Summary
Background
A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first‐line treatment for tuberculosis. However, this regimen can occasionally ...result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug‐induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown.
Objectives
To investigate drug‐specific T‐cell responses in patients with antituberculosis drug (ATD)‐induced cutaneous hypersensitivity and its underlying mechanism.
Methods
We enrolled eight patients with ATD‐induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug‐specific T‐cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug‐specific proliferative responses and counted the drug‐specific interferon (IFN)‐γ/granzyme B‐producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigen‐restricted T‐cell responses.
Results
Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin‐specific T cells from patients, which consisted primarily of CD4+ T cells. Drug‐specific CD4+ T cells proliferated and secreted IFN‐γ/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid‐responsive T‐cell clones did not proliferate in the presence of rifampicin and vice versa. Drug‐specific T‐cell responses were blocked in the presence of anti‐HLA class II antibodies.
Conclusions
This study identifies the presence of isoniazid/rifampicin‐specific T cells in patients with ATD‐induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug‐specific T‐cell immune responses in the pathogenesis of these reactions.
What's already known about this topic?
Antituberculosis drug (ATD) treatment often induces severe adverse drug reactions including hepatotoxicity, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and maculopapular exanthema.
What does this study add?
This study identified an isoniazid/rifampicin‐specific T‐cell response in patients with ATD‐induced maculopapular exanthema and DRESS.
This study describes the nature of isoniazid/rifampicin‐specific CD4+ T cells and the mechanism of drug‐specific T‐cell activation in ATD‐induced maculopapular exanthema and DRESS syndrome.
What is the translational message?
As the first‐line treatment for tuberculosis is a combination regimen, the culprit drug is frequently not identified.
A lymphocyte transformation test for ATDs would be beneficial to assess the risk of drug hypersensitivity reaction.
Linked Comment: Pavlos et al. Br J Dermatol 2017; 176:292–293.
Objective
To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature.
Design
A multicentre, randomised, open‐label, ...equivalence trial and a meta‐analysis.
Setting
Tertiary referral hospitals in South Korea.
Population
Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm).
Methods
Eligible women were screened and randomised at 16‒22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α‐hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237).
Main outcome measure
Preterm birth (PTB) before 37 weeks of gestation.
Results
A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention‐to‐treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI −7.6 to 13.8%), which was within the equivalence margin of 15%. The meta‐analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments.
Conclusion
Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
Tweetable
Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.
Transparent flexible thin‐film transistors (see Figure) have been made using single‐walled carbon nanotube networks of high and moderate coverages as the conducting and semiconducting layers. ...Electrical (e.g., good performance on plastic), optical (e.g. transparency to visible wavelengths), and mechanical (e.g. extreme flexibility) characteristics that would be difficult, or impossible, to achieve with conventional materials are reported.
Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including ...prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.
Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).
The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.
These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.
Summary
Background. Chronic urticaria (CU) is a common skin disorder that affects the well‐being and quality of life (QOL) of patients. Recently, we developed and validated a questionnaire for ...measuring QOL in Korean patients with CU, called the Chronic Urticaria‐Specific Quality of Life (CU‐QOL) questionnaire.
Aim. To evaluate the clinical significance of a computerized version of the CU‐QOL, in adult patients with CU.
Methods. This was a cross‐sectional observational study that enrolled 249 Korean patients with CU from five university hospitals and measured computerized CU‐QOL scores and Urticaria Activity Score (UAS) simultaneously. The internal consistency of the computerized CU‐QOL was analysed using Cronbach α. To identify clinical correlations between the CU‐QOL and patient characteristics, the atopic status and serum autoantibodies, including antinuclear, antithyroglobulin and antimicrosome antibodies, were measured. Multiple linear regression models were used to identify CU‐QOL predictors.
Results. Cronbach α was 0.94 for the overall computerized CU‐QOL score. The CU‐QOL scores correlated significantly with the UAS (r = −0.49, P < 0.001). Of the factors aggravating CU, delayed pressure, sunlight exposure and emotional stress significantly influenced the overall CU‐QOL scores in the univariate analysis. Multivariate regression models indicated that UAS and emotional stress were significant predictors of the four domains and of the total CU‐QOL scores.
