Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis.

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.

Association Between Sarcopenic Obesity and Pulmonary Function in Korean Elderly: Results from the Korean National Health and Nutrition Examination Survey.

Although body composition is related to lung function, few studies have reported the effects of sarcopenic obesity on lung function. Thus, the aim of this study was to investigate the associations between lung function and sarcopenia in the presence and in the absence of obesity. We analyzed nationally representative data of 3044 adults aged > 60 years as collated by the 'Korean National Health and Nutrition Examination Survey 2014-2016. Subjects were classified into four groups: non-sarcopenic non-obese (S-O-), non-sarcopenic obese (S-O+), sarcopenic non-obese (S+O-), and sarcopenic obese (S+O+) according to handgrip strength (GS) and body mass index (BMI). GS was found to be positively associated with forced volume vital capacity (FVC). The S+O+ group had significantly lower FVC values than the S-O- group. Subjects in the S+O+ group were more likely to have restrictive lung disease than those in the S-O- group (odds ratios [ORs] 2.81, 95% confidence interval [CI] 1.72-4.59), and the ORs of restrictive lung disease in S+O+ group were higher than in the S-O+ or S+O- groups. These results were consistent after stratifying by sex and age (61-70 and 71-80). FEV1/FVC ratios (a marker for obstructive lung disease) were not significantly different between S+O+ and S-O- groups. Sarcopenic obesity is associated with a higher risk of restrictive lung disease in Korean elderly.

Association between thoracic fat measured using computed tomography and lung function in a population without respiratory diseases.

BACKGROUND: Local fat distribution patterns and their local or systemic effects have recently attracted significant attention. The aim of this study was to assess the impact of thoracic adiposity on lung function in a population without respiratory diseases according to sex. METHODS: A total of 455 subjects (282 males and 173 females), who had undergone spirometry, and chest and abdominal computed tomography between June 2012 and June 2016 at medical healthcare center, were included. Pericardial fat, intrathoracic fat, subcutaneous thoracic fat, and both visceral and subcutaneous abdominal fat were measured by directly assessing tissue volume using computed tomography. Multiple linear regression analyses adjusted for pack-years of smoking, high-density lipoprotein, and high-sensitivity C-reactive protein were performed to evaluate the association between fat volumes and lung function. RESULTS: In males, intrathoracic fat and visceral abdominal fat were inversely associated with forced expiratory volume in 1 s (FEV1) % predicted (P=0.025, P=0.010, respectively), and subcutaneous thoracic fat volumes showed a negative correlation with both FEV1% and forced vital capacity (FVC) % predicted (P=0.019, P=0.045, respectively). In females, subcutaneous thoracic fat demonstrated a negative correlation with both FEV1% and FVC % predicted (P=0.031 and P=0.008, respectively). CONCLUSIONS: The influence of local thoracic fat distribution on lung function differed according to sex. Visceral fat and subcutaneous thoracic fat in males and subcutaneous fat in females were significantly associated with decreased lung function.

Improved oxygenation 48 hours after high-flow nasal cannula oxygen therapy is associated with good outcome in immunocompromised patients with acute respiratory failure.

BACKGROUND: Respiratory failure requiring intubation is a risk factor for mortality in immunocompromised patients, therefore, noninvasive methods to avoid intubation are preferred in such patients. A high-flow nasal cannula (HFNC) is an alternative noninvasive technique for oxygen delivery but can be potentially harmful in cases of delayed intubation. We sought to identify the physiological predictors of outcome to assess the responsiveness to HFNC of immunocompromised patients with acute respiratory failure. METHODS: We retrospectively analyzed the medical records of immunocompromised patients treated with HFNC in 2015 and 2016 in a tertiary hospital. Oxygenation was assessed by calculating the SpO2/FiO2 (SF) ratio. Subjects were defined as "SF-improved" when HFNC resulted in an increase in the SF ratio compared with baseline. The values were collected at baseline, 12, 24, and 48 h. RESULTS: Ninety-one patients with a median age of 64 years were analyzed; 68.1% were men. There was no significant difference between the SF48-improved and the SF48-nonimproved groups in clinical baseline characteristics or severity of illness as evaluated at the time of initiation of HFNC by APACHE II, SAPS II, and SOFA. The 28-day mortality was significantly lower in the SF48-improved compared with the SF48-nonimproved group. In univariate analysis, mortality was significantly associated with body mass index (BMI), poor functional status, do-not-intubate (DNI) status, the "SF48-improved" group, the reason for immunocompromise, and the severity of illness at the time of initiation of HFNC. In multivariate analysis, "SF48-improved" group was not significantly associated with increased mortality [odds ratio (OR) 0.462; 95% confidence interval (CI), 0.107-1.988; P=0.299]. CONCLUSIONS: In immunocompromised patients with acute respiratory failure, an improved SF ratio 48 h after HFNC treatment was associated with improved 28-day mortality.

