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BACKGROUND: Although low-dose computed tomography (LDCT) screening is known to be effective for the detection of lung cancers localized in peripheral lung regions at a curable stage, limited data is available regarding the characteristics and outcomes of central lung cancers diagnosed in a screening cohort. This study aimed to determine whether LDCT screening could effectively detect central lung cancers at an early stage and offer survival benefits. METHODS: We analyzed 52,615 adults who underwent lung cancer screening with LDCT between May 2003 and Dec 2019 at a tertiary center in South Korea. Characteristics and outcomes of those diagnosed with lung cancer, stratified by screen-detection status and cancer location, were evaluated. RESULTS: A total of 352 individuals (281 screen-detected, 71 non-screen-detected) were diagnosed with lung cancer. Compared to screen-detected cancers, non-screen-detected cancers tended to be centrally-located (11.4% vs. 64.8%, P

BACKGROUND: Intratumoral heterogeneity is a cause of drug resistance that leads to treatment failure. We investigated the clinical implication of intratumoral heterogeneity inferred from the number of subclones that constituted a tumor and reasoned the etiology of subclonal expansion using RNA sequencing data. METHODS: Simple nucleotide variation, clinical data, copy number variation, and RNA-sequencing data from 481 The Cancer Genome Atlas-Lung Squamous Cell Carcinoma (TCGA-LUSC) cases were obtained from the Genomic Data Commons data portal. Clonal status was estimated from the allele frequency of the mutated genes using the SciClone package. RESULTS: The number of subclones that comprised a tumor had a positive correlation with the total mutations in a tumor (σ=0.477, P-value

Proton pump inhibitors (PPIs), followed by histamine 2 receptor antagonists (H2RAs), are the most commonly used drugs to prevent gastrointestinal bleeding in critically ill patients through stress ulcer prophylaxis. The relative efficacy and drug-related adverse events of PPIs and H2RAs remain unclear. In this retrospective, observational, comparative cohort study, PPIs and H2RAs for stress ulcer prophylaxis in critically ill patients were compared using a common data model. After propensity matching, 935 patients from each treatment group (PPI or H2RA) were selected. The PPI group had a significantly higher 90-day mortality than the H2RA group (relative risk: 1.28; P = 0.01). However, no significant inter-group differences in the risk of clinically important gastrointestinal bleeding were observed. Moreover, there were no significant differences between the groups concerning the risk of pneumonia or Clostridioides difficile infection, which are known potential adverse events related to these drugs. Subgroup analysis of patients with high disease severity were consistent with those of the total propensity score-matched population. These findings do not support the current recommendations, which prefer PPIs for gastrointestinal bleeding prophylaxis in the intensive care unit.

Cognitive impairment has high prevalence in older adults with airway diseases, and may influence their competence in inhaler use, thereby negatively affecting patient prognosis. We aimed to evaluate the relationship between cognitive function and competence in inhaler technique. We enrolled 108 inhaler naive older adults (≥60 years) with airway disease in this prospective observational study and performed the Korean version of the Mini-Mental State Examination (K-MMSE). After explaining the inhaler technique, we scored its competence. While the total K-MMSE score was unrelated to the inhaler score, the orientation for place (estimates=0.62, p = 0.009), registration (estimates=0.988, p = 0.037), and recall (estimates=0.161, p = 0.048) were positively associated with the score. Low K-MMSE scores were associated with lower odds ratio for the competence of the “exhale” step (adjusted odds ratio= 0.23, p = 0.018). Thus, a K-MMSE-mediated evaluation of cognitive function in older adults with airway disease can be a useful tool to predict inhaler competence.

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years, 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration &lt, 50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.

Neuropathic pain is associated with an increased sensitivity to painful stimuli or abnormal sensitivity to otherwise innocuous stimuli. However, in addition to adverse effects, currently available drugs have shown limited response in patients with neuropathic pain, which provides a rationale to explore new drug classes acting on novel targets and with better efficacy and safety profiles. Here, we found that saikosaponins potently inhibit agonist-induced activation of the transient receptor potential A1 (TRPA1) channel, which has been reported to mediate neuropathic pain by sensing a variety of chemical irritants. Molecular docking and site-directed mutagenesis analyses suggested that saikosaponins bind to the hydrophobic pocket in TRPA1 near the Asn855 residue, which, when mutated to Ser, was previously associated with enhanced pain perception in humans. In support of these findings, saikosaponin D significantly attenuated agonist-induced nociceptive responses and vincristine-induced mechanical hypersensitivity in mice. These results indicate that saikosaponins are TRPA1 antagonists and provide a basis for further elaboration of saikosaponin derivatives for the development of new therapeutics for neuropathic pain.

