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Myung Ha Seo, Won Young SungDepartment of Emergency Medicine, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Republic of KoreaAbstract: Sudden unexpected death in epilepsy (SUDEP) refers to the sudden and unexpected death of an epileptic patient with no other health issues, during normal activity, and for whom no other particular cause of death can be found. The exact cause of SUDEP has not been established yet; however, it is assumed to be caused by multiple organ failure involving the respiratory and cardiovascular systems. Some of the known risk factors are generalized tonic-clonic seizure, frequent epileptic seizure, early onset of epilepsy, long duration of seizure, nocturnal seizure, and combined therapy with antiepileptics. A number of seizure-related cardiac arrhythmia cases have been reported. Arrhythmias are mostly benign tachycardia or bradycardia, and ventricular fibrillation (VF) or asystole is very rare. It is considered that fatal cardiac arrhythmia is a cause of SUDEP. Here, we describe the case of a near-SUDEP patient who was successfully revived without complications by immediate defibrillation with an automated external defibrillator and cardiopulmonary resuscitation, although VF occurred after a convulsive seizure. Based on our experience, when treating a patient with an epileptic seizure, one should always keep in mind the possibility of SUDEP as a seizure-induced emergency situation involving fatal arrhythmia and cardiac arrest, even in young healthy adults.Keywords: seizure, cardiac arrhythmia, sudden unexpected death in epilepsy, ventricular fibrillation

Background: Recurrent simple febrile seizure (SFS) refers to febrile seizure (FS) that recurs within 24 hours. Patients with recurrent SFS often undergo unnecessary neurodiagnostic tests. To address this, we compared the clinical characteristics of recurrent SFS with those of SFS and investigated the risk factors associated with recurrent SFS., Methods: We retrospectively reviewed electronic medical records of patients aged six to 60 months who had been hospitalized for FS at two training hospitals between January 2016 and December 2019. The primary outcome was a comparison of the clinical features of patients with SFS and recurrent SFS. Additionally, the risk factors associated with seizure recurrence within 24 hours were evaluated., Results: Three quarters (n = 191, 75.2%) of the 254 enrolled patients experienced a single seizure episode during the febrile illness period. The remaining 63 patients (24.8%) were diagnosed with recurrent SFS. Significant differences between SFS and recurrent SFS were observed in the history of recurrent SFS, time from fever onset to seizure, and body temperature on hospital arrival. Multiple logistic regression analysis revealed that a history of previous recurrent SFS (odds ratio [OR] 10.161) and a body temperature below 39°C on arrival (OR 2.377) were significantly associated with early seizure recurrence., Conclusions: This study highlights that early FS recurrence is common and has a self-limiting clinical course similar to that of SFS. We recommend close monitoring of the patient for six to eight hours when a history of early recurrence is present or if the seizure occurs at a low body temperature., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Perampanel (PER) is expanding the therapeutic scope for pediatric epilepsy owing to its efficacy and favorable safety profile. However, concerns about psychiatric and behavioral adverse events (PBAEs) in combination therapy with levetiracetam (LEV) continue to contribute to hesitation in its prescription. We investigated the risk profiles for PBAEs when adding PER to pediatric epilepsy treatment and analyzed the differences according to the presence of concomitant LEV., Methods: We retrospectively reviewed the medical records of children aged 4-18 years with epilepsy who were prescribed PER as adjunctive therapy from March 2016 to February 2023. We compared the occurrence and management of PBAEs between the PER without LEV and PER with LEV groups. The risk factors for PBAEs were also analyzed., Results: Ninety-four patients (53 boys and 41 girls) were included in this study. The median age of total patients at the time of adding PER was 14.9 years (12.3-16.4 years), and 53 patients (56.4 %) had concomitant LEV. Forty-seven PBAEs occurred in 34 patients (36.2 %), with no significant differences depending on whether concomitant LEV is present or not. The most common PBAEs were aggression (14.9 %), irritability (9.6 %), affect lability (7.4 %), and acute psychosis (6.4 %). PBAEs occurred at a lower dosage (2-6 mg/day) in 70.6 % of the patients. In addition, 73.5 % of patients with PBAEs continued PER treatment by follow-up observation or by reducing the PER dosage. No risk factors, such as the presence of concomitant LEV or lamotrigine, any comorbid conditions, higher PER dosage (8-12 mg/day), two or more concomitant anti-seizure medications, and younger age (<13 years) at PER add-on, showed significant associations., Conclusion: When expanding the use of anti-seizure medications in pediatric patients, real-world evidence on safety issues is crucial for pediatric epileptologists. We confirmed that combination therapy with PER and LEV did not increase the risk profile of PBAEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS., Competing Interests: The authors declare no conflict of interest.

