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Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity

The B-box zinc-finger transcription factors are important for plant growth, development, and various physiological processes such as photomorphogenesis, light signaling, and flowering, as well as for several biotic and abiotic stress responses. However, there is relatively little information available regarding Brassica B-box genes and their expression. In this study, we identified 51, 52, and 101 non-redundant genes encoding B-box proteins in Brassica rapa (BrBBX genes), B. oleracea (BoBBX genes), and B. napus (BnBBX genes), respectively. A whole-genome identification, characterization, and evolutionary analysis (synteny and orthology) of the B-box gene families in the diploid species B. rapa (A genome) and B. oleracea (C genome) and in the allotetraploid species B. napus (AC genome) revealed segmental duplications were the major contributors to the expansion of the BrassicaBBX gene families. The BrassicaBBX genes were classified into five subgroups according to phylogenetic relationships, gene structures, and conserved domains. Light-responsive cis-regulatory elements were detected in many of the BBX gene promoters. Additionally, BrBBX expression profiles in different tissues and in response to various abiotic stresses (heat, cold, salt, and drought) or hormones (abscisic acid, methyl jasmonate, and gibberellic acid) were analyzed by qRT-PCR. The data indicated that many B-box genes (e.g., BrBBX13, BrBBX15, and BrBBX17) may contribute to plant development and growth as well as abiotic stress tolerance. Overall, the identified BBX genes may be useful as functional genetic markers for multiple stress responses and plant developmental processes.

Chronic obstructive pulmonary disease (COPD) is one of the most frequently occurring concomitant diseases in patients with non-small cell lung cancer (NSCLC). It is characterized by small airways and the hyperinflation of the lung. Patients with hyperinflated lung tend to have more reserved lung function than conventionally predicted after lung cancer surgery. The aim of this study was to identify other indicators in predicting postoperative lung function after lung resection for lung cancer. Patients with NSCLC who underwent curative lobectomy with mediastinal lymph node dissection from 2017 to 2019 were included. Predicted postoperative FEV1 (ppoFEV1) was calculated using the formula: preoperative FEV1 × (19 segments-the number of segments to be removed) ÷ 19. The difference between the measured postoperative FEV1 and ppoFEV1 was defined as an outcome. Patients were categorized into two groups: preserved FEV1 if the difference was positive and non-preserved FEV1, if otherwise. In total, 238 patients were included: 74 (31.1%) in the FEV1 non-preserved group and 164 (68.9%) in the FEV1 preserved group. The proportion of preoperative residual volume (RV)/total lung capacity (TLC) ≥ 40% in the FEV1 non-preserved group (21.4%) was lower than in the preserved group (36.1%) (p = 0.03). In logistic regression analysis, preoperative RV/TLC ≥ 40% was related to postoperative FEV1 preservation. (adjusted OR, 2.02, p = 0.041). Linear regression analysis suggested that preoperative RV/TLC was positively correlated with a significant difference. (p = 0.004) Preoperative RV/TLC ≥ 40% was an independent predictor of preserved lung function in patients undergoing curative lobectomy with mediastinal lymph node dissection. Preoperative RV/TLC is positively correlated with postoperative lung function.

Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases.In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed.Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (Funded by Insmed; WILLOW ClinicalTrials.gov number, NCT03218917.).

Background Presence of purulent sputum during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is considered sufficient indication for starting empirical antibiotics. We investigated the relationship between detection of potentially pathogenic bacteria (PPB) using sputum culture or polymerase chain reaction (PCR) and clinical response and sought the risk factors for PPB growth. Methods In 342 outpatients with AECOPD, we compared detection rates of H. influenzae (HI) and S. pneumoniae (SP) using conventional sputum culture versus PCR. The utility of either technique to predict clinical cure or failure after effective antibiotics was assessed. The factors predicting positive sputum cultures were evaluated using logistic regression. Results Using sputum culture, 132 PPB were detected. The predominant bacteria were HI (40.9%) and SP (19.7%). Detection of HI or SP in sputum was higher using PCR than culture growth (60.8% vs 18.6%; P

SummaryAim To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. Methods Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported ‘dissatisfied’ or ‘a little satisfied’ were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. Results Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001–1.014), high serum PSA (OR = 1.543, 95% CI: 1.136–2.095) and small prostate size (OR = 0.970, 95% CI: 0.947–0.994) (p

