Functional Characterization of Endo- and Exo-Hydrolase Genes in Arabinan Degradation Gene Cluster of Bifidobacterium longum subsp. suis.

Bifidobacteria are probiotic microorganisms commonly found in the gastrointestinal tract, some of which are known to utilize linear arabino-oligosaccharides (AOS) as prebiotic carbohydrates. In general, the synergistic actions of exo-type α-l-arabinofuranosidases (ABFs) and endo-α-1,5-l-arabinanases (ABNs) are required for efficient arabinan degradation. In this study, the putative gene cluster for arabinan degradation was discovered in the genome of Bifidobacterium longum subsp. suis. It consists of a variety of genes encoding exo- and endo-hydrolases, sugar-binding proteins, ABC-binding cassettes, and transcriptional regulators. Among them, two endo-ABNs GH43 (BflsABN43A and BflsABN43B), two exo-ABFs GH43 (BflsABF43A and BflsABF43B), and an exo-ABF GH51 (BflsABF51) were predicted to be the key hydrolases for arabinan degradation. These hydrolase genes were functionally expressed in Escherichia coli, and their enzymatic properties were characterized. Their synergism in arabinan degradation has been proposed from the detailed modes of action. Extracellular endo-BflsABN43A hydrolyzes sugar beet and debranched arabinans into the short-chain branched and linear AOS. Intracellularly, AOS can be further degraded into l-arabinose via the cooperative actions of endo-BflsABN43B, exo-BflsABF43A with debranching activity, α-1,5-linkage-specific exo-BflsABF43B, and exo-BflsABF51 with dual activities. The resulting l-arabinose is expected to be metabolized into energy through the pentose phosphate pathway by three enzymes expressed from the ara operon of bifidobacteria. It is anticipated that uncovering arabinan utilization gene clusters and their detailed functions in the genomes of diverse microorganisms will facilitate the development of customized synbiotics.

Relationship between asthma and sarcopenia in the elderly: a nationwide study from the KNHANES.

OBJECTIVE: Few studies have investigated the relationship between asthma and sarcopenia. We aimed to examine the relationship between asthma and sarcopenia in a community-dwelling geriatric population, especially regarding lung function and asthma control. METHODS: A cross-sectional dataset from the Korean National Health and Nutrition Examination Survey 2008-2011 was utilized. Data regarding asthma history, age at asthma onset, recent asthma exacerbations, and hospitalization for asthma exacerbations were obtained using structured questionnaires. Appendicular skeletal muscle was calculated as the sum of the skeletal muscle mass, and physical activity was assessed using the International Physical Activity Questionnaire. RESULTS: Asthma presented an estimated incidence of 6.17 ± 0.37% in the elderly. Groups were divided and analyzed according to asthma, muscle mass, and physical activity. Sarcopenia was associated with aging, male sex, smoking history, low body mass index (BMI), and reduced lung function with or without asthma. Sarcopenic asthma had a younger onset and reduced physical activity than non-sarcopenic asthma. Obstructive patterns were more frequent in asthmatics exhibiting low or moderate physical activity levels than in those with high activity, but asthma control was not associated with sarcopenia and physical activity. Multivariate logistic regression analyses showed that compared with control, sarcopenic asthma was associated with FEV1 < 60%, and airway obstruction, and with aging, male, and lower BMI, compared with non-sarcopenic asthma. CONCLUSIONS: Our findings suggest that decreased muscle mass and physical activity levels contribute to reduced lung function in elderly asthmatics. Furthermore, sarcopenic asthma was associated with aging, low BMI, and reduced lung function in the elderly.

Design and Methods of a Prospective Smartphone App-Based Study for Digital Phenotyping of Mood and Anxiety Symptoms Mixed With Centralized and Decentralized Research Form: The Search Your Mind (S.Y.M., ) Project.

