Effects of aerobic and resistance exercise for 9 months on serum free light chains in type 2 diabetes.

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes trial (HART-D) were randomly assigned to no exercise (n = 27), aerobic exercise alone (n = 41), resistance exercise alone (n = 49), or a combination of aerobic and resistance exercise (n = 47). Fasting serum samples were collected before and after completion of the intervention to quantify changes in kappa and lambda FLCs, and serum creatinine, using commercially-available ELISAs. Results: At baseline, combined kappa and lambda FLCs (FLC sum; calculated as kappa + lambda FLCs) were positively correlated with high-sensitive C-reactive protein (hs-CRP) (r = 0.237, p < 0.05) and fat mass (r = 0.162, p < 0.05), and negatively associated with aerobic fitness (r = -0.238, p < 0.05). While non-exercise controls exhibited an increase in FLCs over the 9-month study, exercise training blunted this increase (Δ FLC sum control arm: 3.25 ± 5.07 mg∙L-1 vs. all exercise arms: -0.252 ± 6.60 mg∙L-1, p < 0.05), regardless of exercise modality. Conclusion: Serum FLCs were associated with physical fitness and body composition in patients with type 2 diabetes. 9-month of exercise training prevented the accumulation of FLCs, regardless of exercise modality. Unlike hs-CRP-which did not change during the trial-serum FLCs may serve as a more sensitive biomarker of chronic low-grade inflammation in this population.

PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.

Proliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residues of PCNA in maintaining genomic integrity using in vitro, and cell-based assays and structural prediction. The predicted PCNAΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNAΔSL47 shows a defective interaction with PCNAWT leading to defects in homo-trimerization in vitro. PCNAΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNAΔSL47-expressing cells. Accordingly, PCNAΔSL47-expressing cells exhibit an increased number of single-stranded DNA gaps and higher levels of γH2AX, and sensitivity to DNA-damaging agents, highlighting the importance of PCNA Ser46-Leu47 residues in maintaining genomic integrity.

Effects of infusion tubing line lengths and syringe sizes on infusion system compliance: an experimental study using a syringe-type infusion pump at low flow rate.

Ideally, the flow delivery of an infusion system is proportional only to the rate of mechanical actuation of the syringe pump plunger. However, in the real world, overall infusion system compliance may be affected by components such as an extension of tubing lines, or different sizes of syringes. With higher compliance, there may be greater chances of flow irregularity. In this experimental study, we investigated the effects of lengths of infusion lines and syringe sizes on the compliance of syringe pumps with low flow rate (2 ml h-1). In the first experiment, infusion system compliance was measured in various settings by occlusion release. As the infusion tubing length and size of the syringe increased, the time to reach each pressure was delayed and the infusion system compliance increased. The contributions to system compliance from syringes were significantly greater compared to those of extended infusion lines. In the occlusion alarm experiment, the occlusion alarm could be delayed by 69.76 ± 3.98 min for the 50-ml syringe with a 560 cm infusion line set-up. In conclusion, the compliance of a syringe pump system increases as the loaded syringe size, or the length of the infusion tubing increases. The occlusion alarm may be much delayed and not useful in highly compliant systems with respect to the potential occlusion of the infusion system, so more attention is required when using a highly compliant infusion system.

Remimazolam dose for successful insertion of a supraglottic airway device with opioids: a dose-determination study using Dixon's up-and-down method.

