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Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021). The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P =.658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P =.569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P =.609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P =.361, Brier score = 0.112) showed good discrimination ability and calibration. PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. ClinicalTrials.gov; No.: NCT02991924; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Abstract: Geochemical characteristics of marine sediment from the southern Drake Passage were analyzed to reconstruct variations in sediment provenance and transport paths during the late Quaternary. The 5.95m gravity core used in this study records paleoenvironmental changes during the last approximately 600ka. Down-core variations in trace element, rare earth element, and Nd and Sr isotopic compositions reveal that sediment provenance varied according to glacial cycles. During glacial periods, detrital sediments in the southern Drake Passage were mostly derived from the nearby South Shetland Islands and shelf sediments. In contrast, interglacial sediments are composed of mixed sediments, derived from both West Antarctica and East Antarctica. The East Antarctic provenance of the interglacial sediments was inferred to be the Weddell Sea region. Sediment input from the Weddell Sea was reduced during glacial periods by extensive ice sheets and weakened current from the Weddell Sea. Sediment supply from the Weddell Sea increased during interglacial periods, especially those with higher warmth such as MIS 5, 9, and 11. This suggests that the influence of deep water from the Weddell Sea increases during interglacial periods and decreases during glacial periods, with the degree of influence increasing as interglacial intensity increases. [Copyright &y& Elsevier]

The clay mineralogy of a Holocene sediment core from the shelf of Livingston Island, South Shetland Islands, Antarctica has been investigated by X-ray diffraction (XRD), lattice imaging, bulk chemical analysis of fine clay fractions and analytical transmission electron microscopy (ATEM). The clay minerals identified by XRD of <2 μm fraction are smectite 63%, chlorite 25% and illite 12%, with little downcore variation. Lattice imaging of clay particles has confirmed the presence of interstratified illite-smectite and interstratified chlorite-smectite. ATEM of Ca-saturated samples showed that the smectitic clay particles are rich in K, Fe and Mg. K in the smectitic particles is mostly present as a fixed cation in the interlayer, confirming the presence of interstratified illite. A comparison of the mineralogy of the bedrock/soils in the probable source area and the core sediment strongly supports the view that the clay minerals must have originated by glacial erosion, physical weathering and reworking of hydrothermally altered volcanic bedrock and tephra of the South Shetland Islands. [Copyright &y& Elsevier]

Core A9-EB2 from the eastern Bransfield Basin, Antarctic Peninsula, consists of pelagic (diatom ooze-clay couplets and bioturbated diatom ooze) and hemipelagic (bioturbated mud) sediments interbedded with turbidites (homogeneous mud and silt–clay couplets). The cyclic and laminated nature of these pelagic sediments represents alternation between the deposition of diatom-rich biogenic sediments and of terrigenous sediments. Sediment properties and geochemical data explain the contrasting lamination, with light layers being finer-grained and relatively rich in total organic carbon and biogenic silica content. Also, the high-resolution magnetic susceptibility (MS) variations highlight distinct features: high MS values coincide with clastic-rich sections and low MS values correspond to biogenic sections. The chronology developed for core A9-EB2 accounts for anomalous ages associated with turbidites and shows a linear sedimentation rate of approximately 87 cm/103 yr, which is supported by an accumulation rate of 80 cm/103 yr calculated from 210Pb activity. The late Holocene records clearly identify Neoglacial events of the Little Ice Age (LIA) and Medieval Warm Period (MWP). Other unexplained climatic events comparable in duration and amplitude to the LIA and MWP events also appear in the MS record, suggesting intrinsically unstable climatic conditions during the late Holocene in the Bransfield Basin of Antarctic Peninsula. [Copyright &y& Elsevier]

Analyses of sedimentological, geochemical and micropaleontological parameters from radiocarbon-dated sediment cores retrieved from the Antarctic Peninsula’s western continental shelf reveal a detailed paleoclimatic and/or paleoceanographic history over the last 15 000 radiocarbon years. Deglaciation of the outer shelf off Anvers Island commenced prior to at least 15 000 yr BP, marked by the deposition of distal glaciomarine diamicton (facies 2) beneath a floating ice shelf, and lasted for 3800 years with increasing diatom abundance and total organic carbon (TOC) over time. A return to colder conditions occurred between 12 800 and 11 600 yr BP with a drop in TOC content and diatom abundance, which is coincident with the Younger Dryas event in the North Atlantic region. At this time, an abrupt increase in percentage sea-ice taxa as well as in the ratio of (Fragilariopsis curta+Fragilariopsis cylindrus)/Thalassiosira antarctica suggests renewed ice-shelf advance. In contrast, the inner shelf was deglaciated somewhat later about 11 000 yr BP, that is, 3000 years after the outer shelf. Prior to 11 000 yr BP, deposition of proximal glaciomarine diamicton (facies 1) close to the grounding line under a floating ice shelf and/or persistent sea ice may have occurred on the inner shelf. After this date, deposition of distal glaciomarine diamicton (facies 2) followed. A climatic optimum is recognized between 6000 and 2500 yr BP, coinciding with a ‘mid-Holocene climatic optimum’ from several other Antarctic sites, e.g. the Palmer Deep. During this time, as the glacial system receded from the shelf, greatly enhanced primary productivity occurred in open marine conditions, resulting in the deposition of diatomaceous mud (facies 3) and causing post-depositional dissolution of calcareous benthic and planktonic foraminifers in sediment. Around 2500 yr BP (the onset of the Neoglacial), diatomaceous sandy mud (facies 4), characterized by a decrease in TOC and diatom abundance, reflects the formation of more extensive and seasonally persistent sea ice, as evidenced by an increase in percentage of sea-ice taxa and in the ratio of (F. curta+F. cylindrus)/T. antarctica. Our results provide evidence of climatic change on the Antarctic Peninsula’s western shelf that helps to refine the existence and timing of late Pleistocene and Holocene millennial-scale climatic events in the Southern Hemisphere. [Copyright &y& Elsevier]

This article [1] has been retracted at the request of the Editors-in-Chief because it has been previously published by Bae, S.H., Yoon, H.I., Park, B. et al [2]. This article is therefore redundant. [ABSTRACT FROM AUTHOR]

Background: Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC).Research Question: Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC?Study Design and Methods: We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses.Results: STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity.Interpretation: Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS. [ABSTRACT FROM AUTHOR]