(1) Background: It is widely accepted that aberrant methylation patterns contribute to the development of systemic lupus erythematosus (SLE). Ten-eleven translocation (TET) methylcytosine dioxygenase is an essential enzyme of which there are three members, TET1, 2, and 3, involved in hydroxymethylation, a newly uncovered mechanism of active DNA methylation. The epigenomes of gene transcription are regulated by 5-hydroxymethylcytocine (5-hmC) and TETs, leading to dysregulation of the immune system in SLE. The purpose of this study was to investigate the global hydroxymethylation status in SLE peripheral blood mononuclear cells (PBMCs) and to explore the role of TETs in changing the patterns of methylation. (2) Methods: We collected PBMCs from 101 SLE patients and 100 healthy donors. TaqMan real-time polymerase chain-reaction assay was performed for the detection of 5-methylcytosine (5-mC), 5-hmC, and TET2 mRNA expression and single-nucleotide polymorphism genotyping. The methylation rates in different CpG sites of TET2 promoters were examined using next-generation sequencing-based deep bisulfite sequencing. Putative transcription factors were investigated using the UCSC Genome Browser on the Human Dec. 2013 (GRCh38/hg38) Assembly. (3) Results: 5-mC and 5-hmC were both decreased in SLE. The mRNA expression level of TET2 was notably high and found to be correlated with the levels of immunologic biomarkers that are indicative of SLE disease activity. The analysis of methylation rates in the TET2 promoter revealed that SLE patients had significantly higher and lower rates of methylation in TET2 105146072-154 and TET2 105146218-331, respectively. (4) Conclusions: TET2 may play an important role in 5-mC/5-hmC dynamics in the PBMCs of SLE patients. The epigenetic modification of TET2 promoters could contribute to the pathogenesis of SLE and the intensity of the immunologic reaction.

We examined the impact of COVID-19 pandemic on the emergency department length of stay (EDLOS) and clinical outcomes of patients with severe pneumonia admitted to the intensive care unit (ICU) through the emergency department (ED). This single-center retrospective observational study included adult patients with pneumonia admitted to the ICU through the ED between January and December 2019 (pre-pandemic) and between March 2020 and February 2021 (during-pandemic). We compared and analyzed the EDLOS by dividing it into pre-, mid-, and post-EDLOS and in-hospital mortality of patients with pneumonia admitted to the ICU according to the time of ED visits before and during the COVID-19 pandemic. Risk factors for in-hospital mortality according to the time of ED visits were analyzed using multiple logistic regression analysis. In total, 227 patients (73 patients pre-pandemic and 154 patients during the pandemic) with pneumonia admitted to the ICU through the ED were analyzed. During the COVID-19 pandemic, pre-, mid-, and post-EDLOS increased (P < .05), and the in-hospital mortality rate increased by 10.4%; however, this was not significant (P = .155). Multivariate logistic regression analysis revealed post-EDLOS (ED waiting time after making ICU admission decision) as an independent risk factor for in-hospital mortality of patients with pneumonia admitted to the ICU, pre-pandemic (odds ratio [OR] = 2.282, 95% confidence interval [CI]: 1.367-3.807, P = .002) and during the pandemic (OR = 1.126, 95% CI: 1.002-1.266, P = .047). Mid-EDLOS (ED time to assess, care, and ICU admission decision) was an independent risk factor for in-hospital mortality of patients with pneumonia admitted to the ICU during the COVID-19 pandemic (OR = 1.835, 95% CI: 1.089-3.092, P = .023). During the pandemic of emerging respiratory infectious diseases, to reduce in-hospital mortality of severe pneumonia patients, it is necessary to shorten the ED waiting time for admission by increasing the number of isolation ICU beds. It is also necessary to accelerate the assessment and care process in the ED, and make prompt decisions regarding admission to the ICU., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune-mediated inflammatory processes, although it remains unknown whether CREM is involved in RA., Methods: This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real-time polymerase chain reaction. The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulphite sequencing. Differences between groups and correlations between variables were assessed with Student's t-tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression., Results: Rheumatoid arthritis patients exhibited increased CREM expression (p < .0001), which was decreased by methotrexate (p = .0223) and biologics (p = .0001), but could not be attributed to CREM variants. Interestingly, rs17499247 displayed a significant association with serositis (p = .0377), and rs1213386 increased the risk of lymphadenopathy (p = .0398). Furthermore, seven CpG sites showed decreased methylation in RA (p = .0477~ p < .0001)., Conclusions: Collectively, our results indicate that CREM hypomethylation and CREM upregulation occur in RA and that CREM variants are involved in the development of serositis and lymphadenopathy in RA. This study highlights the novel roles of CREM in RA pathophysiology., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The insertion of a neck central venous catheter (CVC) is a common procedure in medical practice; however, malposition and complications frequently occur. A 66-year-old woman had CVC inserted through the right internal jugular vein. CVC malposition was observed on chest radiography and computed tomography. The catheter was accidentally inserted via the vertebral vein and had entered the C6-C7 intervertebral foramen, penetrating the spinal canal with the tip at the T2 epidural space. We present this rare CVC complication to demonstrate the possibility of incorrect insertion of the catheter and penetration of the spinal canal, possibly causing neuronal damage., (Copyright © 2021. Published by Elsevier Inc.)