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine, was recently approved in numerous jurisdictions as an induction drug for general anesthesia. We aimed to determine the doses of remimazolam that would allow placement of a supraglottic airway device (SGD) in 50% and 95% of nonparalyzed patients (ED50 and ED95). METHODS: In this prospective study, 30 American Society of Anesthesiology Physical Status I-II grade female patients scheduled for hysteroscopic surgery were enrolled. Anesthesia was induced with 1 µg·kg-1 of fentanyl and continuous infusion of remimazolam without neuromuscular blockade. An i-gel® SGD was inserted 2.5 min after the start of remimazolam infusion. We used Dixon's up-and-down method and isotonic regression to determine the ED50 and ED95 of remimazolam for insertion of an SGD. RESULTS: Twenty-eight patients were included in the final analysis. The ED50 and ED95 of remimazolam required for successful i-gel insertion were 8.8 mg·kg-1·hr-1 (95% confidence interval [CI], 6.3 to 10.6) and 10.7 mg·kg-1·hr-1 (95% CI, 10.6 to 11.7), respectively. A nonfully relaxed jaw was found in 7/13 patients (54%) in the success group and 14/15 patients (93%) in the failure group (difference in proportions, 40%; 95% CI, 7 to 65; P = 0.02). Bucking or other movements during SGD insertion only occurred in the failure group (11/15, 73%). CONCLUSION: In 95% of nonparalyzed female patients undergoing hysteroscopy, 10.7 mg·kg-1·hr-1 of remimazolam with 1 µg·kg-1 of fentanyl facilitates i-gel insertion. Remimazolam showed a high incidence of poor jaw relaxation and bucking or other movements during SGD insertion. STUDY REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006527, https://cris.nih.go.kr ; registered 1 September 2021; principal investigator: Ji Seon Jeong).

RéSUMé: OBJECTIF: Le remimazolam, une benzodiazépine à action ultra-brève, a récemment été approuvé dans de nombreuses juridictions comme agent d'induction pour l'anesthésie générale. Notre objectif était de déterminer les doses de remimazolam qui permettraient l'insertion d'un dispositif supraglottique (DSG) chez 50 % et 95 % des patients non paralysés (DE50 et DE95). MéTHODE: Dans cette étude prospective, 30 patientes de statut physique I-II selon l'American Society of Anesthesiology devant bénéficier d'une chirurgie hystéroscopique ont été recrutées. L'anesthésie a été induite avec 1 µg·kg−1 de fentanyl et une perfusion continue de remimazolam sans bloc neuromusculaire. Un DSG i-gel® a été inséré 2,5 minutes après l'amorce de la perfusion de remimazolam. Nous avons utilisé la méthode de l'escalier de Dixon et la régression isotonique pour déterminer la DE50 et DE95 de remimazolam pour l'insertion d'un DSG. RéSULTATS: Vingt-huit patientes ont été incluses dans l'analyse. Les DE50 et DE95 du remimazolam requises pour une insertion réussie de l'i-gel était de 8,8 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 6,3 à 10,6) et 10,7 mg·kg−1·h−1 (IC 95 %, 10,6 à 11,7), respectivement. Une mâchoire non complètement détendue a été observée chez 7 patientes sur 13 (54 %) dans le groupe d'intubation réussie et chez 14/15 patientes (93 %) dans le groupe d'échec d'intubation (différence de proportions, 40 %; IC 95 %, 7 à 65; P = 0,02). Le fléchissement ou d'autres mouvements pendant l'insertion du DSG ne se sont produits que dans le groupe d'échec de l'induction (11/15, 73 %). CONCLUSION: Chez 95 % des patientes non paralysées bénéficiant d'une hystéroscopie, 10,7 mg·kg−1·h−1 de remimazolam avec 1 µg·kg−1 de fentanyl ont facilité l'insertion d'un dispositif i-gel. Le remimazolam a montré une incidence élevée de mauvaise relaxation de la mâchoire et de fléchissement ou d'autres mouvements lors de l'insertion du DSG. ENREGISTREMENT DE L'éTUDE: Registre des essais cliniques de la République de Corée (KCT0006527, https://cris.nih.go.kr ; enregistrée le 1er septembre 2021; chercheur principal : Ji Seon Jeong).

Ir(III)-Catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling for the synthesis of N-H indoles.