Background and objective Inhaled medications have been widely applied to patients with airflow limiting non-cystic fibrosis (non- CF) bronchiectasis. However, the association between the use of inhalers and the development of haemoptysis has rarely been explored. The objective of this study was to assess the association between the risk of haemoptysis and the use of inhalers in patients with non- CF bronchiectasis. Methods A nested case-control study was performed using a national claims database from 1 January 2009 to 31 December 2011. Inhalers including inhaled corticosteroids ( ICS), long-acting β2 agonists ( LABA), long-acting muscarinic antagonists ( LAMA), short-acting β2 agonists ( SABA), short-acting muscarinic antagonists ( SAMA) and their combinations were tested for the risk of clinically significant haemoptysis events. Results Among the 62 530 eligible new users of inhalers with non- CF bronchiectasis, 6180 patients with haemoptysis and 27 486 strictly matched controls were selected. In the unadjusted analyses, SAMA, LAMA, SABA and ICS/ LABA significantly increased the risk of haemoptysis. After adjustment for other inhaled respiratory medications, comorbidities, health-care utilization and concomitant medications, SAMA, SABA and LAMA consistently increased the risk of haemoptysis ( SAMA: odds ratio ( OR), 1.6; 95% confidence interval ( CI), 1.1-1.4; LAMA: OR, 1.2; 95% CI: 1.1-1.2; SABA: OR, 1.2; 95% CI: 1.1-1.2). The association between anticholinergics ( SAMA and LAMA) and risk of haemoptysis showed a dose-dependent trend ( P for trend, <0.001). Conclusions The use of SABA and inhaled anticholinergics in patients with non- CF bronchiectasis increased the risk of haemoptysis. The risk-benefit ratio of inhaled bronchodilators should be considered in the haemoptysis-susceptible population. [ABSTRACT FROM AUTHOR]

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271–4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF. [ABSTRACT FROM AUTHOR]

The accumulation of heavy metals in plant communities has been investigated in the maritime Antarctica but their sources are not clearly identified yet. Here we measured Pb isotope ratios in the mosses Sanionia uncinata (Hedw.) Loeske, soils and bedrocks on King George Island, South Shetland Islands, West Antarctica in order to elucidate the sources of Pb in the moss samples. The enrichment factor of Pb indicated that the moss samples near the research station and oil tank are highly enriched in Pb which is attributed to either leaded gasoline and/or Patagonian aeolian dust. However, Pb isotope ratios clearly indicated that leaded gasoline is the main source of Pb in the moss within 1 km from the station and that chemical weathering of soil and bedrock controls Pb content in the moss far from the station (over 1 km from the station). This study clearly demonstrated that Pb in plant communities, especially moss Sanionia uncinata (Hedw.) Loeske, on King George Island is mainly originated from a mixture of leaded gasoline and chemical weathering with a little effect of Patagonian aeolian dust. [ABSTRACT FROM AUTHOR]

Purpose: The importance of dying with dignity in the intensive care unit (ICU) has been emphasized. The South Korean government implemented the "well-dying law" in 2018, which enables patients to refuse futile life-sustaining treatment (LST) after being determined as terminally ill. We aimed to study whether the well-dying law is associated with a significant change in the quality of death in the ICU. Methods: The Quality of Dying and Death (QODD) questionnaires were prospectively collected from the doctors and nurses of deceased patients of four South Korean medical ICUs after the law was passed (January 2019 to May 2020). Results were compared with those of our previous study, which used the same metric before the law was passed (June 2016 to May 2017). We compared baseline characteristics of the deceased patients, enrolled staff, QODD scores, and staff opinions about withdrawing LST from before to after the law was passed. Results: After the well-dying law was passed, deceased patients (N = 252) were slightly older (68.6 vs. 66.6, p = 0.03) and fewer patients were admitted to the ICU for post-resuscitation care (10.3% vs. 20%, p = 0.003). The mean total QODD score significantly increased after the law was passed (36.9 vs. 31.3, p = 0.001). The law had a positive independent association with the increased QODD score in a multiple regression analysis. Conclusion: Our study is the first to show that implementing the well-dying law is associated with quality of death in the ICU, although the quality of death in South Korea remains relatively low and should be further improved. [ABSTRACT FROM AUTHOR]

Background: The purpose of a rapid response system (RRS) is to reduce the incidence of preventable cardiopulmonary arrests (CPAs) and patient deterioration in general wards. The objective of this study is to investigate the incidence and temporal trends of preventable CPAs and determine factors associated with preventable CPAs in a hospital with a mature RRS. Methods: This was a single-center prospective cohort study of all CPAs occurring in the general ward between March 2017 and June 2020. The RRS operates from 07:00 to 23:00 on weekdays and from 07:00 to 12:00 on Saturdays. All CPAs were reviewed upon biweekly conference, and a panel of intensivists judged their preventability. Trends of preventable CPAs were analyzed using Poisson regression models and factors associated with preventable CPAs were analyzed using multivariable logistic regression. Results: There were 253 CPAs over 40 months, and 64 (25.3%) of these were preventable. The incidence rate of CPAs was 1.07 per 1000 admissions and that of preventable CPAs was 0.27 per 1000 admissions. The number of preventable CPAs decreased by 24% each year (incidence rate ratio = 0.76; p = 0.039) without a change in the total CPA incidence. The most common contributor to the preventability was delayed response from physicians (n = 41, 64.1%). A predictable CPA with a pre-alarm sign had increased odds in the occurrence of preventable CPAs, while a cardiac cause of CPAs and RRS operating hours had decreased odds in terms of occurrence of preventable CPA. Conclusion: Our study showed that one-fourth of all CPAs occurring in the general wards were preventable, and these arrests decreased each year. A mature RRS can evolve to reduce preventable CPAs with regular self-evaluation. Efforts should be directed at improving physicians' response time since a delay in their response was the most common cause of preventable CPAs. [ABSTRACT FROM AUTHOR]

