A Natural Virucidal and Microbicidal Spray Based on Polyphenol-Iron Sols.

Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).

The prognosis of non-small cell lung cancer patients according to endobronchial metastatic lesion.

To evaluate the prognosis of non-small cell lung cancer (NSCLC) patients according to endobronchial metastatic lesion (EML), especially those not identified on positron emission tomography or computed tomography. We evaluated progression-free survival (PFS) and overall survival (OS) according to the presence of EML in patients with NSCLC who were diagnosed at a tertiary hospital between January 2010 and December 2019. A total of 364 patients were enrolled in this study. EML was found in 69 (19.0%) patients with NSCLC. In the patients with EML versus the patients without EML, median PFS was 7.0 (3.5-13.5) and 9.5 (5.5-17.5) months (P = 0.011), and median OS was 12.0 (6.0-30.0) versus 20.0 (10.0-39.0) months (P = 0.016), respectively. Median PFS and OS rates were highest in epidermal growth factor receptor (EGFR) (+) and EML (-) patients and lowest in EGFR (-) and EML (+) patients (P < 0.001). By multivariate cox regression analysis, PFS in overall patients with NSCLC was significantly associated with EML, EGFR mutation, performance status, and pleural effusion. NSCLC patients with EML had worse prognoses of PFS and OS than patients without EML.

Abdominal lymph node metastasis by lymphatic spread through the thoracic duct in patients with non-small-cell lung cancer.

BACKGROUND: Abdominal lymph node metastasis (ALNM) is common in patients with metastatic non-small-cell lung cancer (NSCLC). However, its mechanism of spread remains to be elucidated. We investigated whether thoracic duct has the role as a pathway for ALNM in NSCLC using clinical data. METHODS: We classified ALNM into subgroups by their location and evaluated its prevalence and association with clinical characteristics in 892 patients with metastatic NSCLC. The abdominal lymph nodes were classified into direct or indirect groups depending on whether they drain directly into the trunk (intestinal trunk or lumbar trunks) connected to the cisterna chyli. RESULTS: One hundred-five patients (11.8%) had ALNM. The paraaortic lymph node was most commonly involved, followed by the aortocaval, left gastric, paracaval, and celiac lymph nodes. After grouping the patients by location of ALNM, 56 patients (53.3%) with ALNM were in the "direct only" group, only seven patients (6.7%) were in the "indirect only" group, and 42 patients (40.0%) were in "both" groups. In patients whose intrathoracic lesions were limited to the right thorax, there was a significantly lower prevalence of ALNM (3.4% vs. 14.3%, p < 0.001). On multivariate logistic regression analysis of clinical variables, higher N category was associated with increased risk of ALNM. CONCLUSIONS: This study suggests that the thoracic duct is one of the potential routes of lymphatic spread to the abdominal lymph nodes. Clinicians should assess for the presence of ALNM during staging work-up and follow-up for NSCLC patients with intrathoracic lesion in left thorax and with high N category.

Comparison of Antiviral Activity of Gemcitabine with 2'-Fluoro-2'-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human transmission. Nevertheless, there are no specific treatments clinically approved. This study aimed to compare antiviral activity of gemcitabine and its analogue 2'-fluoro-2'-deoxycytidine (2FdC) against SARS-CoV-2 as well as cytotoxicity in vitro. Fluorescent image-based antiviral assays revealed that gemcitabine was highly potent, with a 50% effective concentration (EC50) of 1.2 µM, more active than the well-known nucleoside monophosphate remdesivir (EC50 = 35.4 µM). In contrast, 2FdC was marginally active (EC50 = 175.2 µM). For all three compounds, the 50% cytotoxic concentration (CC50) values were over 300 µM toward Vero CCL-81 cells. Western blot and quantitative reverse-transcription polymerase chain reaction analyses verified that gemcitabine blocked viral protein expression in virus-infected cells, not only Vero CCL-81 cells but also Calu-3 human lung epithelial cells in a dose-dependent manner. It was found that gemcitabine has a synergistic effect when combined with remdesivir. This report suggests that the difluoro group of gemcitabine is critical for the antiviral activity and that its combination with other evaluated antiviral drugs, such as remdesivir, could be a desirable option to treat SARS-CoV-2 infection.

A variety of bacterial aetiologies in the lower respiratory tract at patients with endobronchial tuberculosis.