Introduction. Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer development, and small cell lung cancer (SCLC) comprises 15-20% of lung cancers with IPF. The objective of this study was to investigate survival outcomes and treatment-related complications according to GAP (gender, age, and physiology) stage in patients having SCLC with IPF (SCLC-IPF). Materials and Methods. Retrospectively collected data of SCLC-IPF patients from two tertiary care university hospitals in South Korea were reviewed. A total of 59 SCLC-IPF patients were identified and categorized according to GAP stage, which was proposed by Ley et al. in 2012 to predict the prognosis of IPF. Survival outcomes and treatment-related complications were compared between the two groups. Results. In a total of 59 patients, the median age was 71 years and 58 (98.3%) were male. In a comparison of the median overall survival (OS) according to GAP stage, median OS of the advanced GAP stage group was significantly shorter than median OS of GAP stage I group (7.1 months vs. 16.1 months; p = 0.002). Treatment-related complications occurred more frequently in the advanced GAP stage group; advanced GAP stage was the only predictor that exhibited a significant association with the incidence of acute exacerbation of IPF. Conclusions. Inferior survival outcome and higher incidence of treatment-related pulmonary toxicities were noted in the advanced GAP stage group. Furthermore, advanced GAP stage was the only predictor of treatment-related acute exacerbation of IPF. Physicians should thus consider GAP stage, which reflects the severity of IPF, during treatment of SCLC-IPF.

Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, there are currently no clinical guidelines for LC surveillance in IPF. This study aimed to investigate the cumulative incidence and survival outcomes of LC in IPF. Using the National Health Insurance Service database, including medical information on people aged ≥ 40 years between 2011 and 2016, we identified IPF patients and confirmed the presence of comorbid LC. Patients diagnosed with IPF in 2011 were washed out, and mortality data were analyzed from 2012 to 2018. A total of 7277 newly diagnosed IPF patients were identified among Korean citizens aged ≥ 40 years (about 50 million people) between 2011 and 2016. Their average age was 71.5 years and 72.8% of them were male. The prevalence of LC in the IPF cases was 6.4%. The cumulative incidence rates of LC in IPF patients who did not have LC at the time of IPF diagnosis were 1.7%, 4.7%, and 7.0%, at 1, 3, and 5 years, respectively. The median time from IPF diagnosis to LC development was 16.3 (Interquartile range, 8.2–28.8) months. The survival rate was significantly lower in the IPF with LC group than the IPF without LC group (P

Rapid response systems (RRSs) have been introduced to intervene with patients experiencing non-code medical emergencies and operate widely around the world. An RRS has four components: an afferent limb, an efferent limb, quality improvement, and administration. A proper triggering system, a hospital culture that embraces the RRS from the afferent limb, experienced primary responders, and dedicated physicians from the efferent limb are key for successful implementation. After initial implementation, quality improvement through objective outcome measures and self-evaluation are crucial, which lead to a better outcome when this process is well performed. Furthermore, better outcomes lead to more investment, which is essential for effective development of the system. The RRS is successfully maintained when these four components are closely interconnected.

Pirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the efficacy of low-dose pirfenidone (that is, less than 1200 mg/day). We retrospectively reviewed the medical records of patients with IPF. The patients were divided into the following three groups, those who were not treated with pirfenidone (control) and those who were treated with pirfenidone at doses

Background: Pirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). Several patients take reduced doses of pirfenidone, rather than the recommended dose, due to adverse drug reactions. The aim of this study was to evaluate the efficacy of low-dose pirfenidone (that is, less than 1200 mg/day). Methods: We retrospectively reviewed the medical records of patients with IPF who were treated in a tertiary care hospital in South Korea. The patients were divided into the following three groups, those who were not treated with pirfenidone (control) and those who were treated with pirfenidone at doses Results: In total, 234 patients with IPF were analyzed (92 control, 79 low-dose, and 63 high-dose groups). The median age was 69.0 years, and 74.4% were men. The adjusted mean changes in forced vital capacity (FVC) in 1 year were -200.7, -87.8, and -89.2 mL in the control, low-dose, and highdose groups, respectively (p = 0.021). The FVC declined more significantly in the control group than in the low-dose and high-dose groups. No significant difference in FVC change was observed between the low-dose and high-dose groups. Dyspepsia, anorexia, and nausea were significantly more frequent in the low-dose group than in the high-dose group, whereas other adverse events did not show a significant difference between the groups, suggesting that dose reduction is attributed to gastrointestinal tract-related adverse events. Conclusions: Dose reduction may help patients to better control gastrointestinal tract-related adverse events; continuing taking the medication at low doses is also expected to be effective in reducing the FVC decline.

BackgroundIdiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.ObjectivesThis study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.MethodsWe reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).ResultsIn total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; PConclusionsIPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.

Allergic asthma is a complex disorder characterized by chronic airway inflammation. Patients with asthma often show poor adherence to corticosteroid therapy owing to prominent side effects, which provides a rationale to explore new drug classes with a better safety profile. In this study, we sought to discover natural products that inhibit the activity of phosphodiesterase 4, which is considered a potential molecular target for anti-inflammatory therapy. The screening of a plant extract library led to the identification of Distylium racemosum, which inhibited phosphodiesterase 4 activity in vitro and suppressed lipopolysaccharide-induced inflammatory signaling in cultured cells. In a mouse model of ovalbumin-induced allergic asthma, D. racemosum treatment significantly reduced inflammatory responses in the lung, as well as serum immunoglobulin E levels. Although the active constituents of D. racemosum extract and the exact mechanism underlying the in vivo action of D. racemosum remain to be elucidated, our results provide a basis for further investigation of D. racemosum extract as a novel anti-inflammatory agent for allergic asthma.