In this study, the Search Your Mind (S.Y.M., ) project aimed to collect prospective digital phenotypic data centered on mood and anxiety symptoms across psychiatric disorders through a smartphone application (app) platform while using both centralized and decentralized research designs: the centralized research design is a hybrid of a general prospective observational study and a digital platform-based study, and it includes face-to-face research such as informed written consent, clinical evaluation, and blood sampling. It also includes digital phenotypic assessment through an application-based platform using wearable devices. Meanwhile, the decentralized research design is a non-face-to-face study in which anonymous participants agree to electronic informed consent forms on the app. It also exclusively uses an application-based platform to acquire individualized digital phenotypic data. We expect to collect clinical, biological, and digital phenotypic data centered on mood and anxiety symptoms, and we propose a possible model of centralized and decentralized research design.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.

Hydrolysis of Arabinoxylo-oligosaccharides by α-L-Arabinofuranosidases and ß-D-Xylosidase from Bifidobacterium dentium.

Two α-L-arabinofuranosidases (BfdABF1 and BfdABF3) and a ß-D-xylosidase (BfdXYL2) genes were cloned from Bifidobacterium dentium ATCC 27679, and functionally expressed in E. coli BL21(DE3). BfdABF1 showed the highest activity in 50 mM sodium acetate buffer at pH 5.0 and 25°C. This exo-enzyme could hydrolyze p-nitrophenyl arabinofuranoside, arabino-oligosaccharides (AOS), arabinoxylo-oligosaccharides (AXOS) such as 32-α-L-arabinofuranosyl-xylobiose (A3X), and 23-α-Larabinofuranosyl-xylotriose (A2XX), whereas hardly hydrolyzed polymeric substrates such as debranched arabinan and arabinoxylans. BfdABF1 is a typical exo-ABF with the higher specific activity on the oligomeric substrates than the polymers. It prefers to α-(1,2)-L-arabinofuranosidic linkages compared to α-(1,3)-linkages. Especially, BfdABF1 could slowly hydrolyze 23,33-di-α-L-arabinofuranosyl-xylotriose (A2+3XX). Meanwhile, BfdABF3 showed the highest activity in sodium acetate at pH 6.0 and 50°C, and it has the exclusively high activities on AXOS such as A3X and A2XX. BfdABF3 mainly catalyzes the removal of L-arabinose side chains from various AXOS. BfdXYL2 exhibited the highest activity in sodium citrate at pH 5.0 and 55°C, and it specifically hydrolyzed p-nitrophenyl xylopyranoside and xylo-oligosaccharides (XOS). Also, BfdXYL2 could slowly hydrolyze AOS and AXOS such as A3X. Based on the detailed hydrolytic modes of action of three exo-hydrolases (BfdABF1, BfdABF3, and BfdXYL2) from Bf. dentium, their probable roles in the hemiceulloseutilization system of Bf. dentium are proposed in the present study. These intracellular exo-hydrolases can synergistically produce L-arabinose and D-xylose from various AOS, XOS, and AXOS.

Development of a prognostic scoring system in patients with pneumonia requiring ventilator care for more than 4 days: a single-center observational study.

BACKGROUND: The aim of the present study was to develop a prognostic model using demographic characteristics, comorbidities, and clinical variables measured on day 4 of mechanical ventilation (MV) for patients with prolonged acute mechanical ventilation (PAMV; MV for >96 hours). METHODS: Data from 437 patients (70.9% male; median age, 68 years) were obtained over a period of 9 years. All patients were diagnosed with pneumonia. Binary logistic regression identified factors predicting mortality at 90 days after the start of MV. A PAMV prognosis score was calculating ß-coefficient values and assigning points to variables. RESULTS: The overall 90-day mortality rate was 47.1%. Five factors (age ≥65 years, body mass index <18.5 kg/m2, hemato-oncologic diseases as comorbidities, requirement for vasopressors on day 4 of MV and requirement for neuromuscular blocking agents on day 4 of MV) were identified as prognostic indicators. Each factor was valued as +1 point, and used to develop a PAMV prognosis score. This score showed acceptable discrimination (area under the receiver operating characteristic curve of 0.695 for mortality, 95% confidence interval 0.650-0.738, p<0.001), and calibration (Hosmer-Lemeshow chi-square=6.331, with df 7 and p=0.502). The cutoff value for predicting mortality based on the maximum Youden index was ≤2 (sensitivity, 87.5%; specificity, 41.3%). For patients with PAMV scores ≤1, 2, 3 and ≥4, the 90-day mortality rates were 29.2%, 45.7%, 67.9%, and 90.9%, respectively (P<0.001). CONCLUSIONS: Our study developed a PAMV prognosis score for predicting 90-day mortality. Further research is needed to validate the utility of this score.

Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis: Comparison of Pre- and Post-Public-Private Mix Periods.

BACKGROUND: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. METHODS: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. RESULTS: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m2, previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. CONCLUSION: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

The role of allergen-specific IgE in predicting allergic symptoms on dog and cat exposure among Korean pet exhibition participants.

BACKGROUND: The values of the skin prick test (SPT) and allergen-specific IgE (sIgE) measurement in predicting dog and cat allergies remain unclear. We aimed to evaluate the usefulness of SPT and sIgE measurement in predicting self-reported allergic symptoms during exposure to dogs and cats in Korean adults. METHODS: A total of 552 participants in a pet exhibition in Korea completed questionnaires regarding exposure to dog or cat and the development of allergic symptoms during exposure. Study participants also underwent SPT using 3 different commercially available reagents, and had their blood drawn for measurement of serum total IgE and dog/cat-dander-IgE using ImmunoCAP®. RESULTS: Measurement of sIgE for dog and cat dander allergens provided the highest positive and negative predictive values and sensitivity, but not specificity (58%, 87.2%, 67.9%, and 93.1% for allergic symptoms on dog exposure; 64.7%, 83.2%, 74.8%, and 88.9% for those on cat exposure, respectively), in predicting self-reported allergic symptoms on dog and cat exposure. The sIgE level consistently exhibited the highest area under the receiver operating characteristic curve (0.749 and 0.719 for allergic symptoms on dog and cat exposure, respectively). Careful interpretation of SPT and sIgE measurements maximized the positive and negative predictive values, sensitivity, and specificity for predicting allergic symptoms on dog exposure (71.4%, 87.3%, 75.3%, and 99.3%) and those on cat exposure (71.4%, 85.3%, 79.3%, and 98.9%). CONCLUSIONS: The measurement of dog and cat dander sIgE levels may be useful for the exclusion of allergic symptoms related to pet exposure. Collective interpretation of SPT and sIgE tests facilitates identification of allergic symptoms on dog or cat exposure, giving a better rule-in test result.

Effect of Early Tracheostomy on Clinical Outcomes in Patients with Prolonged Acute Mechanical Ventilation: A Single-Center Study.

BACKGROUND: The purpose of this study was to investigate the effect of early tracheostomy on clinical outcomes in patients requiring prolonged acute mechanical ventilation (≥96 hours). METHODS: Data from 575 patients (69.4% male; median age, 68 years), hospitalized in the medical intensive care unit (ICU) of a university-affiliated tertiary care hospital March 2008-February 2017, were retrospectively evaluated. Early and late tracheostomy were designated as 2-10 days and >10 days after translaryngeal intubation, respectively. RESULTS: The 90-day cumulative mortality rate was 47.5% (n=273) and 258 patients (44.9%) underwent tracheostomy. In comparison with the late group (n=115), the early group (n=125) had lower 90-day mortality (31.2% vs. 47.8%, p=0.012), shorter stays in hospital and ICU, shorter ventilator length of stay (median, 43 vs. 54; 24 vs. 33; 23 vs. 28 days; all p<0.001), and a higher rate of transfer to secondary care hospitals with post-intensive care settings (67.2% vs. 43.5% p<0.001). Also, the total medical costs of the early group were lower during hospital stays than those of the late group (26,609 vs. 36,973 USD, p<0.001). CONCLUSION: Early tracheostomy was associated with lower 90-day mortality, shorter ventilator length of stay and shorter lengths of stays in hospital and ICU, as well as lower hospital costs than late tracheostomy.

Evaluation of Drug-Induced Liver Injury Developed During Hospitalization Using Electronic Health Record (EHR)-Based Algorithm.

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm. METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI. RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13-0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction. CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.

Prevalence and impact of comorbid laryngeal dysfunction in asthma: A systematic review and meta-analysis.