Pulmonary paragonimiasis can occasionally induce bilateral pneumothorax and cause lesions in ectopic organs such as the liver. We report the case of a 26-year-old man who had been treated for bilateral hydropneumothorax one month earlier and returned to the emergency center complaining of epigastric pain that had persisted for four months. After being diagnosed with pulmonary and hepatic paragonimiasis, he was treated with praziquantel and his condition improved without complications.

Breast cancer has the highest incidence among all cancers for women in Taiwan. The current screening policy in Taiwan provides biennial mammogram tests for all women aged 45 to 69 years. A recommendation for further investigation is sent via post to women with a BI-RADS result of 0. The proportion of women who followed-up with a recall request for further investigation after an abnormal mammogram has been below 92.5% in recent years. Therefore, we aimed to explore the experiences of these women who refused recall for further investigation despite an abnormal mammogram. Purposive sampling was conducted on 13 women who refused recall for further examination of abnormal screening mammograms. Data collection included inductive, in-depth interviews or telephone interviews. A content analysis was applied. Three themes were identified: (1) negative screening experiences, (2) struggling with 'to go or not to go', and (3) rationalizing without a follow-up examination. The first theme included three subthemes: (1) pain of examination, (2) the inconvenience of medical treatment; waiting, and (3) dissatisfaction with having to pay for further examination. The second major theme included three subthemes: (1) perceiving one's susceptibility to breast cancer as very low, (2) questioning the accuracy of the results, and (3) procrastinating with a "head-in-the-sand" mentality. The third major theme included two subthemes: (1) fatalism and (2) paying attention to self-cultivation. In conclusion, the findings provide important information to healthcare providers involved in case management related to the actual living experiences of women with abnormal screening mammogram results and the additional education required to raise breast cancer awareness in the general public to achieve overall caring goals.

Rationale: Studies have previously reported misidentifying Caltha palustris (C. palustris) as Ligularia fischeri and its subsequent ingestion leading to abdominal pain and gastrointestinal symptoms, which are alleviated immediately. Bradycardia and hypotension may persist for several days, and an infusion of dopamine can restore a healthy state without complications. We report a case of C. palustris poisoning with protein-losing enteropathy that has not been reported previously. The patient died of multiple organ failure, and exhibited more severe clinical deterioration than previous cases due to prolonged shock., Patient Concerns: A 70-year-old woman was admitted to the emergency department (ED) with complaints of epigastric pain, vomiting, and diarrhea after ingestion of a poisonous plant presumed to be C. palustris. The patient presented with bradycardia and hypotension after ED admission, and vasopressor infusion improved bradycardia but not hypotension, while the patient complained of severe epigastric pain., Diagnoses: Abdominal computed tomography showed luminal distention and edematous thickening of the entire stomach lining, as well as small and large intestinal wall edema, indicating severe gastritis and enterocolitis. The laboratory test results suggested severe hypoalbuminemia, while the arterial blood gas analyses showed a continuous increase in metabolic acidosis., Interventions: As plant poisoning was suspected, activated charcoal was administered to the patient, followed by administration of vasopressors and other conservative therapies. Continuous renal replacement therapy (CRRT) was used for metabolic acidosis of increasing severity., Outcomes: Despite the administration of vasopressors and other conservative therapies, the state of shock persisted, and metabolic acidosis did not improve even after CRRT. Ultimately, the patient died of multiple organ failure., Lessons: For many poisonous wild plants, the precise profile of toxic compounds and mechanisms of action remain to be identified; when there is insufficient literature reporting on suspected plant poisoning, the medical personnel providing the treatment should consider the various side effects that differ from the reported ones and the possibility of more severe clinical progress and poor prognosis., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

A roll angle displacement measurement technique with high resolution for large-range measurement is presented. The proposed technique is based on the birefringence effect and phase detection of polarization interferometry with a polarization camera. The phase difference variation between the s - and p -polarized light induced by a rolling birefringent crystal can be obtained by a polarization camera. The roll angle displacement of the birefringent crystal can be determined from the detected phase difference variation. Several experiments were performed to evaluate the feasibility and performance of the proposed technique. The experimental results demonstrate that the resolution of the system can reach 0.003° with a 10° measurement range. The nonlinear and periodic errors of the system are also analyzed.