Recently, our understanding of the elusive bacterial communities in the lower respiratory tract and their role in chronic lung disease has increased significantly. However, little is known about the respiratory microorganisms in patients with endobronchial tuberculosis (EBTB), which is a chronic inflammatory disease characterized by destruction of the tracheobronchial tree due to Mycobacterium tuberculosis (MTB) infection. We retrospectively reviewed data for histopathologically and microbiologically confirmed EBTB patients diagnosed at a tertiary referral hospital in South Korea between January 2013 and January 2019. Bacterial cultures were performed on bronchial washing from these patients at the time of EBTB diagnosis. A total of 216 patients with EBTB were included in the study. The median age was 73 years and 142 (65.7%) patients were female. Bacteria were detected in 42 (19.4%) patients. Additionally, bacterial co-infection was present in 6 (2.8%) patients. Apart from MTB, the most common microorganisms identified were Staphylococcus aureus (n = 14, 33.3%) followed by Klebsiella species (n = 12, 28.6%; 10 Klebsiella pneumoniae, 2 Klebsiella oxytoca), Streptococcus species (n = 5, 11.9%), Enterobacter species (n = 4, 9.5%), and Pseudomonas aeruginosa (n = 3, 7.1%). A variety of microorganisms were isolated from the bronchial washing indicating that changes in microorganism composition occur in the airways of patients with EBTB. Further studies are needed to investigate the clinical significance of this finding.

Polysomnographic phenotype as a risk factor for cardiovascular diseases in patients with obstructive sleep apnea syndrome: a retrospective cohort study.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with the development of cardiovascular diseases caused by hypoxemia during sleeping. We classified OSAS phenotypes based on polysomnographic findings and aimed to evaluate that the unique phenotypes would be differentially associated with risk of cardiovascular disease. METHODS: This retrospective and observational study assessed adult patients who underwent polysomnography at the Wonju Severance Christian Hospital from November 2008 to February 2018. The OSAS phenotypes were classified as apnea-predominant, hypopnea-predominant, and respiratory effort-related arousal (RERA)-predominant based on the polysomnography results. The polysomnographic data were collected and analysed, and clinical features such as medical history and comorbidities were assessed by a review of the electronic medical records. RESULTS: A total of 860 adult patients were classified as apnea-predominant (n=220), hypopnea-predominant (n=119), or RERA-predominant (n=275). The hypopnea-predominant group had significantly higher rates of hyperlipidaemia (P<0.001), heart failure (15.5%, P<0.001), and coronary artery disease (20.9%, P=0.005) than the other groups. After classifying the patients according to severity of the hypopnea index, logistic regression analyses adjusted for age, sex, and smoking history revealed that the hypopnea index increased the risk for coronary artery disease and heart failure. CONCLUSIONS: The hypopnea-predominant group would be a specific phenotype that has a differential association with the risks for coronary artery disease and heart failure.

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

BACKGROUND: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. METHODS: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. RESULTS: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. CONCLUSIONS: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Feasibility of Bronchial Washing Fluid-Based Approach to Early-Stage Lung Cancer Diagnosis.

A blood-based approach such as circulating tumor DNA remains challenging in diagnosis for early-stage disease. Bronchial washing (BW) is a minimally invasive procedure that yields fluids that may contain tumor DNA. Therefore, we prospectively enrolled 12 patients with early-stage non-small cell lung cancer without endoscopically visible tumors. Somatic mutations were analyzed using ultra-deep next-generation sequencing in 48 paired specimens (primary tumor tissue, normal tissue, BW supernatant, and BW precipitate). In primary tumors, 130 missense mutations/indels (5-16 per patient) and 20 driver mutations (0-3 per patient) were found. Concordance of driver mutations between BW fluids and primary tumors was 95.0%. The allele frequencies for missense mutations/indels in BW supernatants significantly correlated with those in primary tumors and were higher than those in BW precipitates. These findings suggest that BW supernatants are reflective of tumor-associated mutations and could be used for early-stage lung cancer diagnosis.

A national survey of lung cancer specialists' views on low-dose CT screening for lung cancer in Korea.

Lung cancer specialists play an important role in designing and implementing lung cancer screening. We aimed to describe their 1) attitudes toward low-dose lung computed tomography (LDCT) screening, 2) current practices and experiences of LDCT screening and 3) attitudes and opinions towards national lung cancer screening program (NLCSP). We conducted a national web-based survey of pulmonologists, thoracic surgeons, medical oncologists, and radiological oncologists who are members of Korean Association for Lung Cancer (N = 183). Almost all respondents agreed that LDCT screening increases early detection (100%), improves survival (95.1%), and gives a good smoking cessation counseling opportunity (88.6%). Most were concerned about its high false positive results (79.8%) and the subsequent negative effects. Less than half were concerned about radiation hazard (37.2%). Overall, most (89.1%) believed that the benefits outweigh the risks and harms. Most (79.2%) stated that they proactively recommend LDCT screening to those who are eligible for the current guidelines, but the screening propensity varied considerably. The majority (77.6%) agreed with the idea of NLCSP and its beneficial effect, but had concerns about the quality control of CT devices (74.9%), quality assurance of radiologic interpretation (63.3%), poor access to LDCT (56.3%), and difficulties in selecting eligible population using self-report history (66.7%). Most (79.2%) thought that program need to be funded by a specialized fund rather than by the National Health Insurance. The opinions on the level of copayment for screening varied. Our findings would be an important source for health policy decision when considering for NLCSP in Korea.

