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Air embolism is a rare, fatal complication of computed tomography (CT)‐guided transthoracic needle biopsy (TTNB) of the lung. Here, we report a patient who developed an air embolism after CT‐guided TTNB, which led to ST‐elevation myocardial infarction and acute cerebral ischemia. The patient recovered completely without critical sequelae and was diagnosed with adenocarcinoma harboring activating epidermal growth factor receptor (EGFR) mutation. The patient responded to subsequent treatment with gefitinib. Key points Signficant findings of the study Air embolism is a rare, fatal complication of CT‐guided transthoracic lung biopsy. Only a few cases have been previously reported where myocardial and cerebral infarction occurred after TTNB, demonstrated not only on CT scan, but also electrocardiogram and electroencephalogram. What this study adds Detection of driver gene mutation is crucial for planning lung cancer treatment. Despite the need for tissue biopsy, air embolism propagation to vital organs could result in severe end‐organ damage and multidisciplinary approaches are needed to improve initial outcomes., Systemic air embolism developed after CT‐guided TTNB, leading to ST‐elevation, myocardial infarction and acute ischemic stroke. The patient recovered completely without sequelae and was diagnosed with adenocarcinoma harboring activating EGFR mutation. Treatment with gefitinib showed a response.

Background The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. Case presentation A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. Conclusions Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

BackgroundDendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.MethodsThe study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.ResultsCirculating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.ConclusionsThis study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

Purpose Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. Methods ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. Results Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. Conclusion Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.

Background/aims Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment. Methods We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014. Results Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs. Conclusion Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.

BACKGROUND In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re-biopsy specimens included small biopsy, surgical tissue, or liquid-based cytology. EGFR mutation was tested using peptide nucleic acid-mediated clamping PCR. RESULTS Of the 230 NSCLC patients that experienced progression after EGFR-TKI therapy, 105 (45.7%) underwent re-biopsy. Re-biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re-biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re-biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR-TKIs (P

Rationale: Current guidelines for advanced non-small cell lung cancer (NSCLC) recommend the use of targeted agents for specific driver genes after confirming genetic alterations. Although epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are usually mutually exclusive, EGFR and ALK co-alterations have been reported increasingly in cases of NSCLC. However, the optimal treatment for these cases has not been established. Patient concerns: This case series describes three patients diagnosed with advanced non-squamous NSCLC who harbored EGFR and ALK co-alterations. The complaints for each case are as follows: 57-year-old woman with coughing and dyspnea in case 1, 32-year-old man with diplopia in case 2 and 77-year-old woman with chest discomfort in case 3. Diagnoses: Three never-smokers were diagnosed pathologically with stage IV adenocarcinoma of the lung. Subsequent molecular studies revealed the EGFR L858R mutation gene and ALK rearrangement, which were proven by real-time polymerase chain reaction and fluorescence in situ hybridization, respectively. Interventions: All 3 patients received first-line therapy with EGFR-tyrosine kinase inhibitors (TKIs). Cases 1 and 2 were treated with ALK-TKIs as second-line therapy and received additional EGFR-TKIs as third- and fourth-line regimens. Outcomes: The patients achieved partial responses to EGFR-TKIs according to radiologic findings. However, second-line ALK-TKI therapy was ineffective in cases 1 and 2. Lessons: Cases of NSCLC with concomitant EGFR mutation and ALK rearrangement are rare, and the selection of an optimal targeted therapy is challenging. Here, EGFR-TKI appeared to yield better outcomes than ALK-TKI in patients with NSCLC who harbored EGFR/ALK co-alterations.

Objective This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. Methods We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). Results Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2–73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0–3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). Conclusions Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

Rational Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis. Patient concerns An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred. Diagnoses The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding. Intervention Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered. Outcomes The plasma fibrinogen level normalized and bleeding signs did not recur. Lessons It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected.

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign neoplasm that predominantly affects middle‐aged Asian women. PSP is often asymptomatic and demonstrates a solitary pulmonary nodule on radiologic examination. We report a case of PSP initially misdiagnosed as lung cancer because of strong 18F‐fluorodeoxyglucose (FDG) uptake revealed by 18F‐FDG positron emission tomography‐computed tomography scan. After surgery, pathology revealed that the tumor cells were immunopositive for epithelial membrane antigen and thyroid transcription factor‐1. The patient has been followed up without complication or recurrence.

