Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Early discontinuation of ethambutol in pulmonary tuberculosis treatment based on results of the GenoType MTBDRplus assay: A prospective, multicenter, non-inferiority randomized trial in South Korea.

No studies have investigated whether discontinuation of ethambutol (EMB) based on the susceptibility to isoniazid and rifampin as determined by the GenoType MTBDRplus assay would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of intensive phase treatment based on the result of MTBDRplus assay in patients with pulmonary tuberculosis (PTB). This prospective, multicenter non-inferiority randomized trial was conducted at 12 referral centers in South Korea in drug-susceptible PTB patients who initiated the standard four-drug regimen for PTB. Based on the results of the assay, EMB was discontinued in the MTBDRplus group after the confirmation that M. tuberculosis isolate was susceptible to isoniazid and rifampin. The timepoint for EMB discontinuation in the Guideline group was determined using the results of the phenotypic drug susceptibility test based on the Korean National TB Guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Of 600 randomized patients, the treatment outcome analysis was performed for 493 patients (MTBDRplus group, 244; Guideline group, 249). Treatment success rates were 93.9% (229/224) in the MTBDRplus group and 93.6% (233/249) in the Guideline group and did not differ between groups; relative risk 1.00 (95% CI 0.95-1.06). The 1-year recurrence rate between the two groups (0.9% vs. 0.5%, respectively) and differences in adverse drug reactions did not differ between groups. In conclusion, early discontinuation of EMB based on the results of the MTBDRplus assay did not affect the treatment outcomes in PTB.

Association analysis of ILVBL gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.

BACKGROUND: We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype. METHODS: We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped. RESULTS: In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P = 0.001-0.004, OR = 0.59-0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P = 0.033), but the other four SNPs in hapblock2 were not. CONCLUSION: To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition.

Right Common Iliac Artery Occlusion in a Patient with Severe COVID-19.

In patients with coronavirus disease 2019 (COVID-19), thromboembolism is a frequently reported complication. However, it is reported that the incidence of arterial occlusion is rare. We experienced a case of 70-year-old male patient who developed a complication of Right common iliac arterial occlusion while treating him for confirmed COVID-19 who did not have any risk factors, such as diabetes or smoking. As in our case, it is necessary to carefully observe whether this complication occurs while treating COVID-19 patients.

OView-AI Supporter for Classifying Pneumonia, Pneumothorax, Tuberculosis, Lung Cancer Chest X-ray Images Using Multi-Stage Superpixels Classification.

The deep learning approach has recently attracted much attention for its outstanding performance to assist in clinical diagnostic tasks, notably in computer-aided solutions. Computer-aided solutions are being developed using chest radiography to identify lung diseases. A chest X-ray image is one of the most often utilized diagnostic imaging modalities in computer-aided solutions since it produces non-invasive standard-of-care data. However, the accurate identification of a specific illness in chest X-ray images still poses a challenge due to their high inter-class similarities and low intra-class variant abnormalities, especially given the complex nature of radiographs and the complex anatomy of the chest. In this paper, we proposed a deep-learning-based solution to classify four lung diseases (pneumonia, pneumothorax, tuberculosis, and lung cancer) and healthy lungs using chest X-ray images. In order to achieve a high performance, the EfficientNet B7 model with the pre-trained weights of ImageNet trained by Noisy Student was used as a backbone model, followed by our proposed fine-tuned layers and hyperparameters. Our study achieved an average test accuracy of 97.42%, sensitivity of 95.93%, and specificity of 99.05%. Additionally, our findings were utilized as diagnostic supporting software in OView-AI system (computer-aided application). We conducted 910 clinical trials and achieved an AUC confidence interval (95% CI) of the diagnostic results in the OView-AI system of 97.01%, sensitivity of 95.68%, and specificity of 99.34%.

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea.

Background: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT. Methods: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated. Results: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders. Conclusions: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

Daily 300 mg dose of linezolid for multidrug-resistant and extensively drug-resistant tuberculosis: updated analysis of 51 patients.