Indicators and Qualitative Assessment of Lung Cancer Management by Health Insurance Review and Assessment Service (HIRA) of Korea in 2015.

Cancer is the leading cause of death in the Republic of Korea and cancer death accounts for 27.8% of the total deaths, which is not only a social issue but also a concern for the public. Among the cancer death rates, lung cancer mortality account for 34 deaths per 100,000 populations, making it the number one cancer death rate. In a preliminary report on cancer death in 2012, the lung cancer mortality ratio showed the regional variation indicating that there were differences in the qualitative level and the structure among the medical care benefit agency and in the assessment of the treatment process. Therefore, the Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the assessment of lung cancer treatment since 2014 to improve the quality of lung cancer care through evaluation and feeds back the results of lung cancer care process. In this report, authors described the current Indicators for the lung cancer adequacy assessment proposed by HIRA and results of the evaluation reported in 2017.

Nonspecific Bronchoprovocation Test.

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.

Effect of high-dose furosemide on the prognosis of critically ill patients.

PURPOSE: Diuretics are used frequently in critically ill patients. We investigated the effects of furosemide on the prognosis. MATERIALS AND METHODS: Following a retrospective review of patients admitted to the medical intensive care unit (ICU), we analyzed risk factors with variables including initial furosemide dose for ICU mortality. RESULTS: A total of 448 patients were included. Total furosemide dose during the first three days of the ICU stay (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.01-5.02) and fluid balance during the same period (OR 3.04, 95% CI 1.46-6.31) were associated with ICU mortality, as were malignancy, chronic furosemide use, and APACHE II score. However, in oliguric patients, positive fluid balance was associated with ICU mortality (OR 22.33, 95% CI 1.82-273.72) but the high-dose furosemide was not. In contrast, in non-oliguric patients, high-dose furosemide was associated with ICU mortality (OR 2.47, 95% CI 1.01-5.68); however, the positive fluid balance showed only a trend for high ICU mortality. CONCLUSION: Early high-dose furosemide use is associated with ICU mortality, particularly in non-oliguric patients. We suggest that furosemide should be used with caution even in non-oliguric critically ill patients until the safety is confirmed in powered study.

Lung cancer specialist physicians' attitudes towards e-cigarettes: A nationwide survey.

OBJECTIVES: Despite a sharp increase in e-cigarette use, there is debate about whether e-cigarettes are a viable alternative for harm reduction, and the forms that regulation should take. Healthcare providers can be effective in offering guidance to patients and their families and shaping regulatory policy. We described lung cancer specialists' attitudes toward e-cigarettes and its regulation. METHODS: We undertook a nationwide survey of pulmonologists, thoracic surgeons, medical and radiological oncologists who are members of Korean Association for Lung Cancer. Survey items included beliefs and attitudes toward e-cigarettes, attitudes toward e-cigarette regulation and preparedness on discussing e-cigarettes with their patients. RESULTS: Most respondents believed that e-cigarettes are not safer than conventional tobacco cigarettes (75.7%) or smokeless tobacco (83.2%), and feared that discussing e-cigarettes with the patients would encourage use (65.4%). They did not consider it a smoking cessation treatment (78.3%), and thus would not recommend it to smokers who do not want to quit (82.2%) or who failed to quit with conventional smoking cessation treatment (74.1%). Most respondents supported all examples of e-cigarette regulations, including the safety and quality check (97.8%), warning label (97.8%), advertisement ban (95.1%), restriction of flavoring (78.4%), minimum purchasing age (99.5%), and restriction of indoor use (94.6%). Most learned about e-cigarettes from media and advertisements, or conversation with patients rather than through professional scientific resources, and reported discomfort when discussing e-cigarette with patients. CONCLUSION: Lung cancer specialist physicians in Korea doubt the safety of e-cigarette and use of e-cigarette as smoking cessation treatment, and supported strict regulation. However, only 20% reported that they obtained information on e-cigarettes from the scientific literature and many lacked adequate knowledge based on scientific evidence, suggesting the need for better preparedness. Nevertheless, the views of professionals revealed from our study could help to develop clinical guidelines and regulatory guidance.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

Clinical and microbiological features of patients admitted to the intensive care unit with nursing and healthcare-associated pneumonia.

