Background: Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. Methods: We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Results: Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). Conclusion Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

Background: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. Methods: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. Results: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. Conclusion These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

The purpose of this study was to compare the palatal dimensions (volume, width, length, and height) in different malocclusions (Class I, II, and III) in mixed dentition using a three-dimensional digital scanner. The study was performed on 30 selected casts from 1400 casts that were taken at the Department of Pediatric Dentistry at Dankook University. Casts consisted of Class I, II, and III malocclusion groups in Hellman’s dental age IIIA. The mean age was 8 years and 6 months ± 11 months. Each cast was scanned by three-dimensional digital scanner, Medit T710 (Medit, Seoul, Korea), and shaped into the three-dimensional image and calculated palatal dimensions using the Plan T program (SMD solution, Seoul, Korea). The values were statistically compared and evaluated by Kruskal-Wallis followed by the Mann-Whitney test. According to our results, subjects with Class II malocclusion showed lower palatal width and longer palatal length compared to those with Class I and Class III. For palatal height, Class III malocclusion subjects in mixed dentition exhibited a larger number than Class II and Class I. Lastly, for palatal volume, compared to other malocclusions, Class III showed higher results; however, there were no significant differences. The form of the palate differs in types of malocclusions and understanding of these differences is important in clinical significance. Based on this study, the understanding of the relationship between the shape of the palate and the skeletal pattern provides useful information about orthodontic treatment plans, early diagnosis of malocclusion, and morphological integration mechanisms. Orthopedic treatment in the maxilla should be performed during early and intermediate mixed dentition to enhance treatment efficiency.

Background: Endobronchial ultrasound‒guided transbronchial needle aspiration (EBUS-TBNA) is a standard diagnostic method for mediastinal and hilar lymphadenopathy. Although rare, fatal infectious complications can occur following EBUS-TBNA. However, to date, there is a lack of effective preventive strategies to reduce these complications. We started a trial to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. Methods: This study is a single-center, parallel-group, assessor-blinded randomized controlled trial (RCT). We will enroll 112 adult participants undergoing EBUS-TBNA using a convex probe, and randomly assign them to two groups at a 1:1 ratio. The intervention group will gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA, while the control group will have no mouthrinse before the procedure. Immediately after completion of EBUS-TBNA on all targeted lesions with an aspiration needle, a needle wash sample will be taken by instilling 5 mL of sterile saline into the used needle. The primary outcome is colony forming unit (CFU) counts in aerobic cultures of the needle wash samples. Secondary outcomes are CFU counts in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. Conclusion This trial was designed as the first RCT to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. Results from this trial can provide clinical evidence for a simple, safe, and cost-effective strategy to prevent infectious complications following EBUS-TBNA (ClinicalTrials.gov ID: NCT04718922, registered on 22 January 2021).

Background: Endobronchial ultrasound‒guided transbronchial needle aspiration (EBUS-TBNA) is a standard diagnostic method for mediastinal and hilar lymphadenopathy. Although rare, fatal infectious complications can occur following EBUS-TBNA. However, to date, there is a lack of effective preventive strategies to reduce these complications. We started a trial to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. Methods: This study is a single-center, parallel-group, assessor-blinded randomized controlled trial (RCT). We will enroll 112 adult participants undergoing EBUS-TBNA using a convex probe, and randomly assign them to two groups at a 1:1 ratio. The intervention group will gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA, while the control group will have no mouthrinse before the procedure. Immediately after completion of EBUS-TBNA on all targeted lesions with an aspiration needle, a needle wash sample will be taken by instilling 5 mL of sterile saline into the used needle. The primary outcome is colony forming unit (CFU) counts in aerobic cultures of the needle wash samples. Secondary outcomes are CFU counts in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. Conclusion This trial was designed as the first RCT to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. Results from this trial can provide clinical evidence for a simple, safe, and cost-effective strategy to prevent infectious complications following EBUS-TBNA (ClinicalTrials.gov ID: NCT04718922, registered on 22 January 2021).