Anesthesiologists commonly use video bronchoscopy to facilitate intubation or confirm the location of the endotracheal tube; however, depth and orientation in the bronchial tree can often be confused because anesthesiologists cannot trace the airway from the oropharynx when it is performed using an endotracheal tube. Moreover, the decubitus position is often used in certain surgeries. Although it occurs rarely, the misinterpretation of tube location can cause accidental extubation or endobronchial intubation, which can lead to hyperinflation. Thus, video bronchoscopy with a decision supporting system using artificial intelligence would be useful in the anesthesiologic process. In this study, we aimed to develop an artificial intelligence model robust to rotation and covering using video bronchoscopy images. We collected video bronchoscopic images from an institutional database. Collected images were automatically labeled by an optical character recognition engine as the carina and left/right main bronchus. Except 180 images for the evaluation dataset, 80% were randomly allocated to the training dataset. The remaining images were assigned to the validation and test datasets in a 7:3 ratio. Random image rotation and circular cropping were applied. Ten kinds of pretrained models with < 25 million parameters were trained on the training and validation datasets. The model showing the best prediction accuracy for the test dataset was selected as the final model. Six human experts reviewed the evaluation dataset for the inference of anatomical locations to compare its performance with that of the final model. In the experiments, 8688 images were prepared and assigned to the evaluation (180), training (6806), validation (1191), and test (511) datasets. The EfficientNetB1 model showed the highest accuracy (0.86) and was selected as the final model. For the evaluation dataset, the final model showed better performance (accuracy, 0.84) than almost all human experts (0.38, 0.44, 0.51, 0.68, and 0.63), and only the most-experienced pulmonologist showed performance comparable (0.82) with that of the final model. The performance of human experts was generally proportional to their experiences. The performance difference between anesthesiologists and pulmonologists was marked in discrimination of the right main bronchus. Using bronchoscopic images, our model could distinguish anatomical locations among the carina and both main bronchi under random rotation and covering. The performance was comparable with that of the most-experienced human expert. This model can be a basis for designing a clinical decision support system with video bronchoscopy. [ABSTRACT FROM AUTHOR]

Abstract: A 4.96-m-long sediment core from the Hanon paleo-maar in Jeju Island, Korea was studied to investigate the paleoclimatic change and East Asian monsoon variations during the latest Pleistocene to early Holocene (23,000–9000 cal yr BP). High-resolution TOC content, magnetic susceptibility, and major element composition data indicate that Jeju Island experienced the coldest climate around 18,000 cal yr BP, which corresponds to the last glacial maximum (LGM). Further, these multi-proxy data show an abrupt shift in climatic regime from cold and arid to warm and humid conditions at around 14,000 cal yr BP, which represents the commencement of the last major deglaciation. After the last major deglaciation, the TOC content decreased from 13,300 to 12,000 cal yr BP and from 11,500 to 9800 cal yr BP, thereby reflecting the weakening of the summer monsoon. The LGM in Jeju Island occurred later in comparison with the Chinese Loess Plateau. Such a disparity in climatic change events between central China and Jeju Island appears to be caused by the asynchrony between the coldest temperature event and the minimum precipitation event in central China and by the buffering effect of the Pacific Ocean. [Copyright &y& Elsevier]

Abstract: Several reworked tephra layers in gravity-flow deposits are present in lacustrine core sediments collected from Hotel and Rudy Lakes on King George Island, South Shetland Islands, maritime sub-Antarctica. This study tests the values of tephra for establishing regional tephrochronologies for lakes in ice-covered landscapes in the vicinity of volcanoes. The tephra record is more abundant in a long Hotel Lake core (515cm long). This study uses volcanic glass samples from five tephra layers of Hotel Lake and from one tephra layer of Rudy Lake. Morphologically, tephras are mixtures of basaltic and pumice shards, both having various degrees of vesicularity. Major element analyses of glass shards reveal that the majority of the glass fragments belong to basic glass (<60wt% SiO2), compositionally ranging from basalt to low-silica andesite and subalkaline series medium-K tholeiites, probably sourced from Deception Island located 130km southwest of King George Island. Less than 20% of tephra belongs to silicic glass and occurs in three tephra horizons E of Hotel Lake. However, source volcano(es) for about 10% of basic tephra and silicic tephra are not readily identified from nearby volcanic centers. Except for the studied tephra in Rudy Lake, all tephra samples in Hotel Lake are not ashfall deposits but reworked and redeposited pyroclasts derived from retreating ice sheet, resulting in the occurrence of geochemically equivalent tephra samples in different tephra horizons. The dating of the studied tephra horizons represents the timing of deglaciation rather than that of volcanic eruptions. The result of this study implies that combined with sedimentological information more chemical criterion is necessary to study tephrochronology and regional correlation and to understand paleoenvironmental changes using tephra. [Copyright &y& Elsevier]

Summary: Ground-glass opacity (GGO) attracts attention because of the possibility of early lung cancer. However, some lesions are reduced in size or disappear at follow-up. This study was designed to explore the natural history of solitary GGO, to determine the prevalence of malignancy and to identify factors predictive of benignity or malignancy. Solitary and focal GGO lesions [pGGO (p=pure) and mGGO (m=mixed) based on the presence of a solid component] of less than 3cm were included. Lesions of less than 1cm were followed up by chest HRCT 3 months later and lesions over 1cm were investigated by percutaneous needle biopsy (PCNB). One hundred and eighty-six patients (69 pGGO and 117 mGGO) were enrolled. Of the 69 pGGO lesions, 7 were diagnosed as pre-malignant or malignant lesions, 3 as benign lesions and 26 pGGO lesions (37.6%) were reduced or disappeared (transient lesions) at follow-up chest HRCT. The other 33 lesions showed no significant change during follow-up. Thus, the probability of malignancy in pGGO was 7/36 (19.4%). On the other hand, of the 117 mGGO lesions, 26 were found to be malignant, 3 were diagnosed as benign and 57 lesions (48.7%) were reduced or had disappeared at follow-up chest HRCT. The other 31 lesions showed no change during follow-up, and thus the probability of malignancy in mGGO was 26/86 (30.2%). A female sex and a spiculated mGGO border were found to be related with malignancy. However, a high blood eosinophil count was strongly associated with regressing or transient mGGO, suggesting that pulmonary infiltrate with eosinophilia (PIE) might have been responsible. We recommend short-term follow-up by chest HRCT be conducted for mGGO lesions in the presence of high eosinophilia—regardless of lesion size. [Copyright &y& Elsevier]

