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Background: HLA‐B*58:01 is a well‐known risk factor for allopurinol‐induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA‐B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol‐induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA‐B*58:01. Methods: Subjects with B*58:01 were enrolled (21 allopurinol‐induced DRESS and 52 allopurinol‐tolerant control). HLA‐A, ‐B, ‐C and ‐DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol‐induced SCAR in separate populations was performed to support the results. Kruskal‐Wallis test, Pearson's chi‐square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development. Results: Frequencies of A*24:02 (71.4 vs. 17.3%, p < 0.001, odds ratio [OR] = 12.0; 95% confidence interval [CI], 3.6–39.2) were significantly higher in B*58:01 (+) DRESS than B*58:01 (+) tolerant controls. In addition, DRB1*13:02 further increased the risk of DRESS. The phenotype frequency of A*24:02/DRB1*13:02 was significantly higher in the B*58:01 (+) DRESS group than in the B*58:01 (+) tolerant controls (52.4% vs. 5.8%, p < 0.001, OR, 66.0; 95% CI, 6.1–716.2). In 2782 allopurinol user cohort, the overall prevalence of DRESS was 0.22%, which increased to 1.62% and 2.86% in the presence of B*58:01 and B*58:01/A*24:02, respectively. Conclusion: The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol‐induced DRESS in B*58:01 carriers. [ABSTRACT FROM AUTHOR]

Cell migration during specialized stages of osteoclast precursors, mononuclear preosteoclasts, and multinucleated mature osteoclasts remain uncertain. M-CSF- and osteopontin-induced osteoclastic cell migration was inhibited by function-blocking monoclonal antibodies specific to the integrin αv and β3 subunits, suggesting that integrin αvβ3 mediates migratory signaling induced by M-CSF and osteopontin. M-CSF and osteopontin stimulation was shown to regulate two branched signaling processes, PI3K/PKCα/RhoA axis and PI3K/PKCδ/Rac1 axis. Interestingly, inactivation of RhoA or Rac1 blocked preosteoclast and mature osteoclast migration but not osteoclast precursor migration in a transwell-based cell migration assay. Moreover, the inhibitory effect on preosteoclast and mature osteoclast migration induced by Rac1 inactivation was more effective than that by RhoA inactivation. Collectively, our findings suggest that osteoclast precursor migration depends on PI3K/PKCα-PKCδ signaling mediated via integrin αvβ3 bypassing RhoA and Rac1, whereas preosteoclast and mature osteoclast migration relies on PI3K/PKCα-PKCδ/RhoA-Rac1 axis signaling mediated via integrin αvβ3 with increased dependency on PKCδ/Rac1 signaling route as differentiation progresses. [ABSTRACT FROM AUTHOR]

Purpose: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. Methods: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. Results: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. Conclusions: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs. [ABSTRACT FROM AUTHOR]

Background: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. Objective: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. Methods: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. Results: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37–0.79] and 1.88 [1.28–2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09–2.98]). Conclusion: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response. [ABSTRACT FROM AUTHOR]

Purpose: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. Methods: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). Results: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. Conclusions: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes. [ABSTRACT FROM AUTHOR]

Determination of modifiable factors associated with changes in health perception can be beneficial for improvement in health perception and health-related quality of life. The purpose of this study was to examine if changes in physical symptoms, functional status, and depressive symptoms were associated with changes in health perception at three months and the mediator effect of physical symptoms. Data were collected at baseline and three months later (N = 65). Process Macro for SPSS was used to analyze the data. Only changes in depressive symptoms (p <.001) were associated with changes in physical symptoms. Then, only changes in physical symptoms (p =.026) were significantly associated with changes in health perception. Changes in physical symptoms played significant roles in changes in health perception directly and also through the mediator role. Clinicians and researchers need to assess and manage these two modifiable factors to improve health perception in this population. [ABSTRACT FROM AUTHOR]