OBJECTIVE: To evaluate clinical and microbiological features in patients with nursing and healthcare-associated pneumonia (NHCAP), admitted to the intensive care unit (ICU). METHODS: Demographic, clinical and microbiological data were retrospectively reviewed from patients with NHCAP admitted to a respiratory ICU. Patients were categorized into one of four NHCAP groups: (A) residence in a long-term nursing-home setting or healthcare home; (B) hospital discharge in the preceding 90 days; (C) elderly or physically disabled patients who stay at home but require healthcare; (D) continuously receiving outpatient endovascular therapy including chronic dialysis, anticancer drugs, and immunosuppressants. Pneumonia severity index (PSI), CURB-65, duration of ICU stay and 30-day mortality were evaluated. RESULTS: Out of 428 patients reviewed (male, 67.1%; mean age, 71.2 ± 11.9 years), 30-day mortality was 25.5%, and duration of ICU stay was 13.8 ± 13.3 days. Mortality rate was not significantly different between the four NHCAP groups; duration of ICU stay was significantly longer in groups C and D. PSI score, serum HCO3(-) level, duration of ICU stay, extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae and multidrug resistant (MDR) Acinetobacter baumannii were significantly associated with 30-day mortality. CONCLUSION: ESBL-producing K. pneumoniae, MDR A. baumannii and PSI score should be considered in ICU patients with NHCAP.

Moderate hemoptysis: recurrent hemoptysis and mortality according to bronchial artery embolization.

INTRODUCTION: The studies on hemoptysis have focused mainly on hemoptysis causes and massive or life-threatening hemoptysis. And there is a limited data that non-massive hemoptysis, especially moderate hemoptysis. OBJECTIVES: We analyzed the prognosis and severity of bleeding on flexible bronchoscopy (FB) between moderate and massive hemoptysis. METHODS: We reviewed total 852 subjects (59.9 ± 16.0 years) identified with hemoptysis. Reviewed database included severity of subjective hemoptysis, bleeding on FB, comorbid conditions, time from admission to bronchial artery embolization (BAE), recurrent hemoptysis and mortality. RESULTS: In subjective hemoptysis, recurrent hemoptysis occurred in mild 8.0%, moderate 40.7%, massive hemoptysis 33.8%, and mortality was 4.7%, 13.4% and 13.5%. Especially, no statistical difference was shown in recurrent hemoptysis [hazard ratio (HR) = 0.795; 95% confidence interval (CI) 0.562-1.125, P = 0.196] and mortality (HR = 1.054; 95% CI 0.596-1.864, P = 0.856) between moderate and massive hemoptysis. In moderate hemoptysis patients, oozing or active bleeding on FB took up 83.3%. In this review, recurrent hemoptysis was more in oozing bleeding than active bleeding (HR = 1.781; 95% CI 1.214-2.431, P = 0.002), but mortality was similar (HR = 1.611; 95% CI 0.930-2.790, P = 0.089). Recurrent hemoptysis significantly decreased in the group with BAE performed within 24 h (HR = 0.308; 95% CI 0.149-0.637, P = 0.001) in moderate hemoptysis. Also, recurrent hemoptysis and mortality were significantly increased in the patients with smoking (≥40 pack-years), oozing or active bleeding on FB, and hypertension. CONCLUSION: Moderate hemoptysis has shown similar prognosis of recurrent hemoptysis and mortality to massive hemoptysis. Therefore, the more aggressive FB and BAE should be considered in moderate hemoptysis.

The effects of bronchoscope diameter on the diagnostic yield of transbronchial lung biopsy of peripheral pulmonary nodules.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a valuable diagnostic tool for peripheral pulmonary lesions. The diagnostic yield of TBLB reportedly ranges from 41%-60%. Many studies demonstrated the various factors that influence the yield of TBLB, including size, location, and distance from the carina or pleura. However, no study has evaluated the effects of the bronchoscope diameter. We evaluated whether the bronchoscope diameter affected the diagnostic yield of TBLB. METHODS: We reviewed records from 178 patients who underwent TBLB using bronchoscopes of two different diameters (5.7 mm, thick outer diameter, Olympus BF-200; 4.9 mm, thin, BF-260). The fluoroscopic guidance rates, yield of TBLB and flexible bronchoscopy (FB) were compared between the two groups. Additionally, we compared the results of the procedures with respect to diagnosis, distance from the pleura, and size of the lesion. RESULTS: The results of fluoroscopic guidance, TBLB, and FB yield using thin diameter bronchoscope were significantly better than those obtained with a thick diameter bronchoscope (p=0.021, p=0.036, and p=0.010, respectively). Particularly, when the distance from the pleura was ≤ 10 mm, success rates for fluoroscopic guidance and FB with thin bronchoscope were higher (p=0.013 and p=0.033, respectively), as compared to with thick bronchoscope. CONCLUSION: A thinner diameter bronchoscope increased the yield of bronchoscopy, and bronchial washing in conjunction with TBLB was useful in the diagnosis of peripheral pulmonary nodules.