Herein, an iridium(III)-catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling of unprotected 2-alkenyl anilines is described. The developed method allows the synthesis of a variety of 3-substituted N-H indole scaffolds under undivided electrolytic conditions. Mechanistic studies suggest that the reaction proceeds through the electro-oxidation induced reductive elimination pathway.

Biopatterned Reorganization of Alkaloids Enabled by Ring-Opening Functionalization of Tertiary Amines.

Biosynthetic processes often involve reorganization of one family of natural products to another. Chemical emulation of nature's rearrangement-based structural diversification strategy would enable the conversion of readily available natural products to other value-added secondary metabolites. However, the development of a chemical method that can be universally applied to structurally diverse natural products is nontrivial. Key to the successful reorganization of complex molecules is a versatile and mild bond-cleaving method that correctly places desired functionality, facilitating the target synthesis. Here, we report a ring-opening functionalization of a tertiary amine that can introduce desired functionalities in the context of alkaloids reorganization. The semistability of the difluoromethylated ammonium salt, accessed by the reaction of tertiary amine and in situ generated difluorocarbene, enabled the attack at the α-position by various external nucleophiles. The utility and generality of the method is highlighted by its applications in the transformation of securinega, iboga, and sarpagine alkaloids to neosecurinega, chippiine/dippinine, and vobasine-type bisindole alkaloids, respectively. During the course of these biosynthetically inspired reorganizations, we could explore chemical reactivities of biogenetically relevant precursors.

Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair.

Reactive oxygen species (ROS) generate oxidized bases and single-strand breaks (SSBs), which are fixed by base excision repair (BER) and SSB repair (SSBR), respectively. Although excision and repair of damaged bases have been extensively studied, the function of the sliding clamp, proliferating cell nuclear antigen (PCNA), including loading/unloading, remains unclear. We report that, in addition to PCNA loading by replication factor complex C (RFC), timely PCNA unloading by the ATPase family AAA domain-containing protein 5 (ATAD5)-RFC-like complex is important for the repair of ROS-induced SSBs. We found that PCNA was loaded at hydrogen peroxide (H2O2)-generated direct SSBs after the 3'-terminus was converted to the hydroxyl moiety by end-processing enzymes. However, PCNA loading rarely occurred during BER of oxidized or alkylated bases. ATAD5-depleted cells were sensitive to acute H2O2 treatment but not methyl methanesulfonate treatment. Unexpectedly, when PCNA remained on DNA as a result of ATAD5 depletion, H2O2-induced repair DNA synthesis increased in cancerous and normal cells. Based on higher H2O2-induced DNA breakage and SSBR protein enrichment by ATAD5 depletion, we propose that extended repair DNA synthesis increases the likelihood of DNA polymerase stalling, shown by increased PCNA monoubiquitination, and consequently, harmful nick structures are more frequent.

Compact Measurement of the Optical Power in High-Power LED Using a Light-Absorbent Thermal Sensor.

LED (Light-Emitting Diode) presents advantages such as luminescence, reliability, durability compared with conventional lighting. It has been widely applied for life, healthcare, smart farm, industry, and lighting from indoor to the automotive headlamp. However, the LED is vulnerable to thermal damage originated from the high junction temperature, especially in high power applications. Hence, it requires precise qualification on the optical power and the junction temperature from the pilot line to secure reliability. In this study, the photo-thermal sensor is proposed by employing a sheet-type thermocouple composed of photo-absorbent metal film and thermocouple. This sensor aims low-cost qualification in pilot line for high-power luminous devices and optical monitoring of costly luminaire such as automobile LED headlamp. The sensor is designed to detect the increased temperature response of LED hot spots from the transferred thermal power and absorbed optical power. The temperature response of each sheet-type thermocouple is utilized as a signal output of the absorbed optical power and hot spot temperature based on the introduced sensor equation. The proposed thermal sensor is evaluated by comparing the experiment with the measured reference value from the integrating sphere and the attached thermocouple at a junction. The experiment result reveals 3% of the maximum error for the optical power of 645 mW.

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer.

