. In this study, we investigate the role of a cyclin-dependent kinase 1 (CDK1) regulatory loop in controlling lens fiber cell denucleation (LFCD). Methods: We examined lens differentiation histologically in two different vertebrate models. An embryonic chick lens culture system was used to test the role of CDK1, cell division cycle 25 (CDC25), WEE1, and PP2A in LFCD. Additionally, we used three mouse models that express high levels of the CDK inhibitor p27 to test whether increased p27 levels affect LFCD. Results: Using chick lens organ cultures, small-molecule inhibitors of CDK1 and CDC25 inhibit LFCD, while inhibiting the CDK1 inhibitory kinase WEE1 potentiates LFCD. Additionally, treatment with an inhibitor of PP2A, which indirectly inhibits CDK1 activity, also increased LFCD. Three different mouse models that express increased levels of p27 through different mechanisms show impaired LFCD. Conclusions: Here we define a conserved nonmitotic role for CDK1 and its upstream regulators in controlling LFCD. We find that CDK1 functionally interacts with WEE1, a nuclear kinase that inhibits CDK1 activity, and CDC25 activating phosphatases in cells where CDK1 activity must be exquisitely regulated to allow for LFCD. We also provide genetic evidence in multiple in vivo models that p27, a CDK1 inhibitor, inhibits lens growth and LFCD.

Laparoscopic fluorescence imaging technique for visualizing biliary structures using sodium fluorescein: the result of a preclinical study in a porcine model

Purpose@#Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue-light fluorescence cholangiography during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue-light fluorescence for cholangiography in a porcine model. @*Methods@#Five millimeters of sodium fluorescein (SF) solution was administered into the gallbladder of 20 male 3-way crossbred (Landrace × Yorkshire × Duroc) pigs in laparoscopic approach. The biliary tree was observed under blue light (a peak wavelength of 450 nm) emitted from a commercialized light-emitting diode (LED) light source (XLS1 extreme, Chammed). @*Results@#In 18 of 20 porcine models, immediately after SF solution was administered into the gallbladder, it was possible to visualize the biliary tree under blue light emitted from the LED light source. @*Conclusion@#This study provided a preclinical basis for using blue-light fluorescence cholangiography using SF in laparoscopic surgery. The clinical feasibility of blue-light fluorescence imaging techniques for laparoscopic cholecystectomy remained to be demonstrated.

Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases.

OBJECTIVES: Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19. METHODS: Using the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated. RESULTS: 607 CYP with RMDs <19 years old from 25 different countries with SARS-CoV-2 infection were included, the majority with juvenile idiopathic arthritis (JIA; n=378; 62%). Forty-three (7%) patients were hospitalised; three of these patients died. Compared with JIA, diagnosis of systemic lupus erythematosus, mixed connective tissue disease, vasculitis, or other RMD (OR 4.3; 95% CI 1.7 to 11) or autoinflammatory syndrome (OR 3.0; 95% CI 1.1 to 8.6) was associated with hospitalisation, as was obesity (OR 4.0; 95% CI 1.3 to 12). CONCLUSIONS: This is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised.

Feasibility and Efficacy of Online Strategies to Recruit Parents of Children With Rheumatic Diseases for Research.

OBJECTIVE: We aimed to determine the feasibility and efficacy of online strategies to recruit parents of children with pediatric rheumatic diseases (PRDs) for research and to evaluate the degree to which known features of various rheumatic disease groups were present in the online cohort. METHODS: We studied two cohorts; the first was composed of respondents from a cross-sectional parental survey of children with PRDs contacted through patient support groups and social media platforms, and the second cohort was composed of participants from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) legacy clinical registry. RESULTS: In the social media cohort, 712 complete surveys were analyzed. Most (65.9%) were referred from Facebook. The most common rheumatic disease was juvenile idiopathic arthritis (JIA) (27.1%), followed by juvenile dermatomyositis (22.1%). In the CARRA registry cohort, 7985 records were included. JIA was the largest disease group (70.3%), followed by systemic lupus erythematosus (12.0%). The age at disease onset for most PRDs was similar between those in the social media and CARRA registry cohorts (mean difference = 1.3 years). CONCLUSION: Recruitment through Facebook was the most fruitful. The clinical characteristics of the social media cohort were similar to those of patients recruited through a clinical registry, suggesting the utility of online recruitment for engaging disease-relevant cohorts. Parents of children with rare PRDs were overrepresented in the social media cohort, perhaps reflecting the increased need of those parents to find online information and receive emotional support. Social media recruitment for research studies may help expand the number and diversity of participants in clinical research, especially by including those with rare diseases.