BACKGROUND: Laryngeal or vocal cord dysfunction has long been regarded as a mimic of asthma; however, recent evidence indicates that it may be a significant comorbid condition in patients with asthma. OBJECTIVE: We aimed to systematically estimate the prevalence of comorbid laryngeal dysfunction (LD) in adults with asthma and characterize its clinical impact on asthma. METHODS: Electronic databases were searched for relevant studies published until June 2019. Studies were included if LD was objectively defined by direct visualization of laryngeal movement. Outcomes included the prevalence of LD and its association with clinical asthma indicators, such as severity, control, and quality of life. Random effects meta-analyses were performed to calculate the estimates. RESULTS: A total of 21 studies involving 1637 patients were identified. Overall, the pooled prevalence of LD in adults with asthma was 25% (95% CI = 15%-37%; I2 = 96%). Prevalence estimates differed according to the diagnostic test utilized, with the lowest overall prevalence (4% [95% CI = 0%-10%; I2 = 90%]) seen when LD was diagnosed by resting laryngoscopy without external stimuli; however, it was much higher when diagnosed by laryngoscopy studies utilizing an external trigger, such as exercise (38% [95% CI = 24%-53%; I2 = 90%]) or in studies using a computed tomography-based diagnostic protocol (36% [95% CI = 24%-49%; I2 = 78%]). Only 7 studies reported the associations between LD and clinical asthma indicators; inconsistencies between studies limited meaningful conclusions. CONCLUSION: LD may be a common comorbidity in asthma, affecting about 25% of adult patients. Further prospective studies are needed to better characterize its clinical impact and the benefits of detecting and managing LD in patients with asthma.

Validation of the Prescreening Intradermal Skin Test for Predicting Hypersensitivity to Iodinated Contrast Media: A Prospective Study with ICM Challenge.

BACKGROUND: The number of hypersensitivity reactions associated with iodinated contrast media (ICM) is increasing with widespread use of radiographic contrast agents. These hypersensitivity reactions are unpredictable and sometimes lead to severe reactions such as anaphylaxis. OBJECTIVE: To investigate the value of intradermal skin test (IDT) as a clinical screening tool for prediction of a hypersensitivity reaction to ICM. METHODS: We performed IDT in the patients scheduled to receive an iodinated contrast agent between September 2015 and April 2017. After IDT, the contrast agent tested was administered intravenously, regardless of the results of skin testing, and the patients were carefully monitored. RESULTS: We recruited 2,918 patients in 2 hospitals, and 2,843 were included in the final analysis. Fifteen (0.5%) of the 2843 patients had a positive IDT result before scheduled computed tomography scan; however, none of these patients experienced a hypersensitivity reaction after the administration of a full dose of ICM. Meanwhile, 19 patients who experienced hypersensitivity reactions after ICM challenge had showed a negative IDT result. The sensitivity and the positive predictive value of IDT for ICM were both 0%. CONCLUSIONS: Routine IDT before the administration of an iodinated contrast agent does not predict hypersensitivity considering its extremely low sensitivity and a low positive predictive value.

Clinical characteristics of eperisone-induced immediate-type hypersensitivity.

BACKGROUND: Eperisone is a commonly prescribed oral muscle relaxant, but few studies have been conducted of eperisone-induced hypersensitivity reactions. OBJECTIVE: The purpose of this study was to investigate the clinical manifestations of eperisone-induced immediate-type hypersensitivity, and to evaluate the role of an intradermal test (IDT) in eperisone-induced anaphylaxis. METHODS: This study was based on a retrospective review of medical records from 23 patients diagnosed as eperisone-induced immediate-type hypersensitivity with certain or probable causality. Intradermal tests were performed with a sterile 10 mg/mL eperisone solution. RESULTS: Immediate-type hypersensitivity reactions to eperisone occurred within 15 minutes in 8.7%, within 30 minutes in 52.2%, and within 60 minutes in 82.6% of the patients, cumulatively. All patients showed cutaneous symptoms. Gastrointestinal symptoms were the second-most frequent (65.2%), respiratory symptoms (56.5%) followed, and cardiovascular symptoms were the least (39.1%). Nine (39.1%) patients were categorized as severe anaphylaxis. The mean onset time of severe anaphylaxis was 28.89 minutes, which was significantly shorter than non-severe anaphylaxis (p = 0.011). Five patients among the severe anaphylaxis group were evaluated with IDT, and all showed positive results. In contrast, all of the four patients who have done IDT among the moderate anaphylaxis group showed negative results. There was a significant relationship between severe anaphylaxis and positive IDT results (p = 0.008). CONCLUSIONS: Eperisone-induced immediate-type hypersensitivity is not uncommon in Korea, and the IDT could be a useful and safe diagnostic tool, especially in severe anaphylaxis.