Conclusions. The computerized CU‐QOL is a convenient and valid tool for measuring QOL in patients with CU. This study suggests that UAS, dermatographism and emotional stress are strong CU‐QOL predictors in Korean patients with CU.
Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study ...was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events.
We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea.
Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher RR 1.612, 95% CI, 1.065-2.440,
=0.024. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant RR 1.003, 95% CI, 1.001-1.005,
=0.006.
Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high.
Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N-methyltransferase (HNMT). To investigate the functional variability of HNMT gene in relation ...to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU). Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3'-untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'-UTR reporter construct to examine mRNA stability and fluorescence-tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'-UTR construct and in the patients' red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined. The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils. The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.
To evaluate the vascular response at 9 months after zotarolimus-eluting stent (ZES; Endeavor) implantation using optical coherence tomography (OCT). These findings were compared with those after ...implantation of a sirolimus-eluting stent (SES; Cypher Select).
Cross-sectional observational study with prospective OCT registry.
Nine months after ZES or SES implantation.
A total of 68 patients (32 ZES and 36 SES) underwent OCT at 9 months after stent implantation. The neointima hyperplasia (NIH) thickness inside each strut and percentage of NIH area at every 1 mm cross section were measured.
The degree of neointimal coverage and the prevalence of malapposition at 9 months after ZES and SES implantation using OCT.
The mean (SD) NIH thickness (251.2 (110.0) mum vs 85.5 (53.3) mum, p<0.001) and percentage of NIH area (27.9 (9.1)% vs 11.2 (7.1)%, p<0.001) were significantly greater in ZES than in SES. The prevalence of uncovered strut as well as malapposed strut was significantly lower in ZES than in SES (0.3% vs 12.3%, p<0.001 and 0.08% vs 2.6%, p<0.001). Thrombus was not observed in ZES (0.0% in ZES vs 27.8% in SES, p = 0.001).
Neointimal coverage in ZES was almost complete and malapposition was very rare at 9-months' follow-up.
The use of antibiotics is based on the clinician's experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease ...(AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.
We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.
A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (
=0.010 and
=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification odds ratios =1.744; 95% confidence interval, 1.107-2.749;
=0.017 and bacterial-viral pathogen co-identification odds ratios=2.075; 95% confidence interval, 1.081-3.984;
=0.028 were higher in the group with eosinophil count less than 2%.
In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.
Summary
Background
Increased vessel number and permeability are important features of the nasal mucosa in allergic rhinitis (AR), and are mediated in part by the cytokine vascular endothelial growth ...factor (VEGF). Eosinophils are the major effector cells in the nasal secretions of patients with AR during the responses to allergen challenges. To evaluate the involvement of VEGF in nasal allergic inflammation, we monitored the levels of VEGF, eosinophil cationic protein (ECP), and specific antibodies in the nasal lavage fluids (NLFs) of patients with AR in response to Dermatophagoides pteronyssinus (Dpt).
Methods
Sixty‐three subjects with sensitization to Dpt were enrolled: 29 patients with AR (group I) who showed positive responses in a nasal provocation test (NPT) with Dpt; and 34 asymptomatic controls (group II) who showed sensitization to Dpt but negative NPT results. NLF samples were collected at baseline, 10, 30, and 60 min, and at 3, 6, and 24 h during the NPT. The ECP levels in the NLF samples were measured using the ImmunoCAP system. VEGF and Dpt‐specific IgE, IgA, and IgG in the NLF samples were detected by ELISA.
Results
The eosinophil counts and ECP levels in the samples were significantly increased in group I, but not in group II, during the early and late responses. Although the baseline VEGF level was not significantly different between groups I and II, increased VEGF production was noted in group I after the NPT, especially during the early response. The level of Dpt‐specific IgA was significantly increased in group I during the NPT. A relationship was found between the levels of VEGF and ECP or Dpt‐specific IgA in the NLF samples collected at 10 min and at 3–6 h (P<0.05, respectively).
Conclusion
Nasal VEGF secretion in response to allergen exposure may augment eosinophilic inflammation in the nasal mucosa of patients with AR.
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