Host Chitinase 3-like-1 is a Universal Therapeutic Target for the Delta, Omicron and Other SARS-CoV-2 Viral Variants in COVID 19

COVID 19 is the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; SC2) which has caused a world-wide pandemic with striking morbidity and mortality. Evaluation of SC2 strains demonstrated impressive genetic variability and many of these viral variants are now defined as variants of concern (VOC) that cause enhanced transmissibility, decreased susceptibility to antibody neutralization or therapeutics and or the ability to induce severe disease. Currently, the delta ({delta}) and omicron (o) variants are particularly problematic based on their impressive and unprecedented transmissibility and ability to cause break through infections. The delta variant also accumulates at high concentrations in host tissues and has caused waves of lethal disease. Because studies from our laboratory have demonstrated that chitinase 3-like-1 (CHI3L1) stimulates ACE2 and Spike (S) priming proteases that mediate SC2 infection, studies were undertaken to determine if interventions that target CHI3L1 are effective inhibitors of SC2 viral variant infection. Here we demonstrate that CHI3L1 augments epithelial cell infection by pseudoviruses that express the alpha, beta, gamma, delta or omicron S proteins and that the CHI3L1 inhibitors anti-CHI3L1 and kasugamycin inhibit epithelial cell infection by these VOC pseudovirus moieties. Thus, CHI3L1 is a universal, VOC-independent therapeutic target in COVID 19.

Surgical treatment for obesity

Bariatric or metabolic surgery is a safe and effective intervention for patients with obesity at higherrisk. In 2019, after the reimbursement in Korea, the number of metabolic surgery cases has rapidly increased. We aimed to introduce the current metabolic surgery concepts.Current Concepts: Patients with a body mass index (BMI) of ≥35 kg/m2 without coexisting medical problems and those with a BMI of ≥30 kg/m2 and ≥1 severe obesity-related complication remediable by weight loss could be considered as the candidates for metabolic surgery. The standardized and effective procedures are adjustable gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch. The decision on bariatric procedures should be based on the characteristics of patients considering the effectiveness and anticipated complications.Discussion and Conclusion: Metabolic surgery was shown to induce greater weight loss, better control of comorbidities, such as type 2 diabetes, hypertension, and dyslipidemia, and more significant decrease in death compared to that of the nonsurgical approach. Postoperatively, a comprehensive approach consisting of psychosocial, behavioral, nutritional, and pharmacological aspects should be performed to amplify and maintain the effectiveness of metabolic surgery.

Impact of inland waters on highly pathogenic avian influenza outbreaks in neighboring poultry farms in South Korea

Background@#Since 2003, the H5 highly pathogenic avian influenza (HPAI) subtype has caused massive economic losses in the poultry industry in South Korea. The role of inland water bodies in avian influenza (AI) outbreaks has not been investigated. Identifying water bodies that facilitate risk pathways leading to the incursion of the HPAI virus (HPAIV) into poultry farms is essential for implementing specific precautionary measures to prevent viral transmission. @*Objectives@#This matched case-control study (1:4) examined whether inland waters were associated with a higher risk of AI outbreaks in the neighboring poultry farms. @*Methods@#Rivers, irrigation canals, lakes, and ponds were considered inland water bodies.The cases and controls were chosen based on the matching criteria. The nearest possible farms located within a radius of 3 km of the case farms were chosen as the control farms.The poultry farms were selected randomly, and two HPAI epidemics (H5N8 [2014–2016] and H5N6 [2016–2017]) were studied. Conditional logistic regression analysis was applied. @*Results@#Statistical analysis revealed that inland waters near poultry farms were significant risk factors for AI outbreaks. The study speculated that freely wandering wild waterfowl and small animals contaminate areas surrounding poultry farms. @*Conclusions@#Pet birds and animals raised alongside poultry birds on farm premises may wander easily to nearby waters, potentially increasing the risk of AI infection in poultry farms. Mechanical transmission of the AI virus occurs when poultry farm workers or visitors come into contact with infected water bodies or their surroundings. To prevent AI outbreaks in the future, poultry farms should adopt strict precautions to avoid contact with nearby water bodies and their surroundings.