Context A recently developed whole-blood interferon γ (IFN-γ) assay based on stimulation with the Mycobacterium tuberculosis–specific antigens early secreted antigenic target 6 and culture filtrate protein 10 shows promise for the diagnosis of latent tuberculosis (TB) infection. Objective To compare the tuberculin skin test (TST) and the whole-blood IFN-γ assay in the diagnosis of latent TB infection according to the intensity of exposure. Design and Setting A prospective comparison between the whole-blood IFN-γ assay and the TST using a 2-TU dose of purified protein derivative RT23 in a population with intermediate TB burden was conducted sequentially between February 1, 2004, and February 28, 2005, in a Korean tertiary referral hospital. Participants Of 273 participants, 220 (95.7%) had received BCG vaccine. Participants were grouped according to their risk of infection: group 1, no identifiable risk of M tuberculosis infection (n = 99); group 2, recent casual contacts (n = 72); group 3, recent close contacts (n = 48); group 4, bacteriologically or pathologically confirmed TB patients (n = 54). Main Outcome Measures Levels of agreement between the TST and the IFN-γ assay and the likelihood of infection in the various groups. Results For the TST with a 10-mm induration cutoff, the positive response rate in group 1 was 51%; group 2, 60%; group 3, 71%, and group 4, 78%. For the IFN-γ assay, the positive response rate in group 1 was 4%; group 2, 10%; group 3, 44%; and group 4, 81%. The overall agreement between the TST and the IFN-γ assay in healthy volunteers was κ = 0.16. The odds of a positive test result per unit increase in exposure across the 4 groups increased by a factor of 5.31 (95% confidence interval [CI], 3.62-7.79) for the IFN-γ assay and by a factor of 1.52 (95% CI, 1.20-1.91) for the TST (P<.001). Using a 15-mm induration cutoff for the TST did not make a substantial difference to the test results. Conclusion The IFN-γ assay is a better indicator of the risk of M tuberculosis infection than TST in a BCG-vaccinated population. [ABSTRACT FROM AUTHOR]

Fine fractions of soils on the Barton Peninsula, King George Island, West Antarctica have been forming during the last 6000 yr since the last deglaciation. Texturally, they are mostly composed of mineral and rock fragments with some volcanic ashes, which are also indicated by geochemical compositions representing for the nonclay silicate minerals and low values of chemical index of alteration. No significant changes are observed in major- and trace element abundances. Such geochemical characteristics suggest that chemical weathering of bedrocks on the Barton Peninsula seems insignificant and that the soils are composed of physically weathered mineral and rock fragments which are mixed with eolian additions of volcanic ashes and Patagonian dusts. Chondrite-normalized rare earth element (REE) distribution patterns of the Barton Peninsula soils are slightly different from those of bedrocks, indicating that the REE abundances and characteristics were influenced by eolian additions. Mixing calculations, which mass-balance the REEs, suggest that volcanic ashes blown from Deception Island were the major eolian contributor, followed by atmospheric dusts sourced from Patagonia, South America. Even in the warmer and humid climatic conditions in the maritime Antarctic region, the chemical weathering of bedrocks appears to be insignificant, probably due to the relatively short duration of weathering since the last deglaciation. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Microbiological criteria for nontuberculous mycobacterial pulmonary disease (NTM-PD) require cultures from two separate sputum or one non-sputum specimen. However, there is limited data on the progression of NTM-PD following non-sputum culture-based diagnosis. We compared the disease progression of NTM-PD diagnosed with non-sputum vs sputum cultures. We included 833 patients and divided them into sputum NTM isolation (n = 123), sputum NTM-PD (n = 558), and non-sputum NTM-PD groups (n = 152). Disease progression, defined as radiographic aggravation and therapy initiation, was compared between groups. The median observation time was 60.5 months (interquartile range, 31.4–96.0). The non-sputum NTM-PD group showed longer treatment-free survival (log-rank test; p = 0.009) and lower risk of treatment (adjusted hazard ratio [aHR] of sputum NTM-PD group, 1.36; 95% confidence interval (CI), 1.01–1.84) than the sputum NTM-PD group. The non-sputum NTM-PD group showed longer radiographic aggravation-free survival (Log-rank test; p = 0.015) and lower risk of radiographic aggravation (aHR of sputum NTM-PD group, 1.52; 95% CI, 1.06–2.19) than the sputum NTM-PD group. NTM-PD diagnosed using methods other than sputum culture showed a low risk of disease progression and progressed slower than NTM-PD diagnosed from a sputum culture. NTM-PD diagnosed using methods other than sputum culture may be a mild disease, not equivalent to NTM-PD diagnosed from sputum culture. [ABSTRACT FROM AUTHOR]

Background: Pyrazinamide (PZA) is a common drug that causes serious adverse events (SAEs). The aim of this study was to determine the incidence of and risk factors for SAEs due to PZA during first-line anti-tuberculosis treatment. Methods: The medical records of patients with tuberculosis (TB) treated with PZA-containing regimens including first-line drugs—ethambutol, rifampicin, and isoniazid—from January 2003 to June 2016 were reviewed. SAEs were defined as side effects that led to drug discontinuation. The causative drug was determined based on the disappearance of the SAEs upon drug withdrawal and/or the recurrence of the same SAEs with re-challenge. Results: Of 2,478 patients with TB, 16.4% experienced SAEs. The incidence of SAEs increased significantly as age increased, except with rifampin. PZA accounted for most SAEs (55.8%). Hepatotoxicity was the most common SAE due to PZA (44.5%), followed by gastrointestinal (GI) intolerance (23.8%). The risk of SAEs due to PZA increased significantly as age increased, when sex and comorbidities were adjusted (odds ratio, 1.013; 95% confidence interval, 1.004–1.023; P = 0.007). In the subgroup analysis, older age was an independent risk factor for GI intolerance but not for hepatotoxicity. Conclusion: PZA was the most common drug associated with SAEs among the first-line anti-TB drugs, and old age was an independent factor for SAE occurrence. This study suggests that the early recognition of whether the causative agent is PZA may improve effective treatment compliance, particularly in elderly patients. [ABSTRACT FROM AUTHOR]

Over the past few decades the Arctic has warmed up more than the lower latitudes. Soil organic carbon (SOC) in the Arctic is vulnerable to climate change, and carbon dioxide (CO2) produced via SOC decomposition can amplify atmospheric temperature increase. Although SOC composition is relevant to decomposability, studies on its compositional changes with warming are scarce, particularly in the Arctic. Therefore, we investigated the responses of SOC and the bacterial community to climate manipulation under Cassiope and Salix heath vegetation communities in permafrost‐affected soil in Zackenberg, Greenland. After 8–9 years of experimental warming, we evaluated changes in SOC quantity and quality of three density fractions of soil: free light fraction (FLF), occluded light fraction (OLF) and heavy fraction (HF). The SOC content at 0–5‐cm depth was significantly reduced with warming under Cassiope, and it was accompanied by decreased FLF content, attributed to accelerated decomposition of the FLF by warming. However, SOC molecular composition and bacterial community composition were not affected by warming. By contrast, there was no warming effect on SOC under Salix, which could be partially due to smaller temperature increases caused by higher moisture levels associated with larger silt and clay contents, or to different responses of the dominant plant species to temperature. In both soils, more than 55% of SOC was associated with minerals, and its molecular composition indicated microbial decomposition. Our results suggested that long‐term warming in the high Arctic could induce the loss of SOC, particularly in the FLF; however, the response could vary with vegetation type and/or soil properties, that is, soil texture. Highlights: We show decreased SOC with long‐term (8‐year) warming of heath soils in the high ArcticParticularly, the free light fraction of SOC in topsoil decreased with warming in a Cassiope heath siteMineral‐associated SOC content was more than 55% and showed signs of microbial processingEffects of warming differed according to soil properties and/or plant community composition [ABSTRACT FROM AUTHOR]