Rationale Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza. Patient concerns A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia. Diagnoses Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected. Intervention He received peramivir plus oseltamivir and broad-spectrum antibiotics. Outcomes The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission. Lessons We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A>G), which has never been reported. The patient was treated with afatinib for more than four months. She showed rapid radiologic response within a month, and maintained stable state until the last dose of afatinib., Graphical Abstract

Background: For patients requiring prolonged mechanical ventilation (PMV), weaning is difficult and mortality is very high. PMV has been defined recently, by consensus, as constituting ≥21 consecutive days of mechanical ventilation (MV) for ≥6 hours per day. This study aimed to evaluate the clinical factors predicting weaning failure in patients undergoing PMV in medical intensive care unit (ICU). Methods: We retrospectively reviewed the clinical and laboratory characteristics of 127 patients who received MV for more than 21 days in the medical ICU at Chonnam National University Hospital in South Korea between January 2005 and December 2014. Patients who underwent surgery or experienced trauma were excluded from this study. Results: Among the 127 patients requiring PMV, 41 (32.3%) were successfully weaned from MV. The median age of the weaning failure group was higher than that of the weaning success group (74.0 vs . 70.0 years; P=0.003). The proportion of male patients was 58.5% in the weaning success group and 72.1% in the weaning failure group, respectively. The most common reasons for ICU admission were respiratory causes (66.1%) followed by cardiovascular causes (16.5%) in both groups. ICU mortality and in-hospital mortality rates were 55.1% and 55.9%, respectively. In the multivariate analysis, respiratory causes of ICU admission [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.29–12.30; P=0.016] and a high sequential organ failure assessment (SOFA) score on day 21 of MV (OR, 1.47; 95% CI, 1.17–1.85; P=0.001) were significantly associated with weaning failure in patients requiring PMV. The area under the receiver operating characteristic (ROC) curve of the SOFA score on day 21 of MV for predicting weaning failure was 0.77 (95% CI, 0.67–0.87; P=0.000). Conclusions: Respiratory causes of ICU admission and a high SOFA score on day 21 of MV could be predictive of weaning failure in patients requiring PMV.

Chlorine-containing bleach can cause acute respiratory distress syndrome (ARDS) and chemical burns. However, simultaneous occurrence of the two conditions caused by this agent is very rare. We describe the case of a 74-year-old female who presented with shortness of breath and hemoptysis following accidental exposure to chlorine-containing bleach. She had second- to third-degree chemical burns on both buttocks and thighs, and received mechanical ventilation because of the development of ARDS. Mechanical ventilation was discontinued on day 6 of hospitalization because of the rapid improvement of hypoxemia, and the patient was transferred to another hospital for further management of the chemical burns on day 18.

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD- 1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS

Background Since the introduction of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. Methods The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. Results Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. Conclusion Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Background: The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). Methods: We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. Results: Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8–218.3 in ICU group vs. median 133.0, IQR 109.8–160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5–118.5 vs. median 86.0, IQR 75.0–103.5), low albumin levels (median 2.9 g/dL, IQR 2.6–3.6 vs . median 3.4, IQR 3.0–3.7), and anemia (73.3% vs . 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO 2 levels (median 53.1 mmHg in ICU group, IQR 38.5–84.6 vs . median 39.7, IQR 34.2–48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. Conclusions: The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU transfer in both groups.

Background Epidermal growth factor receptor (EGFR) gene mutation is a reliable predictive factor for response to EGFR-tyrosine kinase inhibitors (TKIs). The quantified EGFR value may also predict response and survival within an EGFR mutated group. Methods We conducted a retrospective study of 836 lung cancer patients. The patient sample was divided into two groups based on the mean delta cycle threshold (∆Ct) value. EGFR mutation tests using peptide nucleic acid (PNA)-mediated clamping polymerase chain reaction (PCR) were performed. The efficiency of PCR clamping was determined by measuring the Ct value and EGFR quantification was determined by the corrected ∆Ct value. Results EGFR mutation positivity was 30.1% and there were 235 single activating mutations. In this mutation group, the higher corrected ∆Ct value (≥ mean value) group showed better objective response (70.9% vs. 54.9%, P = 0.022) and clinical benefit rates (86.4% vs. 68.3%, P = 0.003) than the lower group. In addition, corrected ∆Ct values were significantly and inversely correlated with disease response (r = −0.184, P = 0.017). In multivariate analysis, both female gender (P = 0.014) and higher corrected ΔCt value (P = 0.012) were independent predictive factors for better clinical benefit rate. The higher corrected ΔCt value group had a tendency for longer progression-free survival than the lower group (P = 0.050). Conclusion The corrected ∆Ct value, which refers to EGFR quantification by PNA-mediated PCR clamping, can predict better clinical response to EGFR-TKI therapy. However, further study is warranted to determine its value as a biomarker to reflect survival.

Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment.This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for >1 month, combined with a World Health Organization-recommended regimen.Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38.5–61.0) years. 42 (68.9%) patients had fluoroquinolone-resistant MDR-TB and 16 (26.2%) had extensively drug-resistant TB. The median (IQR) duration of treatment with bedaquiline and/or delamanid was 168 (166.5–196.5) days, with 33 (54.1%) receiving linezolid for a median (IQR) of 673 (171–736) days. Of the 55 patients with positive sputum cultures at the start of bedaquiline and/or delamanid treatment, 39 (70.9%) achieved sputum culture conversion within a median of 119 days. Treatment was halted in four patients (6.6%) because of prolonged Fridericia's corrected QT interval.Bedaquiline and delamanid were effective and safe for treating MDR-TB, with initial evidence of sequential administration of these two drugs as a viable treatment strategy for patients when an adequate treatment regimen cannot be constructed.

Background The sensitivity of interferon-gamma release assays (IGRAs) in the detection of Mycobacterium tuberculosis infection could be affected by conditions of immune dysregulation. For this reason, diabetes mellitus (DM) may increase the frequency of indeterminate results of IGRAs. However, there have been inconsistent reports of role of DM on indeterminate IGRA results. Methods We retrospectively reviewed all patients who underwent QuantiFERON-TB Gold In-Tube testing (QFT-GIT) at Chonnam National University Hospital. We collected the clinical and laboratory data of these patients. Results Of all 3,391 subjects, 1,265 (37.3%) had a positive QFT-GIT result, 266 (7.8%) had an indeterminate result, and 1,860 (54.9%) had a negative result. The mean age was 54.8 ± 18.1 years and 55.0% of the patients were male. There were 512 (15.1%) patients with DM. Multivariable analysis revealed that systemic corticosteroid use, tuberculosis, lymphocytopenia, low serum albumin, and high serum C-reactive protein (CRP) levels were significantly associated with indeterminate QFT-GIT results. However, DM was not associated with indeterminate QFT-GIT results (adjusted odds ratio, 0.98; 95% confidence interval, 0.69-1.41; P = 0.939). After propensity score matching, DM was not associated with indeterminate results of QFT-GIT. Conclusion In this large cohort study, DM does not affect the incidence of indeterminate results of QFT-GIT.

Background: Glutathione peroxidase 3 (GPx3) which is an extracellular secretory protein is down regulated in patients with early stage lung cancer. We examined the usefulness of serum GPx3 as a biomarker for monitoring of relapse after surgery. Methods: We prospectively collected serial serum samples at baseline, 3 months (3m), 6 months (6m), and 12 months (12m) after operation from the patients who underwent surgery during the year 2013. GPx3 levels were measured three times per sample using the enzyme-linked immunosorbent assay, and the mean values were analyzed by t-test and paired t-test. Results: A total of 170 (100 adenocarcinoma, 41 squamous cell carcinoma, 29 others) patients were analyzed in this study. Mean age was 64.1 years old (range, 39-80) and 27 (15.9%) out of 165 lung cancer patients were confirmed relapse during the median follow-up period of 597.5 days (range, 5-938). The mean GPx3 value at postoperative 6m was significantly elevated in relapsed group than control group (7.90 ± 2.44 mg/mL vs. 6.99 ± 1.79 mg/mL, p1⁄40.047). The mean GPx3 differences were significantly higher in relapsed group than control group at 3m (-0.38 ± 0.39 mg/mL vs. -0.21 ± 0.36 mg/mL, p1⁄40.044), 6m (-0.37 ± 0.42 mg/mL vs. -0.19 ± 0.30 mg/mL, p1⁄40.024), and 12m (-0.38 ± 0.42 mg/mL vs. -0.19 ± 0.28 mg/mL, p1⁄40.012). The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m (694.83 ± 31.86 days vs. 839.05 ± 24.31 days, p1⁄40.007). The mean time to relapse was significantly shorter in high GPx3 difference group between baseline and postoperative 3m (729.76 ± 34.89 days vs. 838.18 ± 24.03 days, p1⁄40.002). Conclusion: Serum mean GPx3 value at postoperative 6m and the mean GPx3 difference were significantly elevated in relapsed lung cancer. The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m. More large scaled validation studies are warranted.