Exposure to Porphyromonas gingivalis and Modifiable Risk Factors Modulate Risk for Early Diabetic Retinopathy.

Purpose: We hypothesized that exposure to Porphyromonas gingivalis (Pg) increases the risk for early diabetic retinopathy (DR) and that the risk can be modulated. Methods: We identified 116 early DR cases, and 116 non-DR controls were selected randomly by frequency matching for age, sex, race, and education from the US Third National Health and Nutrition Examination Survey. DR was assessed using non-mydriatic fundus photographs and graded by trained graders using the Modified Airlie House Classification scheme and the Early Treatment for Diabetic Retinopathy Study severity scale. Serum Pg immunoglobulin G (IgG) antibody (Ab) was measured in enzyme-linked immunosorbent assay units. Logistic regression was used to relate serum Pg IgG Ab levels to the risk for early DR. Results: Per tenfold increase in Pg IgG Ab levels, there was an over 60% increased risk for early DR (odds ratio = 1.64; 95% confidence interval, 1.36-1.97), and a linear trend was noted for the estimated probabilities of early DR at various Pg IgG Ab levels (P for trend = 0.0053). The analysis also suggested that moderate alcohol consumption (less than 12 drinks in the past 12 months; P for interaction = 0.0003) and maintaining a normal serum glycated hemoglobulin level (HbA1c ≤ 5.7%; P for interaction < 0.0001) helped reduce the Pg-related DR risk. Conclusions: The increased Pg-related DR risk could be alleviated by managing alcohol consumption and maintaining a normal blood glucose level. Translational Relevance: Findings from this study provide new directions for developing novel therapeutics and prevention strategies for DR.

Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19

COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP-inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.

Restoration for the foregut surgery: bridging gaps between foregut surgery practice and academia

Foregut surgery largely involves benign diseases, and not only malignant diseases. However, for foregut surgeons in Asia, this fact has not been extensively utilized in their clinical practice due to the high burden of gastric cancer surgery. Although the prevalence of gastroesophageal reflux disease (GERD) in Eastern Asia, including Korea, is increasing, antireflux surgery (ARS) is still a fairly rare procedure in Korea. ARS is effective as proton pump inhibitors and is cost-effective compared to continuous double-dose proton pump inhibitors in patients with severe GERD. Therefore, we should focus on ARS as a treatment option for GERD also in Asian population. Similarly, although bariatric/metabolic surgery is effective in weight reduction and diabetes mellitus (DM) remission in patients with morbid obesity or DM, bariatric/metabolic surgery is only performed in a limited number of patients. Given that the prevalence of obesity and DM is continuously increasing in Korea, bariatric/metabolic surgery should become an interest among Korean foregut surgeons and should be considered a treatment for obesity and DM. Furthermore, there are new surgical fields that can control both benign and malignant diseases. Oncometabolic surgery is a field under foregut surgery that treats both malignant and benign components of a condition, an example being the control of metabolic syndrome while performing gastric cancer surgery. Therefore, in future gastric cancer treatment, oncometabolic surgery can be applied to patients with gastric cancer accompanied by obesity or metabolic syndrome.