Background: High-flow nasal cannula (HFNC) oxygen therapy has been widely used in critically ill patients. Despite the effectiveness of HFNC as a treatment, optimal methods to withdraw HFNC after recovery from preexisting conditions have not been investigated to date. In this study, we will evaluate the safety and efficacy of simultaneous reduction of flow and fraction of inspired oxygen (FiO2) compared with sequential reduction of either flow first or FiO2 reduction first in patients with HFNC.Methods/design: This is a prospective, investigator-initiated, randomized controlled trial with three experimental intervention groups. A total of 100 adult patients receiving HFNC and satisfying weaning criteria will be enrolled and randomly assigned to one of the following groups: flow reduction (FR) first, FiO2 reduction (OR) first, or simultaneous reduction (SR). In the FR group, flow will be reduced first by 10 L/min/h. When it reaches 20 L/min, FiO2 will then be reduced by 0.1 /h until it reaches 0.3. In the OR group, the FiO2 will be gradually reduced first by 0.1 /h until it reaches 0.3, then flow will be reduced by 10 L/min until it reaches 20 L/min. Finally, in the SR group, both the flow and FiO2 will be gradually reduced simultaneously by 10 L/min and 0.1/h, respectively. Weaning will proceed only when patients satisfy the weaning criteria at every weaning point. When the HFNC weaning-off targets are reached (20 L/min and 0.3 for flow and FiO2, respectively), the patient will be transferred to conventional oxygen therapy (mainly low-flow nasal prongs). The primary outcome is the time to successful weaning from HFNC for 24 h. Secondary outcomes will include the success or failure rate in weaning off HFNC and changes in arterial blood gas analyses, intolerance rate, length of hospital stay, and in-hospital mortality.Discussion: This study will be the first clinical trial to investigate the safety and efficacy of three different methods of weaning in adult patients receiving HFNC. Once this study is completed, we expect to be able to suggest the better strategy for withdrawal of HFNC based on the results.Trial Registration: ClinicalTrials.gov, NCT03845244. Registered on 19 February 2019. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality, therefore the prediction of mortality in COPD patients is crucial. In the current study, the abilities of different categorization systems to predict mortality in stable COPD patients from a prospective cohort were compared. Methods: The ability to predict mortality was compared in terms of discrimination by Harrell's C (HC) index and calibration using graphical comparison among the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011, GOLD 2017, GOLD grade, BODE (BMI, Airflow Obstruction, Dyspnea, Exercise), updated BODE, BODEx (BMI, Airflow Obstruction, Dyspnea, Exacerbation), e-BODE (Exacerbation and BODE), ADO (Age, Dyspnea, Airflow Obstruction), COPD prognostic index (CPI), and simplified/optimized B-AE-D (BMI, Acute Exacerbation, Dyspnea) indexes. Results: The study included 520 patients, of whom 63 died during a median 40-month follow-up period. Combined prediction systems exhibited higher discrimination properties than single predictors. The CPI exhibited the highest with a HC of 0.768, followed by the simplified B-AE-D (HC 0.761), ADO (HC 0.760), and optimized B-AE-D (HC 0.756). The BODE and its variants other than the ADO exhibited relatively lower HCs (0.656–0.705), and GOLD exhibited the lowest discrimination ability among the combined indices (HCs 0.628–0.637). Subjective symptom questionnaires such as the modified Medical Research Council (mMRC) scale (HC 0.693) and SGRQ (HC 0.679) exhibited the highest ability to predict mortality among the single indices. Conclusion: The ADO, simplified B-AE-D, optimized B-AE-D, and GOLD 2017 exhibited good calibration properties, but the CPI did not. The simplified and optimized B-AE-Ds and the ADO index had good discrimination and calibration properties for the prediction of mortality in stable COPD patients. [ABSTRACT FROM AUTHOR]

Background: Although scoring and machine learning methods have been developed to predict patient deterioration, bedside assessment by nurses should not be overlooked. This study aimed to evaluate the performance of subjective bedside assessment of the patient by the rapid response team (RRT) nurses in predicting short-term patient deterioration. Methods: Patients noticed by RRT nurses based on the vital sign instability, abnormal laboratory results, and direct contact via phone between November 1, 2016, and December 12, 2017, were included. Five RRT nurses visited the patients according to their shifts and assessed the possibility of patient deterioration. Patient acuity rating (PAR), a scale of 1–7, was used as the tool of bedside assessment. Other scores, including the modified early warning score, VitalPAC early warning score, standardised early warning score, and cardiac arrest risk triage, were calculated afterwards. The performance of these scores in predicting mortality and/or intensive care unit admission within 1 day was compared by calculating the area under the receiver operating curve. Results: A total of 1,426 patients were included in the study, of which 258 (18.1%) died or were admitted to the intensive care unit within 1 day. The area under the receiver operating curve of PAR was 0.87 (95% confidence interval [CI] 0.84–0.89), which was higher than those of modified early warning score (0.66, 95% CI 0.62–0.70), VitalPAC early warning score (0.69, 95% CI 0.66–0.73), standardised early warning score (0.67, 95% CI 0.63–0.70) and cardiac arrest risk triage (0.63, 95% CI 0.59–0.66) (P<0.001). Conclusions: PAR assessed by RRT nurses can be a useful tool for assessing short-term patient prognosis in the RRT setting. [ABSTRACT FROM AUTHOR]