Future Risks in Patients With Severe Asthma.

A major burden of severe asthma is the future risk of adverse health outcomes. Patients with severe asthma are prone to serious exacerbation and deterioration of lung function and may experience side effects of medications such as oral corticosteroids (OCSs). However, such future risk is not easily measurable in daily clinical practice. In particular, currently available tools to measure asthma control and asthma-related quality of life incompletely predict the future risk of medication-related morbidity. This is a significant issue in asthma management. This review summarizes the current evidence of future risk in patients with severe asthma. As future risk is poorly perceived by controlled asthmatics, our review focuses on the risk in patients with 'controlled' severe asthma. Of note, it is likely that long-term OCS therapy may not prevent future asthma progression, including lung function decline. In addition, the risk of drug side effects increases even during low-dose OCS therapy. Thus, novel treatments are highly desirable for reducing future risks without any loss of asthma control.

Cough-Related Laryngeal Sensations and Triggers in Adults With Chronic Cough: Symptom Profile and Impact.

PURPOSE: Recent evidence suggests that cough hypersensitivity may be a common feature of chronic cough in adults. However, the clinical relevance remains unclear. This study evaluated the cough-related symptom profile and the clinical relevance and impact of cough hypersensitivity in adults with chronic cough. METHODS: This cross-sectional multi-center study compared cough-related laryngeal sensations and cough triggers in patients with unexplained chronic cough following investigations and in unselected patients newly referred for chronic cough. A structured questionnaire was used to assess abnormal laryngeal sensations and cough triggers. Patients with unexplained cough were also evaluated using the Leicester Cough Questionnaire (LCQ) and a cough visual analogue scale (VAS), and these scores were assessed for correlations with the number of triggers and laryngeal sensations. RESULTS: This study recruited 478 patients, including 62 with unexplained chronic cough and 416 with chronic cough. Most participants reported abnormal laryngeal sensations and cough triggers. Laryngeal sensations (4.4 ± 1.5 vs. 3.9 ± 1.9; P = 0.049) and cough triggers (6.9 ± 2.6 vs. 5.0 ± 2.8; P < 0.001) were more frequent in patients with unexplained chronic cough than in those with chronic cough. The number of triggers and laryngeal sensations score significantly correlated with LCQ (r = -0.51, P < 0.001) and cough VAS score (r = 0.53, P < 0.001) in patients with unexplained chronic cough. CONCLUSIONS: Cough hypersensitivity may be a common feature in adult patients with chronic cough, especially those with unexplained chronic cough. Cough-related health status and cough severity were inversely associated with the number of triggers and laryngeal sensations, suggesting potential relevance of assessing cough hypersensitivity in chronic cough patients.

Novel Strategy for the Prevention of Recurrent Hypersensitivity Reactions to Radiocontrast Media Based on Skin Testing.

BACKGROUND: Hypersensitivity reactions to iodinated contrast media (ICM) is a persistent clinical issue with increased use of computed tomography. With the evidence indicating underlying allergic mechanisms, there have been studies regarding the skin tests using ICM. OBJECTIVE: This study aimed to evaluate the intradermal skin test (IDT) as a tool for preventing recurrent hypersensitivity reactions to ICM in patients with prior reactions to a known culprit agent. METHODS: Sixty-nine patients who had experienced immediate hypersensitivity reactions to ICM were included in the study. All patients underwent IDT with 7 different ICMs, including the causative ICM. We analyzed clinical data from 38 patients who were reexposed to ICMs, grouped by the IDT results to their original culprit ICM. RESULTS: Thirty-eight patients showed positive IDT results to the culprit ICM (CULPRIT+), whereas 31 patients showed negative results (CULPRIT-). Sixteen patients from the CULPRIT+ group and 22 from the CULPRIT- group were subsequently exposed to an ICM. In the CULPRIT+ group, 4 of the 5 patients who were subsequently exposed to an IDT-positive ICM reexperienced hypersensitivity reactions. When patients were exposed to IDT-negative ICM as an alternative, hypersensitivity reactions were not observed. In the CULPRIT- group, IDT-positive ICMs did not provoke hypersensitivity reactions whereas 2 patients using IDT-negative ICMs experienced hypersensitivity reactions. CONCLUSIONS: When the IDT results are positive for the culprit ICM, additional IDTs with other ICMs are needed to select a safe alternative. If the IDT results are negative against the culprit ICM, further IDTs might not play a role in selecting a safe alternative.