The Conductive-bridge random-access memory (CBRAM) cell is a promising candidate for a terabit-level non-volatile memory due to its remarkable advantages. We present for the first time TiN as a diffusion barrier in CBRAM cells for enhancing their reliability. CuO solid-electrolyte-based CBRAM cells implemented with a 0.1-nm TiN liner demonstrated better non-volatile memory characteristics such as ~ 106 AC write/erase endurance cycles with 100-μs AC pulse width and a long retention time of ~ 7.4-years at 85 °C. In addition, the analysis of Ag diffusion in the CBRAM cell suggests that the morphology of the Ag filaments in the electrolyte can be effectively controlled by tuning the thickness of the TiN liner. These promising results pave the way for faster commercialization of terabit-level non-volatile memories.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL) is a rare type of lymphoma that accounts for only 5%–18% of all cases of non-Hodgkin lymphoma (NHL). In published series, 60%–90% of NK/T-cell lymphomas are localized to the nasal and upper airway. We describe a 55-year man who presented with cough, sputum, dyspnea on exertion, and a chest computed tomography scan shows diffuse ground glass opacities (GGOs), suggestive of an interstitial lung disease. He was treated with a corticosteroid and his symptoms improved. However, when the corticosteroid was tapered, his symptoms recurred. The patient underwent a surgical lung biopsy and ENKTCL was diagnosed. We present this case because ENKTCL involving only the lung is very rare but very informative. To our knowledge, our patient is the first case that primary pulmonary ENKTCL is presented with GGOs., Graphical Abstract

We report a case of tacrolimus-induced transplant-associated thrombotic microangiopathies (TA-TMA) after lung transplantation. A 71-year-old man underwent lung transplantation secondary to idiopathic pulmonary fibrosis. After 4 months, he presented with abdominal discomfort and dyspnea, and was diagnosed with hemolytic anemia and thrombocytopenia. Tacrolimus was considered the cause of the TMA. Tacrolimus was stopped and several sessions of plasma exchange were performed immediately after diagnosis of TA-TMA. However, his platelet count did not normalize, gastrointestinal bleeding was recurrent, and severe pneumonia developed, following which he died. TA-TMA are rare but severe, life-threatening complications in lung transplant recipients. Therefore, the possibility of TA-TMA should be considered in posttransplant recipients.

Asthma is a chronic inflammatory disease of lung airways, and pharmacological inhibitors of cyclic adenosine monophosphate-specific phosphodiesterase 4 (PDE4) have been considered as therapeutics for the treatment of asthma. However, development of PDE4 inhibitors in clinical trials has been hampered because of the severe side effects of non-selective PDE4 inhibitors. Here, screening of a plant extract library in conjunction with dereplication technology led to identification of baicalin as a new type of PDE4-selective inhibitor. We demonstrated that while rolipram inhibited the enzyme activity of a range of PDE4 subtypes in in vitro enzyme assays, baicalin selectively inhibited the enzyme activity of PDE4A and 4B. In addition, baicalin suppressed lipopolysaccharide-induced TNF-α expression in macrophage where PDE4B plays a key role in lipopolysaccharide-induced signaling. Furthermore, baicalin treatment in an animal model of allergic asthma reduced inflammatory cell infiltration and TNF-α levels in bronchoalveolar lavage fluids, indicating that the antiinflammatory effects of baicalin in vivo are attributable, in part, to its ability to inhibit PDE4.

Nanoscale (∼28 nm) non-volatile multi-level conductive-bridging-random-access-memory (CBRAM) cells are developed by using a CuO solid-electrolyte, providing a Vset of ∼0.96 V, a Vreset of ∼−1.5 V, a ∼1 × 102 memory margin, ∼3 × 106 write/erase endurance cycles with 100 μs AC pulse, ∼6.63 years retention time at 85 °C, ∼100 ns writing speed, and multi-level (four-level) cell operation. Their non-volatile memory cell performance characteristics are intensively determined by studying material properties such as crystallinity and poly grain size of the CuO solid-electrolyte and are found to be independent of nanoscale memory cell size. In particular, the CuO solid-electrolyte-based CBRAM cell vertically connecting with p/n/p-type oxide (CuO/IGZO/CuO) selector shows the operation of 1S(selector)1R(resistor), demonstrating a possibility of cross-bar memory-cell array for realizing terabit-integration non-volatile memory cells.

An event means a flow which has a time attribute such as a symptom of patient. Stream data collected by sensors can be summarized as an interval event which has a time interval between the start-time point and the end-time point in multiple stream data environment. Most of temporal mining techniques have considered only the frequent events. However, these approaches may ignore the infrequent event even if it is important. In this paper, we propose a new temporal data mining that can find association rules for the significant temporal relation based on interval events in multidimensional stream data environment. Our method considers the weight of events and stream data on the sensing time point of abnormal events. And we can discover association rules on the significant temporal relation regardless of the occurrence frequency of events. The experimental analysis has shown that our method provide more useful knowledge than other conventional methods.