Antimicrobial Resistance and Clinical Outcomes in Nursing Home-Acquired Pneumonia, Compared to Community-Acquired Pneumonia.

PURPOSE: Patients with nursing home-acquired pneumonia (NHAP) should be treated as hospital-acquired pneumonia (HAP) according to guidelines published in 2005. However, controversy still exists on whether the high mortality of NHAP results from multidrug resistant pathogens or underlying disease. We aimed to outline differences and factors contributing to mortality between NHAP and community-acquired pneumonia (CAP) patients. MATERIALS AND METHODS: We retrospectively evaluated patients aged 65 years or older with either CAP or NHAP from 2008 to 2014. Patients with healthcare-associated pneumonia other than NHAP or HAP were excluded. RESULTS: Among 317 patients, 212 patients had CAP and 105 had NHAP. Patients with NHAP had higher mortality, more frequently used a ventilator, and had disease of higher severity than CAP. The incidences of aspiration, tube feeding, and poor functional status were higher in NHAP. Twenty three out of 54 NHAP patients and three out of 62 CAP patients had multidrug resistant pathogens (p<0.001). Eleven patients with NHAP died at discharge, compared to 7 patients with CAP (p=0.009). However, there was no association between mortality rate and presence of multidrug-resistant pathogens. The number of involved lobes on chest X-ray [odds ratio (OR)=1.708; 95% confidence interval (CI), 1.120 to 2.605] and use of mechanical ventilation (OR=9.537; 95% CI, 1.635 to 55.632) were significantly associated with in-hospital mortality. CONCLUSION: Patients with NHAP had higher mortality than patients with CAP. The excess mortality among patients with NHAP and CAP was related to disease severity but not to the presence of multidrug resistant pathogens.

Relationship between FEV1 and Cardiovascular Risk Factors in General Population without Airflow Limitation.

Purpose. We aimed to determine the value of lung function measurement for predicting cardiovascular (CV) disease by evaluating the association between FEV1 (%) and CV risk factors in general population. Materials and Methods. This was a cross-sectional, retrospective study of subjects above 18 years of age who underwent health examinations. The relationship between FEV1 (%) and presence of carotid plaque and thickened carotid IMT (≥0.8 mm) was analyzed by multiple logistic regression, and the relationship between FEV1 (%) and PWV (%), and serum uric acid was analyzed by multiple linear regression. Various factors were adjusted by using Model 1 and Model 2. Results. 1,003 subjects were enrolled in this study and 96.7% (n = 970) of the subjects were men. In both models, the odds ratio of the presence of carotid plaque and thickened carotid IMT had no consistent trend and statistical significance. In the analysis of the PWV (%) and uric acid, there was no significant relationship with FEV1 (%) in both models. Conclusion. FEV1 had no significant relationship with CV risk factors. The result suggests that FEV1 may have no association with CV risk factors or may be insensitive to detecting the association in general population without airflow limitation.

Visceral abdominal obesity is associated with an increased risk of irritable bowel syndrome.