Breakthrough reactions during rapid drug desensitization: Clinical outcome and risk factors.

BACKGROUND: Severe hypersensitivity reactions (HSRs) interfere with the administration of necessary drugs for patients; drug desensitization can be a good alternative strategy. Although rapid drug desensitization (RDD) has been shown to be safe and effective, some patients still experience breakthrough reactions (BTRs) during desensitization. OBJECTIVE: We aimed to estimate clinical outcomes of RDD and to identify risk factors for BTR. METHODS: From January 2015 to December 2017, retrospective analysis was done in cancer patients with HSRs to chemotherapy and monoclonal antibody who underwent 3-bag, 12-step RDD in Asan Medical Center. RESULTS: A total of 58 patients (42 females; mean age, 54.7 ± 11.0) underwent 234 desensitization procedures. The most common underlying malignancy was gynecologic cancer (n = 26, 44.8%), and platinum-based drugs were common target drugs (135 cases of 36 patients). Twenty-six of 58 patients (44.8%) experienced 56 BTRs, whereas 178 cases (76.1%) of total desensitization did not show any reactions. Among them, 12 patients (20.7%) had moderate BTRs requiring systemic steroids, and 3 (5.1%) experienced severe BTRs requiring epinephrine administration. Logistic regression analysis revealed more severe initial HSRs (OR = 17.94, 95% CI = 1.78-181.68, P = .015), drug allergy history (OR = 7.83, 95% CI = 1.48-41.44, P = .035), and frequency of exposure to the chemotherapeutic agents (OR = 1.14, 95% CI = 1.01-1.28, P = .016) increased the risk of moderate to severe BTR. CONCLUSION: The standardized 12-step protocol for RDD was effective and safe for most patients. Severity of initial HSR, history of drug allergy, and previous high exposure to the chemotherapeutic agent showed a positive correlation with BTR above moderate grade. Studies are needed to propose an individualized protocol according to patient-specific risk assessment.

Differences in Adverse Reactions Among Iodinated Contrast Media: Analysis of the KAERS Database.

BACKGROUND: The various adverse drug reactions (ADRs) arise from different types of iodinated contrast media (ICM). OBJECTIVE: Thus, we investigated the occurrence rate and types of ADRs according to the total usage cases of the 7 most common ICM. METHODS: We retrospectively reviewed 74,242 causal ADRs caused by ICM from the Korea Adverse Event Reporting System database between January 2014 and December 2016. The 11,712,796 total usage cases that represent all administrations of ICM reported from individual medical institutions were received from the Health Insurance Review and Assessment Service. A proportionality test was used to examine the differences in the frequency ratio of causal ADRs to total usage cases. RESULTS: Immediate hypersensitivity (44,467 cases, 88.56%) occurred more frequently than delayed hypersensitivity (5,725 cases, 11.4%; P < .001). The overall occurrence rate of causal ADRs and serious ADRs considering total usage cases was 0.37% and 0.02%, respectively (P < .001). The ICM most commonly resulting in ADRs were iomeprol (0.7%) and iopromide (0.59%). The serious ADRs were most common for iomeprol (0.05%). When ADRs were classified according to the system organ class, "skin and appendages disorders" (47,065 cases, 63.4%) occurred most common. Iodixanol resulted in the highest frequency of "urinary system disorders." CONCLUSIONS: By comparison of the ADRs considering total usage cases, the incidence and classification of ADRs were different for each contrast medium. A prospective study is needed because the differences in these 7 major contrast media may assist in the selection of ICM tailored for each patient.