OBJECTIVES: Linezolid may be an effective treatment for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). The objective was to evaluate the efficacy, tolerability and adverse events of a 300 mg daily dose of linezolid in the treatment of MDR/XDR-TB. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 51 MDR-TB patients, including 26 patients (51%) with XDR-TB, to evaluate the safety, tolerability and efficacy of therapy with 300 mg/day linezolid. All patients had failed previous treatments with second-line anti-TB drugs. RESULTS: Patients were treated with linezolid for a median of 413 days (IQR 237-622 days). Favourable treatment outcome (treatment success or still on treatment after culture conversion) was achieved in 40 patients (78%) with culture conversion at a median of 55 days (IQR 41-91 days) from the start of linezolid therapy. Eleven patients (22%) had unfavourable outcomes (treatment failure or death) and 14 (27%) discontinued treatment due to neurotoxicity (peripheral or optic neuropathy) after a median of 278 days (IQR 174-412 days). CONCLUSIONS: Our findings suggest that linezolid at a daily dose of 300 mg is effective against intractable MDR/XDR-TB, and may be associated with fewer neuropathic side effects than a daily dose of 600 or 1200 mg.

Prediction Model of Acute Respiratory Failure in Patients with Acute Pesticide Poisoning by Intentional Ingestion: Prediction of Respiratory Failure in Pesticide Intoxication (PREP) Scores in Cohort Study.

Acute respiratory failure is the primary cause of mortality in patients with acute pesticide poisoning. The aim of the present study was to develop a new and efficient score system for predicting acute respiratory failure in patients with acute pesticide poisoning. This study was a retrospective observational cohort study comprised of 679 patients with acute pesticide poisoning by intentional poisoning. We divided this population into a ratio of 3:1; training set (n = 509) and test set (n = 170) for model development and validation. Multivariable logistic regression models were used in developing a score-based prediction model. The Prediction of Respiratory failure in Pesticide intoxication (PREP) scoring system included a summation of the integer scores of the following five variables; age, pesticide category, amount of ingestion, Glasgow Coma Scale, and arterial pH. The PREP scoring system developed accurately predicted respiratory failure (AUC 0.911 [0.849-0.974], positive predictive value 0.773, accuracy 0.873 in test set). We came up with four risk categories (A, B, C and D) using PREP scores 20, 40 and 60 as the cut-off for mechanical ventilation requirement risk. The PREP scoring system developed in the present study could predict respiratory failure in patients with pesticide poisoning, which can be easily implemented in clinical situations. Further prospective studies are needed to validate the PREP scoring system.

Chest computed tomography is more likely to show latent tuberculosis foci than simple chest radiography in liver transplant candidates.

Although the detection and treatment of latent tuberculosis infections (LTBIs) in transplant candidates are essential, current diagnostic methods for LTBIs are limited, especially in immunocompromised subjects. Pretransplant chest computed tomography (CT) may reveal more LTBI foci and thus predict the development of posttransplant tuberculosis (TB) more efficiently; however, this hypothesis has not yet been investigated. Thirty-six liver transplantation (LT) recipients who developed TB (the TB group) and 144 LT recipients who did not develop TB (the control group) were retrospectively enrolled into a study with a nested case-control design, and their clinical characteristics and radiological findings were compared. Tuberculin skin tests (TSTs) were not performed, and none of these patients had been treated for LTBIs. Thirty-six of 2549 LT recipients (1.4%) were diagnosed with TB after LT (median = 10 months, range = 1-80 months). Twenty-eight patients (77.8%) successfully completed the treatment. There were no significant differences in the clinical characteristics of the 2 groups. Abnormal CT findings (40.0% versus 17.3%, P = 0.018) and chest X-ray (CXR) findings (25.0% versus 11.8%, P = 0.044) suggestive of healed TB were significantly more frequent in the TB group versus the control group. Of the 10 patients who underwent chest CT and developed TB, 5 (50%) showed abnormal findings only on chest CT scans, whereas their CXR results were normal. In conclusion, a pretransplant chest CT scan is more likely to show an LTBI than a CXR in those with post-LT TB. The usefulness of chest CT along with traditional methods such as TSTs for LTBI screening should be further investigated.

Prognostic significance of 18F-fluorodeoxyglucose uptake of bone marrow measured on positron emission tomography in patients with small cell lung cancer.