Objectives: Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the "well-dying" law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death.Design: A multicenter cross-sectional survey study.Setting: Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals.Patients: Deceased patients from June 2016 to May 2017.Interventions: Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient's death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death.Measurements and Main Results: A total of 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death.Conclusions: The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients' families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the occurrence rate and risk factors of cardiopulmonary arrest (CPA) during intra-hospital transport (IHT) among critically ill patients, accompanied by a rapid response team (RRT). Methods: We performed a retrospective cohort study in a 1300-bed tertiary-care teaching hospital. Data of all admitted patients transported within the hospital and accompanied by the RRT from October 2012 to May 2016 were included. We compared patients with CPA (+) and patients without CPA (-) to identify risk factors for CPA during transport. Results: Among 535 patients, CPA occurred in eight (1.5%) patients during IHT. There were no significant differences in age, sex, and comorbidities between groups. More patients in the CPA (+) group than in the CPA (-) group received manual ventilation during IHT (75% vs. 23.0%, p = 0.001). An increased risk of CPA (p<0.001) corresponded with a higher number of vasopressors used during IHT. In univariate logistic regression analysis, history of myocardial infarction (OR 10.7, 95% CI 2.4–50.5, p = 0.005), manual ventilation (OR 10.1, 95% CI 2.0–50.5, p = 0.005), and use of three or more vasopressors (OR 11.1, 95% CI 2.5–48.9, p = 0.001) were significantly associated with risk of CPA during RRT-led IHT. Conclusions: Despite accompaniment by a specialized team such as the RRT, CPA can occur during IHT. History of myocardial infarction, manual ventilation with bag-valve mask, and the use of three or more vasopressors were independent risk factors of CPA during IHT of critically ill patients accompanied by the RRT. [ABSTRACT FROM AUTHOR]

Purpose: Intensive care unit (ICU)-related mortality for lung cancer is ranked highest among the solid tumors and little information exists on the role of intensivists on clinical outcomes. This study aimed to elucidate the intensivist’s contribution toward clinical outcomes. Materials and methods: Data of advanced lung cancer patients, including stage IIIB or IV non-small cell lung cancer and extensive-stage small cell lung cancer, admitted to the ICU from 2005 to 2016 were analyzed. Multivariate logistic regression was performed to determine variables associated with ICU and in-hospital mortality. Autoregressive integrated moving average (ARIMA) for time-series was used to assess the intensivist’s impact. Results: Of 264 patients, 85 (32.2%) were admitted to the ICU before and 179 (67.8%) after organized intensive care introduction in 2011. Before and after 2011, the changes observed were as follows: ICU mortality rate, 43.5% to 40.2%, respectively (p = 0.610); hospital mortality rate, 82.4% to 65. 9% (p = 0.006). The duration of ICU and hospital stay decreased after 2011 (14.5±16.5 vs. 8.3 ± 8.6, p < 0.001; 36.6 ± 37.2 vs. 22.0 ± 19.6, p < 0.001). On multivariate analysis, admission after 2011 was independently associated with decreased hospital mortality (Odds ratio 0.42, 95% confidence interval 0.21–0.77, p = 0.006). In ARIMA models, intensivist involvement was associated with significantly reduced hospital mortality. (Estimate -17.95, standard error 5.31, p = 0.001) Conclusion: In patients with advanced lung cancer, organized intensive care could contribute to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.Methods: We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Patients, aged 20-80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460.Findings: Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI -4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and -1·1% (-11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient.Interpretation: Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis.Funding: Ministry of Health and Welfare, South Korea. [ABSTRACT FROM AUTHOR]

Background: This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.Methods: A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.Results: ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p < 0.001). Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs. 0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs. 0.12, p = 0.03).Conclusions: Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators. ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients' characteristics. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated tracheobronchitis (VAT) is an important risk factor for ventilator-associated pneumonia (VAP). The efficacy of aerosolized vancomycin (AV) in treating VAT has not been clearly demonstrated. Methods: Four mechanically ventilated patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia were treated with an additional AV. AV (250 mg twice per day) was administered through a vibrating mesh device for 5 days. All patients were receiving intravenous vancomycin and had severe tracheobronchitis, based on bronchoscopic findings before or soon after additional AV treatment. Results: After several days of AV treatment, follow-up bronchoscopies showed dramatic improvement of tracheobronchitis. All patients achieved microbiological eradication of MRSA. Finally, two of four patients survived through to hospital discharge. Conclusion: This case series study suggests a potential role of AV in the treatment of MRSA tracheobronchitis, which were accompanied by VAP. Clinical trial addressing the efficacy of AV in MRSA VAT and/or VAP should be needed. [ABSTRACT FROM AUTHOR]

Highlights • Immune checkpoint inhibitors can cause pneumonitis in lung cancer patients. • Interstitial lung disease was associated with a higher incidence of pneumonitis. • Extrathoracic metastasis was associated with a lower incidence of pneumonitis. Abstract Objectives Immune checkpoint inhibitors (ICIs) can cause pneumonitis in lung cancer patients. We aimed to identify the clinical and radiologic characteristics, incidence, and risk factors of ICI-related pneumonitis in patients with non-small cell lung cancer (NSCLC). Materials and Methods Medical records and chest computed tomography scans of NSCLC patients treated with an ICI over a 5-year period at a tertiary hospital were retrospectively analyzed. Clinical characteristics were compared between patients with and without ICI-related pneumonitis to identify risk factors. Results Data from 167 eligible patients were analyzed. The incidences of all-grade and grade 3–4 pneumonitis were 13.2% and 4.2%, respectively. The presence of preexisting interstitial lung disease [odd ratio (OR), 6.03; 95% confidence interval (CI), 1.19–30.45; P = 0.030] was associated with a higher incidence of ICI-related pneumonitis. The presence of extrathoracic metastasis [OR, 0.34; 95% CI, 0.13–0.92; P = 0.034] was associated with a lower incidence of ICI-related pneumonitis. The dominant radiologic pattern (72.7%) of ICI-related pneumonitis was organizing pneumonia. Half of the patients with pneumonitis completely recovered or improved; however, the mortality rate was 18.2%. Conclusion ICIs should be used with caution when treating lung cancer patients who have underlying chronic lung disease, especially interstitial lung disease. [ABSTRACT FROM AUTHOR]

Magnetic susceptibility (MS) values in Scotia Sea sediments showed strong correlations to ice core non-sea salt Ca 2+ concentration (dust input), which emphasizes the role of atmospheric circulation in the Southern Ocean. As a result, the correlation between these values was suggested as a powerful tool for age reconstruction of marine sediments in the Southern Ocean. However, controls on MS variation in Scotia Sea sediments are not clear. In this study, we documented records of grain size, MS values (10 −6  CGS/g) of bulk sediments, and MS values of sand-sized (>63 μm), coarse silt-sized (16–63 μm), and fine sediment fractions (<16 μm) at sediment cores from the Southern Ocean off the northern Antarctic Peninsula (the south Scotia Sea and the northern Powell Basin) to reveal which size fraction is responsible for increased MS values during the glacial period and how this size fraction is transported to the Southern Ocean deep-sea. The MS values of all cores GC02-SS02, GC03-C2, GC03-C4, and GC04-G03 increased along with increased sand- and coarse silt-sized fractions and decreased fine sediment fraction. Although The MS values of all size fractions increased during the glacial period, the increased glacial MS values are more related to fine sand- to coarse silt-sized fractions than they are to the fine sediment fraction. The fine sand- to coarse silt-sized sediments with the highest MS values during the glacial period show (semi-)normal distribution patterns, indicating that they are transported by the same mechanism. The sediments are considered to be transported as ice rafted debris (IRD) during the glacial period. Based on our record, the strong correlation between marine core MS values and ice core dust record thus suggests a strong linkage between the cryosphere (iceberg calving activity) and atmospheric circulation (dust) in the Southern Ocean off the northern Antarctic Peninsula. [ABSTRACT FROM AUTHOR]