Chemical synthesis based on the skeletal variation has been prolifically utilized as an attractive approach for modification of molecular properties. Given the ubiquity of unstrained cyclic amines, the ability to directly alter such motifs would grant an efficient platform to access unique chemical space. Here, we report a highly efficient and practical strategy that enables the selective ring-opening functionalization of unstrained cyclic amines. The use of difluorocarbene leads to a wide variety of multifaceted acyclic architectures, which can be further diversified to a range of distinctive homologative cyclic scaffolds. The virtue of this deconstructive strategy is demonstrated by successful modification of several natural products and pharmaceutical analogues.

Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.

There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.

Delineating Physical Organic Parameters in Site-Selective C-H Functionalization of Indoles.

Site-selective C-H functionalization is a great challenge in homogeneous transition-metal catalysis. Herein, we present a physical organic approach to delineate the origin of regioselective amidation of N-acylindoles through Ir(III) catalysis. Bulkiness of N-directing groups of indole substrates and electronics of carboxylate additives were identified as two major factors in controlling C2 and C7 selectivity, and their microscopic mechanisms were studied with DFT-based transition state analysis. Computational insights led us to interrogate a linear free energy relationship, and parametrization of molecular determinants enabled the establishment of an intuitive yet robust statistical model that correlates an extensive number of validation data points in high accuracy. This mechanistic investigation eventually allowed the development of a new C2 amidation and alkenylation protocol of indoles, which affords the exclusive functionalization at the C2 position with up to >70:1 selectivity.

Clinical course of asthma patients with H1N1 influenza infection and oseltamivir.

BACKGROUND: H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections. METHODS: We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups. RESULTS: A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011). CONCLUSIONS: H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.

Importance of indoor dust biological ultrafine particles in the pathogenesis of chronic inflammatory lung diseases.

The role of infectious agents in the etiology of inflammatory diseases once believed to be non-infectious is increasingly being recognized. Many bacterial components in the indoor dust can evoke inflammatory lung diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, so-called extracellular vesicles (EV). which are pathophysiologically related to inflammatory diseases. Microbiota compositions in the indoor dust revealed the presence of both Gram-negative and Gram-positive bacteria. Escherichia coli is a model organism of Gram-negative Enterobacteriaceae. The repeated inhalation of E. coli-derived EVs caused neutrophilic inflammation and emphysema in a dose-dependent manner. The emphysema induced by E. coli-derived EVs was partially eliminated by the absence of Interferon-gamma or interleukin-17, suggesting that Th1 and/or Th17 cell responses are important in the emphysema development. Meanwhile, the repeated inhalation of Staphylococcus aureus-derived EVs did not induce emphysema, although they induced neutrophilic inflammation in the lung. In terms of microbial EV compositions in the indoor dust, genera Pseudomonas, Acinetobacter, Enterobacter, and Staphylococcus were dominant. As for the clinical significance of sensitization to EVs in the indoor dust, EV sensitization was closely associated with asthma, chronic obstructive pulmonary disorder (COPD), and lung cancer. These data indicate that biological ultrafine particles in the indoor dust, which are mainly composed of microbial EVs, are important in the pathogenesis of chronic lung diseases associated with neutrophilic inflammation. Taken together, microbial EVs in the indoor dust are an important diagnostic and therapeutic target for the control of chronic lung diseases, such as asthma, COPD, and lung cancer.

Transition Metal-Catalyzed C-H Amination: Scope, Mechanism, and Applications.

Catalytic transformation of ubiquitous C-H bonds into valuable C-N bonds offers an efficient synthetic approach to construct N-functionalized molecules. Over the last few decades, transition metal catalysis has been repeatedly proven to be a powerful tool for the direct conversion of cheap hydrocarbons to synthetically versatile amino-containing compounds. This Review comprehensively highlights recent advances in intra- and intermolecular C-H amination reactions utilizing late transition metal-based catalysts. Initial discovery, mechanistic study, and additional applications were categorized on the basis of the mechanistic scaffolds and types of reactions. Reactivity and selectivity of novel systems are discussed in three sections, with each being defined by a proposed working mode.