Aims: F11R gene encodes junctional adhesion molecule-A protein (JAM-A), which is expressed in various types of cells and is involved in leukocyte extravasation during inflammation. Sjögren's syndrome (SS) is a chronic systemic inflammatory disease that involves lymphocytes invasion of exocrine glands. F11R has been studied in autoimmune diseases, but any association between F11R and SS has not yet been investigated. Therefore, experiments were undertaken to examine the relationships among F11R gene polymorphism, messenger RNA (mRNA) expression and SS patients., Methods: Three hundred and twenty-nine patients with SS, and 223 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan real-time polymerase chain reaction (PCR). F11R mRNA expression was quantitated by quantitative real-time PCR with TaqMan Gene Expression Assay., Results: Our study showed the genotype -688A/C (rs6695707) was not found in relation to SS patients. The odds ratio of -436A/G (rs12567886) genotype was notably associated with less susceptibility of SS in human leukocyte antigen (HLA)-DR2 negative and HLA-DR3 negative individuals. F11R mRNA expression was lower in SS patients than in the cells of healthy controls., Conclusion: The result indicated that G allele of -436A/G genotype has the potential protective effect against SS disease condition. F11R mRNA was expressed significantly lower in SS patients., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation and extra-articular manifestations. Many questions in the pathogenesis, clinical manifestation, and disease spectrum are answered after the discovery of the first autoantibody namely rheumatoid factor (RF). The finding of the second autoantibody named anti-citrullinated protein antibody (ACPA), which unearths the importance of protein citrullination process. It further provides the insight how immune cells and complement interact to perpetuate the inflammatory response. These two autoantibodies pave the way for our better understanding of RA. This review article focuses on the history, pathophysiology, and clinical association of these two autoantibodies in RA., Competing Interests: Conflict of Interest No potential conflicts of interest were disclosed., (© 2021 Wang Yu Sung et al., published by Sciendo.)

The proposed total internal reflection (TIR)-based technique can be used for measuring the refractive index of lenses. Distribution of the phase difference between the s - and p -polarization states of the reflected light induced by TIR can be obtained by a polarization camera. The refractive index of the lens can be determined from the detected maximum phase difference, with the specific measurement equation. Only the maximum phase difference needs to be measured. Information about the incident angle, thickness of the lens, and the matching liquid is not needed. The experimental results demonstrate that the resolution of the system can reach 4.8×10 -4 R I U .

Rationale: Renal vein pseudoaneurysm after blunt trauma is an extremely rare clinical disease. Different interventions, such as conservative, surgical, and endovascular treatments, can be considered. However, previous studies have not described the optimal treatment strategies for this condition. Furthermore, there is a significant lack of prior case reports and of standardized treatment guidelines for trauma-induced renal vein pseudoaneurysm patients who previously maintained antithrombotic agent., Patient Concerns: A 23-year-old female patient visited the emergency department after sustaining blunt injury caused by falling. The patient was diagnosed with multiple limb and rib fractures. A right renal vein pseudoaneurysm was found on abdominal computed tomography scan. Initially, there was no other organ damage, and the patient was hemodynamically stable. Thus, nonsurgical, conservative management was considered. However, the patient's hematocrit and hemoglobin levels decreased, and there was no hemodynamic improvement. The patient required lifelong treatment with aspirin because she previously underwent Fontan surgery, and orthopedic surgery for multiple fractures was planned. Thus, considering these factors, the treatment method was changed from conservative management to endovascular stent insertion., Diagnoses: Abdominal computed tomography and renal venography revealed a right renal vein pseudoaneurysm., Interventions: On the basis of the abdominal computed tomography scan and renal venography findings, the endovascular stent graft was inserted across the pseudoaneurysm area., Outcomes: Upon placement of the endovascular stent, hemoglobin and hematocrit levels gradually returned to normal. The patient's vital signs and general condition had improved. The patient recovered without any complications and was discharged 29 days after hospitalization., Lessons: Some patients with traumatic renal vein pseudoaneurysm do not experience hemodynamic improvement despite conservative treatment. Hence, endovascular procedure may be considered for these patients, particularly those who require antithrombotic treatment for a previous disease., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against proinflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL- 17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

Antimicrobial peptides are class of small, positively charged peptides known for their broad-spectrum antimicrobial activity. Antimicrobial activities for most antimicrobial peptides have largely remained elusive, particularly in the lactic acid bacteria. However, recently our investigation using LPcin-YK3, an antimicrobial peptide from bovine milk, suggests that in vitro antimicrobial activity was reduced over 100-fold compared with pathogenic bacteria. Additionally, for the structural study of how antimicrobial peptide undergoes its reaction at the proteolytic pathway of lactic acid bacteria based on degradation assay and propidium iodide staining, we performed molecular docking for interaction between oligopeptide-binding protein A and LPcin-YK3 peptide. Given that degradation related to the LPcin-YK3 peptide in lactic acid bacteria proteolytic system, the inhibitory inactivity of LPcin-YK3 against beneficial lactic acid bacteria strains may be one of the primary pharmacological properties of recombinant peptide discovered in bovine milk. These results provide structural and functional insights into the proteolytic mechanism and possibility as a putative substrate of oligopeptide-binding protein A in respect of LPcin-YK3 peptide., (© 2020 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.