Background Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized. Methods We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner. Results Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10–15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than

Background Although immune checkpoint blockers (ICBs) can lead to favorable results by reinvigorating the anti-tumor immune response in some patients, many other patients experience poor prognosis and even tumor overgrowth can be seen in real practice. We aimed to assess these hyperprogressive disease (HPD). Methods We reviewed NSCLC patients (n = 243) treated with ICBs. HPD was defined as a tumor growth kinetic ratio (TGKr)>2 and a time-to-failure of less than 2 months. We analyzed the association of Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and CRP-albumin ratio (CAR) with HPD and the immune compositional change in TME by multiplex IHC(mIHC). Panel 1/2 showed CD4, CD8, FOXP3, CD45RO as T cell markers and CD3, TIM3, LAG3, PD-L1 as co-inhibitory signal markers. Panel 3/4 examined macrophages and NK cells with CD68, CD14, CD163, CD206, CCR7, CD86, CD103, CD56, CD11c and CD16. Results Overall, 231 patients were evaluated. 25 patients (10.8%) met the HPD. Patients with HPD (median, 5.6 mo; P Conclusions Despite improved recognition of HPD, its etiology remains unclear, but it is clear that the prognosis becomes poor when it occurs. We observed that some serologic biomarkers (NLR, PLR, CAR) and mIHC can be used not only to predict HPD, but also to validate its mechanism. Furthermore, we undergo whole exon sequencing and experiment with murine model to understand mechanism of HPD. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Aim To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients. Materials and methods Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared. Results Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was −69.1% in group A and −70.4% in group B (both p

Background We investigated the safety and effectiveness of routine harvest of the left kidney for renal transplantation regardless of the presence of multiple renal arteries to obtain the longer renal vein. Patients and Methods Between February 2000 and July 2008, 325 patients underwent left hand-assisted laparoscopic living donor nephrectomy. The true renal arterial anatomy as evaluated intraoperatively was compared with the renal arterial anatomy by computed tomography (CT). We compared the results for the patients with a single renal artery (group I) with the patients with multiple renal arteries (group II) in terms of the donor and recipient outcomes. Results Multiple renal arteries in left kidney were identified in 86 patients (26.5%). Thirty-seven CTs (11.4%) were in discord with the renal arterial anatomy evaluated intraoperatively. There was no difference in age, gender, body mass index, estimated blood loss, complication rate, or length of hospital stay between the 2 groups in the donor. Although the warm ischemic time and the operation time were significantly longer in group II (P = .008 and .001), overall graft survival was similar between the groups. Conclusion Routine harvest of the left kidney can be performed safely and effectively for the donor and recipient, even in the presence of multiple renal arteries.

Background The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. Methods All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. Results Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p

We aimed to evaluate the efficacy and safety of combination treatment using anticholinergics with α-blocker for initial treatment of both overactive bladder (OAB) and other lower urinary tract symptoms (LUTS), secondary to BPH. A 12-week, randomized, double-blind, placebo-controlled trial was conducted at four urology clinics in Korea, involving men, aged 50 years or older, with LUTS related to BPH and OAB. A total of 176 patients were randomly assigned to receive doxazosin (4 mg) plus placebo or doxazosin (4 mg) plus tolterodine SR (4 mg), once a day for 12 weeks. Changes from baseline in total International Prostate Symptom Score (IPSS), bladder diary variables, patient perception of bladder condition (PPBC), uroflowmetry, postvoid residual volume and IPSS subscores (voiding and storage) were analyzed. Of the 176 enrolled patients, 91 had doxazosin gastrointestinal therapeutic system (GITS) and placebo, and 85 had combined medication with doxazosin GITS and tolterodine SR. Compared with the doxazosin plus placebo group, the doxazosin plus tolterodine group showed significant reductions in IPSS storage subscore and improvement in the quality of life item, urgency episodes, as well as in micturition frequency at weeks 4 and 12. However, it failed to improve PPBC at week 4 as well as at week 12. Earlier intervention with anticholinergics plus α-blocker was tolerated well, including the questions about urinary retention (n=1) and dry mouth (n=2). Initial combination treatment of anticholinergics plus α-blocker showed positive results for men with LUTS related to BPH and OAB symptoms and did not increase the risk of urinary retention.

Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized.We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner.Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10-15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (15% ALK FISH split) than10% ALK FISH split group.Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease.