Yee Hyung Kim

Treatment Outcomes for HIV-Uninfected Patients with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

BACKGROUND Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. METHODS This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index >/=18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. CONCLUSIONS Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.

The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC)

We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.

Surgical Treatment of Pulmonary Diseases Due to Nontuberculous Mycobacteria

Although the treatment of pulmonary diseases due to nontuberculous mycobacteria (NTM) requires the long-term use of antibiotics in combination, the treatment success rates are unsatisfactory. We evaluated the clinical characteristics and surgical outcomes of 23 patients with NTM lung diseases who had underwent pulmonary resection. The median age of the patients was 45 yr. Of the 23 patients, 10 had Mycobacterium avium-intracellulare complex infection, 12 had M. abscessus infection, and one had M. xenopi infection. The indications for surgery were antibiotic therapy failure (n=11), remnant cavitary lesion with high probability of relapse (n=8), and massive hemoptysis (n=4). The most common procedure was lobectomy (48%). Postoperative complications occurred in eight patients (35%), including postoperative pneumonia (n=3) and late bronchopleural fistula (n=2). Negative sputum culture conversion was achieved and maintained in all except two mortalities. Although it is associated with a relatively high complication rate, patients with NTM lung disease whose disease is localized to one lung and who can tolerate resectional surgery might be considered for surgery, if there has been poor response to drug therapy or if the patients develop significant disease-related complications such as hemoptysis.

The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

BACKGROUND Prone positioning for acute respiratory distress syndrome (ARDS) has no impact on mortality despite significant improvements in oxygenation. However, a recent trial demonstrated reduced mortality rates in the prone position for severe ARDS. We evaluated effects of prone position duration and protective lung strategies on mortality rates in ARDS. METHODS We extensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) reporting on prone positioning during acute respiratory failure in adults for inclusion in our meta-analysis. RESULTS Eight trials met our inclusion criteria, Totals of 1,099 and 1,042 patients were randomized to the prone and supine ventilation positions. The mortality rates associated with the prone and supine positions were 41% and 47% [risk ratio (RR), 0.90; 95% confidence interval (CI), 0.82-0.98, P=0.02], but the heterogeneity was moderate (P=0.01, I(2)=61%). In a subgroup analysis, the mortality rates for lung protective ventilation (RR 0.73, 95% CI, 0.62-0.86, P=0.0002) and duration of prone positioning >12 h (RR 0.75, 95% CI, 0.65-0.87, P<0.0001) were reduced in the prone position. Prone positioning was not associated with an increased incidence of cardiac events (RR 1.01, 95% CI, 0.87-1.17) or ventilator associated pneumonia (RR 0.88, 95% CI, 0.71-1.09), but it was associated with an increased incidence of pressure sores (RR 1.23, 95% CI, 1.07-1.41) and endotracheal dislocation (RR 1.33, 95% CI, 1.02-1.74). CONCLUSIONS Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare. However, further additional randomized controlled design to study are required for confirm benefit of prone position in ARDS.

Risk Factors for Death during Pulmonary Tuberculosis Treatment in Korea: A Multicenter Retrospective Cohort Study

The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. Graphical Abstract

Two cases of pulmonary and pleural sparganosis confirmed by tissue biopsy and immunoserology

Sparganosis in humans is an incidental infection and is known to be associated with eating insufficiently cooked meat of frogs and snakes or drinking unboiled stream water. Although it can involve various internal organs, pulmonary and pleural involvement due to sparganum is rare. Because we recently experienced two cases involving lung parenchyma and pleura that were misdiagnosed as bacterial pneumonia and lung cancer, we herein intend to present them in detail.

The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study

Background Uncontrolled diabetes, unlike controlled diabetes, is associated with an impaired immune response. However, little is known about the impact of the status of diabetes control on clinical features and treatment outcomes in patients with pulmonary TB (PTB). We conducted this study to evaluate whether the status of diabetes control influences clinical manifestations and treatment responses in PTB. Methods A multicentre prospective study was performed between September 2012 and September 2014. The patients were categorised into three groups according to the glycated haemoglobin (HbA1C) level: PTB without diabetes mellitus (non-DM), PTB with controlled diabetes (controlled-DM) and PTB with uncontrolled diabetes (uncontrolled-DM). The primary outcome was the sputum culture conversion rate after 2 months of intensive treatment. Results Among 661 patients with PTB, 157 (23.8%) had diabetes and 108 (68.8%) had uncontrolled diabetes (HbA1C≥7.0%). The uncontrolled-DM group exhibited more symptoms, positive sputum smears (p<0.001) and presence of cavities (p<0.001) than the non-DM group. Regarding treatment responses, patients with uncontrolled-DM were more likely to have a positive culture after 2 months (p=0.009) and either treatment failure (p=0.015) or death (p=0.027) compared with the non-DM group. In contrast, those with controlled-DM showed similar treatment responses to the non-DM group. In multivariable analysis, uncontrolled diabetes was an independent risk factor for a positive sputum culture after 2 months of treatment (adjusted OR, 2.11; p=0.042) and either treatment failure or death (adjusted OR, 4.11; p=0.022). Conclusions Uncontrolled diabetes is an independent risk factor for poor treatment response in PTB.

Association of the Neutrophil-to-Lymphocyte Ratio with Lung Function and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease.

Background The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation. Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population. Methods We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals. We determined the relationship of NLR levels to severity of lung function using a linear regression model. In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles. Results NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively). In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041). Adding an NLR to FEV1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021). Conclusions The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD.

Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes

RATIONALE We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. OBJECTIVES To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. MEASUREMENTS AND MAIN RESULTS Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). CONCLUSIONS The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

Factors that Predict Negative Results of QuantiFERON-TB Gold In-Tube Test in Patients with Culture-Confirmed Tuberculosis: A Multicenter Retrospective Cohort Study

Background Interferon-γ release assays such as the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infections, whether latent or manifesting as disease. However, a substantial number of persons with culture-confirmed tuberculosis (TB) have negative QFT-GITs. Information on host factors contributing to false-negative and indeterminate results are limited. Methods A multicenter retrospective cohort study was performed with 1,264 culture-confirmed TB patients older than 18 years who were subjected to the QFT-GIT at one of the six hospitals between May 2007 and February 2014. Patients with human immunodeficiency virus infection were excluded. Clinical and laboratory data were collected in South Korea. Results Of all patients, 87.6% (1,107/1,264) were diagnosed with pulmonary TB and 12.4% (157/1,264) with extrapulmonary TB. The rate of negative results was 14.4% (182/1,264). The following factors were highly correlated with false-negative results in the QFT-GIT: advanced age (age ≥ 65 years, odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03–2.39), bilateral disease as determined by chest radiography (OR 1.75, 95% CI 1.13–2.72), malignancy (OR 2.42, 95% CI 1.30–4.49), and lymphocytopenia (total lymphocyte count < 1.0 × 109/L, OR 1.86, 95% CI 1.21–2.87). Conclusions Consequently, QFT-GIT results need to be interpreted with caution in patients with these host risk factors such as the elderly, bilateral disease on chest radiography, or malignancy, or lymphocytopenia.