Background: Rheumatoid arthritis (RA) is an autoimmune disease where both genetics and epigenetics are contributing factors. In order to discover genetic and epigenetic associations with RA and its phenotypes, we analysed RNA expression, DNA variations and DNA methylation of programmed cell death 1 (PDCD1) in a cohort of RA patients and healthy controls., Methods: RA patients (n = 206) and healthy controls (n = 234) were included for analysis of PDCD1 expression, PDCD1 polymorphisms and PDCD1 methylation. Differences in continuous variables between groups were compared by applying t tests. Associations between phenotypes and genotypes were evaluated with contingency tables. Sensitivity analyses were conducted to confirm the robustness of results, considering potential confounding factors and different treatment response definitions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated., Results: Higher expression of PDCD1 was found in RA compared to controls (P < 0.001), with similar PDCD1 polymorphisms in RA and controls. rs36084323 decreased inadequate response to conventional synthetic disease-modifying antirheumatic drugs (OR = 0.37, 95% CI = 0.19-0.72, P = 0.003), and rs41386349 increased rheumatoid factor seropositivity (OR = 11.89, 95% CI = 1.57-89.87, P = 0.003). Sensitivity analysis adjusting for further potential confounders and using different treatment response definition indicated similar results. Additionally, DNA methylation change at regulatory region of PDCD1 was detected in RA (P = 0.036)., Conclusion: Altogether, this was the first study to suggest genetic and epigenetic changes of PDCD1 in RA subsets and RA. Independent prospective cohorts are awaited to address the implications of these genetic and epigenetic changes in disease pathogenesis and phenotypes of RA., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

BACKGROUND Snakebite envenoming results from injection of a mixture different toxins following snakebite. Coagulopathy and life-threatening hemorrhage can occur, or venom-induced consumption coagulopathy (VICC). A rare case is presented of spontaneous splenic hemorrhage due to VICC that was successfully treated by non-surgical splenic artery embolization. CASE REPORT A 62-year-old man was admitted to the emergency department after an episode of dizziness and loss of consciousness following a snakebite. He was transferred to our hospital with hypotension and an abnormal blood coagulation test. On admission, he was hypotensive, with reduced hemoglobin and hematocrit levels, but did not complain of abdominal pain. The occult source of bleeding was identified by abdominal computed tomography (CT) as splenic hemorrhage. Treatment began with the administration of antivenom and blood transfusion. Splenic artery angio-embolization was performed to control the bleeding and was without complication. CONCLUSIONS Snakebite envenoming associated with VICC is a serious and life-threatening condition. Because of the possibility of associated occult bleeding from internal organs or blood vessels, imaging studies should be performed as soon as possible. For patients who are hemodynamically stabilized and have atraumatic hemorrhage from the spleen, non-operative treatment using angio-embolization may be performed with intensive monitoring and follow-up.

Using next-generation sequencing to decipher methylome and transcriptome and underlying molecular mechanisms contributing to rheumatoid arthritis (RA) for improving future therapies, we performed methyl-seq and RNA-seq on peripheral blood mononuclear cells (PBMCs) from RA subjects and normal donors. Principal component analysis and hierarchical clustering revealed distinct methylation signatures in RA with methylation aberrations noted across chromosomes. Methylation alterations varied with CpG features and genic characteristics. Typically, CpG islands and CpG shores were hypermethylated and displayed the greatest methylation variance. Promoters were hypermethylated and enhancers/gene bodies were hypomethylated, with methylation variance associated with expression variance. RA genetically associated genes preferentially displayed differential methylation and differential expression or interacted with differentially methylated and differentially expressed genes. These differentially methylated and differentially expressed genes were enriched with several signaling pathways and disease categories. 10 genes ( CD86, RAB20, XAF1 , FOLR3, LTBR , KCNH8 , DOK7, PDGFA, PITPNM2, CELSR1 ) with concomitantly differential methylation in enhancers/promoters/gene bodies and differential expression in B cells were validated. This integrated analysis of methylome and transcriptome identified novel epigenetic signatures associated with RA and highlighted the interaction between genetics and epigenetics in RA. These findings help our understanding of the pathogenesis of RA and advance epigenetic studies in regards to the disease.

Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA-target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA-target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease.

Background: GADD45 genes are stress sensors in response to cellular stress response, activated signal pathways leading to the stimulation of inflammatory cytokines. This study is to examine the associations of GADD45a and GADD45b genes with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients., Methods: 230 patients of RA, 140 patients of SLE, and 191 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan assay. RNA expression was quantitated with real-time polymerase chain reaction., Results: The RNA expression of the GADD45b gene was significantly lower in RA patients than the control cases ( p = 0.03). The odds ratio of GADD45a genotype -589 CC (rs581000) was significantly low (OR = 0.36, 95% CI, 0.15-0.87) in DR4-negative RA patients. The odds ratio of GADD45b genotype -712CT (rs3795024) in DR4-negative RA patients was 0.41 (95% CI, 0.18-0.95). In clinical manifestation, the odds ratio of GADD45b -712CT genotype with anti-RNP antibody was 4.14 (95% CI, 1.10-15.63) in SLE patients. GADD45a genotype -589GG+GC was associated with rheumatoid factor (RF) in SLE patients., Conclusions: Genotypes GADD45a -589CC and GADD45b -712CT were shown to be less susceptible to RA and related to the disease state in SLE patients.