Efforts to detect patient deterioration early have led to the development of early warning score (EWS) models. However, these models are disease-nonspecific and have shown variable accuracy in predicting unexpected critical events. Here, we propose a simpler and more accurate method for predicting risk in respiratory ward patients. This retrospective study analyzed adult patients who were admitted to the respiratory ward and detected using the rapid response system (RRS). Study outcomes included transfer to the intensive care unit (ICU) within 24 hours after RRS activation and in-hospital mortality. Prediction power of existing EWS models including Modified EWS (MEWS), National EWS (NEWS), and VitalPAC EWS (ViEWS) and SpO2/FiO2 (SF) ratio were compared to each other using the area under the receiver operating characteristic curve (AUROC). Overall, 456 patients were included; median age was 75 years (interquartile range: 65–80) and 344 (75.4%) were male. Seventy-three (16.0%) and 79 (17.3%) patients were transferred to the ICU and died. The SF ratio displayed better or comparable predictive accuracy for unexpected ICU transfer (AUROC: 0.744) compared to MEWS (0.744 vs. 0.653, P = 0.03), NEWS (0.744 vs. 0.667, P = 0.04), and ViEWS (0.744 vs. 0.675, P = 0.06). For in-hospital mortality, although there was no statistical difference, the AUROC of the SF ratio (0.660) was higher than that of each of the preexisting EWS models. In comparison with the preexisting EWS models, the SF ratio showed better or comparable predictive accuracy for unexpected ICU transfers in the respiratory wards. [ABSTRACT FROM AUTHOR]

Background: Mediastinal lymph node enlargement (LNE) is common in idiopathic pulmonary fibrosis (IPF) and is known to be associated with the severity of lung fibrosis. However, the relationship between mediastinal LNE and the prognosis of IPF has not been determined to date. Methods: This study included patients with IPF from the interstitial lung disease registry at Seoul National University Bundang Hospital, from January 2012 to March 2016. Two thoracic radiologists independently reviewed mediastinal LNE and lung parenchymal fibrosis and ground glass opacities in chest computed tomography scans of each patient, which were obtained upon diagnosis. Mortality and admission rates were analyzed. Results: In total, 132 patients (104 [78.8%] male; median age, 72 years; range, 51–84 years) were enrolled and 73 (55.3%) patients had mediastinal LNE (short axis ≥ 10 mm in diameter). Mortality was significantly higher among patients with LNE than among those without LNE (hazard ratio 2.26 [95% confidence interval 1.20–4.23], p = 0.011). Of the patients with LNE, 24.7% experienced acute exacerbation and 43.8% experienced hospital admission for respiratory causes, in comparison with 16.9% and 40.0% of patients without LNE respectively. Although patients with LNE had a tendency to have increased rate of acute exacerbation, it was not statistically significant. Conclusion: Mediastinal LNE in IPF is associated with increased mortality and its occurrence may be considered a poor prognostic factor in patients with IPF. [ABSTRACT FROM AUTHOR]

Paleoceanographic changes in response to Holocene climate variability in Bigo Bay, west Antarctic Peninsula (WAP) were reconstructed through geochemical, isotopic, sedimentological, and microfossil analysis. Core WAP13-GC47 is composed of 4 lithologic units. Unit 4 was deposited under ice shelf settings. Unit 3 represents the mid-Holocene open marine conditions. Unit 2 indicates lateral sediment transport by a glacier advance during the Neoglacial period. The chronological contrast between the timing of open marine conditions at core WAP13-GC47 ( ca . 7060 cal. yr BP at 540 cm) and the ages of calcareous shell fragments ( ca . 8500 cal. yr BP) in Unit 2b suggests sediment reworking during the Neoglacial period. Unit 1 was deposited during the Medieval Warm Period (MWP) and the Little Ice Age (LIA). Surface water productivity, represented by biogenic opal and total organic carbon (TOC) concentrations, increased and bulk δ 15 N (nitrate utilization) decreased during the warmer early to middle Holocene and the MWP. In contrast, surface water productivity decreased with increased bulk δ 15 N during the colder Neoglacial period and LIA in Bigo Bay. The nitrate utilization was enhanced during cold periods in association with strong surface water stratification resulting from increased sea ice meltwater discharge or proximity to an ice shelf calving front in Bigo Bay. Reduced nitrate utilization during warm periods is related to weak stratification induced by less sea ice meltwater input and stronger Circumpolar Deep Water influence. [ABSTRACT FROM AUTHOR]

Objective: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. Methods: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy. Results: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers. Conclusion: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer. [ABSTRACT FROM AUTHOR]

We measured meteoric 10 Be variation throughout a marine sediment core from the Larsen B embayment (LBE) of the Antarctic Peninsula, and collected in situ 10 Be and 14 C exposure ages on terrestrial glacial deposits from the northern and southern margins of the LBE. We use these data to reconstruct Last Glacial Maximum (LGM) to present deglaciation and ice shelf change in the LBE. Core sedimentary facies and meteoric 10 Be data show a monotonic progression from subglacial deposits to sub-ice-shelf deposits to open-marine conditions, indicating that its collapse in 2002 was unprecedented since the LGM. Exposure-age data from the southern LBE indicate 40 m of ice surface lowering between 14 and 6 ka, then little change between 6 ka and the 2002 collapse. Exposure-age data from the northern LBE show a bimodal distribution in which clusters of apparent exposure ages in the ranges 4.9–5.1 ka and 1.0–2.0 ka coexist near 50 m elevation. Based on these results, other published terrestrial and marine deglaciation ages, and a compilation of sea bed imagery, we suggest a north-to-south progression of deglaciation in the northeast Antarctic Peninsula in response to Holocene atmospheric and oceanic warming. We argue that local topography and ice configuration inherited from the LGM, in addition to climate change, are important in controlling the deglaciation history in this region. [ABSTRACT FROM AUTHOR]