OBJECTIVES: We investigated whether 18F-fluorodeoxyglucse (FDG) uptake of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) has implications for predicting clinical outcomes in patients with small cell lung cancer (SCLC). METHODS: We retrospectively enrolled 70 SCLC patients who underwent FDG PET/CT prior to treatment. On PET/CT, maximum FDG uptake of all tumor lesions (Tmax), coefficient of variation (COV) of FDG uptake of primary tumor, and mean FDG uptake of BM (BM SUV) were measured. The relationships of BM SUV with PET/CT parameters of SCLC and serum markers were evaluated. Univariate and multivariate analyses were performed to assess the significance of BM SUV for predicting progression-free survival (PFS) and overall survival (OS). RESULTS: BM SUV had significant positive correlations with Tmax, COV of primary tumor, white blood cell count, and serum C-reactive protein level (p < .05). On univariate analysis, BM SUV showed significant association with only PFS (p = .006). On multivariate analysis, Veterans Administration Lung Cancer Study Group (VALSG) stage, N stage, M stage, Tmax, and BM SUV were independent prognostic factors for PFS (p < .05) and, for OS, VALSG stage and M stage were independent prognostic factors (p < .05). Among patients with limited disease, patients with high FDG uptake of BM had significantly worse PFS than did those with low FDG uptake of BM (p < .05), but, there was no significant difference in PFS between patients with extensive disease and patients with limited disease and high FDG uptake of BM (p > .05). CONCLUSION: FDG uptake of BM was an independent predictor of disease progression in SCLC patients. Patients with limited disease and high FDG uptake of BM had similar PFS to those with extensive disease.

In Vitro Effect of DFC-2 on Mycolic Acid Biosynthesis in Mycobacterium tuberculosis.

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to 0.39 µg/ml, DFC-2 inhibited both drug-susceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2's action in M. tuberculosis. The most affected functional gene category was "lipid biosynthesis," which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

Naphthofuroquinone derivatives show strong antimycobacterial activities against drug-resistant Mycobacteria.

Tuberculosis, one of the world's major health problems, has become more serious due to the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB). In this study, we performed three anti-MTB assays to evaluate the anti-mycobacterial activity of naphthofuroquinone derivatives against drug-resistant MTB. Among them, methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate (DFC2) exhibited strong anti-mycobacterial activity against MTB H37Ra, H37Rv and four drug-resistant MTB strains. The MIC of DFC2 ranged from 0.19-0.39 µg/ml to 0.78-1.56 µg/ml against all tested MTB strains. Moreover, DFC2 showed low cytotoxicity against fibroblast cells (L929) at concentrations 10-40-fold higher than their MICs. The IC50 value of DFC2 against L929 cells was 15.218 µg/ml. In addition, DFC2 reduced the number of intracellular M. tuberculosis in macrophages in a dose-dependent manner. Taken together, our results indicate DFC2 to be promising new candidate agents for the treatment of tuberculosis.

Two Rare Cases of Intrathoracic Splenosis and Subcutaneous Splenosis: Spleen Scintigraphy Avoided the Need for Invasive Procedures.

Splenosis is defined as the acquired heterotopic autotransplantation of splenic tissue in other sites of the body after splenic rupture, usually due to either traumatic or iatrogenic causes. It is often found incidentally and is usually asymptomatic. These implants are not limited to the left upper quadrant of the abdomen, however, and splenosis in other locations can mimic various pathologic entities. There are several reports on abdominal splenosis, but intrathoracic and subcutaneous splenosis are rare. We report two cases of intrathoracic and subcutaneous splenosis that were diagnosed using spleen scintigraphy, avoiding the need for an invasive procedure.

A shorter treatment duration may be sufficient for patients with Mycobacterium massiliense lung disease than with Mycobacterium abscessus lung disease.

BACKGROUND: Mycobacterium abscessus complex is the second most common organism isolated from patients with nontuberculous mycobacterial (NTM) lung disease in South Korea. This study aimed to compare clinical features and treatment outcomes of M. abscessus and Mycobacterium massiliense lung disease. METHODS: We retrospectively identified stored clinical isolates of M. abscessus complex as either M. abscessus or M. massiliense and reviewed medical records to compare clinical characteristics and treatment responses. All patients were treated empirically over several months with multidrug regimens, including a macrolide and one or more parenteral agents. RESULTS: Of the 249 patient isolates tested, 128 (59 with M. abscessus and 69 with M. massiliense) met the American Thoracic Society diagnostic criteria for NTM pulmonary disease, and treatment outcomes were analyzed in 48 patients (26 with M. abscessus and 22 with M. massiliense). The clinical and radiologic findings were similar between the two groups. Although the durations of parenteral and total treatment were significantly shorter in patients with M. massiliense than in those with M. abscessus (4.7 months vs 7.4 months, P = .006, and 12.1 months vs 16.3 months, P = .043), the treatment success rate was significantly higher in patients with M. massiliense (95.5%) than in M. abscessus cases (42.3%, P < .001). CONCLUSION: Patients with M. massiliense pulmonary infection responded better to this antibiotic strategy than those with M. abscessus infection. A shortened duration of treatment may be sufficient for M. massiliense pulmonary infection.