Objective: Especially in emergency departments (EDs), a lack of internal medicine (IM) residents in charge causes difficulties in medical care and ED overcrowding. Thus, protocols without IM residents in EDs is needed. This study aimed to investigate changes in medical care when emergency medicine residents replaced the roles of IM residents., Methods: This study was conducted at a single-site ED of a university medical center. The study group contained patients admitted to the IM department between September and December 2015, during which IM residents were absent in the ED. The control group contained patients admitted to the IM department between September and December 2014, during which IM residents were present in the ED. Changes in medical care between the presence and absence of IM residents in the ED were studied by comparing admission rates from the ED, length of ED stay, duration of hospitalization, and concordance of diagnoses between admission and discharge by the IM department., Results: The study group contained 2,341 patients; the control group contained 2,215 patients. Admission rates from the ED increased by 53.4% (95% confidence interval [CI], P&lt;0.001); lengths of stay decreased by 15.1% (95% CI, P&lt;0.001); and durations of hospitalization in the pulmonology department decreased by 38.4% (95% CI, P=0.001). Concordance of diagnoses between admission and discharge decreased by 14.2% in the cardiology department (95% CI, P=0.021)., Conclusion: Lengths of stay were reduced without critical declines in diagnostic concordance rates when emergency medicine physicians, instead of IM residents in the ED, decided upon admissions of IM patients.

Objective: Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the 2 diseases, we performed a nationwide cohort study., Methods: We identified all newly diagnosed patients with PM from Taiwan's Registry of Catastrophic Illness Database between January 1, 1998 and December 31, 2011. Each PM patient was matched to ≤5 control patients from the National Health Insurance Research Database by sex, age, and entry date. Cumulative incidence of ALS was calculated by the Kaplan-Meier method and compared using the log rank test. Cox hazard regression was used to calculate the hazard ratio of ALS., Results: A total of 1,778 PM patients and 8,124 control patients were enrolled. PM patients had a higher cumulative incidence of ALS (P < 0.001). There was a positive correlation in being diagnosed with ALS in patients previously diagnosed with PM when stratified by sex. Consistent trends were conserved across different age strata. The strength of this association remained statistically significant after adjusting for sex, age, and concomitant autoimmune diseases (hazard ratio 25.72 [95% confidence interval 2.95-224.58]; P = 0.003)., Conclusion: This study demonstrates that a diagnosis of PM increased the likelihood of a subsequent ALS diagnosis, independent of sex, age, and concomitant autoimmune diseases. Future studies are warranted to clarify the underlying biologic mechanisms and to translate them into clinical therapeutic options., (© 2016, American College of Rheumatology.)

Background: Although dermatomyositis and Sjögren syndrome share serologic autoantibodies and genetic polymorphisms, population data about the incidence of Sjögren syndrome in patients with dermatomyositis is unavailable. We performed a nationwide cohort study to explore the potential relation between dermatomyositis and Sjögren syndrome and, if an association exists, to elucidate whether it varies by sex., Methods: We identified all patients with newly diagnosed dermatomyositis from the Registry of Catastrophic Illness Database in Taiwan between Jan. 1, 1998, and Dec. 31, 2011. Each patient was matched to, at most, 5 control patients from the National Health Insurance Research Database by age, sex and entry date. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of Sjögren syndrome after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis., Results: A total of 1602 patients with dermatomyositis and 7981 control patients were enrolled in the study. There was a positive association of having Sjögren syndrome among patients with dermatomyositis after adjusting for age, sex, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis (HR 2.67, 95% CI 2.01-3.54). The association was more pronounced in the male cohort (HR 2.69, 95% CI 1.19-6.09)., Interpretation: We found a sex differential association of Sjögren syndrome among patients with dermatomyositis independent of age and concomitant autoimmune disease. Further studies are required to determine the clinical importance of this association for both outcomes and therapeutic options., (© 2017 Canadian Medical Association or its licensors.)

On a molecular level, two autoimmune diseases: ulcerative colitis (UC) and dermatomyositis share common genetic determinants. On a clinical level, case reports evidenced the co-occurrence of these two diseases. We therefore hypothesize that UC is potentially associated with increased cumulative incidence of dermatomyositis. The goals of this retrospective cohort study were to evaluate whether UC is associated with increased cumulative incidence of dermatomyositis independent of sex and age. For comparison, we also assessed the cumulative incidence of polymyositis in UC and control subjects. The study enrolled 3,133 UC subjects and 14,726 control subjects. The cumulative incidence of dermatomyositis was significantly higher in UC than that of control subjects (p = 0.026), but the cumulative incidence of polymyositis was comparable between UC and control subjects (p = 0.596). UC was independently associated with the increased incident dermatomyositis (hazard ratio: 6.19, 95% confidence interval = 1.77-21.59, p = 0.004) after adjusting for sex, age, and concomitant rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Similar trends of increased dermatomyositis in UC were observed when patients were stratified based on sex and age. In conclusion, our findings suggest that UC is probably associated with increased cumulative incidence of dermatomyositis, independent of sex, age, and concomitant autoimmune diseases.

Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness.A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01-2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24-2.56, P = 0.002).In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history.