BACKGROUND: For creatinine measurement, the enzymatic method is known to be more accurate than the Jaffe method; however, the latter is still widely used. We evaluated the performance of the CRE2 reagent (Siemens Healthcare Diagnostics Inc., USA), which uses a modified Jaffe method. METHODS: Three quality control standards were used for precision evaluations of CRE2 on Dimension VISTA 500 instrument (Siemens). Moreover, the linearity and carryover characteristics were assessed. Sixty-eight creatinine results obtained using the CRE2 and ECREA (enzymatic) reagents (Siemens) were compared with those obtained using the L-CRE (enzymatic) reagent (Shinyang Diagnostics, Korea). The accuracy of CRE2, ECREA, and L-CRE was evaluated using a standard reference material. RESULTS: The CV of within-run (0.7–2.4%), between-run (0.4–1.7%), between-day precision (0.7–0.9%) for three standards, and total CV for medium (1.6%) and high levels (1.3%) satisfied the analytical goal. The linearity for CRE2 was excellent (R2=0.999). Comparisons of CRE2 and ECREA to L-CRE were well correlated (r=0.996 and 0.997, respectively). In comparison with L-CRE, 5 CRE2 results and 15 ECREA results exceeded minimum bias goal (5.1%) in samples with creatinine levels of >1 mg/dL. The carryover rate was −0.04%. In terms of accuracy, the percent bias values of CRE2, ECREA, and L-CRE were 7.4, −6.4, and −3.4, respectively, for low level; and 3.9, −1.5, and 0.7, respectively, for high level. CONCLUSIONS: For creatinine measurements, the CRE2 reagent showed good performance. It can be used in the diagnosis, treatment monitoring, and risk assessment of kidney diseases.
Bias (Epidemiology) ; Creatinine* ; Delivery of Health Care ; Diagnosis ; Indicators and Reagents ; Kidney Diseases ; Methods ; Quality Control ; Risk Assessment

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.
Acute Lung Injury ; Berlin ; Biopsy* ; Humans ; Korea ; Lung Diseases, Interstitial ; Lung* ; Mortality ; Pathology ; Population Characteristics* ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

BACKGROUND: Tumor-infiltrating lymphocytes, which form a part of the host immune system, affect the development and progression of cancer. This study investigated whether subsets of lymphocytes reflecting host-tumor immunologic interactions are related to the prognosis of patients with acute myeloid leukemia (AML). METHODS: Lymphocyte subsets in the peripheral blood of 88 patients who were newly diagnosed with AML were analyzed by quantitative flow cytometry. The relationships of lymphocyte subsets with AML subtypes, genetic risk, and clinical courses were analyzed. RESULTS: The percentages of T and NK cells differed between patients with acute promyelocytic leukemia (APL) and those with AML with myelodysplasia-related changes. In non-APL, a high proportion of NK cells (>16.6%) was associated with a higher rate of death before remission (P=0.0438), whereas a low proportion of NK cells (≤9.4%) was associated with higher rates of adverse genetic abnormalities (P=0.0244) and relapse (P=0.0567). A multivariate analysis showed that the lymphocyte subsets were not independent predictors of survival. CONCLUSION: Lymphocyte subsets at diagnosis differ between patients with different specific subtypes of AML. A low proportion of NK cells is associated with adverse genetic abnormalities, whereas a high proportion is related to death before remission. However, the proportion of NK cells may not show independent correlations with survival.
Diagnosis ; Flow Cytometry ; Humans ; Immune System ; Killer Cells, Natural ; Leukemia, Myeloid, Acute* ; Leukemia, Promyelocytic, Acute ; Lymphocyte Subsets* ; Lymphocytes* ; Lymphocytes, Tumor-Infiltrating ; Multivariate Analysis ; Prognosis ; Recurrence

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology. OBJECTIVE: The aim of this study was to evaluate the genetic basis of TPMT polymorphism in Korean dermatologic patients and subsequently to investigate the relationship between mutant TPMT and adverse responses to AZA treatment. METHODS: This study was retrospective, single-center study. One hundred forty-nine Korean dermatologic patients who underwent TPMT screening test were included. Each patient's medical records, the result of TPMT screening test, dose and treatment period of AZA, and side effects, were reviewed. Laboratory tests were assessed at each visit in order to monitor adverse drug reactions. Leukopenia grading was used in accordance with the common terminology criteria for adverse events (CTCAE) ver. 4.03. RESULTS: Behçet's disease was the leading disorder among the patients. The frequency of TPMT mutation was 4.0% (6/149) among the participants in this study. Four of the six patients with genetic alterations were treated with a low-dose AZA regimen, but no AZA-related adverse events were observed. CONCLUSION: Our results suggest that 1) TPMT polymorphisms in Korean dermatologic patients are similar to those previously reported in Asian patients with the most common mutant allele being TPMT*3C and 2) AZA can be used in the patients with these polymorphisms under a careful dosing regimen.
6-Mercaptopurine ; Alleles ; Asian Continental Ancestry Group ; Azathioprine ; Behcet Syndrome ; Dermatology ; Drug-Related Side Effects and Adverse Reactions ; Genotype ; Humans ; Korea ; Leukopenia ; Mass Screening ; Medical Records ; Metabolism ; Retrospective Studies ; Thioguanine