Acute Eosinophilic Pneumonia after Combined Use of Conventional and Heat-Not-Burn Cigarettes: A Case Report.

Background: Acute eosinophilic pneumonia (AEP) is a rare acute respiratory disease accompanied by fever, shortness of breath, and cough. Although the pathogenesis of the disease is not yet established, the patient's condition improves with a rapid therapeutic response to systemic corticosteroids. Conventional cigarettes or heat-not-burn cigarettes are the most common cause of AEP among young people. Case Presentation: A 22-year-old woman with dyspnea, cough, and fever did not improve after visiting the local medical center and was admitted to the emergency room. The patient denied having any recent travel history or insect bites. She was treated with appropriate antibiotics according to the community acquired pneumonia, but there was no improvement. Chest radiography showed bilateral patches of pulmonary infiltration, and chest computed tomography revealed bilateral multifocal patchy consolidations with multiple small nodular ground-glass opacities and interlobular septal thickening. The bronchoalveolar lavage result was dominantly eosinophilic. The patient's condition improved rapidly after the use of intravenous methylprednisolone and then a change to oral methylprednisolone. Finally, the patient was hospitalized for 9 days, and the duration of use of methylprednisolone including outpatient visits was 14 days. Results: The early treatment of AEP yields a good prognosis, but since the symptoms of AEP are similar to those of infectious diseases such as community-acquired pneumonia, physicians should be meticulous in differentiating AEP from other diseases. Conclusions: Since AEP shows a good response to steroids, early detection using an appropriate diagnostic method is recommended. In addition, there should be strong education against smoking in any form.

Additional Drug Resistance in Patients with Multidrug-resistant Tuberculosis in Korea: a Multicenter Study from 2010 to 2019.

BACKGROUND: Drug-resistance surveillance (DRS) data provide key information for building an effective treatment regimen in patients with multidrug-resistant tuberculosis (MDR-TB). This study was conducted to investigate the patterns and trends of additional drug resistance in MDR-TB patients in South Korea. METHODS: Phenotypic drug susceptibility test (DST) results of MDR-TB patients collected from seven hospitals in South Korea from 2010 to 2019 were retrospectively analyzed. RESULTS: In total, 633 patients with MDR-TB were included in the analysis. Of all patients, 361 (57.0%) were new patients. All patients had additional resistance to a median of three anti-TB drugs. The resistance rates of any fluoroquinolone (FQ), linezolid, and cycloserine were 26.2%, 0.0%, and 6.3%, respectively. The proportions of new patients and resistance rates of most anti-TB drugs did not decrease during the study period. The number of additional resistant drugs was significantly higher in FQ-resistant MDR-TB than in FQ-susceptible MDR-TB (median of 9.0 vs. 2.0). Among 26 patients with results of minimum inhibitory concentrations for bedaquiline (BDQ) and delamanid (DLM), one (3.8%) and three (11.5%) patients were considered resistant to BDQ and DLM with interim critical concentrations, respectively. Based on the DST results, 72.4% and 24.8% of patients were eligible for the World Health Organization's longer and shorter MDR-TB treatment regimen, respectively. CONCLUSION: The proportions of new patients and rates of additional drug resistance in patients with MDR-TB were high and remain stable in South Korea. A nationwide analysis of DRS data is required to provide effective treatment for MDR-TB patients in South Korea.

Prognostic value of serial neutrophil-to-lymphocyte ratio measurements in hospitalized community-acquired pneumonia.

INTRODUCTION: Several serum inflammatory markers are associated with poor clinical outcomes in community-acquired pneumonia (CAP). However, the prognosis and early treatment response in hospitalized CAP patients based on serial neutrophil-to-lymphocyte ratio (NLR) measurement has never been investigated. METHODS: We performed a retrospective observational study for 175 consecutive patients hospitalized with CAP between February 2016 and February 2018. NLR, C-reactive protein (CRP) and procalcitonin levels were measured on admission day (D1) and on hospital day 4 (D4). The Pneumonia Severity Index (PSI) was also assessed on admission. The primary endpoint was all-cause death within 30 days after admission. The secondary endpoint was early treatment response such as intensive care unit (ICU) admission during hospitalization and clinical unstability on day 4. RESULTS: The 30-day mortality rate was 9.7%. In multivariate analysis, NLR D4 (OR: 1.11; 95% CI: 1.04-1.18; P = 0.003) and its incremental change (NLR D4/D1 >1) (OR: 7.10; 95% CI: 2.19-23.06; P = 0.001) were significant predictors of 30-day mortality. NLR D4 and its incremental change were significant predictors of ICU admission and clinical unstability on day 4 in multivariate analyses. Adding of incremental NLR change significantly improved the prognostic ability of the PSI. The additive value of incremental NLR change for the prognostic ability of the PSI was larger than that of incremental CRP change. CONCLUSION: Serial NLR measurement represents useful laboratory tool to predict the prognosis and early treatment response of hospitalized CAP patients.

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion.

BACKGROUND: Intrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase. METHODS: We retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month. RESULTS: Forty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success. CONCLUSION: Half dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.

Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with non-small cell lung cancer.

BACKGROUND: Somatic mutations of the gene encoding epidermal growth factor receptor (EGFR) are detected in approximately 30%-50% of patients with non-small cell lung cancers (NSCLC), so detection of EGFR mutation is the pivotal step of treatment in patients with advanced NSCLC. However, difficulty in obtaining sufficient tissue and bias from the heterogeneity of the tumor samples are the major obstacles. Although analyzing EGFR with circulating tumor DNA (ctDNA) in plasma is a breakthrough, accuracy is the problem in variable methods. Peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis (PANAMutyper®) is a novel and highly sensitive method of detecting EGFR mutation in tumor tissues. AIMS AND OBJECTIVES: This study was designed to evaluate PANAMutyper® for detecting EGFR mutation with ctDNA of patients with lung cancer. MATERIALS AND METHODS: EGFR mutation status detected by PNA clamp with tissue samples and by PANAMutyper® with ctDNA was compared. Tissue biopsy was done in 158 patients with lung tumor, in which 23 cases were excluded and 135 cases were enrolled. EGFR mutation rate was 23.0% (31/135) in overall patients. All the plasma samples of the cases with mutant EGFR in tissue samples were verified by an already known highly sensitive method of droplet digital polymerase chain reaction (ddPCR). RESULTS: The concordance rate of tissue and plasma samples was 91.9% (124/135). The sensitivity, specificity, negative predictive value, and positive predictive value were 64.5%, 100%, 90.4%, and 100%, respectively, according to the tissue samples as a standard. PANAMutyper® method was not inferior to ddPCR for the detection of EGFR mutation including T790M with ctDNA. These results suggest that the detection of EGFR mutation status using ctDNA in plasma by PANAMutyper® is a feasible test prior to tissue biopsy.

Is Severe and Long-lasting Linezolid-induced Optic Neuropathy Reversible?

Linezolid is a useful drug for treating drug-resistant tuberculosis. However, the associated toxicities, especially optic neuritis, are a major obstacle for its long-term use. We recently experienced a case of severe optic and peripheral neuropathy during the treatment of multidrug-resistant tuberculosis. The treatment continued for 12 months despite severe optic and peripheral neuropathy. At eight months after the discontinuation of the drug, the optic neuropathy recovered, but the peripheral neuropathy did not. Considering the grave prognosis of drug-resistant tuberculosis, the continuation of linezolid despite neurotoxicity under close observation may be a suitable option.

Current Status of Fluoroquinolone Use for Treatment of Tuberculosis in a Tertiary Care Hospital in Korea.

BACKGROUND: Fluoroquinolones are considered important substitutes for the treatment of tuberculosis. This study investigates the current status of fluoroquinolone for the treatment of tuberculosis. METHODS: In 2009, a retrospective analysis was performed at one tertiary referral center for 953 patients diagnosed with tuberculosis. RESULTS: A total of 226 patients (23.6%), who received fluoroquinolone at any time during treatment for tuberculosis, were enrolled in this study. The most common reasons for fluoroquinolone use were adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance (23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the most commonly administered fluoroquinolone, followed by levofloxacin (36.3%, 82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The most common fluoroquinolone-related adverse events were gastrointestinal problems (3.5%, 8/226). There were no significant differences in the treatment success rate between the fluoroquinolone and fluoroquinolone-naïve groups (78.3% vs. 78.4%, respectively). CONCLUSION: At our institution, fluoroquinolones are commonly used for the treatment of both multidrug-resistant tuberculosis and susceptible tuberculosis, especially as a substitute for adverse event-related drugs. Considering the low adverse event rates and the comparable treatment success rates, fluoroquinolones seem to be an invaluable drug for the treatment of tuberculosis.

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design.

Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea.

Rheumatoid arthritis-associated interstitial lung disease: radiologic identification of usual interstitial pneumonia pattern.

PURPOSE: To determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). MATERIALS AND METHODS: All patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a κ score. RESULTS: The histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (κ = 0.67, P < .0001). CONCLUSION: Definite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.

Current levels of conflict of interest disclosure in medical publications from Korea.

Medical research should be fully transparent. The aims of this study were to determine the prevalence of author-related conflict of interest (COI) policies and evaluate the actual state of COI disclosure in Korean medical journals. To determine the prevalence of author-related COI policies, we examined the 198 medical journals listed in the KoreaMed database. To investigate the actual state of COI disclosures in published papers, we analyzed the publications in a representative medical journal, the Journal of the Korean Medical Science, from the perspective of the relevance of the ethics of COI disclosure. A total of 164 (82.8%) journals required an author's statement of COI as a criterion for publication. Of these 164, most of them focused on financial COI, with 101 (61.6%) presenting the information related to COI disclosures as a separate paragraph with a clear title. We identified 114 articles published by the Journal of the Korean Medical Science over a seven-year period, from January, 2006 to December, 2012. Of these, 65 papers (57%) included an author's statement of COI. We found that the policies of Korean medical journals regarding the disclosure of author COIs are still behind the internationally suggested level.

Clinical significance of serum autoantibodies in idiopathic interstitial pneumonia.

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

Disseminated Mycobacterium intracellulare Infection in an Immunocompetent Host.

Disseminated Mycobacterium avium complex (MAC) infection can occur in immunocompromised patients, and rarely in immunocompetent subjects. Due to the extensive distribution of the disease, clinical presentation of disseminated MAC may mimic malignancies, and thorough examinations are required in order to make accurate diagnosis. We report a case of disseminated Mycobacterium intracellulare disease in an immunocompetent patient, which involved the lung, lymph nodes, spleen, and multiple bones. F-18 fluorodeoxyglucose positron-emission tomography imaging showed multiple hypermetabolic lesions, which are suggestive of typical hematogenous metastasis. However, there was no evidence of malignancy in serial biopsies, and M. intracellulare was repeatedly cultured from respiratory specimens and bones. Herein, we should know that disseminated infection can occur in the immunocompetent subjects, and it can mimic malignancies.