Objectives: The purpose of this study is to investigate whether systemic sclerosis is a risk factor for diabetes., Methods: From Taiwan's National Health Insurance Research Database and Registry of Catastrophic Illness database, we enrolled patients with systemic sclerosis and controls. Each systemic sclerosis patient was matched to at most three controls by sex, age, month and year of first diagnosis. Standardized incidence ratio (SIR) of diabetes in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR)., Results: A total of 2671 patients with systemic sclerosis and 7769 controls were enrolled. Patients with systemic sclerosis had decreased type 1 diabetes (SIR: 0.18, 95% CI=0.04-0.82). In female groups, systemic sclerosis patients also had lower rates of incident type 1 diabetes (SIR: 0.21, 95% CI=0.05-0.95). Male and female patients with systemic sclerosis both had lower rates of incident type 2 diabetes (SIR: 0.46, 95% CI=0.29-0.72; SIR: 0.41, 95% CI=0.33-0.51, respectively). Systemic sclerosis patients had decreased type 1 diabetes and type 2 diabetes (HR: 0.18, 95% CI=0.04-0.74; HR: 0.42, 95% CI=0.36-0.50, respectively) after adjusting for age and sex., Conclusions: The results clearly showed that patients with systemic sclerosis had lower incidence of type 1 diabetes and type 2 diabetes compared to control subjects., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Previous studies showed inconsistent results on the association of systemic sclerosis (SSc) with multiple sclerosis (MS), and are limited by a lack of adjustment for sex and age. The goals of this retrospective cohort study were to evaluate whether SSc is associated with increased incident MS independent of sex and age., Methods: We enrolled patients with SSc from Taiwan's Registry of Catastrophic Illness Database and referent subjects from the National Health Insurance Research Database. Each SSc patient was matched to at most three referent subjects by sex, age, month and year of initial diagnosis of SSc. Incidence of MS in SSc patients and corresponding 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR) of MS., Results: The study enrolled 1171 patients with SSc and 3409 referent subjects. Patients with SSc had higher incidence of MS than referent subjects (9.35 per 1000 person-years, 95% CI=6.86-11.85; 0.13 per 1000 person-years, 95% CI=0.03-0.37, respectively). Similar results also occurred in both men and women. SSc was associated with increased incidence of MS after adjusting for sex and age (HR: 69.48, 95% CI=21.69-222.54)., Conclusion: SSc is associated with increased incidence of MS, independent of sex and age of the patients. Multidisciplinary teams should guide the assessment, treatment, and holistic care of SSc patients to reduce its morbidity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: To date, there has been no studies to evaluate the incidence of Crohn's disease in systemic sclerosis patients. The goals of this study were to evaluate the incidence of Crohn's disease and its relationship with sex and age in patients with systemic sclerosis., Methods: We enrolled patients with systemic sclerosis and controls from Taiwan's Registry of Catastrophic Illness Database and National Health Insurance Research Database. Every systemic sclerosis patient was matched to at most three controls by sex, age, month and year of initial diagnosis of systemic sclerosis. The standardized incidence ratio (SIR) of Crohn's disease in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR)., Results: The study enrolled 2,829 patients with systemic sclerosis and 8,257 controls. Male and female patients with systemic sclerosis both had lower rates of incident Crohn's disease (SIR: 0.18, 95% CI = 0.05-0.62; SIR: 0.10, 95% CI = 0.05-0.21, respectively). The risk of incident Crohn's disease in systemic sclerosis was still lower than in controls when we stratified the patients according to their ages. In Cox hazard regression, the hazard rates of Crohn's disease were lower in systemic sclerosis patients after adjusting for genders and ages (HR: 0.12, 95% CI = 0.06-0.21, p < 0.001)., Conclusions: Systemic sclerosis is associated with decreased incidence of, irrespective of sex and age of the patients.

Background: The common toxicities of cement are allergic dermatitis, abrasions, and chemical burns, but reports of cement ingestion are rare. In this study, we report a case of successful treatment of cement ingestion using emergency gastrointestinal endoscopy., Case Report: An 83-year-old female was admitted to the emergency department with altered mental state and abdominal pain. We assumed that she ingested cement based on her medical history and radiologic examination. A previous report recommended surgical removal with gastric lavage. However, we thought that wet cement is highly alkaline, and gastric lavage is contraindicated. We performed emergency gastrointestinal endoscopy, instead of gastric lavage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: If a patient ingests cement, the recommendation is to check the status of the upper gastrointestinal tract and remove the cement by emergency gastrointestinal endoscopy as soon as possible., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the past, there were no studies to evaluate the incidence of Sjogren's syndrome and its relationship with sex and age in patients with systemic sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and 6485 controls from Taiwan's Registry of Catastrophic Illness database and National Health Insurance Research Database. Every patient with systemic sclerosis was matched to at most three controls by sex, age, month, and year of first diagnosis of systemic sclerosis. Standardized incidence ratio (SIR) of Sjogren's syndrome in patients with systemic sclerosis and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). Both male and female patients with systemic sclerosis had higher incidences of Sjogren's syndrome (SIR: 7.59, 95% CI = 2.97-19.51; SIR: 7.59, 95% CI = 5.56-10.42, respectively). The incidence of Sjogren's syndrome in patients with systemic sclerosis was still higher compared with control when stratified according to age. Age at diagnosis of Sjogren's syndrome was earlier in patients with systemic sclerosis in both male and female groups (p = 0.018; p < 0.001, respectively). Systemic sclerosis was associated with Sjogren's syndrome after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI = 4.79-7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk alleles were all potential causes of increased incidence of Sjogren's syndrome in systemic sclerosis.