Eextermination Speed of an Imidacloprid and Flumethrin Polymer Matrix Collar against Larvae, Nymphs and Adults of Haemaphysalis longicornis

The objective of this study was to evaluate the efficacy of an imidacloprid 10% and flumethrin 4.5% polymer matrix collar against the developmental stages of Haemaphysalis longicornis infesting dogs using the hair from treated dogs in a semi-in-vitro assay set. When incubated with 0.5 g of the hair collected from the dogs installed with the drug-embedded collar after 10 days, average death rate of the larval, nymphal, and adult H. longicornis was 21.5%, 77.9%, and 100% at 30 min, 1 hr, and 2 hr, respectively. This study showed the larval stages as well as the nymphal and adult stages of H. longicornis ticks are killed upon contact with the hair from dogs treated with the collar within 2 hr.

Is it Beneficial to Utilize an Articulating Instrument in Single-Port Laparoscopic Gastrectomy?

Purpose@#As the number of gastric cancer survivors is increasing and their quality of life after surgery is being emphasized, single-port surgery is emerging as an alternative to conventional gastrectomy. A novel multi-degree-of-freedom (DOF) articulating device, the ArtiSential ® device (LivsMed, Seongnam, Korea), was designed to allow more intuitive and meticulous control for surgeons facing ergonomic difficulties with conventional tools. In this study, we evaluated the feasibility of this new device during single-port laparoscopic distal gastrectomy (SP-LDG) for early gastric cancer (EGC) patients. @*Materials and Methods@#Consecutive patients diagnosed with EGC who underwent SP-LDG with ArtiSential ® (LivsMed) graspers between April 2018 and August 2020 were enrolled in the study. The clinical outcomes were compared with those of a control group, in which prebent graspers (Olympus Medical Systems Corp) were used for the same procedures. @*Results@#Seventeen patients were enrolled in the ArtiSential ® group. There was no significant difference in operative time (205.4±6.0 vs. 218.1±9.9 minutes, P= 0.270) or the quality of surgery, in terms of the number of retrieved lymph nodes (49.5±3.5 vs. 45.9±4.0, P=0.473), length of hospital stay (15.4±2.0 vs. 12.4±1.3 days, P=0.588), and postoperative complications (40.0% vs. 41.2%, P=0.595), between the ArtiSential ® group and the control group. @*Conclusions@#The new multi-DOF articulating grasper is feasible and can be used as an alternative for prebent graspers during SP-LDG.

Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.

A low glycemic diet protects disease-prone Nrf2-deficient mice against age-related macular degeneration.

Age-related macular degeneration (AMD) is a major blinding disease, affecting over 14% of the elderly. Risk for AMD is related to age, diet, environment, and genetics. Dietary modulation of AMD risk is a promising treatment modality, but requires appropriate animal models to demonstrate advantages of diet. Mice lacking the antioxidant transcription factor Nrf2 (Nfe2l2) develop age-related retinopathy relevant to human AMD. Here we evaluated the effect of consuming high glycemic (HG) or low glycemic (LG) diets until 18-months of age on development of features relevant to AMD in Nrf2-null mice. Nrf2-null mice that consumed HG diets developed atrophic AMD, characterized by photoreceptor degeneration, retinal pigment epithelium (RPE) atrophy and pigmentary abnormalities, basal laminar deposits, and loss of the choriocapillaris. In contrast, Nrf2-null-mice that consumed LG diets did not develop retinal disease phenotypes. Consumption of HG diets was associated with accumulation of advanced glycation end-products in the RPE and systemically, whereas consumption of the LG diet was associated with increased levels of anti-glycative and anti-oxidative detoxification machinery. Together our data indicate that the Nrf2-null HG mouse is a good model for atrophic AMD studies and that the LG diet can activate protective pathways to prevent AMD, even in a genetically predisposed animal.

Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

Purpose@#To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). @*Materials and Methods@#This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. @*Results@#The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693–4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664–1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595–85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502–5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618–3.028; P<0.001) were determined as independent prognostic factors for DFS. @*Conclusions@#S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.