OBJECTIVES: There are several studies considering obesity as the risk factor for various lower gastrointestinal symptoms. But the relationship between visceral abdominal obesity and the incidence of irritable bowel syndrome (IBS) is not studied yet. The aim of this study was to investigate the association between visceral adipose tissue (VAT) and the risk of IBS. METHODS: This is a case-control study comparing the VAT area between subjects with IBS (IBS group) and controls without IBS (non IBS group), who underwent abdomen computerized tomography (CT) for routine health checkup from January 2012 to August 2013 in a health promotion center. A telephone survey was retrospectively conducted to diagnose IBS by Rome III criteria. The association between IBS and abdominal obesity was evaluated by measuring VAT, subcutaneous adipose tissue (SAT), VAT/SAT ratio, body mass index (BMI) and waist circumference (WC). RESULTS: The prevalence of IBS was 19.9% (67/336) among all enrolled subjects. In the univariate analysis, VAT area, VAT/SAT ratio, waist circumference, the presence of reflux esophagitis and the ratio of females were significantly higher in the IBS group than in the non IBS group. However, a higher BMI or a higher SAT area is not associated with an increased risk of IBS. In the multivariate analysis, a higher VAT area (odds ratio (OR)=9.42, 95% confidence interval (CI): 2.90-30.64, highest tertile vs. lowest tertile, P=0.001), VAT/SAT ratio (OR=10.15, 95% CI: 3.05-33.58, highest tertile vs. lowest tertile, P=0.001) and waist circumference (OR=7.81, 95% CI: 2.13-28.66, highest tertile vs. lowest tertile, P=0.002) were independently associated with a risk of IBS. Only in the IBS-D group, not in the IBS-C, visceral adiposity was associated with an increased risk of IBS. CONCLUSIONS: Visceral adiposity measured by VAT, VAT/SAT, and waist circumference is associated with an increased risk of IBS, especially of IBS-D. However, neither SAT nor BMI are associated with an increased risk of IBS.

Clinical Experience of the Use of CT-P13, a Biosimilar to Infliximab in Patients with Inflammatory Bowel Disease: A Case Series.

BACKGROUND: CT-P13 is the first biosimilar monoclonal antibody to infliximab. However, the antibody was tested only in rheumatoid arthritis and ankylosing spondylitis, which demonstrated equivalence to the originator in efficacy, safety, and pharmacokinetic profile. Extrapolation of its efficacy and safety to other pathologies is tenuous. Interchangeability with its originator is another unclear area. AIM: We aimed to describe the experience of CT-P13 use in inflammatory bowel disease at a tertiary center. METHODS: Seventeen subjects diagnosed with Crohn's disease (CD, n = 8) or ulcerative colitis (UC, n = 9) who were administered CT-P13 from November 2012 to October 2013 at Dongguk University Ilsan Hospital were retrospectively enrolled. Medical records analyzed included patients' characteristics, previous history of anti-tumor necrosis factor administration, response and remission to this biosimilar antibody, disease flare-up, and adverse drug reaction. RESULTS: Male-female ratio was 1.8. Mean age was 35.4 years (range 15-57). Mean number of CT-P13 administrations was 4.2 ± 1.9. Induction treatments were done in five UC and three CD patients. Clinical response and remission at 8 weeks were achieved in seven patients (five UC and two CD). One CD patient did not respond to CT-P13. Nine patients in maintenance with the originator were interchanged with CT-P13 (four UC and five CD patients). One UC patient experienced arthralgia and CT-P13 was discontinued. One patient experienced loss of response during the study period. CONCLUSIONS: CT-P13 may have biosimilarity and interchangeability with its originator in inflammatory bowel disease. A large, randomized, double-blind, prospective study is needed.

[The association between the therapeutic agent and the compliance of the patients with inflammatory bowel diseases].

BACKGROUND/AIMS: Adherence of the patients with inflammatory bowel diseases is important to maintain the remission. However, the patients do not always keep their appointments for treatment. The aim of this study was to investigate the clinical factors associated with adherence of patients in terms of appointment keeping. METHODS: A total of 73 subjects were retrospectively investigated from September 2005 to January 2012 at Dongguk University Ilsan Hospital (Goyang, Korea). We reviewed medical records including the age, sex, residence, medications, the disease activity, and the rate of keeping the date. A punctual visit was defined as outpatient visit on the scheduled date ±7 days. Punctual patients for the visit were defined as their punctual visit rates exceed 90%. RESULTS: Male to female ratio was 2.4:1. Mean age was 41.5±15.4 years (range, 20 to 78 years). Ulcerative colitis was 53 cases (72.6%) and Crohn's disease was 20 cases (27.4%). Mean duration of disease was 42.0±41.6 months (range, 4 to 226 months). Mean puntual visit rate was 86.7±16.0% (range, 27 to 100). Thirty-eight patients (52.1%) were punctual patients for the visit. Azathioprine/6-mercaptopurine treatment was associated with punctual patients for the visit (odd ratio, 3.19; 95% confidence interval, 1.12 to 9.09; p=0.03). However, other clinical factors did not influence the punctual visit rates. CONCLUSIONS: Our study demonstrated that the use of azathioprine/6-mercaptopurine was associated with keeping the appointment for meeting the doctor. Further prospective study would be necessary.