The authors report a case of acute methemoglobinemia in a patient treated with naproxen for the common cold. A 42-year-old Asian woman began taking naproxen sodium and methocarbamol formylagia, chills, and coughing. On the day prior to her emergency department (ED) admission,the patient was taking lorazepam, trazodon, and paroxetine in addition to the naproxen and methocarbamol prescribed for the cold symptoms, and she also ingested approximately 300 mL of 20% alcohol. Upon awakening the next morning, the patient experienced dyspnea and dizziness. At the hospital, she was diagnosed with severe methemoglobinemia. After initiation of methylene blue therapy, the patient's symptoms improved substantially and her serum methemoglobin levels decreased. After 10 days in the hospital, the patient was discharged without any complications.Naproxen is known to cause oxidative stress. Alcohol is known to reduce G6PD activity, and thus it is hypothesized that the administration of naproxen in an alcohol-dependent patient caused methemoglobinemia.

Purpose: Unlike other sodium-channel-blocking antiarrhythmic agents, propafenone has β-blocking effects and calcium-channel-blocking effects. Yi et al recently studied insulin's treatment effect on acute propafenone toxicity in rats. However, because the degree of effectiveness of insulin compared to the previously known antidote sodium bicarbonate (NaHCO3) was not studied, the 2 treatment methods were compared for propafenone intoxication in rats., Methods: Rats received intravenous propafenone (36 mg/[kg h]) for 12 minutes. After the induction of toxicity, rats (n = 10 per group) received normal saline solution (NSS), NaHCO3, or insulin with glucose as treatment. Animals in the NSS, NaHCO3, and Insulin groups received an intravenous infusion of 36 mg/(kg h) propafenone until death occurred. For each animal, the mean arterial pressure (MAP, heart rate, PR interval, QRS duration, total hemoglobin, sodium, potassium, potential of hydrogen, bicarbonate, glucose, lactate, and central venous oxygen saturation (Scvo2) were measured and compared among the groups., Results: Survival of the Insulin group was greater than that of the NSS group by log-rank test (P = .021). Sodium bicarbonate prevented the decline of MAP for 55 minutes. In comparison, insulin prevented the decline of MAP and heart rate, and the elongation of the PR interval and QRS duration for 55 minutes (P < .05). Propafenone toxicity led to decreased Ca(2+), potential of hydrogen, and Scvo2 and increased lactate levels. Insulin prevented the decrease of Ca(2+) and Scvo2, whereas NaHCO3 prevented the increase in lactate., Conclusion: Insulin treatment was more effective than NaHCO3 on acute propafenone toxicity in rat. Therefore, when propafenone-induced cardiotoxicity occurs, which is unresponsive to current treatment methods, glucose-insulin infusion may be considered., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been widely used as an analgesic or an adjuvant with morphine in clinics. In rats, it attenuates tolerance and physical dependence caused by morphine, when co-administered. In this study, we investigated the effect of nalbuphine on morphine reward. Using the conditioned place preference (CPP) paradigm in rats, we demonstrated that co-administration of nalbuphine (1mg/kg, i.p.) with morphine (5mg/kg, i.p.) during conditioning could completely block the CPP induced by morphine. However, in experiments examining locomotor activity in rats, nalbuphine showed no effect on the development of behavioral sensitization induced by reported morphine administration. In microdialysis experiments, morphine induced a significant increase in the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in the shell region of the nucleus accumbens. Co-administration of nalbuphine blocked the increase in dopamine metabolites induced by morphine. These results may be due to the attenuating effect of nalbuphine on the dopaminergic activity of mesolimbic pathways. All of these results suggest nalbuphine could have a great potential as a pharmacotherapy for opiate abuse.

The goal of this study is identify early predictors of intractability in childhood epilepsy. A cohort of epileptic children living in the northwest sector of Hong Kong was prospectively identified and monitored. Treatment effect was analyzed at the last follow-up before July 1, 2000. Cases were patients who had an average of at least one unprovoked seizure per month during an observational period of at least 2 years. Controls were children having achieved at least 2 seizure-free years. Strong univariate association was observed between intractability and the following factors: high initial seizure frequency, remote symptomatic etiology, infantile spasms and mixed seizure types, abnormal neurologic status, history of status epilepticus, neonatal seizures, and early breakthrough attacks after treatment initiation. Independent predictors of intractability with multiple regression were abnormal neurodevelopmental status, symptomatic etiology, and more than three seizures in the second 6 months after treatment. Our study suggested that risk of developing intractable epilepsy might be predicted, to some extent, at the early course of illness in children with abnormal neurologic status and lack of early response to treatment.