A Direct Access to 7-Aminoindoles via Iridium-Catalyzed Mild C-H Amidation of N-Pivaloylindoles with Organic Azides.

Ir(III)-catalyzed regioselective direct C-7 amidation of indoles in reaction with organic azides has been developed. While its efficiency was varied by the choice of N-directing groups, N-pivaloylindoles were most effective in undergoing the desired amidation at room temperature over a broad range of substrates. The reaction was scalable, and deprotection of the chelation group was also facile.

Murine subcutaneous immunotherapy models with beneficial immunological and physiological effects.

BACKGROUND: Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far. OBJECTIVE: We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule. METHODS: To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times. RESULTS: Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR. CONCLUSION: This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.

Influence of the Adjuvants and Genetic Background on the Asthma Model Using Recombinant Der f 2 in Mice.

Der f 2 is the group 2 major allergen of a house dust mite (Dermatophagoides farinae) and its function has been recently suggested. To determine the optimal condition of sensitization to recombinant Der f 2 (rDer f 2) in murine model of asthma, we compared the effectiveness with different adjuvants in BALB/c and C57BL/6 mice. Mice from both strains sensitized with rDer f 2 by intraperitoneal injection or subcutaneous injection on days 1 and 14. The dosage was 20 µg. Freund's adjuvants with pertussis toxin (FP) or alum alone were used as adjuvants. On days 28, 29, and 30, mice were challenged intranasally with 0.1% rDer f 2. We evaluated airway hyperresponsivenss, eosinophil proportion in lung lavage, airway inflammation, and serum allergen specific antibody responses. Naive mice were used as controls. Airway hyperresponsiveness was increased in C57BL/6 with FP, and BALB/c with alum (PC200: 13.5±6.3, 13.2±6.7 vs. >50 mg/ml, p<0.05). The eosinophil proportion was increased in all groups; C57BL/6 with FP, BALB/c with FP, C57BL/6 with alum, BALB/c with alum (24.8±3.6, 20.3±10.3, 11.0±6.9, 5.7±2.8, vs. 0.0±0.0%, p<0.05). The serum allergen specific IgE levels were increased in C57BL/6 with FP or alum (OD: 0.8±1.4, 1.1±0.8, vs. 0.0±0.0). C57BL/6 mice were better responders to rDer f 2 and as for adjuvants, Freund's adjuvant with pertussis toxin was better.

Differences in airway inflammation according to atopic status in patients with chronic rhinitis.

BACKGROUND: Chronic rhinitis is a heterogeneous group of diseases that cause nasal inflammation. And the nose may be a window into the lung in the concept of "one airway one disease." OBJECTIVE: This study was conducted to evaluate differences between the different forms of chronic rhinitis in terms of lower airway inflammation. METHODS: Patients that attended the allergy clinic and presented with moderate/severe persistent rhinitis symptoms for more than 1 year were enrolled. The patients with chronic rhinitis were classified into two groups (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis [NAR]) according to the presence of atopy, and additionally according to nasal polyposis and airway hyperresponsiveness, respectively. Medical records were reviewed and the mRNA expression levels of IL-5, IFN-γ, TGF-ß1, IL-17A, and IL-25 were evaluated in induced sputum samples in each group. RESULTS: Induced sputum samples of 53 patients were evaluated. Patients with NAR were significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in NAR patients, regardless of the presence of airway hyperresponsiveness (p = 0.005). CONCLUSION: These results suggest that patients with different forms of chronic rhinitis could have different inflammatory environments in their lower airway and NAR patients might have bronchial inflammation related to the elevated levels of IL-17A compared to HDM-sensitive AR patients.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

BACKGROUND: Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. OBJECTIVES: To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. METHODS: The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. RESULTS: Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. CONCLUSION: A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system.