Use of venovenous extracorporeal membrane oxygenation in central airway obstruction to facilitate interventions leading to definitive airway security.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is useful for providing hypoxic patients with ventilatory support, but its usefulness in the management of patients with central airway obstruction has rarely been reported. Nineteen cases in one center where venovenous (VV) ECMO was used to support patients with severe central airway obstruction while they underwent lifesaving interventions are reported here. METHODS: In total, 113 cases of VV ECMO were performed in Asan Medical Center between January 2009 and June 2012. In 19 cases (18 patients), VV ECMO was used to support patients with severe airway obstruction. RESULTS: Of the 18 patients, 13 were male, and their median age was 62.5 (range, 16-82) years. The main reasons for using ECMO to provide airway security were malignant mass removal with a rigid bronchoscope (8 cases) and insertion of a tracheal stent (7 cases). The median ECMO time was 20.9 (range, 2.2-113.4) hours. In 1 case, a patient died of massive bleeding after a malignant mass was removed. Weaning off ECMO therapy occurred successfully in the remaining 18 cases. CONCLUSIONS: Venovenous ECMO may be useful in patients with central airway obstruction because it provides short-term airway security while lifesaving procedures are being performed.

Outcomes in patients with Mycobacterium abscessus pulmonary disease treated with long-term injectable drugs.

BACKGROUND: The ATS (American Thoracic Society) has recommended periodic administration of multidrug therapy, including a macrolide and one or more parenteral agents or a combination of parenteral agents, over 2-4 months, for treatment of Mycobacterium abscessus pulmonary disease. However, there is little hard evidence supporting these guidelines, and treatment outcomes have not yet been reported. METHODS: We retrospectively evaluated 41 patients with M. abscessus pulmonary disease treated in accordance with ATS guidelines. These patients were treated empirically with multidrug regimens, including a macrolide and one (amikacin) or more (amikacin and cefoxitin or imipenem) parenteral agents, over several months. Treatment outcomes were defined as treatment success, failure, or default. RESULTS: Seventeen (41.5%) patients were prescribed a macrolide and one parenteral agent, and 24 (58.5%) were prescribed a macrolide and two parenteral agents. The median duration of parenteral and total antibiotic treatment were 230 days (range, 60-601 days) and 511 days (range, 164-1249 days), respectively. The treatment success, failure, and default rates were 80.5% (33/41), 12.2% (5/41), and 7.3% (3/41), respectively. Four patients relapsed over 445 days (range, 0-1443 days) of follow-up. There were no significant differences in treatment success and relapse rates between the groups receiving one and two parenteral agents. Adverse reactions developed in 18 of 41 patients (43.9%). CONCLUSIONS: Combination antibiotic therapy, including long-term (minimum 2-4 months) parenteral drugs, as recommended by the ATS, resulted in successful treatment outcomes in 80.5% of patients with M. abscessus lung disease in Korea.

Transmission of Multidrug-resistant Tuberculosis Confirmed by Endobronchial Ultrasound Biopsy of a Mediastinal Lymph Node and DNA Fingerprinting Analysis.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was recently introduced for sampling of mediastinal masses and nodes, for staging of lung cancer, and for diagnosing other benign diseases including tuberculosis (TB). However, EBUS-TBNA has not been used to date to confirm the presence of multidrug-resistant TB (MDR-TB). We here describe the diagnosis of MDR-TB of a mediastinal lymph node by EBUS biopsy. MDR-TB had been transmitted to our patient from her son who had pulmonary TB, and the diagnosis of MDR-TB was confirmed by a restriction fragment length polymorphism analysis of the IS6110 segment of Mycobacterium tuberculosis isolates. Our findings highlight the use of EBUS-TBNA in diagnosing TB, including MDR-TB, and malignancies, in a TB-endemic area.