Myelitis Presenting Anti-Yo Antibody in a Patient with Prostatic Adenocarcinoma

Antineuronal antibody-associated paraneoplastic neurologic syndromes result from tumor-stimulated autoimmune attacks against components of the nervous system. Paraneoplastic myelopathy associated with Purkinje-cell cytoplasmic autoantibody type 1 (anti-Yo) is extremely rare disorder. It is almost exclusively reported in women with gynecological tumors. Even though few cases of anti-Yo-associated paraneoplastic neurologic syndrome related to other cancers are reported, it is a very uncommon condition, especially in males. The author report here the first case of anti-Yo myelopathy with prostatic adenocarcinoma.

Genome-wide association study of degenerative mitral valve disease in Maltese dogs

Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study was conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and to evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Genome-wide single nucleotide polymorphism (SNP) genotyping was performed. The top 30 SNPs from each association of various conditions and genetic variations were mapped to their gene locations. A total of 173,662 loci were successfully genotyped, with an overall genotype completion rate of 99.41%. Quality control analysis excluded 46,610 of these SNPs. Manhattan plots were produced using allelic tests with various candidate clinical conditions. A significant peak of association was observed between mitral valve prolapse (MVP) and SNPs on chromosome 17. The present study revealed significant SNPs in several genes associated with cardiac function, including PDZ2, Armadillo repeat protein detected in velo-cardio-facial syndrome, catenin (cadherin-associated protein) alpha 3, low-density lipoprotein receptor class A domain containing protein 4, and sterile alpha motif domain containing protein 3. To our knowledge, this is the first study of a genetic predisposition to DMVD in Maltese dogs. Although only a limited number of cases were analyzed, these data could be the basis for further research on the genetic predisposition to MVP and DMVD in Maltese dogs.

Workplace violence experienced by emergency department workers and its association with stress and depression assessment

OBJECTIVE: This study examined the incidence of workplace violence (WPV) in an emergency department (ED), and its influence on ED workers' mental health. METHODS: A cross-sectional, anonymous survey was conducted on ED workers employed in a local emergency medical center during August 2018. The survey respondents' data on the demographic characteristics, WPV episode, Korean-translated Brief Encounter Psychosocial Instrument (BEPSI-K), stress questionnaire for Korean National Health and Nutrition Examination Survey (KNHANES), and Patient Health Questionnaire-9 (PHQ-9) were obtained. The results of the stress (BEPSI-K, KNHANES) and depression (PHQ-9) score were compared with the WPV experience of ED workers. RESULTS: A total of 104 of 120 ED workers (86.7%) were exposed to WPV. ED workers that experienced physical violence within the past year had higher KNHANES, BEPSI-K, and PHQ-9 than the workers, who did not experience such violence (P≤0.001). In addition, this survey demonstrated that a physical violence episode within the past year was associated with above moderate depression (P≤0.001; odds ratio, 19.597). CONCLUSION: Recent physical violence can cause psychiatric disorders in ED workers, such as depression or stress disorder. Therefore, policies are needed to prevent WPV in ED and support ED workers who have experienced WPV.

Identifying out-of-hospital cardiac arrest patients by using International Classification of Diseases codes and procedure code

OBJECTIVE: This study was conducted to evaluate the validity of the International Classification of Diseases, 10th revision (ICD-10) codes for identifying patients who suffered out-of-hospital cardiac arrest (OHCA). METHODS: Consecutive data pertaining to adult patients who suffered OHCA or received ICD-10 codes for cardiac arrest were collected. Patient characteristics and clinical data during the period from January 2015 to December 2016 were obtained. The sensitivity and positive predictive value (PPV) of each code for identifying OHCA were calculated and an optimal algorithm using diagnostic and procedure codes to detect OHCA patients was selected. The kappa coefficient was calculated to examine the agreement between algorithm-detected cases and true OHCA patients. RESULTS: A total of 397 patients were included in this study. The single use of ICD-10 codes was an insensitive method for identifying OHCA patients. Combination of diagnostic codes and procedure codes showed a good sensitivity (98.6%) and PPV (94.8%) for identifying OHCA patients. The agreement between the optimal algorithm and true OHCA was excellent (κ=0.970). CONCLUSION: Using ICD-10 codes for identifying OHCA patients is an insensitive method. The combination of ICD-10 codes and procedure codes can be an alternative search method.