Background: Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Methods: Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Results: Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results. Conclusions: The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection. [ABSTRACT FROM AUTHOR]

Background: Although depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF), their impact on the clinical course and prognosis of IPF remain unclear. Purpose: We investigated the prevalence and clinical significance of depression and anxiety in patients with IPF. Methods: The present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. Results: Symptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8). No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC) scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ) scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003). The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without. Conclusions: Our findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF. [ABSTRACT FROM AUTHOR]

Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p -aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight <50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500–750 mg of cycloserine QD, 4.95–6.6 g of PAS twice daily and 750–1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment. [ABSTRACT FROM AUTHOR]

The redox reaction between 4-chlorophenol (4-CP) and chromate (Cr(VI)) (i.e., the simultaneous oxidation of 4-CP by Cr(VI) and reduction of Cr(VI) by 4-CP) in ice (i.e., at −20 °C) was compared with the corresponding reaction in water (i.e., at 25 °C). The redox conversion of 4-CP/Cr(VI), which was negligible in water, was significantly accelerated in ice. This accelerated redox conversion of 4-CP/Cr(VI) in ice is ascribed to the freeze concentration effect occurring during freezing, which excludes solutes (i.e., 4-CP and Cr(VI)) and protons from the ice crystals and subsequently concentrates them in the liquid brine. The concentrations of Cr(VI) and protons in the liquid brine were confirmed by measuring the optical image and the UV–vis absorption spectra of cresol red (CR) as a pH indicator of frozen solution. The redox conversion of 4-CP/Cr(VI) was observed in water when the concentrations of 4-CP/protons or Cr(VI)/protons increased by 100/1000-fold. These results corroborate the freeze concentration effect as the reason for the accelerated redox conversion of 4-CP/Cr(VI) in ice. The redox conversion of various phenolic pollutants/Cr(VI) and 4-CP/Cr(VI) in real wastewater was successfully achieved in ice, which verifies the environmental relevance and importance of freezing-accelerated redox conversion of phenolic pollutants/Cr(VI) in cold regions. [ABSTRACT FROM AUTHOR]

Although there have been concerns that inhaled long-acting muscarinic antagonists increase the risk of stroke, controversies exist. We investigated whether respiratory drugs including long-acting muscarinic antagonists are associated with the risk of stroke. A nested case-control study using the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea) was conducted. Overall, 16,354 stroke cases and 74,451 matched (up to 1:5) controls were identified from 809,684 subjects without acute major cardiovascular events in the past year between January 1, 2010, and December 31, 2011. To determine whether the use of inhaled respiratory drugs is associated with the risk of stroke, conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed. After adjusting for covariates, there were no statistically significant effects of the inhaled drugs on stroke incidence, except for inhaled corticosteroids without a long-acting β 2 -agonists, which was significantly associated with hemorrhagic stroke. Inhaled respiratory medications, including long-acting muscarinic antagonists, did not affect the risk of stroke in the inhaled respiratory drug users. [ABSTRACT FROM AUTHOR]

Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30–49 years, 86.5% and 94.7%; 50–69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. [ABSTRACT FROM AUTHOR]

Background and objective Development of CPE in CAP is associated with prolonged hospital stay and it may increase the morbidity and mortality. We aimed to identify microbiological and clinical factors that predicate a prolonged hospital admission in patients treated with a tube thoracostomy to control CPE. Methods This retrospective cohort included patients with CPE requiring chest tube drainage in a tertiary referral Korean hospital from 1 January 2004 to 30 July 2012. After dichotomous grouping according to the mean duration of hospital stay, clinical, laboratory and microbiological parameters were compared. Results The final analysis included 158 patients with CPE. The majority were male (130, 85.0%), and the mean age was 62.8 years. The mean duration of hospital stay was 17.7 (±10.2) days. The mean duration of chest tube drainage was 9.6 (±6.7) days. Streptococcus viridans (48.4%) was the most common pathogen. Intrapleural fibrinolysis was performed in 85 (53.8%); additional tube insertion was needed in 40 (25.3%) patients. In the multivariate analysis after adjusting for covariates, a prolonged hospital stay was associated with fever (aOR: 3.42, P = 0.02), lower PaO2 (a OR: 4.89, P = 0.007) and haemoglobin (aOR: 4.90, P = 0.003) levels, and an increased blood neutrophil fraction (a OR: 3.83, P = 0.01) on admission as well as the identification of microbes in CPE (a OR: 4.14, P = 0.03), and ineffective pleural drainage (a OR: 3.28, P = 0.03). Conclusions This study suggests that physicians should note the clinical symptoms and laboratory findings of severe infection and effectiveness of pleural drainage to predicate which patients with a CAP needing thoracostomy for CPE will have a prolonged hospital stay. [ABSTRACT FROM AUTHOR]

Background and objective A handful of studies have reported that bronchoscopies influence the clinical outcome of mechanically ventilated patients with aspiration pneumonia. The purpose of the present study is to elucidate the therapeutic role of early bronchoscopy in patients with aspiration who are mechanically ventilated. Methods A retrospective cohort study was conducted via medical record review from 2003 through 2013 in a tertiary hospital. All the diagnoses of pneumonia were supported by the probability of aspiration and consolidation of dependent areas confirmed by computed tomography. Patients who underwent bronchoscopy within 24 h after intubation were categorized as the early bronchoscopy group and the others as the late bronchoscopy group. We compared the demographics, clinical parameters and outcomes between the two groups. Results Of the 154 patients who were included, the early bronchoscopy group ( n = 93) showed significantly lower in-intensive care unit ( ICU) mortality and 90-day mortality (in- ICU: 4.9% vs 24.6%; 90-day: 11.8 vs 32.8%) regardless of the initial empirical antibiotics. In addition, their sequential organ failure assessment score on day 7 tended to decrease more rapidly. Among the survivors, patients in the early bronchoscopy group were extubated earlier with a higher success rate, had a shorter length of mechanical ventilation and had a shorter ICU stay. The early bronchoscopy was associated with lower 90-day mortality in multivariate analysis (odds ratio: 0.412; 95% confidence interval: 0.192-0.883). Conclusions Early bronchoscopy could benefit the clinical outcomes of mechanically ventilated patients with aspiration pneumonia. [ABSTRACT FROM AUTHOR]

Objectives Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy. Patients and methods Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy. Results Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P = 0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P = 0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362–0.796; P = 0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419–1.051; P = 0.080). Conclusion Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]