Mollusks have served as important sources of human food and medicine for a long time. Raw Pisidium coreanum, a freshwater bivalve of the phylum Mollusca, is used in traditional therapies in parts of Asia. However, the therapeutic effects of Pisidium coreanum on bone diseases are not known. We investigated the functional roles of Pisidium coreanum in osteoporotic bone diseases. Pisidium coreanum inhibited the differentiation of bone marrow-derived monocytic cells into mature osteoclasts in vitro. The ovariectomized mice that received oral administration of Pisidium coreanum showed improvements in both trabecular and cortical bones. This preventive activity of Pisidium coreanum against bone loss was due to limited osteoclast maturation with reduced osteoclast surface extent in trabecular bone tissue. The formation of large multinucleated osteoclasts in vitro was significantly decreased in response to Pisidium coreanum, consistent with the reduced expression levels of osteoclast markers and fusion-related genes, such as NFATc1, p65, integrinαvβ3, DC-STAMP, OC-STAMP, Atp6v0d2, FAK, CD44, and MFR. These data suggest that Pisidium coreanum inhibits osteoclast differentiation by negatively regulating the fusion of mononuclear osteoclast precursors. Thus, our data demonstrate the ability of Pisidium coreanum to effectively prevent estrogen-deficient osteoporosis through inhibition of multinucleated osteoclast formation. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the outcomes of re-exposure to low-osmolar iodinated contrast medium (LOCM) in patients with a history of moderate-to-severe hypersensitivity reaction (HSR).Methods: We retrospectively evaluated a cohort comprising all subjects satisfying the following conditions at 11 centres: (1) experienced a moderate-to-severe HSR to LOCM by December 2014, and (2) underwent contrast-enhanced computed tomography after the initial HSR between January 2014 and December 2014.Results: A total of 150 patients with 328 instances of re-exposure were included; the recurrence rate of HSR was 19.5%. Patients with severe initial HSR exhibited a higher recurrence rate of severe HSR compared to patients with moderate initial HSR, despite more intensive premedication. In the multivariate analysis, the independent risk factors for recurrence of HSR were diabetes, chronic urticaria, drug allergy other than to iodinated contrast media (ICM) and severe initial HSR. The risk of recurrent HSR was 67.1% lower in cases where the implicated ICM was changed to another one (odds ratio: 0.329; P = 0.001). However, steroid premedication did not show protective effects against recurrent HSR.Conclusion: In high-risk patients who have previously experienced a moderate-to-severe initial HSR to LOCM, we should consider changing the implicated ICM to reduce recurrence risk.Key Points: • In patients with moderate-to-severe HSR, steroid premedication only shows limited effectiveness. • Changing the implicated ICM can reduce the recurrence of HSR to ICM. • Diabetes, chronic urticaria and drug allergies increase the risk of ICM HSR. [ABSTRACT FROM AUTHOR]

BackgroundThe aim of this study was to evaluate the diagnostic accuracy of the GenoType MTBDRplusassay in detecting drug-resistant tuberculosis (DR-TB) by using acid-fast bacilli (AFB) smear-negative specimens with positive TB-PCR results.MethodsThe MTBDRplusassay was performed with 2 different categories of 117 samples, including AFB smear-positive specimens (n = 53) and AFB smear-negative specimens (n = 64), which exhibited positive TB-PCR results, at a single institution. The results were retrospectively compared with the results of the phenotypic drug susceptibility test (DST), for reference.ResultsA total of 105 tests were finally analyzed. Of these, 54 tests were conducted using AFB smear-negative specimens with positive TB-PCR results. The MTBDRplusassay for these 54 samples demonstrated a sensitivity of 100%, specificity of 98%, positive predictive value (PPV) of 75%, and negative predictive value (NPV) of 100% in detecting rifampicin resistance. With these same species, the sensitivity, specificity, PPV, and NPV values for the MTBDRplusassay were 83.3%, 97.9%, 83.3%, and 97.9%, respectively, for the detection of isoniazid resistance. The overall correlation between the MTBDRplusassay and phenotypic DST demonstrated excellent agreement for detection of rifampicin resistance (κ = 0.847) and for detection of INH resistance (κ = 0.812), respectively.ConclusionsThe MTBDRplusassay can be used effectively even on AFB smear-negative specimens from TB patients, when the TB-PCR is positive. This result might help clinicians to manage patients with suspected DR-TB in difficult situations. [ABSTRACT FROM AUTHOR]

Background and objective It remains difficult to differentiate between chronic obstructive pulmonary disease ( COPD) and asthma in clinical practice, especially in a primary care setting. The purpose of this study was to develop a new scoring system for differentiating between COPD and asthma, and to evaluate its effectiveness. Methods First, to identify important variables differentiating COPD from asthma, the data of 197 patients with COPD and 138 patients with asthma were assessed retrospectively. Secondly, a scoring system that was based on these variables was then developed, and its performance was internally validated using a bootstrapping-based method. Thirdly, the scoring system was externally validated using prospectively collected data from patients with COPD ( n = 104) or asthma ( n = 96). Results The final scoring system was composed of the four variables: age of onset of breathlessness (<40 years, 0 points; 40-60 years, 2 points; >60 years, 4 points), continuous breathlessness (no, 0 points; yes, 1 point), diurnal variation of breathlessness (yes, 0 points; no, 1 point) and emphysematous change in chest X-ray (no, 0 points; yes, 1 point). The patients were classified by their total score into three categories: 0-2 points, probable asthma; 3-4 points, difficult-to-differentiate; 5-7 points, probable COPD. The new scoring system performed well in the external validation dataset (area under the curve, 0.86; 95% confidence interval: 0.813-0.911; P < 0.001). Conclusions The new scoring system that was developed in this study may be a useful tool for differentiating between COPD and asthma in primary care. [ABSTRACT FROM AUTHOR]